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Sample records for augment kidney injury

  1. Injury - kidney and ureter

    Science.gov (United States)

    ... kidney; Ureteral injury; Pre-renal failure - injury, Post-renal failure - injury; Kidney obstruction - injury Images Kidney anatomy Kidney - blood and urine flow References Molitoris BA. Acute kidney injury. In: Goldman ...

  2. [Acute kidney injury

    NARCIS (Netherlands)

    Hageman, D.; Kooman, J.P.; Lance, M.D.; van Heurn, L.W.; Snoeijs, M.G.

    2012-01-01

    - 'Acute kidney injury' is modern terminology for a sudden decline in kidney function, and is defined by the RIFLE classification (RIFLE is an acronym for Risk, Injury, Failure, Loss and End-stage kidney disease).- Acute kidney injury occurs as a result of the combination of reduced perfusion in the

  3. Diabetes increases the susceptibility to acute kidney injury after myocardial infarction through augmented activation of renal Toll-like receptors in rats.

    Science.gov (United States)

    Ohno, Kouhei; Kuno, Atsushi; Murase, Hiromichi; Muratsubaki, Shingo; Miki, Takayuki; Tanno, Masaya; Yano, Toshiyuki; Ishikawa, Satoko; Yamashita, Tomohisa; Miura, Tetsuji

    2017-12-01

    Acute kidney injury (AKI) after acute myocardial infarction (MI) worsens the prognosis of MI patients. Although type 2 diabetes mellitus (DM) is a major risk factor of AKI after MI, the underlying mechanism remains unclear. Here, we examined the roles of renal Toll-like receptors (TLRs) in the impact of DM on AKI after MI. MI was induced by coronary artery ligation in Otsuka-Long-Evans-Tokushima fatty (OLETF) rats, a rat DM model, and Long-Evans-Tokushima-Otsuka (LETO) rats, nondiabetic controls. Sham-operated rats served as no-MI controls. Renal mRNA levels of TLR2 and myeloid differentiation factor 88 (MyD88) were significantly higher in sham-operated OLETF rats than in sham-operated LETO rats, although levels of TLR1, TLR3, and TLR4 were similar. At 12 h after MI, protein levels of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in the kidney were elevated by 5.3- and 4.0-fold, respectively, and their mRNA levels were increased in OLETF but not LETO rats. The increased KIM-1 and NGAL expression levels after MI in the OLETF kidney were associated with upregulated expression of TLR1, TLR2, TLR4, MyD88, IL-6, TNF-α, chemokine (C-C motif) ligand 2, and transforming growth factor-β 1 and also with activation of p38 MAPK, JNK, and NF-κB. Cu-CPT22, a TLR1/TLR2 antagonist, administered before MI significantly suppressed MI-induced upregulation of KIM-1, TLR2, TLR4, MyD88, and chemokine (C-C motif) ligand 2 levels and activation of NF-κB, whereas NGAL levels and IL-6 and TNF-α expression levels were unchanged. The results suggest that DM increases the susceptibility to AKI after acute MI by augmented activation of renal TLRs and that TLR1/TLR2-mediated signaling mediates KIM-1 upregulation after MI. NEW & NOTEWORTHY This is the first report to demonstrate the involvement of Toll-like recpetors (TLRs) in diabetes-induced susceptibility to acute kidney injury after acute myocardial infarction. We propose that the TLR1/TLR2

  4. Epidemiology of RBC Transfusions in Patients With Severe Acute Kidney Injury: Analysis From the Randomized Evaluation of Normal Versus Augmented Level Study.

    Science.gov (United States)

    Bellomo, Rinaldo; Mårtensson, Johan; Kaukonen, Kirsi-Maija; Lo, Serigne; Gallagher, Martin; Cass, Alan; Myburgh, John; Finfer, Simon

    2016-05-01

    To assess the epidemiology and outcomes associated with RBC transfusion in patients with severe acute kidney injury requiring continuous renal replacement therapy. Post hoc analysis of data from a multicenter, randomized, controlled trial. Thirty-five ICUs in Australia and New Zealand. Cohort of 1,465 patients enrolled in the Randomized Evaluation of Normal versus Augmented Level replacement therapy study. Daily information on morning hemoglobin level and amount of RBC transfused were prospectively collected in the Randomized Evaluation of Normal versus Augmented Level study. We analyzed the epidemiology of such transfusions and their association with clinical outcomes. Overall, 977 patients(66.7%) received a total of 1,192 RBC units. By day 5, 785 of 977 transfused patients (80.4%) had received at least one RBC transfusion. Hemoglobin at randomization was lower in transfused than in nontransfused patients (94 vs 111 g/L; p regression analysis, RBC transfusion was independently associated with lower 90-day mortality (hazard ratio, 0.55; 95% CI, 0.38-0.79). However, we found no independent association between RBC transfusions and mortality when the analyses were restricted to patients surviving at least 5 days (hazard ratio, 1.29; 95% CI, 0.90-1.85). We found no independent association between RBC transfusion and renal replacement therapy-free days, mechanical ventilator-free days, or length of stay in ICU or hospital. In patients with severe acute kidney injury treated with continuous renal replacement therapy, we found no association of RBC transfusion with 90-day mortality or other patient-centered outcomes. The optimal hemoglobin threshold for RBC transfusion in such patients needs to be determined in future randomized controlled trials.

  5. Kidney injury in cirrhosis

    DEFF Research Database (Denmark)

    Møller, Søren; Krag, Aleksander; Bendtsen, Flemming

    2014-01-01

    Acute kidney injury (AKI) is frequent in patients with cirrhosis. AKI and hyponatraemia are major determinants of the poor prognosis in advanced cirrhosis. The hepatorenal syndrome (HRS) denotes a functional and potential reversible impairment of renal function. Type 1 HRS, a special type of AKI...

  6. Pediatric Acute Kidney Injury.

    Science.gov (United States)

    Fragasso, Tiziana; Ricci, Zaccaria; Goldstein, Stuart L

    2018-01-01

    Acute kidney injury (AKI) in children is a serious condition with an important impact on morbidity and mortality. Onset can be insidious and it is frequently unrecognized in the early phase when the therapeutic opportunities are theoretically more effective. The present review focuses on the most recent epidemiology studies and the progress in pediatric AKI (pAKI) research. Standardization of definition (presented in the Kidney Disease: Improving Global Outcomes) and novel biomarkers have been developed to help clinicians recognize kidney injury in a timely manner, both in adult and pediatric populations. Strengths and weaknesses of these diagnostic tools are discussed and the clinical scoring system (Renal Angina Index), which aims to provide a rational context for biomarker utilization, is also presented. Even if effective treatments are not currently available for established AKI, specific preventive approaches and some promising pharmacological treatments will be detailed. Renal replacement therapy is currently considered the most effective way to manage fluid balance when severe AKI occurs. Key Messages: Great efforts in pAKI research have today led to new strategies for early AKI detection and prevention strategies. Further studies have to be conducted in the next future in order to definitely improve the outcomes of pediatric patients experiencing this deadly syndrome. © 2018 S. Karger AG, Basel.

  7. Acute Kidney Injury in the Elderly

    Science.gov (United States)

    Abdel-Kader, Khaled; Palevsky, Paul

    2009-01-01

    Synopsis The aging kidney undergoes a number of important anatomic and physiologic changes that increase the risk of acute kidney injury (formerly acute renal failure) in the elderly. This article reviews these changes and discusses the diagnoses frequently encountered in the elderly patient with acute kidney injury. The incidence, staging, evaluation, management, and prognosis of acute kidney injury are also examined with special focus given to older adults. PMID:19765485

  8. Kidney injury molecule-1 and microalbuminuria levels in Zambian ...

    African Journals Online (AJOL)

    Kidney injury molecule-1 and microalbuminuria levels in Zambian population: biomarkers of kidney injury. Mildred Zulu, Trevor Kaile, Timothy Kantenga, Chisanga Chileshe, Panji Nkhoma, Musalula Sinkala ...

  9. Diuretics in acute kidney injury.

    Science.gov (United States)

    Nigwekar, Sagar U; Waikar, Sushrut S

    2011-11-01

    Acute kidney injury (AKI) is common in hospitalized patients and is associated with significant morbidity and mortality. The incidence of AKI is increasing and despite clinical advances there has been little change in the outcomes associated with AKI. A variety of interventions, including loop diuretics, have been tested for the prevention and treatment of AKI; however, none to date have shown convincing benefits in clinical studies, and the management of AKI remains largely supportive. In this article, we review the pharmacology and experimental and clinical evidence for loop diuretics in the management of AKI. In addition, we also review evidence for other agents with diuretic and/or natriuretic properties such as thiazide diuretics, mannitol, fenoldopam, and natriuretic peptides in both the prevention and treatment of AKI. Implications for current clinical practice are outlined to guide clinical decisions in this field. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Transplantation of Kidneys From Donors With Acute Kidney Injury: Friend or Foe?

    NARCIS (Netherlands)

    Boffa, C.; van de Leemkolk, F.; Curnow, E.; Homan van der Heide, J.; Gilbert, J.; Sharples, E.; Ploeg, R. J.

    2017-01-01

    The gap between supply and demand in kidney transplantation has led to increased use of marginal kidneys; however, kidneys with acute kidney injury are often declined/discarded. To determine whether this policy is justified, we analyzed outcomes of donor kidneys with acute kidney injury (AKI) in a

  11. Kidney injury molecule-1 in renal disease

    NARCIS (Netherlands)

    Waanders, Femke; van Timmeren, Mirjan M.; Stegeman, Coen A.; Bakker, Stephan J. L.; van Goor, Harry

    Kidney injury molecule-1 (KIM-1) is a marker for renal proximal tubular damage, the hallmark of virtually all proteinuric, toxic and ischaemic kidney diseases. KIM-1 has gained increasing interest because of its possible pathophysiological role in modulating tubular damage and repair. In this

  12. Acute Kidney Injury in Pregnancy.

    Science.gov (United States)

    Jim, Belinda; Garovic, Vesna D

    2017-07-01

    Pregnancy-related acute kidney injury (AKI) has declined in incidence in the last three decades, although it remains an important cause of maternal and fetal morbidity and mortality. Pregnancy-related causes of AKI such as preeclampsia, acute fatty liver of pregnancy, HELLP (Hemolysis, Elevated Liver function tests, Low Platelets) syndrome, and the thrombotic microangiopathies (thrombotic thrombocytopenic purpura, atypical hemolytic-uremic syndrome [HUS]) exhibit overlapping features and often present as diagnostic dilemmas. Differentiating among these conditions may be difficult or impossible based on clinical criteria only. In difficult and rare cases, a renal biopsy may need to be considered for the exact diagnosis and to facilitate appropriate treatment, but the risks and benefits need to be carefully weighed. The use of eculizumab for the treatment of atypical HUS has demonstrated efficacy in early case reports. Non-pregnancy related causes such as volume depletion and pyelonephritis require early and aggressive resuscitative as well as antibiotic measures respectively. We will discuss in this review the various etiologies of AKI in pregnancy, current diagnostic approaches, and the latest treatment strategies. Given the recent trends of increasing maternal age at the time of pregnancy, and the availability of modern reproductive methods increase the risks of AKI in pregnancy in the coming years. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Automated acute kidney injury alerts.

    Science.gov (United States)

    Kashani, Kianoush B

    2018-05-02

    Acute kidney injury (AKI) is one of the most common and probably one of the more consequential complications of critical illnesses. Recent information indicates that it is at least partially preventable; however, progress in its prevention, management, and treatment has been hindered by the scarcity of knowledge for effective interventions, inconsistencies in clinical practices, late identification of patients at risk for or with AKI, and limitations of access to best practices for prevention and management of AKI. Growing use of electronic health records has provided a platform for computer science to engage in data mining and processing, not only for early detection of AKI but also for the development of risk-stratification strategies and computer clinical decision-support (CDS) systems. Despite promising perspectives, the literature regarding the impact of AKI electronic alerts and CDS systems has been conflicting. Some studies have reported improvement in care processes and patient outcomes, whereas others have shown no effect on clinical outcomes and yet demonstrated an increase in the use of resources. These discrepancies are thought to be due to multiple factors that may be related to technology, human factors, modes of delivery of information to clinical providers, and level of expectations regarding the impact on patient outcomes. This review appraises the current body of knowledge and provides some outlines regarding research into and clinical aspects of CDS systems for AKI. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  14. New biomarkers of acute kidney injury

    Directory of Open Access Journals (Sweden)

    Ruya Ozelsancak

    2013-04-01

    Full Text Available Acute kidney injury is a clinical syndrome which is generally defined as an abrupt decline in glomerular filtration rate causing accumulation of nitrogenous products and rapid development of fluid, electrolyte and acid-base disorders. It is an important clinical problem increasing mortality in patient with several co-morbid conditions. The frequency of acute kidney injury occurrence varies from 5% on the inpatients wards to 30-50% in patients from intensive care units. Serial measurement of creatinine and urine volume do not make it possible to diagnose acute kidney injury at early stages. Serum creatinine may be influenced by age, weight, hydration status and become apparent only when the kidneys have lost 50% of their function. For that reasons we need new markers. Here, we are reviewing the most promising new acute kidney injury markers, neutrophil gelatinase associated lipocalin, cystatin-C, kidney injury molecule-1, liver fatty acid binding proteins and IL-18. [Archives Medical Review Journal 2013; 22(2.000: 221-229

  15. Studies on radiation injury of the kidney

    International Nuclear Information System (INIS)

    Kamiya, Akio

    1982-01-01

    According to many experimental reports on the radiation renal injuries, the influences of irradiation were observed not only in the irradiated kidney, but also in the contralateral kidney. However, its mechanism has not yet been demonstrated clearly. In order to clarify the mechanism of development of pathophysiological changes seen on the kidney of non-irradiated side, a study was made of function and pathological condition of a remaining kidney after the enucleation of ir radiated side kidney after irradiation. Twenty-eitht rabbits were divided into 4 groups. A: 14 rabbits were irradiated on their left kidney with 60 Co- gamma ray 50 Gy doses. B: 6 rabbits were nephrectomized of their left kidney on the first day after 50 Gy irradiation. C: 4 rabbits were nephrectomized of their left kidney on the eighth day after 50 Gy irradiation. D: 4 rabbits were simple nephrectomized. The results suggest that changes on the irradiated side of kidney bring about effect to the contra-lateral kidney at an early stage after the irradiation. (J.P.N.)

  16. Acute kidney injury with hypoxic respiratory failure

    OpenAIRE

    Neubert, Zachary; Hoffmann, Paul; Owshalimpur, David

    2014-01-01

    A 27-year-old Caucasian man was transferred from a remote clinic with acute kidney injury for the prior 7–10 days preceded by gastroenteritis. His kidney biopsy showed non-specific mesangiopathic glomerular changes, minimal tubulointerstitial disease without sclerosis, crescents, nor evidence of vasculitis. On his third hospital day, he developed acute hypoxic respiratory failure requiring intubation and mechanical ventilation. Pulmonary renal syndromes ranked highest on his differential diag...

  17. Fluid management in acute kidney injury

    DEFF Research Database (Denmark)

    Perner, Anders; Prowle, John; Joannidis, Michael

    2017-01-01

    Acute kidney injury (AKI) and fluids are closely linked through oliguria, which is a marker of the former and a trigger for administration of the latter. Recent progress in this field has challenged the physiological and clinical rational of using oliguria as a trigger for the administration...... of crystalloids and colloids on kidney function and the effect of various resuscitation and de-resuscitation strategies on the course and outcome of AKI....

  18. Causes and Outcome of Acute Kidney Injury: Gezira Experience ...

    African Journals Online (AJOL)

    Introduction: A precise operational definition of acute kidney injury remains elusive. Conceptually, acute kidney injury is defined as the loss of renal function, measured by decline in glomerular filtration rate, developing over a period of hours to days. Clinical manifestations of acute kidney injury (AKI) are highly variable; ...

  19. Acute kidney injury in the cancer patient.

    Science.gov (United States)

    Campbell, G Adam; Hu, Daniel; Okusa, Mark D

    2014-01-01

    Acute kidney injury (AKI) is a frequent and significant complication of cancer and cancer therapy. Cancer patients frequently encounter risk factors for AKI including older age, CKD, prerenal conditions, sepsis, exposure to nephrotoxins, and obstructive physiology. AKI can also be secondary to paraneoplastic conditions, including glomerulonephritis and microangiopathic processes. This complication can have significant consequences, including effects on patients' ability to continue to receive therapy for their malignancy. This review will serve to summarize potential etiologies of AKI that present in patients with cancer as well as to highlight specific patient populations, such as the critically ill cancer patient. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  20. Hymenoptera Stings and the Acute Kidney Injury

    Directory of Open Access Journals (Sweden)

    Yashad Dongol

    2013-07-01

    Full Text Available Hymenoptera stings are a health concern. Apidae (bees, Vespidae (hornets, yellow jackets and wasps and Formicidae (ants are medically-important stinging insects under the order Hymenoptera. Clinical features from simple skin manifestations to severe and fatal organ injury are due to the hypersensitivity reactions and/ or the toxic effects of the venom inoculated. Here we discuss on Hymenoptera stings involving apids (honey bees and vespids (wasps, hornets and yellow jackets and their effect on renal function and associated morphological changes in the kidney. Despite the differences in venom composition and quantity released per sting in two insect groups, both lead to similar medical consequences, such as localised normal allergic reactions, mild to severe anaphylaxis and shock and multiple organ and tissue injury leading to multiple organ failure. Acute kidney injury (AKI is one of the unusual complications of Hymenoptera stings and has the basis of both immune-mediated and toxic effects. Evidence has proven that supportive therapy along with the standard medication is very efficient in completely restoring the kidney function without any recurrence.

  1. Impact of Acute Kidney Injury in Patients Hospitalized With Pneumonia.

    Science.gov (United States)

    Chawla, Lakhmir S; Amdur, Richard L; Faselis, Charles; Li, Ping; Kimmel, Paul L; Palant, Carlos E

    2017-04-01

    Pneumonia is a common cause of hospitalization and can be complicated by the development of acute kidney injury. Acute kidney injury is associated with major adverse kidney events (death, dialysis, and durable loss of renal function [chronic kidney disease]). Because pneumonia and acute kidney injury are in part mediated by inflammation, we hypothesized that when acute kidney injury complicates pneumonia, major adverse kidney events outcomes would be exacerbated. We sought to assess the frequency of major adverse kidney events after a hospitalization for either pneumonia, acute kidney injury, or the combination of both. We conducted a retrospective database analysis of the national Veterans Affairs database for patients with a admission diagnosis of International Classification of Diseases-9 code 584.xx (acute kidney injury) or 486.xx (pneumonia) between October 1, 1999, and December 31, 2005. Three groups of patients were created, based on the diagnosis of the index admission and serum creatinine values: 1) acute kidney injury, 2) pneumonia, and 3) pneumonia with acute kidney injury. Patients with mean baseline estimated glomerular filtration rate less than 45 mL/min/1.73 m were excluded. The primary endpoint was major adverse kidney events defined as the composite of death, chronic dialysis, or a permanent loss of renal function after the primary discharge. The observations of 54,894 subjects were analyzed. Mean age was 68.7 ± 12.3 years. The percentage of female was 2.4, 73.3% were Caucasian, and 19.7% were African-American. Differences across the three diagnostic groups were significant for death, 25% decrease in estimated glomerular filtration rate from baseline, major adverse kidney events following admission, and major adverse kidney events during admission (all p pneumonia + acute kidney injury group (51% died and 62% reached major adverse kidney events). In both unadjusted and adjusted time to event analyses, patients with pneumonia + acute kidney injury

  2. Nursing Activities Score and Acute Kidney Injury

    Directory of Open Access Journals (Sweden)

    Filipe Utuari de Andrade Coelho

    Full Text Available ABSTRACT Objective: to evaluate the nursing workload in intensive care patients with acute kidney injury (AKI. Method: A quantitative study, conducted in an intensive care unit, from April to August of 2015. The Nursing Activities Score (NAS and Kidney Disease Improving Global Outcomes (KDIGO were used to measure nursing workload and to classify the stage of AKI, respectively. Results: A total of 190 patients were included. Patients who developed AKI (44.2% had higher NAS when compared to those without AKI (43.7% vs 40.7%, p <0.001. Patients with stage 1, 2 and 3 AKI showed higher NAS than those without AKI. A relationship was identified between stage 2 and 3 with those without AKI (p = 0.002 and p <0.001. Conclusion: The NAS was associated with the presence of AKI, the score increased with the progression of the stages, and it was associated with AKI, stage 2 and 3.

  3. Mechanism of Platinum Derivatives Induced Kidney Injury

    Directory of Open Access Journals (Sweden)

    Feifei YAN

    2015-09-01

    Full Text Available Platinum derivatives are the most widely used chemotherapeutic agents to treat solid tumors including ovarian, head and neck, and testicular germ cell tumors, lung cancer, and colorectal cancer. Two major problems exist, however, in the clinic use of platinum derivatives. One is the development of tumor resistance to the drug during therapy, leading to treatment failure. The other is the drug’s toxicity such as the cisplatin’s nephrotoxicity, which limits the dose that can be administered. This paper describes the mechanism of platinum derivatives induced kidney injury.

  4. Coronary heart disease is not significantly linked to acute kidney injury identified using Acute Kidney Injury Group criteria.

    Science.gov (United States)

    Yayan, Josef

    2012-01-01

    Patients with unstable angina or myocardial infarction are at risk of acute kidney injury, which may be aggravated by the iodine-containing contrast agent used during coronary angiography; however, the relationship between these two conditions remains unclear. The current study investigated the relationship between acute kidney injury and coronary heart disease prior to coronary angiography. All patients were evaluated after undergoing coronary angiography in the cardiac catheterization laboratory of the Vinzentius Hospital in Landau, Germany, in 2011. The study group included patients with both acute coronary heart disease and acute kidney injury (as defined according to the classification of the Acute Kidney Injury Group); the control group included patients without acute coronary heart disease. Serum creatinine profiles were evaluated in all patients, as were a variety of demographic and health characteristics. Of the 303 patients examined, 201 (66.34%) had coronary artery disease. Of these, 38 (18.91%) also had both acute kidney injury and acute coronary heart disease prior to and after coronary angiography, and of which in turn 34 (16.91%) had both acute kidney injury and acute coronary heart disease only prior to the coronary angiography. However, the occurrence of acute kidney injury was not significantly related to the presence of coronary heart disease (P = 0.95, Chi-square test). The results of this study indicate that acute kidney injury is not linked to acute coronary heart disease. However, physicians should be aware that many coronary heart patients may develop kidney injury while hospitalized for angiography.

  5. Sodium hypochlorite-induced acute kidney injury

    Directory of Open Access Journals (Sweden)

    Brandon W Peck

    2014-01-01

    Full Text Available Sodium hypochlorite (bleach is commonly used as an irrigant during dental proce-dures as well as a topical antiseptic agent. Although it is generally safe when applied topically, reports of accidental injection of sodium hypochlorite into tissue have been reported. Local necrosis, pain and nerve damage have been described as a result of exposure, but sodium hypo-chlorite has never been implicated as a cause of an acute kidney injury (AKI. In this report, we describe the first case of accidental sodium hypochlorite injection into the infraorbital tissue during a dental procedure that precipitated the AKI. We speculate that oxidative species induced by sodium hypochlorite caused AKI secondary to the renal tubular injury, causing mild acute tubular necrosis.

  6. Kidney injury and heme oxygenase-1

    Directory of Open Access Journals (Sweden)

    Hai-xing MAI

    2012-02-01

    Full Text Available     Heme oxygenase-1 (HO-1 is one of the main pathways to degrade heme in mammals, and the main degradation products are free iron (Fe2+, carbon monoxide (CO, and bilirubin. Heme plays an important role in promoting cell survival, circulation of intracellular substrates, and immune regulation. Previous studies suggest that HO-1 pathway is an important internal factor in determining the susceptibility and severity of acute kidney injury (AKI. The induction of HO-1 expression can attenuate the severity of renal ischemia-reperfusion injury (IRI, and the inhibition of HO-1 expression will aggravate IRI. The present article summarizes the latest advances in research abroad and at home on protective mechanism by which HO-1 prevents AKI to further deepen our understanding of the role of HO-1 in the treatment of AKI.   

  7. Acute Kidney Injury – An Update

    Directory of Open Access Journals (Sweden)

    Matt Varrier

    2015-07-01

    Full Text Available The syndrome of acute kidney injury (AKI occurs frequently in hospitalised patients, leading to increased morbidity, mortality, and healthcare expenditure. In the context of a precipitating insult, disturbances in both global and microcirculatory renal blood flow, tubular cell damage, and activation of pro- inflammatory pathways lead to impairment of numerous elements of renal function. Classification systems, including the recent ‘Kidney Disease: Improving Global Outcomes’ (KDIGO classification, typically define and stage AKI in terms of the magnitude of rise in serum creatinine (SCr and the presence of oliguria. At present there is no cure for AKI and the key principles of its management include early recognition, haemodynamic optimisation, correction of hypovolaemia, ceasing and avoidance of nephrotoxic medications, and treatment of the underlying cause. Recent data show that the type and volume of fluid therapy can affect renal function and that further guidance is required. In the future it is hoped that novel technologies, including biomarkers and real-time measurement of glomerular filtration rate will allow the earlier identification of patients with AKI, whilst a greater understanding of the pathogenesis of AKI will lead to the identification of new therapeutic targets. Despite SCr usually recovering after an episode of AKI, there is growing recognition that survivors of AKI are at an increased risk of subsequent chronic kidney disease, including end-stage renal failure and premature death.

  8. Acute kidney injury: definition, diagnosis and epidemiology.

    Science.gov (United States)

    Rossaint, Jan; Zarbock, Alexander

    2016-02-01

    Acute kidney injury (AKI) is a common complication in hospitalized patients and great efforts by leading experts have been made in order to establish common definitions of AKI. The clinical use of these consensus definitions has led to a substantially improved understanding of AKI. In addition, the consensus definitions allow to compare AKI incidence and outcomes between different patient populations. As a result, it has become evident that AKI in the Western population represents a clinical syndrome with an incidence close to that of myocardial infarction. The aim of this review is to revisit the current concepts and definitions of AKI, to highlight its diagnosis, and to emphasize its epidemiological characteristics. Here, we will focus on the available literature reporting the epidemiology of AKI in critically ill patients. Sepsis, major surgery, and nephrotoxic drugs are the main causes of AKI in these patients, and its occurrence is associated with an increased risk for sustained chronic kidney injury. We also discuss the concept of renal angina as a possible future concept for improved clinical risk stratification to detect AKI. In this regard, we emphasize the importance of the use of novel biomarkers in the diagnosis of AKI, as they hold the potential to improve early diagnosis and prevention in the clinical setting.

  9. Serum uric acid and acute kidney injury: A mini review

    Directory of Open Access Journals (Sweden)

    Kai Hahn

    2017-09-01

    Full Text Available Acute kidney injury causes great morbidity and mortality in both the community and hospital settings. Understanding the etiological factors and the pathophysiological principles resulting in acute kidney injury is essential in prompting appropriate therapies. Recently hyperuricemia has been recognized as a potentially modifiable risk factor for acute kidney injury, including that associated with cardiovascular surgery, radiocontrast administration, rhabdomyolysis, and associated with heat stress. This review discussed the evidence that repeated episodes of acute kidney injury from heat stress and dehydration may also underlie the pathogenesis of the chronic kidney disease epidemic that is occurring in Central America (Mesoamerican nephropathy. Potential mechanisms for how uric acid might contribute to acute kidney injury are also discussed, including systemic effects on renal microvasculature and hemodynamics, and local crystalline and noncrystalline effects on the renal tubules. Pilot clinical trials also show potential benefits of lowering uric acid on acute kidney injury associated with a variety of insults. In summary, there is mounting evidence that hyperuricemia may have a significant role in the development of acute kidney injury. Prospective, placebo controlled, randomized trials are needed to determine the potential benefit of uric acid lowering therapy on kidney and cardio-metabolic diseases.

  10. Suramin protects from cisplatin-induced acute kidney injury

    Science.gov (United States)

    Dupre, Tess V.; Doll, Mark A.; Shah, Parag P.; Sharp, Cierra N.; Kiefer, Alex; Scherzer, Michael T.; Saurabh, Kumar; Saforo, Doug; Siow, Deanna; Casson, Lavona; Arteel, Gavin E.; Jenson, Alfred Bennett; Megyesi, Judit; Schnellmann, Rick G.; Beverly, Levi J.

    2015-01-01

    Cisplatin, a commonly used cancer chemotherapeutic, has a dose-limiting side effect of nephrotoxicity. Approximately 30% of patients administered cisplatin suffer from kidney injury, and there are limited treatment options for the treatment of cisplatin-induced kidney injury. Suramin, which is Federal Drug Administration-approved for the treatment of trypanosomiasis, improves kidney function after various forms of kidney injury in rodent models. We hypothesized that suramin would attenuate cisplatin-induced kidney injury. Suramin treatment before cisplatin administration reduced cisplatin-induced decreases in kidney function and injury. Furthermore, suramin attenuated cisplatin-induced expression of inflammatory cytokines and chemokines, endoplasmic reticulum stress, and apoptosis in the kidney cortex. Treatment of mice with suramin 24 h after cisplatin also improved kidney function, suggesting that the mechanism of protection is not by inhibition of tubular cisplatin uptake or its metabolism to nephrotoxic species. If suramin is to be used in the context of cancer, then it cannot prevent cisplatin-induced cytotoxicity of cancer cells. Suramin did not alter the dose-response curve of cisplatin in lung adenocarcinoma cells in vitro. In addition, suramin pretreatment of mice harboring lung adenocarcinomas did not alter the initial cytotoxic effects of cisplatin (DNA damage and apoptosis) on tumor cells. These results provide evidence that suramin has potential as a renoprotective agent for the treatment/prevention of cisplatin-induced acute kidney injury and justify future long-term preclinical studies using cotreatment of suramin and cisplatin in mouse models of cancer. PMID:26661653

  11. Determinants of postoperative acute kidney injury.

    Science.gov (United States)

    Abelha, Fernando José; Botelho, Miguela; Fernandes, Vera; Barros, Henrique

    2009-01-01

    Development of acute kidney injury (AKI) during the perioperative period is associated with increases in morbidity and mortality. Our aim was to evaluate the incidence and determinants of postoperative AKI after major noncardiac surgery in patients with previously normal renal function. This retrospective cohort study was carried out in the multidisciplinary Post-Anaesthesia Care Unit (PACU) with five intensive care beds. The study population consisted of 1166 patients with no previous renal insufficiency who were admitted to these intensive care unit (ICU) beds over 2 years. After admission patients were followed for the development of AKI, defined as proposed by The Acute Kidney Injury Network (increment of serum creatinine [greater than or equal to] 0.3 mg/dL or 50% from baseline within 48 hours or urine output 6 hours despite fluid resuscitation when applicable). Patient preoperative characteristics, intraoperative management and outcome were evaluated for associations with acute kidney injury using an univariate and multiple logistic regression model. A total of 1597 patients were admitted to the PACU and of these, 1166 met the inclusion criteria. Eighty-seven patients (7.5%) met AKI criteria. Univariate analysis identified age, American Society of Anesthesiologists (ASA) physical status, emergency surgery, high risk surgery, ischemic heart disease, congestive heart disease and Revised Cardiac Risk Index (RCRI) score as independent preoperative determinants for AKI in the postoperative period. Multivariate analysis identified ASA physical status, RCRI score, high risk surgery and congestive heart disease as preoperative determinants for AKI in the postoperative period. Patients that developed AKI had higher Simplified Acute Physiology Score (SAPS) II and Acute Physiology and Chronic Health Evaluation (APACHE) II, higher PACU length of stay (LOS), higher PACU mortality, higher hospital mortality and higher mortality at 6 months follow-up. AKI was an independent

  12. Snake-bite-induced Acute Kidney Injury

    International Nuclear Information System (INIS)

    Naqvi, R.

    2016-01-01

    Objective: To describe the clinical spectrum and outcome of patients presenting to a tertiary care kidney center, developing acute kidney injury (AKI) after snake-bite. Study Design: An observational study. Place and Duration of Study: Nephrology Department, Sindh Institute of Urology and Transplantation (SIUT), Karachi, from January 1990 to December 2014. Methodology: All patients coming to SIUT identified as having AKI after snake-bite during the study period were included. AKI was defined according to RIFLE criteria with sudden rise in creatinine or decline in urine output or both. Demographics, clinical presentation, laboratory profile, and final outcome was noted. Result: During the studied period, 115 cases of AKI, secondary to snake-bite, were registered at this institution. Median age of patients was 35.92 ±15.04 (range: 6 - 70) years and male to female ratio was 1.6:1. Time from bite and referral to this hospital ranged from 2 to 28 days (mean: 8.77 ±5.58 days). Oligo-anuria was the most common presentation, being found in 98 (93.90 percentage) patients. Bleeding diathesis was reported in 75 (65.21 percentage) patients on presentation. All patients had normal sized, non-obstructed kidneys on ultrasonography, with no previous comorbids. Renal replacement therapy (RRT) was required in 106 (92.17 percentage) patients. Complete recovery was seen in 59 (51.30 percentage), while 15 (13.04 percentage) patients expired during acute phase of illness, 4 (3.47 percentage) developed CKD, 11 (9.56 percentage) required dialysis beyond 90 days, and 26 (22.60 percentage) were lost to long-term follow-up. Conclusion: Snake-bite, leading to multiple complications including renal failure and death, is a major health issue in tropical countries. Late referral of these patients to specialized centres Result in undesirable outcome. (author)

  13. Acute kidney injury: definition, epidemiology, and outcome.

    Science.gov (United States)

    Srisawat, Nattachai; Kellum, John A

    2011-12-01

    Acute kidney injury (AKI) is a common clinical syndrome whose definition has standardized as a result of consensus by leading experts around the world. As a result of these definitions, reported AKI incidences can now be compared across different populations and settings. Evidence from population-based studies suggests that AKI is nearly as common as myocardial infarction, at least in the western world. This review aims to highlight the recent advances in AKI epidemiology as well as to suggest future directions for prevention and management. This review will focus on the recent studies exploring the AKI epidemiology in and outside the ICU. In particular, the risk of AKI in less severe sepsis is notable as is evidence linking AKI to chronic kidney disease. New emphasis on renal recovery is shaping current thinking as is the use and utility of new biomarkers. This article reviews the recent information about the definition, classification, and epidemiology of AKI. Although new biomarkers are being developed, the 'tried and true' markers of serum creatinine and urine output, disciplined by current criteria, will be important components in the definition and classification of AKI for some time to come.

  14. Imperfect Gold Standards for Kidney Injury Biomarker Evaluation

    Science.gov (United States)

    Betensky, Rebecca A.; Emerson, Sarah C.; Bonventre, Joseph V.

    2012-01-01

    Clinicians have used serum creatinine in diagnostic testing for acute kidney injury for decades, despite its imperfect sensitivity and specificity. Novel tubular injury biomarkers may revolutionize the diagnosis of acute kidney injury; however, even if a novel tubular injury biomarker is 100% sensitive and 100% specific, it may appear inaccurate when using serum creatinine as the gold standard. Acute kidney injury, as defined by serum creatinine, may not reflect tubular injury, and the absence of changes in serum creatinine does not assure the absence of tubular injury. In general, the apparent diagnostic performance of a biomarker depends not only on its ability to detect injury, but also on disease prevalence and the sensitivity and specificity of the imperfect gold standard. Assuming that, at a certain cutoff value, serum creatinine is 80% sensitive and 90% specific and disease prevalence is 10%, a new perfect biomarker with a true 100% sensitivity may seem to have only 47% sensitivity compared with serum creatinine as the gold standard. Minimizing misclassification by using more strict criteria to diagnose acute kidney injury will reduce the error when evaluating the performance of a biomarker under investigation. Apparent diagnostic errors using a new biomarker may be a reflection of errors in the imperfect gold standard itself, rather than poor performance of the biomarker. The results of this study suggest that small changes in serum creatinine alone should not be used to define acute kidney injury in biomarker or interventional studies. PMID:22021710

  15. Comparison of 3 kidney injury multiplex panels in rats.

    Science.gov (United States)

    John-Baptiste, Annette; Vitsky, Allison; Sace, Frederick; Zong, Qing; Ko, Mira; Yafawi, Rolla; Liu, Ling

    2012-01-01

    Kidney injury biomarkers have been utilized by pharmaceutical companies as a means to assess the potential of candidate drugs to induce nephrotoxicity. Multiple platforms and assay methods exist, but the comparison of these methods has not been described. Millipore's Kidney Toxicity panel, EMD/Novagen's Widescreen Kidney Toxicity panel, and Meso Scales Kidney Injury panel were selected based on published information. Kidney injury molecule 1, cystatin C, clusterin, and osteopontin were the 4 biomarkers common among all kits tested and the focus of this study. Rats were treated with a low and high dose of para-aminophenol, a known nephrotoxicant, and urine samples were collected and analyzed on the Bio-Plex 200 or MSD's Sector Imager 6000, according to manufacturers specifications. Comparatively, of the 3 kits, Millipore was the most consistent in detecting elevations of 3 out of the 4 biomarkers at both dose levels and indicated time points.

  16. Nursing Activities Score and Acute Kidney Injury.

    Science.gov (United States)

    Coelho, Filipe Utuari de Andrade; Watanabe, Mirian; Fonseca, Cassiane Dezoti da; Padilha, Katia Grillo; Vattimo, Maria de Fátima Fernandes

    2017-01-01

    to evaluate the nursing workload in intensive care patients with acute kidney injury (AKI). A quantitative study, conducted in an intensive care unit, from April to August of 2015. The Nursing Activities Score (NAS) and Kidney Disease Improving Global Outcomes (KDIGO) were used to measure nursing workload and to classify the stage of AKI, respectively. A total of 190 patients were included. Patients who developed AKI (44.2%) had higher NAS when compared to those without AKI (43.7% vs 40.7%), p <0.001. Patients with stage 1, 2 and 3 AKI showed higher NAS than those without AKI. A relationship was identified between stage 2 and 3 with those without AKI (p = 0.002 and p <0.001). The NAS was associated with the presence of AKI, the score increased with the progression of the stages, and it was associated with AKI, stage 2 and 3. avaliar a carga de trabalho de enfermagem em pacientes de terapia intensiva com lesão renal aguda (LRA). estudo quantitativo, em Unidade de Terapia Intensiva, no período de abril a agosto de 2015. O Nursing Activities Score (NAS) e o Kidney Disease Improving Global Outcomes (KDIGO) foram utilizados para medir a carga de trabalho de enfermagem e classificar o estágio da LRA, respectivamente. foram incluídos 190 pacientes. Os pacientes que desenvolveram LRA (44,2%) possuíam NAS superiores quando comparados aos sem LRA (43,7% vs 40,7%), p<0,001. Os pacientes com LRA nos estágios 1, 2 e 3 de LRA demonstraram NAS superiores aos sem LRA, houve relação entre os estágios 2 e 3 com os sem LRA, p=0,002 e p<0,001. o NAS apresentou associação com a existência de LRA, visto que seu valor aumenta com a progressão dos estágios, tendo associação com os estágios 2 e 3 de LRA.

  17. A case of acute kidney injury by near-drowning.

    Science.gov (United States)

    Amir, A; Lee, Y L

    2013-01-01

    Acute kidney injury following immersion or near-drowning is rarely described and no data from Malaysia have been found. We report a case of acute kidney injury following a near-drowning event. A 20-year-old man who recovered from near-drowning in a swimming pool 5 days earlier presented to our clinic with abdominal pain, anorexia, nausea and polyuria. Dipstick urinalysis showed a trace of blood. The serum creatinine level was 10-fold higher than the normal range. A bedside ultrasound showed features suggestive of acute tubular necrosis. He is then referred to the hospital with the diagnosis of acute kidney injury with the possibility of acute tubular necrosis secondary to near-drowning. We suggest that any patient presenting after immersion or near-drowning to be should assessed for potential acute kidney injury.

  18. Acute kidney injury secondary to iatrogenic bilateral ureteric ligation ...

    African Journals Online (AJOL)

    Acute kidney injury secondary to iatrogenic bilateral ureteric ligation following emergency abdominal hysterectomy. Oluseyi A. Adejumo, Olurotimi S. Ogundiniyi, Ayodeji A. Akinbodewa, Lawrence A. Adesunloro, Oladimeji J. Olafisoye ...

  19. A case of acute kidney injury by near-drowning

    Directory of Open Access Journals (Sweden)

    Amirah Amir

    2013-12-01

    Full Text Available Acute kidney injury following immersion or near-drowning is rarely described and no data from Malaysia have been found. We report a case of acute kidney injury following a near-drowning event. A 20-yearold man who recovered from near-drowning in a swimming pool 5 days earlier presented to our clinic with abdominal pain, anorexia, nausea and polyuria. Dipstick urinalysis showed a trace of blood. The serum creatinine level was 10-fold higher than the normal range. A bedside ultrasound showed features suggestive of acute tubular necrosis. He is then referred to the hospital with the diagnosis of acute kidney injury with the possibility of acute tubular necrosis secondary to near-drowning. We suggest that any patient presenting after immersion or near-drowning to be should assessed for potential acute kidney injury

  20. Prevalence and outcomes of acute kidney injury in term neonates ...

    African Journals Online (AJOL)

    Background: The kidney is the most damaged organ in asphyxiated full-term infants. The severity of its damage is correlated with the severity of neurological damage. We determined the prevalence of perinatal asphyxia-associated acute kidney injury (AKI). Methods: We conducted a prospective cohort study including 60 ...

  1. Post-partum acute kidney injury

    Directory of Open Access Journals (Sweden)

    Naresh Pahwa

    2014-01-01

    Full Text Available To determine the risk factors, course of hospital stay and mortality rate among women with post-partum acute kidney injury (AKI, we studied (of 752 patients with AKI admitted to a tertiary care center during the study period between November 2009 and August 2012 27 (3.59% women with post-partum AKI. The data regarding age, parity, cause of renal failure, course of hospital stay and requirement of dialysis were recorded. Sepsis was the major cause (70.3% of post-partum AKI. Other causes included disseminated intravascular coagulation (55.5%, pre-eclampsia/eclampsia (40.7%, ante- and post-partum hemorrhage (40.7% and 22.2% and hemolytic anemia and elevated liver enzymes and low platelet count syndrome (29.6%; most patients had more than one cause of AKI. We found a very high prevalence (18.5% of cortical necrosis in our study patients. A significant correlation was also found between the creatinine level on admission and the period of onset of disease after delivery. In conclusion, several factors are involved in causing post-partum AKI in our population, and sepsis was the most common of them.

  2. Acute kidney injury: Global health alert

    Directory of Open Access Journals (Sweden)

    Philip Kam Tao Li

    2013-01-01

    Full Text Available Acute kidney injury (AKI is increasingly prevalent in developing and developed countries and is associated with severe morbidity and mortality. Most etiologies of AKI can be prevented by interventions at the individual, community, regional and in-hospital levels. Effective measures must include community-wide efforts to increase an awareness of the devastating effects of AKI and provide guidance on preventive strategies, as well as early recognition and management. Efforts should be focused on minimizing causes of AKI, increasing awareness of the importance of serial measurements of serum creatinine in high risk patients, and documenting urine volume in acutely ill people to achieve early diagnosis; there is as yet no definitive role for alternative biomarkers. Protocols need to be developed to systematically manage prerenal conditions and specific infections. More accurate data about the true incidence and clinical impact of AKI will help to raise the importance of the disease in the community, increase awareness of AKI by governments, the public, general and family physicians and other health care professionals to help prevent the disease. Prevention is the key to avoid the heavy burden of mortality and morbidity associated with AKI.

  3. Effects of quercetin on kidney injury induced by doxorubicin.

    Science.gov (United States)

    Yagmurca, M; Yasar, Z; Bas, O

    2015-01-01

    The anthracycline antitumor drug doxorubicine causes severe nephrotoxicity in a variety of experimental animals and may be nephrotoxic to humans. The aim of present study was to determine the protective effects of quercetin against doxorubicin-induced kidney injury with light microscopy. Forty male Wistar albino rats were divided into four groups: control, doxorubicin, doxorubicin+quercetin and quercetin. A single dose of 20 mg/kg/ i.p. doxorubicin was used to induce injury. Quercetin was administrated orally against doxorubicin toxicity. The kidneys were examined under light microscopy after H-E (hematoxylin-eosin) staining and the changes were scored. Significant tissue injury was observed in doxorubicin-administered group. Among these injuries, renal tubular dilatation, tubular vacuolar changes, glomerular vacuolization, decrease in bowman space, bowman capsule thickening, and interstitial infiltration were evident. However, the injury induced by doxorubicin was attenuated with quercetin administration. Quercetin decreased doxorubicin-induced kidney damage (Tab. 1, Fig. 4, Ref. 27).

  4. Acute kidney injury in critically ill child.

    Science.gov (United States)

    Al-Jboor, Wejdan; Almardini, Reham; Al Bderat, Jwaher; Frehat, Mahdi; Al Masri, Hazem; Alajloni, Mohammad Saleh

    2016-01-01

    Acute kidney injury (AKI) is a common and serious complication in patients in the Pediatric Intensive Care Unit (PICU). We conducted this study to estimate the incidence and the mortality rate of AKI in critically ill children as well as to describe some other related factors. A retrospective study was conducted at PICU of Queen Rania Abdulla Children Hospital, Amman, Jordan for the period extending from May 2011 to June 2013. The medical records of all patients admitted during this period, and their demographic data were reviewed. Patients with AKI were identified, and management and outcomes were reviewed and analyzed. AKI was evaluated according to modified RIFLE criteria. Of the 372 patients admitted to PICU, 64 (17.2%) patients developed AKI. Of these 64 patients who had AKI, 28 (43.7%) patients reached RIFLE max of risk, 21 (32.8%) patients reached injury, and 15 (23.4%) reached failure. Mean Pediatric Risk of Mortality II score at admission was significantly higher in patients with AKI than those without P <0.001. The age ranged between one month and 14 years with the median age as 5.4 year. Thirty-five (54.7%) were males. Sepsis was the most common cause of AKI. The mortality rate in critically ill children without AKI was 58.7%, whereas increased in children with AKI to 73.4%. The mortality rate in patients who received renal replacement therapy was 71.4% and was higher (81.5%) in patients who received mechanical ventilation (95%, [confidence interval (CI)] 79.3-83.4%) and was significantly higher in patients with multi-organ system dysfunction 90.3% (95%, [CI] 88.7-92.5%). The incidence of AKI in critically ill children is high and increased their mortality rate and higher mortality seen in the younger age group, especially those below one year. High mortality rate was associated with multi-organ system dysfunction and the need for mechanical ventilation.

  5. Diagnostic value of urinary kidney injury molecule 1 for acute kidney injury: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Xinghua Shao

    Full Text Available BACKGROUND: Urinary Kidney Injury Molecule 1 (KIM-1 is a proximal tubular injury biomarker for early detection of acute kidney injury (AKI, with variable performance characteristics depending on clinical and population settings. METHODS: Meta-analysis was performed to assess the diagnostic value of urinary KIM-1 in AKI. Relevant studies were searched from MEDLINE, EMBASE, Pubmed, Elsevier Science Direct, Scopus, Web of Science, Google Scholar and Cochrane Library. Meta-analysis methods were used to pool sensitivity and specificity and to construct summary receiver operating characteristic (SROC curves. RESULTS: A total of 2979 patients from 11 eligible studies were enrolled in the analysis. Five prospective cohorts, two cross-sectional and four case-control studies were identified for meta-analysis. The estimated sensitivity of urinary KIM-1 for the diagnosis of AKI was 74.0% (95% CI, 61.0%-84.0%, and specificity was 86.0% (95% CI, 74.0%-93.0%. The SROC analysis showed an area under the curve of 0.86(0.83-0.89. Subgroup analysis suggested that population settings and detection time were the key factors affecting the efficiency of KIM-1 for AKI diagnosis. LIMITATION: Various population settings, different definition of AKI and Serum creatinine level used as the standard might have influence on AKI diagnosis. The relatively small number of studies and heterogeneity between them also affected the evaluation. CONCLUSION: Urinary KIM-1 may be a promising biomarker for early detection of AKI with considerable predictive value, especially for cardiac surgery patients, and its potential value needs to be validated in large studies and across a broader scope of clinical settings.

  6. Perioperative aspirin and clonidine and risk of acute kidney injury

    DEFF Research Database (Denmark)

    Garg, Amit X; Kurz, Andrea; Sessler, Daniel I

    2014-01-01

    IMPORTANCE: Acute kidney injury, a common complication of surgery, is associated with poor outcomes and high health care costs. Some studies suggest aspirin or clonidine administered during the perioperative period reduces the risk of acute kidney injury; however, these effects are uncertain...... and each intervention has the potential for harm. OBJECTIVE: To determine whether aspirin compared with placebo, and clonidine compared with placebo, alters the risk of perioperative acute kidney injury. DESIGN, SETTING, AND PARTICIPANTS: A 2 × 2 factorial randomized, blinded, clinical trial of 6905...... patients undergoing noncardiac surgery from 88 centers in 22 countries with consecutive patients enrolled between January 2011 and December 2013. INTERVENTIONS: Patients were assigned to take aspirin (200 mg) or placebo 2 to 4 hours before surgery and then aspirin (100 mg) or placebo daily up to 30 days...

  7. Synthetic marijuana and acute kidney injury: an unforeseen association.

    Science.gov (United States)

    Kazory, Amir; Aiyer, Ravi

    2013-06-01

    Synthetic cannabinoids (SCs) have emerged as drugs of abuse with increasing popularity among young adults. The potential renal complication related to the abuse of SC was not recognized until recently. Here, we present a case of severe acute kidney injury (AKI) that developed after inhalation of SC in an otherwise healthy young patient. A kidney biopsy revealed severe acute tubular necrosis, and supportive management resulted in the recovery of the kidney function. Herein, we briefly summarize the only two previous reports (a total of 21 cases) on the association between SC abuse and renal dysfunction and identify the common aspects in all observations.

  8. Renal oxygenation and hemodynamics in acute kidney injury and chronic kidney disease

    Science.gov (United States)

    Singh, Prabhleen; Ricksten, Sven-Erik; Bragadottir, Gudrun; Redfors, Bengt; Nordquist, Lina

    2013-01-01

    Summary 1. Acute kidney injury (AKI) puts a major burden on health systems that may arise from multiple initiating insults, including ischemia-reperfusion injury, cardiovascular surgery, radio-contrast administration as well as sepsis. Similarly, the incidence and prevalence of chronic kidney disease (CKD) continues to increase with significant morbidity and mortality. Moreover, an increasing number of AKI patients survive to develop CKD and end-stage kidney disease (ESRD). 2. Although the mechanisms for development of AKI and progression of CKD remain poorly understood, initial impairment of oxygen balance is likely to constitute a common pathway, causing renal tissue hypoxia and ATP starvation that will in turn induce extracellular matrix production, collagen deposition and fibrosis. Thus, possible future strategies for one or both conditions may involve dopamine, loop-diuretics, inducible nitric oxide synthase inhibitors and atrial natriuretic peptide, substances that target kidney oxygen consumption and regulators of renal oxygenation such as nitric oxide and heme oxygenase-1. PMID:23360244

  9. Chronic kidney disease: an inherent risk factor for acute kidney injury?

    Science.gov (United States)

    Singh, Prabhleen; Rifkin, Dena E; Blantz, Roland C

    2010-09-01

    Epidemiologic evidence suggests that chronic kidney disease (CKD) is a risk factor for acute kidney injury (AKI) due to the prevalence of CKD in patients who have episodes of AKI. However, the high burden of comorbidities such as age, diabetes, peripheral vascular, cardiovascular, and liver disease accompanying CKD, and the difficulties of defining AKI in the setting of CKD make these observations difficult to interpret. These comorbidities not only could alter the course of AKI but also may be the driving force behind the epidemiologic association between CKD and AKI because of systemic changes and/or increased exposure to potential nephrotoxic risks. Here, we contend that studies suggesting that CKD is a risk factor for AKI may suffer from residual confounding and reflect an overall susceptibility to illness rather than biologic susceptibility of the kidney parenchyma to injury. In support of our argument, we discuss the clinical evidence from epidemiologic studies, and the knowledge obtained from animal models on the pathophysiology of AKI and CKD, demonstrating a preconditioning influence of the previously impaired kidneys against subsequent injury. We conclude that, under careful analysis, factors apart from the inherent pathophysiology of the diseased kidney may be responsible for the increased frequency of AKI in CKD patients, and the impact of CKD on the risk and severity of AKI needs further investigation. Moreover, certain elements in the pathophysiology of a previously injured kidney may, surprisingly, bear out to be protective against AKI.

  10. National Veterans Health Administration inpatient risk stratification models for hospital-acquired acute kidney injury

    OpenAIRE

    Cronin, Robert M; VanHouten, Jacob P; Siew, Edward D; Eden, Svetlana K; Fihn, Stephan D; Nielson, Christopher D; Peterson, Josh F; Baker, Clifton R; Ikizler, T Alp; Speroff, Theodore; Matheny, Michael E

    2015-01-01

    Objective Hospital-acquired acute kidney injury (HA-AKI) is a potentially preventable cause of morbidity and mortality. Identifying high-risk patients prior to the onset of kidney injury is a key step towards AKI prevention.

  11. Dynamics of biochemical parameters of blood serum in kidney injuries

    Directory of Open Access Journals (Sweden)

    Y. L. Podgainiy

    2014-12-01

    Full Text Available Aim. Annually injuries of varying severity are registered in more than 4,5 million people (up to 10% of the population in Ukraine; renal injury in polytrauma is detected in 26,4% of cases and takes 2 – 3 place of injury of the abdominal cavity and retroperitoneal space. In order to study the kidney function and other vital organs systems 108 patients were examined. Methods and results. Laboratory methods (clinical and biochemical parameters of blood and urine tests, ultrasound and CT scans of the kidneys and abdominal organs were used. Conclusion. It was established that polytrauma often occurs in males (73,5% of middle-age. 42% of patients presented renal function violation - nitrogen excretion and 84% of patients had activated blood coagulation in the first 7 – 10 days of injury.

  12. Inhaling Difluoroethane Computer Cleaner Resulting in Acute Kidney Injury and Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Kristen Calhoun

    2018-01-01

    Full Text Available Difluoroethane is the active ingredient in various computer cleaners and is increasingly abused by teenagers due to its ease of access, quick onset of euphoric effects, and lack of detectability on current urine drug screens. The substance has detrimental effects on various organ systems; however, its effects on the kidneys remain largely unreported. The following case report adds new information to the developing topic of acute kidney injury in patients abusing difluoroethane inhalants. In addition, it is one of the first to show a possible relationship between prolonged difluoroethane abuse and the development of chronic kidney disease in the absence of other predisposing risk factors.

  13. Evolutionary trade-offs in kidney injury and repair.

    Science.gov (United States)

    Lei, Yutian; Anders, Hans-Joachim

    2017-11-01

    Evolutionary medicine has proven helpful to understand the origin of human disease, e.g. in identifying causal roles of recent environmental changes impacting on human physiology (environment-phenotype mismatch). In contrast, diseases affecting only a limited number of members of a species often originate from evolutionary trade-offs for usually physiologic adaptations assuring reproductive success in the context of extrinsic threats. For example, the G1 and G2 variants of the APOL1 gene supporting control of Trypanosoma infection come with the trade-off that they promote the progression of kidney disease. In this review we extend the concept of evolutionary nephrology by discussing how the physiologic adaptations (danger responses) to tissue injury create evolutionary trade-offs that drive histopathological changes underlying acute and chronic kidney diseases. The evolution of multicellular organisms positively selected a number of danger response programs for their overwhelming benefits in assuring survival such as clotting, inflammation, epithelial healing and mesenchymal healing, i.e. fibrosis and sclerosis. Upon kidney injury these danger programs often present as pathomechanisms driving persistent nephron loss and renal failure. We explore how classic kidney disease entities involve insufficient or overshooting activation of these danger response programs for which the underlying genetic basis remains largely to be defined. Dissecting the causative and hierarchical relationships between danger programs should help to identify molecular targets to control kidney injury and to improve disease outcomes.

  14. Acute kidney injury from herbal vaginal remedy in Ilorin: a case report

    African Journals Online (AJOL)

    Acute kidney injury from herbal vaginal remedy in Ilorin: a case report. TO Olanrewaju, A Chijioke, IQ Ameh, AA Adewale. Abstract. The use of traditional herbal remedy is very common worldwide, and it is associated with complications such as acute kidney injury. Herbal remedy accounts for 35% of acute kidney injury in ...

  15. Hypothyroidism causing paralytic ileus and acute kidney injury - case report

    Directory of Open Access Journals (Sweden)

    Rodrigo Chaturaka

    2011-02-01

    Full Text Available Abstract We present a patient with severe hypothyroidism complicated by paralytic ileus and acute kidney injury. A 65 year old male patient, diagnosed with hypothyroidism one year ago was transferred to our unit in a state of drowsiness and confusion. He was severely hypothyroid and had paralytic ileus and impaired renal function at the time of transfer. Hypokalaemia was present, and was likely to have contributed to the paralytic ileus and this together with dehydration was likely to have contributed to renal injury. Nonetheless, hypothyroidism is very likely to have been the principal precipitant of both these complications, and both paralytic ileus and acute kidney injury improved with thyroxine replacement. Unfortunately, the patient died unexpectedly eight days after admission to the unit. Hypothyroidism may induce de novo acute kidney injury or it may exacerbate ongoing chronic kidney disease. This rare complication is assumed to be due to the hypodynamic circulatory state created by thyroid hormone deficiency. Paralytic ileus is an even rarer fatal manifestation of hypothyroidism and is thought to be due to an autonomic neuropathy affecting the intestines that is reversible with thyroxine replacement. To our knowledge, both these complications have not been observed in a single patient so far. It is important that clinicians are aware of these rare manifestations of hypothyroidism as in most occasions, thyroxine deficiency may be missed, and treatment can reverse the complications.

  16. Tubular kidney injury molecule-1 in protein-overload nephropathy

    NARCIS (Netherlands)

    van Timmeren, Mirjan M.; Bakker, Stephan J. L.; Vaidya, Vishal S.; Bailly, Veronique; Schuurs, Theo A.; Damman, Jeffrey; Stegeman, Coen A.; Bonventre, Joseph V.; van Goor, Harry

    Kim-1, a recently discovered membrane protein, is undetectable in normal kidneys but markedly induced in proximal tubules after ischemic and toxic injury. The function of Kim-1 is unclear, but it is implicated in damage/repair processes. The Kim-1 ectodomain is cleaved by metalloproteinases and

  17. Acute kidney injury from Paraquat poisoning: a case report. | Slater ...

    African Journals Online (AJOL)

    Acute kidney injury from Paraquat poisoning: a case report. H. E. Slater, O.C.A. Okoye, O. Okperi, N. Rajora. Abstract. Paraquat is a salt widely used as a herbicide. Although paraquat poisoning is rare in the general population, it may be considered as one of the most toxic poisons frequently used for suicide attempts, and is ...

  18. Determinants of modality of management of acute kidney injury in ...

    African Journals Online (AJOL)

    Background: The cost of taking care of children with acute kidney injury (AKI) is enormous and beyond the reach of many caregivers in sub-Saharan Africa which are largely resource poor. It is therefore imperative to determine those who may benefit from conservative management which is comparatively cheaper to the ...

  19. Assessment of knowledge of acute kidney injury among non ...

    African Journals Online (AJOL)

    Background: Adequate knowledge of acute kidney injury (AKI) among doctors is essential for its prevention, early diagnosis and management. Assessing knowledge of AKI among doctors is necessary to identify areas of deficiencies and key areas to be emphasized when organizing educational programs aimed at ...

  20. Outcome of pregnancy related acute kidney injury requiring ...

    African Journals Online (AJOL)

    Background: Pregnancy related acute kidney injury (AKI) severe enough to require dialysis is now rare in developed countries but is still a significant cause of maternal mortality in many resource constrained countries. However, there is scanty information from many sub-Saharan countries about outcomes of patient who ...

  1. Increased podocyte Sirtuin-1 function attenuates diabetic kidney injury.

    Science.gov (United States)

    Hong, Quan; Zhang, Lu; Das, Bhaskar; Li, Zhengzhe; Liu, Bohan; Cai, Guangyan; Chen, Xiangmei; Chuang, Peter Y; He, John Cijiang; Lee, Kyung

    2018-06-01

    Podocyte injury and loss contribute to the progression of glomerular diseases, including diabetic kidney disease. We previously found that the glomerular expression of Sirtuin-1 (SIRT1) is reduced in human diabetic glomeruli and that the podocyte-specific loss of SIRT1 aggravated albuminuria and worsened kidney disease progression in diabetic mice. SIRT1 encodes an NAD-dependent deacetylase that modifies the activity of key transcriptional regulators affected in diabetic kidneys, including NF-κB, STAT3, p53, FOXO4, and PGC1-α. However, whether the increased glomerular SIRT1 activity is sufficient to ameliorate the pathogenesis of diabetic kidney disease has not been explored. We addressed this by inducible podocyte-specific SIRT1 overexpression in diabetic OVE26 mice. The induction of SIRT1 overexpression in podocytes for six weeks in OVE26 mice with established albuminuria attenuated the progression of diabetic glomerulopathy. To further validate the therapeutic potential of increased SIRT1 activity against diabetic kidney disease, we developed a new, potent and selective SIRT1 agonist, BF175. In cultured podocytes BF175 increased SIRT1-mediated activation of PGC1-α and protected against high glucose-mediated mitochondrial injury. In vivo, administration of BF175 for six weeks in OVE26 mice resulted in a marked reduction in albuminuria and in glomerular injury in a manner similar to podocyte-specific SIRT1 overexpression. Both podocyte-specific SIRT1 overexpression and BT175 treatment attenuated diabetes-induced podocyte loss and reduced oxidative stress in glomeruli of OVE26 mice. Thus, increased SIRT1 activity protects against diabetes-induced podocyte injury and effectively mitigates the progression of diabetic kidney disease. Published by Elsevier Inc.

  2. Experimental study on irradiation injury of the kidneys, 2

    International Nuclear Information System (INIS)

    Tomita, Shinichi; Fuzikawa, Kiyozumi; Nishimori, Issei; Tsuda, Nobuo; Miyagawa, Naotaka

    1976-01-01

    In order to investigate irradiation injury of the kidney and effect of injured kidney on the whole body, especially cardiovascular changes, a single kidney was extracted from Wistar female rats and only the remained kidney was irradiated with a great amount of radiation in 4000 R dose experimentally. After seven weeks of irradiation, atrophy and involution of the highest region of the kidney were found. Histologically, fibrous proliferation of interstice accompanied with atrophy of the renal tubule, and slightly increased nuclei and lobulation of the glomerulus were recognized. After 15 weeks of irradiation, atrophy and involution of the whole kidney were found. Histologically, fibrous proliferation of interstice in the kidney accompanied with high degree atrophy of the renal tubule, marked increase and lobulation of mesangium ground substance of the glomerulus and mild hypertrophy of arteriole were recognized. Mild degeneration of myocardium was recognized. In the long-term cases passing 29 and 34 weeks after irradiation, blood pressure just before slaughter rose to 250 mmHg. The kidney showed malignant nephrosclerosis-like lesion, and panarteritis was found in the mesentery and peri-pancreatic artery. In the heart, hypertonic myocardosis was recognized. A rise of blood pressure which was observed in this experiment occurred in circulation degenerations resulted from the secondary hypertrophy of the blood vessels accompanied with fibrous proliferation of the interstice which appeared after degeneration of renal tubule. It was thought that panarteritis of cardiovascular system of the whole body, especially mesentery and peri-pancreatic artery, and fibrinoid degeneration of arteriole of the kidney were due to hypertension and angiopathic factors (non-vasopressor extracts from the injured kidney). (Tsunoda, M.)

  3. Microvascular injury and the kidney in hypertension.

    Science.gov (United States)

    Ruiz-Hurtado, G; Ruilope, L M

    Renal macrocirculation participates in the development of arterial hypertension. The elevation in systemic blood pressure (BP) can damage the kidney starting in the microcirculation. Established arterial hypertension impinge upon the large arteries and stiffness develops. As a consequence central BP raises and BP pulsatility appear and contribute to further damage renal microcirculation by direct transmission of the elevated BP. Copyright © 2017 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Reduced kidney lipoprotein lipase and renal tubule triglyceride accumulation in cisplatin-mediated acute kidney injury

    NARCIS (Netherlands)

    Li, Shenyang; Nagothu, K.; Ranganathan, G.; Ali, S.M.; Shank, B.; Gokden, N.; Ayyadevara, S.; Megysi, J.; Olivecrona, G.; Chugh, S.S.; Kersten, A.H.; Portilla, D.

    2012-01-01

    Peroxisome proliferator-activated receptor-a (PPARa) activation attenuates cisplatin (CP)-mediated acute kidney injury by increasing fatty acid oxidation, but mechanisms leading to reduced renal triglyceride (TG) accumulation could also contribute. Here, we investigated the effects of PPARa and CP

  5. Pharmacological management of acute kidney injury and chronic kidney disease in neonates.

    Science.gov (United States)

    Jetton, Jennifer G; Sorenson, Mark

    2017-04-01

    Both acute kidney injury (AKI) and chronic kidney disease (CKD) are seen more frequently in the neonatal intensive care unit (NICU) as advances in supportive care improve the survival of critically ill infants as well as those with severe, congenital kidney and urinary tract anomalies. Many aspects of the infant's care, including fluid balance, electrolyte and mineral homeostasis, acid-base balance, and growth and nutrition require close monitoring by and collaboration among neonatologists, nephrologists, dieticians, and pharmacologists. This educational review summarizes the therapies widely used for neonates with AKI and CKD. Use of these therapies is extrapolated from data in older children and adults or based on clinical experience and case series. There is a critical need for more research on the use of therapies in infants with kidney disease as well as for the development of drug delivery systems and preparations scaled more appropriately for these small patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Acute Kidney Injury: Epidemiology, Diagnosis, Prognosis, and Future Directions

    Directory of Open Access Journals (Sweden)

    Joana Briosa Neves

    2015-07-01

    Full Text Available Acute kidney injury (AKI is a common problem highly associated with hospitalisation. AKI is the cause of harmful short-term consequences: longer hospital stays, greater disability after discharge, and greater risk of in-hospital mortality, as well as adverse long-term outcomes, such as progression to chronic kidney disease, development of cardiovascular disease, and increased risk of long-term mortality. The concept of AKI has changed since the introduction of the ‘Risk, Injury, Failure, Loss of kidney function, End-stage kidney disease’ (RIFLE classification. More recently, the ‘Kidney Disease Improving Global Outcomes’ (KDIGO classification appears to have provided increased diagnostic sensitivity and outcome-prediction capability. Novel biomarkers and further research on the role of the immune system in AKI may help improve the diagnosis, severity, outcome evaluation, and treatment of the condition. In this review we describe the epidemiology, diagnosis, and prognosis of AKI, as well as possible future directions for its clinical management.

  7. Derivation and External Validation of Prediction Models for Advanced Chronic Kidney Disease Following Acute Kidney Injury.

    Science.gov (United States)

    James, Matthew T; Pannu, Neesh; Hemmelgarn, Brenda R; Austin, Peter C; Tan, Zhi; McArthur, Eric; Manns, Braden J; Tonelli, Marcello; Wald, Ron; Quinn, Robert R; Ravani, Pietro; Garg, Amit X

    2017-11-14

    Some patients will develop chronic kidney disease after a hospitalization with acute kidney injury; however, no risk-prediction tools have been developed to identify high-risk patients requiring follow-up. To derive and validate predictive models for progression of acute kidney injury to advanced chronic kidney disease. Data from 2 population-based cohorts of patients with a prehospitalization estimated glomerular filtration rate (eGFR) of more than 45 mL/min/1.73 m2 and who had survived hospitalization with acute kidney injury (defined by a serum creatinine increase during hospitalization > 0.3 mg/dL or > 50% of their prehospitalization baseline), were used to derive and validate multivariable prediction models. The risk models were derived from 9973 patients hospitalized in Alberta, Canada (April 2004-March 2014, with follow-up to March 2015). The risk models were externally validated with data from a cohort of 2761 patients hospitalized in Ontario, Canada (June 2004-March 2012, with follow-up to March 2013). Demographic, laboratory, and comorbidity variables measured prior to discharge. Advanced chronic kidney disease was defined by a sustained reduction in eGFR less than 30 mL/min/1.73 m2 for at least 3 months during the year after discharge. All participants were followed up for up to 1 year. The participants (mean [SD] age, 66 [15] years in the derivation and internal validation cohorts and 69 [11] years in the external validation cohort; 40%-43% women per cohort) had a mean (SD) baseline serum creatinine level of 1.0 (0.2) mg/dL and more than 20% had stage 2 or 3 acute kidney injury. Advanced chronic kidney disease developed in 408 (2.7%) of 9973 patients in the derivation cohort and 62 (2.2%) of 2761 patients in the external validation cohort. In the derivation cohort, 6 variables were independently associated with the outcome: older age, female sex, higher baseline serum creatinine value, albuminuria, greater severity of acute kidney injury, and higher

  8. Precision Medicine for Acute Kidney Injury (AKI): Redefining AKI by Agnostic Kidney Tissue Interrogation and Genetics.

    Science.gov (United States)

    Kiryluk, Krzysztof; Bomback, Andrew S; Cheng, Yim-Ling; Xu, Katherine; Camara, Pablo G; Rabadan, Raul; Sims, Peter A; Barasch, Jonathan

    2018-01-01

    Acute kidney injury (AKI) currently is diagnosed by a temporal trend of a single blood analyte: serum creatinine. This measurement is neither sensitive nor specific to kidney injury or its protean forms. Newer biomarkers, neutrophil gelatinase-associated lipocalin (NGAL, Lipocalin 2, Siderocalin), or kidney injury molecule-1 (KIM-1, Hepatitis A Virus Cellular Receptor 1), accelerate the diagnosis of AKI as well as prospectively distinguish rapidly reversible from prolonged causes of serum creatinine increase. Nonetheless, these biomarkers lack the capacity to subfractionate AKI further (eg, sepsis versus ischemia versus nephrotoxicity from medications, enzymes, or metals) or inform us about the primary and secondary sites of injury. It also is unknown whether all nephrons are injured in AKI, whether all cells in a nephron are affected, and whether injury responses can be stimulus-specific or cell type-specific or both. In this review, we summarize fully agnostic tissue interrogation approaches that may help to redefine AKI in cellular and molecular terms, including single-cell and single-nuclei RNA sequencing technology. These approaches will empower a shift in the current paradigm of AKI diagnosis, classification, and staging, and provide the renal community with a significant advance toward precision medicine in the analysis AKI. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Nonoperative management of penetrating kidney injuries: a prospective audit.

    Science.gov (United States)

    Moolman, C; Navsaria, P H; Lazarus, J; Pontin, A; Nicol, A J

    2012-07-01

    The role of nonoperative management for penetrating kidney injuries is unknown. Therefore, we review the management and outcome of penetrating kidney injuries at a center with a high incidence of penetrating trauma. Data from all patients presenting with hematuria and/or kidney injury discovered on imaging or at surgery admitted to the trauma center at Groote Schuur Hospital in Cape Town, South Africa during a 19-month period (January 2007 to July 2008) were prospectively collected and reviewed. These data were analyzed for demographics, injury mechanism, perioperative management, nephrectomy rate and nonoperative success. Patients presenting with hematuria and with an acute abdomen underwent a single shot excretory urogram. Those presenting with hematuria without an indication for laparotomy underwent computerized tomography with contrast material. A total of 92 patients presented with hematuria following penetrating abdominal trauma. There were 75 (80.4%) proven renal injuries. Of the patients 84 were men and the median age was 26 years (range 14 to 51). There were 50 stab wounds and 42 gunshot renal injuries. Imaging modalities included computerized tomography in 60 cases and single shot excretory urography in 18. There were 9 patients brought directly to the operating room without further imaging. A total of 47 patients with 49 proven renal injuries were treated nonoperatively. In this group 4 patients presented with delayed hematuria, of whom 1 had a normal angiogram and 3 underwent successful angioembolization of arteriovenous fistula (2) and false aneurysm (1). All nonoperatively managed renal injuries were successfully treated without surgery. There were 18 nephrectomies performed for uncontrollable bleeding (11), hilar injuries (2) and shattered kidney (3). Post-nephrectomy complications included 1 infected renal bed hematoma requiring percutaneous drainage. Of the injuries found at laparotomy 12 were not explored, 2 were drained and 5 were treated with

  10. Volume effect on the radiation injury of rat kidney

    International Nuclear Information System (INIS)

    Lo, Y.-C.; Kutcher, Gerald J.; Ling, Clifton C.

    1996-01-01

    Purpose: To minimize the likelihood of radiation-induced kidney injury in treating tumors, the relationship of tolerance dose and irradiated volume of kidney should be known. We have used a rat model to determine the dose-response relationship when various volumes of the kidney are irradiated. Methods and Materials: Anesthetized adult male rats (CD, 10-12 week old) were irradiated with 250 KV x-rays. The kidney was exteriorized and placed in a jig designed to shield all other tissues. Graded single doses were delivered to each of four volumes: 1/4V (half of one kidney), 1/2V (one whole kidney, or half of each kidney), 3/4V (one and a half kidneys) and 1V, where V is the volume of both kidneys. In addition, to compare radiation injury and surgery, partial nephrectomy was performed for 1/4V, 1/2V and 3/4V. Four to sixteen rats were used for each dose-volume point. The rats have been followed up for 540 days. The endpoints for the damage were: lethality, anemia, glomerular filtration rate, effective renal flow, and histology. Results: We found that: (1) There was a threshold volume for radiation damage; injury did not occur if the volume irradiated was ≤ 1/2V, depending on the endpoints. (2) Median survival times did not depend on the dose when a small volume (i.e., 1/4V or 1/2V) was irradiated. (3) The LD 50 (and the 95% confidence limits) at 450 days were 11.35 (8.08 to 12.13) Gy for 1V, 12.38 (11.08 to 13.40) Gy for 3/4V, 21.16 (17.21 to 26.56) Gy for 1/2V, and 28.80 (21.11 to 65.00) Gy for 1/4V. (4) The ED 50 for animals with hematocrit level ≤0.36 at 365 days was 10.98 (4.96 to 13.67) Gy for 1.0V, and 13.82 (6.16 to 17.97) Gy for 3/4V. For 1/2V, only the 80% confidence limits could be derived, giving ED 50 +40.14 (27.98 to ∞) Gy. (5) The results for all other endpoints were similar to those for hematocrit. (6) The dose response was the same whether to half of each kidney or one whole kidney was irradiated. (7) While the threshold volume for radiation injury

  11. Cell cycle arrest and the evolution of chronic kidney disease from acute kidney injury.

    Science.gov (United States)

    Canaud, Guillaume; Bonventre, Joseph V

    2015-04-01

    For several decades, acute kidney injury (AKI) was generally considered a reversible process leading to complete kidney recovery if the individual survived the acute illness. Recent evidence from epidemiologic studies and animal models, however, have highlighted that AKI can lead to the development of fibrosis and facilitate the progression of chronic renal failure. When kidney injury is mild and baseline function is normal, the repair process can be adaptive with few long-term consequences. When the injury is more severe, repeated, or to a kidney with underlying disease, the repair can be maladaptive and epithelial cell cycle arrest may play an important role in the development of fibrosis. Indeed, during the maladaptive repair after a renal insult, many tubular cells that are undergoing cell division spend a prolonged period in the G2/M phase of the cell cycle. These tubular cells recruit intracellular pathways leading to the synthesis and the secretion of profibrotic factors, which then act in a paracrine fashion on interstitial pericytes/fibroblasts to accelerate proliferation of these cells and production of interstitial matrix. Thus, the tubule cells assume a senescent secretory phenotype. Characteristic features of these cells may represent new biomarkers of fibrosis progression and the G2/M-arrested cells may represent a new therapeutic target to prevent, delay or arrest progression of chronic kidney disease. Here, we summarize recent advances in our understanding of the biology of the cell cycle and how cell cycle arrest links AKI to chronic kidney disease. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  12. Renoprotective mechanisms of chlorogenic acid in cisplatin-induced kidney injury

    International Nuclear Information System (INIS)

    Domitrović, Robert; Cvijanović, Olga; Šušnić, Vesna; Katalinić, Nataša

    2014-01-01

    Highlights: • Chlorogenic acid attenuated cisplatin-induced renal oxidative stress by reducing the expression of 4-HNE, HO-1 and CYP2E1. • The inhibition of inflammatory response was achieved through the reduction of TNF-α and COX-2 expression. • The expression of p53, Bax, active caspase-3 and LC3B was suppressed, suggesting the inhibition of apoptosis and autophagy. • Attenuation of Mrp1 and Mrp2 expression and the increase in Oct2 expression indicated reduced burden of tubular cells. • The recovery of kidneys form cisplatin injury was accompanied by the suppression of cyclin D1 and augmented PCNA expression. - Abstract: The aim of this study was to investigate the renoprotective activity of chlorogenic acid (CA) in a murine model of cisplatin (CP)-induced kidney injury. Male BALB/cN mice were gavaged daily with CA at 3, 10 and 30 mg/kg for two successive days, 48 h after intraperitoneal injection of CP (13 mg/kg). On the fifth day, serum creatinine and blood urea nitrogen (BUN) levels were significantly increased in CP-intoxicated mice, which was recovered by CA. Renal oxidative stress, evidenced by increased 4-hydroxynonenal (4-HNE) expression, was significantly reduced with CA. Simultaneously, the overexpression of heme oxygenase 1 (HO-1) and cytochrome P450 E1 (CYP2E1) was attenuated. The inhibition of inflammatory response by CA was achieved through the reduction of tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2) expression. Additionally, CA significantly suppressed p53, Bax active caspase-3, cyclin D1 and microtubule-associated protein 1 light chain 3 isoform B (LC3B) expression, suggesting the inhibition of both apoptosis and autophagy. The expression of multidrug resistance-associated proteins (Mrp1 and Mrp2) increased and organic cation transporter 2 (Oct2) decreased by CP, protecting the kidneys from nephrotoxicity by reducing the burden of tubular cells. CA dose-dependently restored Mrp1, Mrp2 and Oct2 expression. The recovery

  13. Acute Kidney Injury Classification in Neuro-ICU Patient Group

    Directory of Open Access Journals (Sweden)

    Canan Akıncı

    2012-12-01

    Full Text Available Objective: To investigate the role of acute kidney injury (AKI classification system for kidney injury outcome in neuro-Intensive care unit (ICU patients. Material and Method: Total 432 patients who admitted to ICU between 2005 and 2009 evaluated in this study. All patients’ AKI stage, Acute Physiology and Chronic Health Evaluation (APACHE-II, Sequential Organ Failure Assessment Score (SOFA, Glasgow Coma Score (GCS, Glasgow Outcome Score (GOS, mortality rate, length of ICU stay, need for intubation, and mechanical ventilation were recorded. Results: AKI was found in 24 of all 432 patents’ (5.5%. We found that, patients with AKI had higher APHACE-II score, SOFA score and mortality rates; longer ICU stay, duration of mechanical ventilation and intubation and lower GCS and GOS than without AKI group. Conclusion: Length of ICU stay and mortality rate were higher in AKI positive group.

  14. Kidney Disease and the Nexus of Chronic Kidney Disease and Acute Kidney Injury: The Role of Novel Biomarkers as Early and Accurate Diagnostics.

    Science.gov (United States)

    Yerramilli, Murthy; Farace, Giosi; Quinn, John; Yerramilli, Maha

    2016-11-01

    Chronic kidney disease (CKD) and acute kidney injury (AKI) are interconnected and the presence of one is a risk for the other. CKD is an important predictor of AKI after exposure to nephrotoxic drugs or major surgery, whereas persistent or repetitive injury could result in the progression of CKD. This brings new perspectives to the diagnosis and monitoring of kidney diseases highlighting the need for a panel of kidney-specific biomarkers that reflect functional as well as structural damage and recovery, predict potential risk and provide prognosis. This article discusses the kidney-specific biomarkers, symmetric dimethylarginine (SDMA), clusterin, cystatin B, and inosine. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Contour plot assessment of existing meta-analyses confirms robust association of statin use and acute kidney injury risk.

    Science.gov (United States)

    Chevance, Aurélie; Schuster, Tibor; Steele, Russell; Ternès, Nils; Platt, Robert W

    2015-10-01

    Robustness of an existing meta-analysis can justify decisions on whether to conduct an additional study addressing the same research question. We illustrate the graphical assessment of the potential impact of an additional study on an existing meta-analysis using published data on statin use and the risk of acute kidney injury. A previously proposed graphical augmentation approach is used to assess the sensitivity of the current test and heterogeneity statistics extracted from existing meta-analysis data. In addition, we extended the graphical augmentation approach to assess potential changes in the pooled effect estimate after updating a current meta-analysis and applied the three graphical contour definitions to data from meta-analyses on statin use and acute kidney injury risk. In the considered example data, the pooled effect estimates and heterogeneity indices demonstrated to be considerably robust to the addition of a future study. Supportingly, for some previously inconclusive meta-analyses, a study update might yield statistically significant kidney injury risk increase associated with higher statin exposure. The illustrated contour approach should become a standard tool for the assessment of the robustness of meta-analyses. It can guide decisions on whether to conduct additional studies addressing a relevant research question. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Dexamethasone Modifies Cystatin C-Based Diagnosis of Acute Kidney Injury During Cisplatin-Based Chemotherapy

    Directory of Open Access Journals (Sweden)

    Timothy J. Pianta

    2017-03-01

    Full Text Available Background/Aims: Plasma cystatin C (pCysC may be superior to serum creatinine (sCr as a surrogate of GFR. However, the performance of pCysC for diagnosing acute kidney injury (AKI after cisplatin-based chemotherapy is potentially affected by accompanying corticosteroid anti-emetic therapy and hydration. Methods: In a prospective observational study pCysC, sCr, urinary kidney injury molecule-1 (KIM-1, and urinary clusterin were measured over 2 weeks in 27 patients given first-cycle chemotherapy. The same variables were measured over 2 weeks in Sprague–Dawley rats given a single intraperitoneal injection of dexamethasone, cisplatin, or both, and in controls. Results: In patients, pCysC increases were greater than sCr 41% vs. 16%, mean paired difference 25% (95% CI: 16–34%], relative increases were ≥ 50% in 9 patients (35% for pCysC compared with 2 (8% for sCr (p = 0.04 and increases in sCr were accompanied by increased KIM-1 and clusterin excretion, but increases in pCysC alone were not. In rats, dexamethasone administration produced dose-dependent increases in pCysC (and augmented cisplatin-induced increases in pCysC, but did not augment histological injury, increases in sCr, or KIM-1 and clusterin excretion. Conclusions: In the presence of dexamethasone, elevation of pCysC does not reliably diagnose AKI after cisplatin-based chemotherapy.

  17. Linking acute kidney injury to chronic kidney disease: the missing links.

    Science.gov (United States)

    Kaballo, Mohammed A; Elsayed, Mohamed E; Stack, Austin G

    2017-08-01

    Acute kidney injury (AKI) is considered to be a major public health problem around the globe, and it is associated with major adverse clinical outcomes and significant health care costs. There is growing evidence suggesting that AKI is associated with the subsequent development of chronic kidney disease (CKD). While recovery of kidney function occurs in the majority of patients surviving an AKI episode, a large number of patients do not recover completely. Similarly, CKD is a well-known risk factor for the development of AKI. Recent studies suggest that both AKI and CKD are not separate disease entities but are in fact components of a far more closely interconnected disease continuum. However, the true nature of this relationship is complex and poorly understood. This review explores potential relationships between AKI and CKD, and seeks to uncover a number of "missing links" in this tentative emerging relationship.

  18. Is prolonged cold ischemia a contraindication to using kidneys from acute kidney injury donors?

    Science.gov (United States)

    Orlando, Giuseppe; Khan, Muhammad A; El-Hennawy, Hany; Farney, Alan C; Rogers, Jeffrey; Reeves-Daniel, Amber; Gautreaux, Michael D; Doares, William; Kaczmorski, Scott; Stratta, Robert J

    2018-03-01

    To determine the impact of prolonged cold ischemia time (CIT) on the outcome of acute kidney injury (AKI) renal grafts, we therefore performed a single-center retrospective analysis in adult patients receiving kidney transplantation (KT) from AKI donors. Outcomes were stratified according to duration of CIT. A total of 118 patients receiving AKI grafts were enrolled. Based on CIT, patients were stratified as follows: (i) 20 hours (P = NS). In the nine patients with CIT >40 hours, the 4-year DCGS rate was 100%. We conclude that prolonged CIT in AKI grafts may not adversely influence outcomes and so discard of AKI kidneys because of projected long CIT is not warranted when donors are wisely triaged. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Subclinical chronic kidney disease modifies the diagnosis of experimental acute kidney injury.

    Science.gov (United States)

    Succar, Lena; Pianta, Timothy J; Davidson, Trent; Pickering, John W; Endre, Zoltán H

    2017-09-01

    Extensive structural damage within the kidney must be present before serum creatinine increases. However, a subclinical phase of chronic kidney disease (CKD) usually goes undetected. Here we tested whether experimental subclinical CKD would modify functional and damage biomarker profiles of acute kidney injury (AKI). Subclinical CKD was induced in rats by adenine or aristolochic acid models but without increasing serum creatinine. After prolonged recovery (three to six weeks), AKI was induced with a subnephrotoxic dose of cisplatin. Urinary levels of kidney injury molecule-1 (KIM-1), cytochrome C, monocyte chemotactic protein-1 (MCP-1), clusterin, and interleukin-18 increased during CKD induction, without an increase in serum creatinine. After AKI in adenine-induced CKD, serum creatinine increased more rapidly, while increased urinary KIM-1, clusterin, and MCP-1 were delayed and reduced. Increased serum creatinine and biomarker excretion were associated with diffuse tubulointerstitial injury in the outer stripe of outer medulla coupled with over 50% cortical damage. Following AKI in aristolochic acid-induced CKD, increased serum creatinine, urinary KIM-1, clusterin, MCP-1, cytochrome C, and interleukin-18 concentrations and excretion were greater at day 21 than day 42 and inversely correlated with cortical injury. Subclinical CKD modified functional and damage biomarker profiles in diametrically opposite ways. Functional biomarker profiles were more sensitive, while damage biomarker diagnostic thresholds and increases were diminished and delayed. Damage biomarker concentrations and excretion were inversely linked to the extent of prior cortical damage. Thus, thresholds for AKI biomarkers may need to be lower or sampling delayed in the known presence of CKD. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  20. Derivation of a Predictive Model for Graft Loss Following Acute Kidney Injury in Kidney Transplant Recipients.

    Science.gov (United States)

    Molnar, Amber O; van Walraven, Carl; Fergusson, Dean; Garg, Amit X; Knoll, Greg

    2017-01-01

    Acute kidney injury (AKI) is common in the kidney transplant population. To derive a multivariable survival model that predicts time to graft loss following AKI. Retrospective cohort study using health care administrative and laboratory databases. Southwestern Ontario (1999-2013) and Ottawa, Ontario, Canada (1996-2013). We included first-time kidney only transplant recipients who had a hospitalization with AKI 6 months or greater following transplant. AKI was defined using the Acute Kidney Injury Network criteria (stage 1 or greater). The first episode of AKI was included in the analysis. Graft loss was defined by return to dialysis or repeat kidney transplant. We performed a competing risk survival regression analysis using the Fine and Gray method and modified the model into a simple point system. Graft loss with death as a competing event was the primary outcome of interest. A total of 315 kidney transplant recipients who had a hospitalization with AKI 6 months or greater following transplant were included. The median (interquartile range) follow-up time was 6.7 (3.3-10.3) years. Graft loss occurred in 27.6% of the cohort. The final model included 6 variables associated with an increased risk of graft loss: younger age, increased severity of AKI, failure to recover from AKI, lower baseline estimated glomerular filtration rate, increased time from kidney transplant to AKI admission, and receipt of a kidney from a deceased donor. The risk score had a concordance probability of 0.75 (95% confidence interval [CI], 0.69-0.82). The predicted 5-year risk of graft loss fell within the 95% CI of the observed risk more than 95% of the time. The CIs of the estimates were wide, and model overfitting is possible due to the limited sample size; the risk score requires validation to determine its clinical utility. Our prognostic risk score uses commonly available information to predict the risk of graft loss in kidney transplant patients hospitalized with AKI. If validated

  1. Improving acute kidney injury diagnostics using predictive analytics.

    Science.gov (United States)

    Basu, Rajit K; Gist, Katja; Wheeler, Derek S

    2015-12-01

    Acute kidney injury (AKI) is a multifactorial syndrome affecting an alarming proportion of hospitalized patients. Although early recognition may expedite management, the ability to identify patients at-risk and those suffering real-time injury is inconsistent. The review will summarize the recent reports describing advancements in the area of AKI epidemiology, specifically focusing on risk scoring and predictive analytics. In the critical care population, the primary underlying factors limiting prediction models include an inability to properly account for patient heterogeneity and underperforming metrics used to assess kidney function. Severity of illness scores demonstrate limited AKI predictive performance. Recent evidence suggests traditional methods for detecting AKI may be leveraged and ultimately replaced by newer, more sophisticated analytical tools capable of prediction and identification: risk stratification, novel AKI biomarkers, and clinical information systems. Additionally, the utility of novel biomarkers may be optimized through targeting using patient context, and may provide more granular information about the injury phenotype. Finally, manipulation of the electronic health record allows for real-time recognition of injury. Integrating a high-functioning clinical information system with risk stratification methodology and novel biomarker yields a predictive analytic model for AKI diagnostics.

  2. STUDY OF ACUTE KIDNEY INJURY IN SNAKE BITE PATIENTS

    Directory of Open Access Journals (Sweden)

    Suma Dasaraju

    2017-04-01

    Full Text Available BACKGROUND Snake venom is well known to cause toxic damage to the kidneys (Schreiner and Maher, 1965. This study is an attempt to evaluate the snakebite-induced Acute Kidney Injury (AKI. MATERIALS AND METHODS 50 patients with snakebite-induced acute kidney injury were selected randomly and their clinical profile was assessed. Acute kidney injury was evaluated using noninvasive laboratory methods. Inclusion Criteria- 1. History of snakebite; 2. Presence of AKI. Exclusion Criteria- Pre-existing renal diseases, after establishing the diagnosis, patients were started on conservative treatment including ASV, blood/blood products and haemodialysis as required. RESULTS Out of 50 patients included in the study, majority of them were males (62% with mean age of presentation 43.8 ± 12.63 years. The mean interval between snakebite and presentation to hospital was 15.37 hours. In them, 98% patients presented with local signs of inflammation, 52% of patients presented with coagulation abnormality and 60% with decreased urine output. Comparison between good outcome (recovered from AKI and poor outcome (not recovered from AKI shows significant pvalue for ‘lapse of time in hours’ in presenting to the hospital after snakebite (p value 0.005 and ‘alternative treatment taken’ before coming to the hospital (p value 0.001. CONCLUSION Poisonous snakebites have common manifestations of cellulitis, abnormal coagulation profile and decreased urine output. Overall mortality due to snakebite-induced AKI is 6%. Patients who did not recover from AKI had lapse of time in presenting to the hospital and abnormal coagulation profile.

  3. Erythropoietin protects against rhabdomyolysis-induced acute kidney injury by modulating macrophage polarization

    Science.gov (United States)

    Wang, Shuo; Zhang, Chao; Li, Jiawei; Niyazi, Sidikejiang; Zheng, Long; Xu, Ming; Rong, Ruiming; Yang, Cheng; Zhu, Tongyu

    2017-01-01

    Erythropoietin (EPO) is a well-known hormone that is clinically used for the treatment of anemia. Very recently, an increasing body of evidence showed that EPO could still regulate bioactivities of macrophages. However, the details about the immunomodulatory effect of EPO on macrophages are not fully delineated, particularly in the setting of renal damages. Therefore, in the present study, we determined whether EPO could exert an impact on the dynamics of macrophages in a well-established model of rhabdomyolysis-induced acute kidney injury and explored the potential mechanisms. EPO was found to ameliorate kidney injuries by reducing macrophages recruitment and promoting phenotype switch toward M2 macrophages in vivo. It was also confirmed that EPO could directly suppress pro-inflammatory responses of M1 macrophages and promote M2 marker expression in vitro. Data indicated the possible involvement of Jak2/STAT3/STAT6 pathway in the augmentation of EPO on M2 polarization. These results improved the understanding of the immunoregulatory capacity of EPO on macrophages, which might optimize the therapeutic modalities of EPO. PMID:28383559

  4. Clinical review: Optimal dose of continuous renal replacement therapy in acute kidney injury.

    Science.gov (United States)

    Prowle, John R; Schneider, Antoine; Bellomo, Rinaldo

    2011-01-01

    Continuous renal replacement therapy (CRRT) is the preferred treatment for acute kidney injury in intensive care units (ICUs) throughout much of the world. Despite the widespread use of CRRT, controversy and center-specific practice variation in the clinical application of CRRT continue. In particular, whereas two single-center studies have suggested survival benefit from delivery of higher-intensity CRRT to patients with acute kidney injury in the ICU, other studies have been inconsistent in their results. Now, however, two large multi-center randomized controlled trials - the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network (ATN) study and the Randomized Evaluation of Normal versus Augmented Level (RENAL) Replacement Therapy Study - have provided level 1 evidence that effluent flow rates above 25 mL/kg per hour do not improve outcomes in patients in the ICU. In this review, we discuss the concept of dose of CRRT, its relationship with clinical outcomes, and what target optimal dose of CRRT should be pursued in light of the high-quality evidence now available.

  5. Vitamin D deficiency aggravates chronic kidney disease progression after ischemic acute kidney injury.

    Directory of Open Access Journals (Sweden)

    Janaína Garcia Gonçalves

    Full Text Available Despite a significant improvement in the management of chronic kidney disease (CKD, its incidence and prevalence has been increasing over the years. Progressive renal fibrosis is present in CKD and involves the participation of several cytokines, including Transforming growth factor-β1 (TGF-β1. Besides cardiovascular diseases and infections, several studies show that Vitamin D status has been considered as a non-traditional risk factor for the progression of CKD. Given the importance of vitamin D in the maintenance of essential physiological functions, we studied the events involved in the chronic kidney disease progression in rats submitted to ischemia/reperfusion injury under vitamin D deficiency (VDD.Rats were randomized into four groups: Control; VDD; ischemia/reperfusion injury (IRI; and VDD+IRI. At the 62 day after sham or IRI surgery, we measured inulin clearance, biochemical variables and hemodynamic parameters. In kidney tissue, we performed immunoblotting to quantify expression of Klotho, TGF-β, and vitamin D receptor (VDR; gene expression to evaluate renin, angiotensinogen, and angiotensin-converting enzyme; and immunohistochemical staining for ED1 (macrophages, type IV collagen, fibronectin, vimentin, and α-smooth mucle actin. Histomorphometric studies were performed to evaluate fractional interstitial area.IRI animals presented renal hypertrophy, increased levels of mean blood pressure and plasma PTH. Furthermore, expansion of the interstitial area, increased infiltration of ED1 cells, increased expression of collagen IV, fibronectin, vimentin and α-actin, and reduced expression of Klotho protein were observed. VDD deficiency contributed to increased levels of plasma PTH as well as for important chronic tubulointerstitial changes (fibrosis, inflammatory infiltration, tubular dilation and atrophy, increased expression of TGF-β1 and decreased expression of VDR and Klotho protein observed in VDD+IRI animals.Through inflammatory

  6. EPOXYEICOSATRIENOIC ACID ANALOG ATTENUATES ANGIOTENSIN II HYPERTENSION AND KIDNEY INJURY

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    Md. Abdul Hye Khan

    2014-09-01

    Full Text Available Epoxyeicosatrienoic acids (EETs contribute to blood pressure regulation leading to the concept that EETs can be therapeutically targeted for hypertension and the associated end-organ damage. In the present study, we investigated anti-hypertensive and kidney protective actions of an EET analog, EET-B in angiotensin II (ANG II-induced hypertension. EET-B was administered in drinking water for 14 days (10mg/kg/d and resulted in a decreased blood pressure elevation in ANG II hypertension. At the end of the two-week period, blood pressure was 30 mmHg lower in EET analog-treated ANG II hypertensive rats. The vasodilation of mesenteric resistance arteries to acetylcholine was impaired in ANG II hypertension; however, it was improved with EET-B treatment. Further, EET-B protected the kidney in ANG II hypertension as evidenced by a marked 90% decrease in albuminuria and 54% decrease in nephrinuria. Kidney histology demonstrated a decrease in renal tubular cast formation in EET analog-treated hypertensive rats. In ANG II hypertension, EET-B treatment markedly lowered renal inflammation. Urinary monocyte chemoattractant protein-1 excretion was decreased by 55% and kidney macrophage infiltration was reduced by 52% with EET-B treatment. Overall, our results demonstrate that EET-B has anti-hypertensive properties, improves vascular function, and decreases renal inflammation and injury in ANG II hypertension.

  7. Rhabdomyolysis and acute kidney injury in the injured war fighter.

    Science.gov (United States)

    Elterman, Joel; Zonies, David; Stewart, Ian; Fang, Raymond; Schreiber, Martin

    2015-10-01

    Rhabdomyolysis is a recognized complication of traumatic injury. The correlation of an elevated creatine kinase (CK) level and the development of acute kidney injury (AKI) has been studied in the civilian population. We sought to review the prevalence of rhabdomyolysis in injured war fighters and determine if peak CK levels correlate with AKI. This is a retrospective cohort study of patients admitted at a US military treatment facility from January to November 2010. Inclusion criteria were active duty patients transported after explosive, penetrating, or blunt injury. Patients with burns or non-trauma-related admissions were excluded. Rhabdomyolysis was defined as a CK level greater than 5,000 U/L. AKI was defined using the Kidney Disease: Improving Global Outcomes classification. Mann-Whitney U-tests were used to determine the significance for continuous data. Correlations were determined using Spearman's ρ. Significance was set at p Rhabdomyolysis developed in 79 patients (24.8%). The median peak CK for all patients was 4,178 U/L and ranged from 208 U/L to 120,000 U/L. Stage 1, 2, and 3 AKI developed in 56 (17.6%), 3 (0.9%), and 7 (2.2%) patients, respectively. There was a weak but statistically significant correlation between peak CK and AKI (r = 0.26, p rhabdomyolysis in combat casualties and would allow for standardized comparisons in future work. Epidemiologic/prognostic study, level III.

  8. DNA damage response in nephrotoxic and ischemic kidney injury

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Mingjuan; Tang, Chengyuan [Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011 (China); Ma, Zhengwei [Department of Cellular Biology & Anatomy, Medical College of Georgia at Augusta University and Charlie Norwood VA Medical Center, Augusta, GA 30912 (United States); Huang, Shuang [Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, FL (United States); Dong, Zheng, E-mail: zdong@augusta.edu [Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011 (China); Department of Cellular Biology & Anatomy, Medical College of Georgia at Augusta University and Charlie Norwood VA Medical Center, Augusta, GA 30912 (United States)

    2016-12-15

    DNA damage activates specific cell signaling cascades for DNA repair, cell cycle arrest, senescence, and/or cell death. Recent studies have demonstrated DNA damage response (DDR) in experimental models of acute kidney injury (AKI). In cisplatin-induced AKI or nephrotoxicity, the DDR pathway of ATR/Chk2/p53 is activated and contributes to renal tubular cell apoptosis. In ischemic AKI, DDR seems more complex and involves at least the ataxia telangiectasia mutated (ATM), a member of the phosphatidylinositol 3-kinase-related kinase (PIKK) family, and p53; however, while ATM may promote DNA repair, p53 may trigger cell death. Targeting DDR for kidney protection in AKI therefore relies on a thorough elucidation of the DDR pathways in various forms of AKI.

  9. Quantified kidney echogenicity in mice with renal ischemia reperfusion injury: evaluation as a noninvasive biomarker of acute kidney injury.

    Science.gov (United States)

    Murata, Shinya; Sugiyama, Noriyuki; Maemura, Kentaro; Otsuki, Yoshinori

    2017-09-01

    The purpose is to evaluate quantified kidney echogenicity as a biomarker for the early diagnosis of acute kidney injury (AKI) and predicting progression to chronic kidney disease (CKD) in a mouse model of ischemia-reperfusion injury (IRI). Two separate protocols of murine models of IRI were used: (1) 10, 30, and 40 min of bilateral ischemia duration and (2) 45 and 60 min of unilateral ischemia duration. Renal echogenicity was measured with ultrasound and compared with serum creatinine or urine neutrophil gelatinase-associated lipocalin (NGAL) at various timepoints after IRI. In mice subjected to 10, 30, and 40 min of bilateral ischemia, renal echogenicity increased about 2 h after IRI for all ischemia times, earlier than serum creatinine or urine NGAL. In those subjected to 45 and 60 min of unilateral ischemia, 60 min of unilateral ischemia, which represents atrophic changes 28 days after IRI, resulted in a sustained high level of echogenicity and was significantly different 24 h after IRI, while 45 min of unilateral ischemia resulted in trivial levels of histological damage 28 days after IRI. Renal echogenicity might have the potential to be a biomarker for the early diagnosis of AKI and the prognosis of CKD.

  10. Physical Activity and Kidney Injury in Pediatric and Young Adult Kidney Transplant Recipients.

    Science.gov (United States)

    Wolf, Mattie F; George, Roshan P; Warshaw, Barry; Wang, Elizabeth; Greenbaum, Larry A

    2016-12-01

    To quantify physical activity and grip strength in pediatric kidney transplant recipients and describe attitudes about exercise and exercise counseling given concerns about allograft injury. This was a cross-sectional analysis of 101 kidney transplant recipients (7-21 years old) >6 months post-transplant. Patients completed the Physical Activity Questionnaire (PAQ). Grip strength was measured with a dynamometer. We asked about activity limitations and provider counseling. Univariate analysis and multiple linear regression were used to determine independent predictors of PAQ score and grip strength z score. We enrolled 101 of 122 eligible patients. Median PAQ score was 2.2 (range 0-5) and was lower compared with controls (P < .001). The average grip strength z score was -1.1 and -0.7 in the right and left hand, respectively. Predictors of lower grip strength were younger age (P = .036), non-African American race (P = .029), lower height z score (P = .010), and longer percentage of lifetime with kidney disease (P = .029). Although 49% and 67% limited exercise before and after transplant, respectively, 67% reported increased activity after transplant. By parent report, provider counseling included limiting certain activities (71%) and encouraging regular exercise (45%). Physical activity and grip strength are low after kidney transplant. Patients perceive an emphasis on exercise limitations rather than the benefits of regular exercise. Interventions that encourage physical activity may be beneficial. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Ischaemia-reperfusion injury: a major protagonist in kidney transplantation.

    Science.gov (United States)

    Ponticelli, Claudio

    2014-06-01

    Ischaemia-reperfusion injury (IRI) is a frequent event in kidney transplantation, particularly when the kidney comes from a deceased donor. The brain death is usually associated with generalized ischaemia due to a hyperactivity of the sympathetic system. In spite of this, most donors have profound hypotension and require administration of vasoconstrictor agents. Warm ischaemia after kidney vessels clamping and the cold ischaemia after refrigeration also reduce oxygen and nutrients supply to tissues. The reperfusion further aggravates the state of oxidation and inflammation created by ischaemia. IRI first attacks endothelial cells and tubular epithelial cells. The lesions may be so severe that they lead to acute kidney injury (AKI) and delayed graft function (DGF), which can impair the graft survival. The unfavourable impact of DGF is worse when DGF is associated with acute rejection. Another consequence of IRI is the activation of the innate immunity. Danger signals released by dying cells alarm Toll-like receptors that, through adapter molecules and a chain of kinases, transmit the signal to transcription factors which encode the genes regulating inflammatory cells and mediators. In the inflammatory environment, dendritic cells (DCs) intercept the antigen, migrate to lymph nodes and present the antigen to immunocompetent cells, so activating the adaptive immunity and favouring rejection. Attempts to prevent IRI include optimal management of donor and recipient. Calcium-channel blockers, l-arginine and N-acetylcysteine could obtain a small reduction in the incidence of post-transplant DGF. Fenoldopam, Atrial Natriuretic Peptide, Brain Natriuretic Peptide and Dopamine proved to be helpful in reducing the risk of AKI in experimental models, but there is no controlled evidence that these agents may be of benefit in preventing DGF in kidney transplant recipients. Other antioxidants have been successfully used in experimental models of AKI but only a few studies of poor

  12. Acute kidney injury in pediatric patients: diagnosis and management in the emergency department [digest].

    Science.gov (United States)

    Mohrer, Daniel; Langhan, Melissa; Chaudhari, Pradip

    2017-05-22

    Pediatric acute kidney injury is a condition that is underdiagnosed among children seen in the emergency department, and it has been associated with significant morbidity and mortality, including increased risk for chronic kidney disease. The most common etiologies in pediatric patients are now known to be due to hypovolemia, sepsis, shock, and cardiac dysfunction. This issue compares 3 classification systems for the diagnosis and staging of acute kidney injury and reviews the etiologies that lead to kidney injury in children. The management of pediatric acute kidney injury focuses on identifying patients at high risk, monitoring intravascular volume status, avoiding nephrotoxic medication exposure, and involving a pediatric nephrologist once acute kidney injury is diagnosed. [Points & Pearls is a digest of Pediatric Emergency Medicine Practice].

  13. Splenectomy exacerbates lung injury after ischemic acute kidney injury in mice

    Science.gov (United States)

    Andrés-Hernando, Ana; Altmann, Christopher; Ahuja, Nilesh; Lanaspa, Miguel A.; Nemenoff, Raphael; He, Zhibin; Ishimoto, Takuji; Simpson, Pete A.; Weiser-Evans, Mary C.; Bacalja, Jasna

    2011-01-01

    Patients with acute kidney injury (AKI) have increased serum proinflammatory cytokines and an increased occurrence of respiratory complications. The aim of the present study was to examine the effect of renal and extrarenal cytokine production on AKI-mediated lung injury in mice. C57Bl/6 mice underwent sham surgery, splenectomy, ischemic AKI, or ischemic AKI with splenectomy and kidney, spleen, and liver cytokine mRNA, serum cytokines, and lung injury were examined. The proinflammatory cytokines IL-6, CXCL1, IL-1β, and TNF-α were increased in the kidney, spleen, and liver within 6 h of ischemic AKI. Since splenic proinflammatory cytokines were increased, we hypothesized that splenectomy would protect against AKI-mediated lung injury. On the contrary, splenectomy with AKI resulted in increased serum IL-6 and worse lung injury as judged by increased lung capillary leak, higher lung myeloperoxidase activity, and higher lung CXCL1 vs. AKI alone. Splenectomy itself was not associated with increased serum IL-6 or lung injury vs. sham. To investigate the mechanism of the increased proinflammatory response, splenic production of the anti-inflammatory cytokine IL-10 was determined and was markedly upregulated. To confirm that splenic IL-10 downregulates the proinflammatory response of AKI, IL-10 was administered to splenectomized mice with AKI, which reduced serum IL-6 and improved lung injury. Our data demonstrate that AKI in the absence of a counter anti-inflammatory response by splenic IL-10 production results in an exuberant proinflammatory response and lung injury. PMID:21677145

  14. Reduced Production of Creatinine Limits Its Use as Marker of Kidney Injury in Sepsis

    OpenAIRE

    Doi, Kent; Yuen, Peter S.T.; Eisner, Christoph; Hu, Xuzhen; Leelahavanichkul, Asada; Schnermann, Jürgen; Star, Robert A.

    2009-01-01

    Although diagnosis and staging of acute kidney injury uses serum creatinine, acute changes in creatinine lag behind both renal injury and recovery. The risk for mortality increases when acute kidney injury accompanies sepsis; therefore, we sought to explore the limitations of serum creatinine in this setting. In mice, induction of sepsis by cecal ligation and puncture in bilaterally nephrectomized mice increased markers of nonrenal organ injury and serum TNF-α. Serum creatinine, however, was ...

  15. Rhabdomyolysis-Associated Acute Kidney Injury With Normal Creatine Phosphokinase.

    Science.gov (United States)

    Kamal, Faisal; Snook, Lindsay; Saikumar, Jagannath H

    2018-01-01

    Rhabdomyolysis is a syndrome characterized by the breakdown of skeletal muscle and leakage of intracellular myocyte contents, such as creatine phosphokinase (CPK) and myoglobin, into the interstitial space and plasma resulting in acute kidney injury (AKI). Elevated CPK of at least 5 times the upper limit of normal is an important diagnostic marker of Rhabdomyolysis. We present a case of rhabdomyolysis with severe AKI with a normal CPK at presentation. A 32-year-old man presented with acute respiratory failure and AKI after an overdose of recreational drugs. Urinalysis at presentation showed trace amounts of blood, identified as rare red blood cells under microscopy. CPK was 156 U/L at presentation. Workup for glomerulonephritis and vasculitis was negative. He was initiated on renal replacement therapy, and a kidney biopsy showed severe acute tubular injury with positive myoglobin casts. Supportive management and renal replacement therapy was provided, and renal function spontaneously improved after a few weeks. This is an uncommon clinical presentation of severe rhabdomyolysis complicated by AKI. This suggests that CPK alone may not be a sensitive marker for rhabdomyolysis-induced AKI in some cases. Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  16. Risk Predictors for Postcontrast Acute Kidney Injury.

    Science.gov (United States)

    Krause, Trudy Millard; Ukhanova, Maria; Lee Revere, Frances; Finkel, Kevin W

    2018-05-22

    To evaluate risk predictors of acute kidney injury (AKI) after contrast-media procedures in a broader cohort of patients than previously reported. Comprehensive medical and pharmacy commercial claims data from 2012 to 2014. Claims associated with contrast-media procedures for 2,737,020 persons between January 1, 2012 and November 30, 2014, were reviewed. The overall incidence of AKI after a contrast-media procedure was 0.85%. AKI occurred in 26% of cases that had two or more contrast procedures within 30 days, compared with 9% of non-AKI cases. Although the incidence of postcontrast AKI was low, 10% of patients who developed AKI had a recent previous episode of AKI. In cases when AKI had occurred within 180 days of contrast administration, the odds of subsequent kidney injury was 9.39. Overall, there is a low risk (0.85%) of developing an AKI after a procedure with contrast-media consistent with several recent studies. However, in adults with a recent history of AKI, physicians must consider this history as a risk factor for subsequent AKI. Copyright © 2018 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  17. Effect of melatonin on kidney cold ischemic preservation injury

    Science.gov (United States)

    Aslaner, Arif; Gunal, Omer; Turgut, Hamdi Taner; Celik, Erdal; Yildirim, Umran; Demirci, Rojbin Karakoyun; Gunduz, Umut Riza; Calis, Hasan; Dogan, Sami

    2013-01-01

    Melatonin is a potent free radical scavenger of reactive oxygen species, nitric oxide synthase inhibitor and a well-known antioxidant secreted from pineal gland. This hormone has been reported to protect tissue from oxidative damage. In this study, we aim to investigate the effect of melatonin on kidney cold ischemia time when added to preservation solution. Thirty male Wistar albino rats were divided equally into three groups; Ringer Lactate (RL) solution, University of Wisconsin (UW) solution with and without melatonin. The serum Lactate Dehydrogenase (LDH) activities of the preservation solutions at 2nd, 24th, 36th, and 48th hours were determined. Tissue malondialdehyde (MDA) levels were also measured and a histological examination was performed at 48th hour. Melatonin that added to preservation solution prevented enzyme elevation and decreased lipid peroxidation in preservation solution when compared to the control group (p<0.05). The histological examination revealed that UW solution containing melatonin significantly prevented the kidney from pathological injury (p<0.05). Melatonin added to preservation solutions such as UW solution seemed to protect the tissue preserved effectively from cold ischemic injury for up to 48 hour. PMID:24179573

  18. Acute Kidney Injury by Radiographic Contrast Media: Pathogenesis and Prevention

    Science.gov (United States)

    Faga, Teresa; Pisani, Antonio; Michael, Ashour

    2014-01-01

    It is well known that iodinated radiographic contrast media may cause kidney dysfunction, particularly in patients with preexisting renal impairment associated with diabetes. This dysfunction, when severe, will cause acute renal failure (ARF). We may define contrast-induced Acute Kidney Injury (AKI) as ARF occurring within 24–72 hrs after the intravascular injection of iodinated radiographic contrast media that cannot be attributed to other causes. The mechanisms underlying contrast media nephrotoxicity have not been fully elucidated and may be due to several factors, including renal ischaemia, particularly in the renal medulla, the formation of reactive oxygen species (ROS), reduction of nitric oxide (NO) production, and tubular epithelial and vascular endothelial injury. However, contrast-induced AKI can be prevented, but in order to do so, we need to know the risk factors. We have reviewed the risk factors for contrast-induced AKI and measures for its prevention, providing a long list of references enabling readers to deeply evaluate them both. PMID:25197639

  19. Acute kidney injury in septua- and octogenarians after cardiac surgery

    Directory of Open Access Journals (Sweden)

    Schmid Christof

    2011-08-01

    Full Text Available Abstract Background An increasing number of septua- and octogenarians undergo cardiac surgery. Acute kidney injury (AKI still is a frequent complication after surgery. We examined the incidence of AKI and its impact on 30-day mortality. Methods A retrospective study between 01/2006 and 08/2009 with 299 octogenarians, who were matched for gender and surgical procedure to 299 septuagenarians at a university hospital. Primary endpoint was AKI after surgery as proposed by the RIFLE definition (Risk, Injury, Failure, Loss, End-stage kidney disease. Secondary endpoint was 30-day mortality. Perioperative mortality was predicted with the logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE. Results Octogenarians significantly had a mean higher logistic EuroSCORE compared to septuagenarians (13.2% versus 8.5%; p -1 × 1.73 m-2. In contrast, septuagenarians showed a slightly higher median body mass index (28 kg × m-2 versus 26 kg × m-2 and were more frequently active smoker at time of surgery (6.4% versus 1.6%, p The RIFLE classification provided accurate risk assessment for 30-day mortality and fair discriminatory power. Conclusions The RIFLE criteria allow identifying patients with AKI after cardiac surgery. The high incidence of AKI in septua- and octogenarians after cardiac surgery should prompt the use of RIFLE criteria to identify patients at risk and should stimulate institutional measures that target AKI as a quality improvement initiative for patients at advanced age.

  20. Biomarkers of acute kidney injury in neonatal encephalopathy.

    LENUS (Irish Health Repository)

    Sweetman, D U

    2013-03-01

    Acute kidney injury (AKI) is a common complication of neonatal encephalopathy (NE). The accurate diagnosis of neonatal AKI, irrespective of the cause, relies on suboptimal methods such as identification of rising serum creatinine, decreased urinary output and glomerular filtration rate. Studies of AKI biomarkers in adults and children have shown that biomarkers can improve the early diagnosis of AKI. Hypoxia-ischaemia is the proposed aetiological basis of AKI in both NE and cardiopulmonary bypass (CPB). However, there is a paucity of studies examining the role of AKI biomarkers specifically in NE. Urinary cystatin C (CysC), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18, kidney injury molecule-1, liver-type fatty acid-binding protein, serum CysC and serum NGAL all show good ability to predict early AKI in a heterogeneous critically ill neonatal population including infants post-CPB. Moreover, serum and urinary NGAL and urinary CysC are early predictors of AKI secondary to NE. These findings are promising and open up the possibility of biomarkers playing a significant role in the early diagnosis and treatment of NE-related AKI. There is an urgent need to explore the role of AKI biomarkers in infants with NE as establishing the diagnosis of AKI earlier may allow more timely intervention with potential for improving long-term outcome.

  1. Drug induced acute kidney injury: an experimental animal study

    International Nuclear Information System (INIS)

    Khan, M.W.A.; Khan, B.T.; Qazi, R.A.; Ashraf, M.; Waqar, M.

    2017-01-01

    Objective: To assess the extent of drug induced nephrotoxicity in laboratory animals for determining the role and extent of iatrogenic kidney damage in patients exposed to nephrotoxic drugs in various clinical setups. Study Design: Randomized control trail. Place and Duration of study: Pharmacology department and animal house of Army Medical College from Jan 2011 to Aug 2011. Material and Methods: Thirty six mixed breed rabbits were used in this study. Animals were randomly divided into six groups consisting of six rabbits in each. Groups were named A, B, C, D, E and F. Group A was control group. Group B was given 0.9% normal saline. Group C rabbits were given acute nephrotoxic single dose of amphotericin B deoxycholate. Group D received 0.9% normal saline 10ml/kg followed by amphotericin B infusion. Group E was injected acute nephrotoxic regimen of cyclosporine and amphotericin B infusion. Group F received saline loading along with acute nephrotoxic regimen of cyclosporine and amphotericin B infusion. Results: Biochemical and histopathological analysis showed significant kidney injury in rabbits exposed to acute nephrotoxic doses of amphotericin B and cyclosporine. Toxicity was additive when the two drugs were administered simultaneously. Group of rabbits with saline loading had significantly lesser kidney damage. Conclusion: Iatrogenic acute kidney damage is a major cause of morbidity in experimental animals exposed to such nephrotoxic drugs like amphotericin B and cyclosporine, used either alone or in combination. Clinical studies are recommended to assess the extent of iatrogenic renal damage in patients and its economic burden. Efficient and cost effective protective measure may be adopted in clinical setups against such adverse effects. (author)

  2. Serial Manifestation of Acute Kidney Injury and Nephrotic Syndrome in a Patient with TAFRO syndrome.

    Science.gov (United States)

    Ito, Seigo; Uchida, Takahiro; Itai, Hiroki; Yamashiro, Aoi; Yamagata, Akira; Matsubara, Hidehito; Imakiire, Toshihiko; Shimazaki, Hideyuki; Kumagai, Hiroo; Oshima, Naoki

    2018-06-06

    A 76-year-old woman suddenly developed anasarca and a fever, and an examination revealed thrombocytopenia, reticulin fibrosis, and acute kidney injury, yielding the diagnosis of TAFRO syndrome. Renal replacement therapy and steroid treatment were soon started. Her proteinuria was minor at first; however, once the kidney function improved, nephrotic syndrome occurred. A kidney biopsy showed membranoproliferative glomerulonephritis-like glomerulopathy with massive macrophage infiltration. Although kidney dysfunction is often observed in TAFRO syndrome patients, its detailed mechanism is unclear. This case suggests that TAFRO syndrome involves both acute kidney injury with minor proteinuria and nephrotic syndrome, and these disorders can develop serially in the same patient.

  3. Modification of Measures of Acute Kidney Injury to Risk Stratify Combat Casualties

    Science.gov (United States)

    2017-08-26

    REPORT TYPE 08/26/2017 Poster 4. TJTLE AND SUBTITLE t\\.1odification of l’vfeasures,of Acute Kidney Injury to Risk Stratify Cotnbat Casualties 6...profiles and potential future conflicts , identifying acute kidney injury (AKI) early can help us determine the need for rapidity of evacuation

  4. Perioperative Aspirin and Clonidine and Risk of Acute Kidney Injury A Randomized Clinical Trial

    NARCIS (Netherlands)

    Garg, Amit X.; Kurz, Andrea; Sessler, Daniel I.; Cuerden, Meaghan; Robinson, Andrea; Mrkobrada, Marko; Parikh, Chirag R.; Mizera, Richard; Jones, Philip M.; Tiboni, Maria; Font, Adrià; Cegarra, Virginia; Gomez, Maria Fernanda Rojas; Meyhoff, Christian S.; VanHelder, Tomas; Chan, Matthew T. V.; Torres, David; Parlow, Joel; de Nadal Clanchet, Miriam; Amir, Mohammed; Bidgoli, Seyed Javad; Pasin, Laura; Martinsen, Kristian; Malaga, German; Myles, Paul; Acedillo, Rey; Roshanov, Pavel S.; Walsh, Michael; Dresser, George; Kumar, Priya; Fleischmann, Edith; Villar, Juan Carlos; Painter, Thomas; Biccard, Bruce; Bergese, Sergio; Srinathan, Sadeesh; Cata, Juan P.; Chan, Vincent; Mehra, Bhupendra; Wijeysundera, Duminda N.; Leslie, Kate; Forget, Patrice; Whitlock, Richard; Yusuf, Salim; Devereaux, P. J.; Alvarez, A.; Bulach, R.; Hannon, S.; Ives, K.; de Hert, S.

    2014-01-01

    IMPORTANCE Acute kidney injury, a common complication of surgery, is associated with poor outcomes and high health care costs. Some studies suggest aspirin or clonidine administered during the perioperative period reduces the risk of acute kidney injury; however, these effects are uncertain and each

  5. Clinical Relevance and Predictive Value of Damage Biomarkers of Drug-Induced Kidney Injury.

    Science.gov (United States)

    Kane-Gill, Sandra L; Smithburger, Pamela L; Kashani, Kianoush; Kellum, John A; Frazee, Erin

    2017-11-01

    Nephrotoxin exposure accounts for up to one-fourth of acute kidney injury episodes in hospitalized patients, and the associated consequences are as severe as acute kidney injury due to other etiologies. As the use of nephrotoxic agents represents one of the few modifiable risk factors for acute kidney injury, clinicians must be able to identify patients at high risk for drug-induced kidney injury rapidly. Recently, significant advancements have been made in the field of biomarker utilization for the prediction and detection of acute kidney injury. Such biomarkers may have a role both for detection of drug-induced kidney disease and implementation of preventative and therapeutic strategies designed to mitigate injury. In this article, basic principles of renal biomarker use in practice are summarized, and the existing evidence for six markers specifically used to detect drug-induced kidney injury are outlined, including liver-type fatty acid binding protein, neutrophil gelatinase-associated lipocalin, tissue inhibitor of metalloproteinase-2 times insulin-like growth factor-binding protein 7 ([TIMP-2]·[IGFBP7]), kidney injury molecule-1 and N-acetyl-β-D-glucosaminidase. The results of the literature search for these six kidney damage biomarkers identified 29 unique articles with none detected for liver-type fatty acid binding protein and [TIMP-2]·[IGFBP7]. For three biomarkers, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin and N-acetyl-β-D-glucosaminidase, the majority of the studies suggest utility in clinical practice. While many questions need to be answered to clearly articulate the use of biomarkers to predict drug-induced kidney disease, current data are promising.

  6. Hyperglycemia and acute kidney injury in critically ill children

    Directory of Open Access Journals (Sweden)

    Gordillo R

    2016-08-01

    Full Text Available Roberto Gordillo,1 Tania Ahluwalia,2 Robert Woroniecki3 1Department of Pediatrics, Division of Nephrology, 2Department of Pediatrics, University of Illinois College of Medicine, Peoria, IL, USA; 3Division of Pediatric Nephrology and Hypertension, Stony Brook Children’s Hospital, Stony Brook, NY, USA Background: Hyperglycemia and acute kidney injury (AKI are common in critically ill children and have been associated with higher morbidity and mortality. The incidence of AKI in children is difficult to estimate because of the lack of a standard definition for AKI. The pediatric RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease criteria can be used to define AKI in children. Various biomarkers in urine and blood have been studied to detect AKI in critically ill children. However, it is not clear whether hyperglycemia is associated with AKI. Our objective was to evaluate the effect of hyperglycemia on kidney function and its effect on neutrophil gelatinase-associated lipocalin (NGAL in children. Methods: We studied retrospective and prospective cohorts of pediatric critically ill subjects admitted to the pediatric intensive care unit (PICU. We analyzed data from admission that included estimated glomerular filtration rate, plasma and urine NGAL, serum glucose and peak glycemia (highest glycemia during PICU admission, and length of hospital and PICU stay from two different institutions. Results: We found that the prevalence of hyperglycemia was 89% in the retrospective cohort and 86% in the prospective cohort, P=0.99. AKI was associated with peak glycemia, P=0.03. There was a statistically significant correlation between peak glycemia and hospital and PICU stays, P=<0.001 and P<0.001, respectively. Urine NGAL and plasma NGAL were not statistically different in subjects with and without hyperglycemia, P=0.99 and P=0.85, respectively. Subjects on vasopressors had lower estimated glomerular filtration rate and higher

  7. Urinary NGAL in patients with and without acute kidney injury in a cardiology intensive care unit

    Science.gov (United States)

    Watanabe, Mirian; Silva, Gabriela Fulan e; da Fonseca, Cassiane Dezoti; Vattimo, Maria de Fatima Fernandes

    2014-01-01

    Objective To assess the diagnostic and prognostic efficacy of urine neutrophil gelatinase-associated lipocalin in patients admitted to an intensive care unit. Methods Longitudinal, prospective cohort study conducted in a cardiology intensive care unit. The participants were divided into groups with and without acute kidney injury and were followed from admission to the intensive care unit until hospital discharge or death. Serum creatinine, urine output and urine neutrophil gelatinase-associated lipocalin were measured 24 and 48 hours after admission. Results A total of 83 patients admitted to the intensive care unit for clinical reasons were assessed, most being male (57.8%). The participants were divided into groups without acute kidney injury (N=18), with acute kidney injury (N=28) and with severe acute kidney injury (N=37). Chronic diseases, mechanical ventilation and renal replacement therapy were more common in the groups with acute kidney injury and severe acute kidney injury, and those groups exhibited longer intensive care unit stay and hospital stay and higher mortality. Serum creatinine did not change significantly in the group with acute kidney injury within the first 24 hours of admission to the intensive care unit, although, urine neutrophil gelatinase-associated lipocalin was high in the groups with acute kidney injury and severe acute kidney injury (p<0.001). Increased urine neutrophil gelatinase-associated lipocalin was associated with death. Conclusion An increase in urine neutrophil gelatinase-associated lipocalin precedes variations in serum creatinine in patients with acute kidney injury and may be associated with death. PMID:25607262

  8. (Pro)renin Receptor Is an Amplifier of Wnt/β-Catenin Signaling in Kidney Injury and Fibrosis.

    Science.gov (United States)

    Li, Zhen; Zhou, Lili; Wang, Yongping; Miao, Jinhua; Hong, Xue; Hou, Fan Fan; Liu, Youhua

    2017-08-01

    The (pro)renin receptor (PRR) is a transmembrane protein with multiple functions. However, its regulation and role in the pathogenesis of CKD remain poorly defined. Here, we report that PRR is a downstream target and an essential component of Wnt/ β -catenin signaling. In mouse models, induction of CKD by ischemia-reperfusion injury (IRI), adriamycin, or angiotensin II infusion upregulated PRR expression in kidney tubular epithelium. Immunohistochemical staining of kidney biopsy specimens also revealed induction of renal PRR in human CKD. Overexpression of either Wnt1 or β -catenin induced PRR mRNA and protein expression in vitro Notably, forced expression of PRR potentiated Wnt1-mediated β -catenin activation and augmented the expression of downstream targets such as fibronectin, plasminogen activator inhibitor 1, and α -smooth muscle actin ( α -SMA). Conversely, knockdown of PRR by siRNA abolished β -catenin activation. PRR potentiation of Wnt/ β -catenin signaling did not require renin, but required vacuolar H + ATPase activity. In the mouse model of IRI, transfection with PRR or Wnt1 expression vectors promoted β -catenin activation, aggravated kidney dysfunction, and worsened renal inflammation and fibrotic lesions. Coexpression of PRR and Wnt1 had a synergistic effect. In contrast, knockdown of PRR expression ameliorated kidney injury and fibrosis after IRI. These results indicate that PRR is both a downstream target and a crucial element in Wnt signal transmission. We conclude that PRR can promote kidney injury and fibrosis by amplifying Wnt/ β -catenin signaling. Copyright © 2017 by the American Society of Nephrology.

  9. Rhabdomyolysis and Acute Kidney Injury Associated with Hypothyroidism and Statin Therapy

    OpenAIRE

    Ahn, Pyoung; Min, Hyun-Jun; Park, Sang-Hyun; Lee, Byoung-Mu; Choi, Myung-Jin; Yoon, Jong-Woo; Koo, Ja-Ryong

    2013-01-01

    Rhabdomyolysis is a syndrome involving the breakdown of skeletal muscle that causes myoglobin and other intracellular proteins to leak into the circulatory system, resulting in organ injury including acute kidney injury. We report a case of statin-induced rhabdomyolysis and acute kidney injury that developed in a 63-year-old woman with previously undiagnosed hypothyroidism. Untreated hypothyroidism may have caused her hypercholesterolemia requiring statin treatment, and it is postulated that ...

  10. Predictors of Renal Replacement Therapy in Acute Kidney Injury

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    Michael J. Koziolek

    2012-09-01

    Full Text Available Backgrounds: Criteria that may guide early renal replacement therapy (RRT initiation in patients with acute kidney injury (AKI currently do not exist. Methods: In 120 consecutive patients with AKI, clinical and laboratory data were analyzed on admittance. The prognostic power of those parameters which were significantly different between the two groups was analyzed by receiver operator characteristic curves and by leave-1-out cross validation. Results: Six parameters (urine albumin, plasma creatinine, blood urea nitrogen, daily urine output, fluid balance and plasma sodium were combined in a logistic regression model that estimates the probability that a particular patient will need RRT. Additionally, a second model without daily urine output was established. Both models yielded a higher accuracy (89 and 88% correct classification rate, respectively than the best single parameter, cystatin C (correct classification rate 74%. Conclusions: The combined models may help to better predict the necessity of RRT using clinical and routine laboratory data in patients with AKI.

  11. Hypothyroidism and acute kidney injury: an unusual association.

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    Neves, Precil Diego Miranda de Menezes; Bridi, Ramaiane Aparecida; Balbi, André Luis; Ponce, Daniela

    2013-08-09

    Association between severe hypothyroidism and acute kidney injury (AKI) is rare. A 40-year-old woman presented with 15 days history of generalised muscle pain, weakness, weight gain and oedema. hypertension and hypothyroidism. dry skin, peripheral/periorbital oedema, slow thought and speaking, thyroid increased. Laboratory examinations: high levels of creatine kinase , creatinine, uric acid and lactate dehydrogenase. Free T4 was very low (hypothyroidism-induced rhabdomyolysis. Intravenous fluids were started, urinary alkalisation and increased l-thyroxine dose replacement. On the day after admission, forced diuresis with furosemide was introduced leading to a progressive improvement of symptoms. Although hypothyroidism and AKI is unusual, it should be suspected in patients presenting decrease of renal function and high creatine kinase in the absence of other causes of rhabdomyolysis.

  12. Metformin-Associated Acute Kidney Injury and Lactic Acidosis

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    David Arroyo

    2011-01-01

    Full Text Available Objectives. Metformin is the preferred oral antidiabetic agent for type 2 diabetes. Lactic acidosis is described as a rare complication, usually during an acute kidney injury (AKI. Material and Methods. We conducted a prospective observational study of metformin-associated AKI cases during four years. 29 cases were identified. Previous renal function, clinical data, and outcomes were recorded. Results. An episode of acute gastroenteritis precipitated the event in 26 cases. Three developed a septic shock. Three patients died, the only related factor being liver dysfunction. More severe metabolic acidosis hyperkalemia and anemia were associated with higher probabilities of RRT requirement. We could not find any relationship between previous renal dysfunction and the outcome of the AKI. Conclusions. AKI associated to an episode of volume depletion due to gastrointestinal losses is a serious complication in type 2 diabetic patients on metformin. Previous renal dysfunction (mild-to-moderate CKD has no influence on the severity or outcome.

  13. Renal Support for Acute Kidney Injury in the Developing World

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    Rajeev A. Annigeri

    2017-07-01

    Full Text Available There is wide variation in the management of acute kidney injury (AKI and the practice of renal replacement therapy (RRT around the world. Clinicians in developing countries face additional challenges due to limited resources, reduced availability of trained staff and equipment, cultural and socioeconomic aspects, and administrative and governmental barriers. In this article, we report the consensus recommendations from the 18th Acute Dialysis Quality Initiative conference in Hyderabad, India. We provide the minimal requirements for provision of acute RRT in developing countries, including patient selection, choice of RRT modality and monitoring, transition, and termination of acute RRT. We also discuss areas of uncertainty and propose themes for future research. These recommendations can serve as a foundation for clinicians to implement renal support for AKI in low resource settings.

  14. Choice of Reference Serum Creatinine in Defining Acute Kidney Injury.

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    Siew, Edward D; Matheny, Michael E

    2015-01-01

    The study of acute kidney injury (AKI) has expanded with the increasing availability of electronic health records and the use of standardized definitions. Understanding the impact of AKI between settings is limited by heterogeneity in the selection of reference creatinine to anchor the definition of AKI. In this mini-review, we discuss different approaches used to select reference creatinine and their relative merits and limitations. We reviewed the literature to obtain representative examples of published baseline creatinine definitions when pre-hospital data were not available, as well as literature evaluating the estimation of baseline renal function, using PubMed and reference back-tracing within known works. (1) Pre-hospital creatinine values are useful in determining reference creatinine, and in high-risk populations, the mean outpatient serum creatinine value 7-365 days before hospitalization closely approximates nephrology adjudication, (2) in patients without pre-hospital data, the eGFR 75 approach does not reliably estimate true AKI incidence in most at-risk populations, (3) using the lowest inpatient serum creatinine may be reasonable, especially in those with preserved kidney function, but may generously estimate AKI incidence and severity and miss community-acquired AKI that does not fully resolve, (4) using more specific definitions of AKI (e.g., KIDGO stages 2 and 3) may help to reduce the effects of misclassification when using surrogate values and (5) leveraging available clinical data may help refine the estimate of reference creatinine. Choosing reference creatinine for AKI calculation is important for AKI classification and study interpretation. We recommend obtaining data on pre-hospital kidney function, wherever possible. In studies where surrogate estimates are used, transparency in how they are applied and discussion that informs the reader of potential biases should be provided. Further work to refine the estimation of reference creatinine

  15. Autophagy, Innate Immunity and Tissue Repair in Acute Kidney Injury

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    Pu Duann

    2016-05-01

    Full Text Available Kidney is a vital organ with high energy demands to actively maintain plasma hemodynamics, electrolytes and water homeostasis. Among the nephron segments, the renal tubular epithelium is endowed with high mitochondria density for their function in active transport. Acute kidney injury (AKI is an important clinical syndrome and a global public health issue with high mortality rate and socioeconomic burden due to lack of effective therapy. AKI results in acute cell death and necrosis of renal tubule epithelial cells accompanied with leakage of tubular fluid and inflammation. The inflammatory immune response triggered by the tubular cell death, mitochondrial damage, associative oxidative stress, and the release of many tissue damage factors have been identified as key elements driving the pathophysiology of AKI. Autophagy, the cellular mechanism that removes damaged organelles via lysosome-mediated degradation, had been proposed to be renoprotective. An in-depth understanding of the intricate interplay between autophagy and innate immune response, and their roles in AKI pathology could lead to novel therapies in AKI. This review addresses the current pathophysiology of AKI in aspects of mitochondrial dysfunction, innate immunity, and molecular mechanisms of autophagy. Recent advances in renal tissue regeneration and potential therapeutic interventions are also discussed.

  16. Are diuretics harmful in the management of acute kidney injury?

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    Ejaz, A Ahsan; Mohandas, Rajesh

    2014-03-01

    To assess the role of diuretics in acute kidney injury (AKI) and their effectiveness in preventing AKI, achieving fluid balance, and decreasing progression to chronic kidney disease (CKD). Diuretics are associated with increased risk for AKI. The theoretical advantage of diuretic-induced preservation of renal medullary oxygenation to prevent AKI has not been proven. A higher cumulative diuretic dose during the dialysis period can cause hypotension and increase mortality in a dose-dependent manner. Data on the use of forced euvolemic diuresis to prevent AKI remains controversial. Positive fluid balance has emerged as an independent predictor of adverse outcomes. Post-AKI furosemide dose had a favorable effect on mortality due in part to the reduction of positive fluid balance. There are exciting experimental data suggesting that spironolactone may prevent AKI once an ischemic insult has occurred and thus prevent the progression to CKD. Diuretics are ineffective and even detrimental in the prevention and treatment of AKI, and neither shorten the duration of AKI, nor reduce the need for renal replacement therapy. Diuretics have an important role in volume management in AKI, but they are not recommended for the prevention of AKI. There is increased emphasis on the prevention of progression of AKI to CKD.

  17. Acute Kidney Injury: Definition, Pathophysiology and Clinical Phenotypes.

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    Makris, Konstantinos; Spanou, Loukia

    2016-05-01

    Acute kidney injury (AKI) is a clinical syndrome that complicates the course and worsens the outcome in a significant number of hospitalised patients. Recent advances in clinical and basic research will help with a more accurate definition of this syndrome and in the elucidation of its pathogenesis. With this knowledge we will be able to conduct more accurate epidemiologic studies in an effort to gain a better understanding of the impact of this syndrome. AKI is a syndrome that rarely has a sole and distinct pathophysiology. Recent evidence, in both basic science and clinical research, is beginning to change our view for AKI from a single organ failure syndrome to a syndrome where the kidney plays an active role in the progress of multi-organ dysfunction. Accurate and prompt recognition of AKI and better understanding of the pathophysiologic mechanisms underlying the various clinical phenotypes are of great importance to research for effective therapeutic interventions. In this review we provide the most recent updates in the definition, epidemiology and pathophysiology of AKI.

  18. The Role of Y-Box Binding Protein 1 in Kidney Injury: Friend or Foe?

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    Ke, Ben; Fan, Chuqiao; Tu, Weiping; Fang, Xiangdong

    2018-01-01

    Y-box-binding protein 1 (YB-1) is a multifunctional protein involved in various cellular processes via the transcriptional and translational regulation of target gene expression. YB-1 promotes acute or chronic kidney injury through multiple molecular pathways; however, accumulating evidence suggests that significantly increased YB-1 levels are of great importance in renoprotection. In addition, YB-1 may contribute to obesity-related kidney disease by promoting adipogenesis. Thus, the role of YB-1 in kidney injury is complicated, and no comprehensive review is currently available. In this review, we summarise recent progress in our understanding of the function of YB-1 in kidney injury and provide an overview of the dual role of YB-1 in kidney disease. Moreover, we propose that YB-1 is a potential therapeutic target to restrict kidney disease. © 2018 The Author(s). Published by S. Karger AG, Basel.

  19. Urine stability studies for novel biomarkers of acute kidney injury.

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    Parikh, Chirag R; Butrymowicz, Isabel; Yu, Angela; Chinchilli, Vernon M; Park, Meyeon; Hsu, Chi-Yuan; Reeves, W Brian; Devarajan, Prasad; Kimmel, Paul L; Siew, Edward D; Liu, Kathleen D

    2014-04-01

    The study of novel urinary biomarkers of acute kidney injury has expanded exponentially. Effective interpretation of data and meaningful comparisons between studies require awareness of factors that can adversely affect measurement. We examined how variations in short-term storage and processing might affect the measurement of urine biomarkers. Cross-sectional prospective. Hospitalized patients from 2 sites: Yale New Haven Hospital (n=50) and University of California, San Francisco Medical Center (n=36). We tested the impact of 3 urine processing conditions on these biomarkers: (1) centrifugation and storage at 4°C for 48 hours before freezing at -80°C, (2) centrifugation and storage at 25°C for 48 hours before freezing at -80°C, and (3) uncentrifuged samples immediately frozen at -80°C. Urine concentrations of 5 biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), kidney injury molecule 1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), and cystatin C. We measured urine biomarkers by established enzyme-linked immunosorbent assay methods. Biomarker values were log-transformed, and agreement with a reference standard of immediate centrifugation and storage at -80°C was compared using concordance correlation coefficients (CCCs). Neither storing samples at 4°C for 48 hours nor centrifugation had a significant effect on measured levels, with CCCs higher than 0.9 for all biomarkers tested. For samples stored at 25°C for 48 hours, excellent CCC values (>0.9) also were noted between the test sample and the reference standard for NGAL, cystatin C, L-FABP and KIM-1. However, the CCC for IL-18 between samples stored at 25°C for 48 hours and the reference standard was 0.81 (95% CI, 0.66-0.96). No comparisons to fresh, unfrozen samples; no evaluation of the effect of protease inhibitors. All candidate markers tested using the specified assays showed high stability with both short-term storage at 4°C and without centrifugation

  20. Dynamic changes in Bach1 expression in the kidney of rhabdomyolysis-associated acute kidney injury.

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    Masakazu Yamaoka

    Full Text Available Free heme, a pro-oxidant released from myoglobin, is thought to contribute to the pathogenesis of rhabdomyolysis-associated acute kidney injury (RM-AKI, because renal overexpression of heme oxygenase-1 (HO-1, the rate-limiting enzyme in heme catabolism, confers protection against RM-AKI. BTB and CNC homology 1 (Bach1 is a heme-responsive transcription factor that represses HO-1. Here, we examined the changes with time in the gene expression of Bach1, HO-1, and δ-aminolevulinate synthase (ALAS1, a heme biosynthetic enzyme in the rat kidney using an RM-AKI model induced by the injection of 50% glycerol (10 mL/kg body weight into bilateral limbs. We also examined the protein expression of Bach1 in the nucleus and cytosol, and HO-1 in the rat kidney. Glycerol treatment induced significant elevation of serum creatinine kinase and aspartate aminotransferase levels followed by the marked elevation of serum blood urea nitrogen and creatinine levels, which caused serious damage to renal tubules. Following glycerol treatment, HO-1 mRNA and protein levels were significantly up-regulated, while ALAS1 mRNA expression was down-regulated, suggesting an increase in the free renal heme concentration. The Bach1 mRNA level was drastically increased 3 h after glycerol treatment, and the increased level was maintained for 12 h. Nuclear Bach1 protein levels were significantly decreased 3 h after treatment. Conversely, cytosolic Bach1 protein levels abruptly increased after 6 h. In conclusion, we demonstrate the dynamic changes in Bach1 expression in a rat model of RM-AKI. Our findings suggest that the increase in Bach1 mRNA and cytosolic Bach1 protein expression may reflect de novo Bach1 protein synthesis to compensate for the depletion of nuclear Bach1 protein caused by the induction of HO-1 by free heme.

  1. Rescue therapy with Tanshinone IIA hinders transition of acute kidney injury to chronic kidney disease via targeting GSK3β

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    Jiang, Chunming; Zhu, Wei; Yan, Xiang; Shao, Qiuyuan; Xu, Biao; Zhang, Miao; Gong, Rujun

    2016-01-01

    Acute kidney injury (AKI) remains challenging for clinical practice and poses a risk of developing progressive chronic kidney disease (CKD) with no definitive treatment available yet. Tanshinone IIA, an active ingredient of Chinese herbal Salvia miltiorrhiza, has been widely used in Asia for the remarkable organoprotective activities. Its effect on established AKI, however, remains unknown. In mice with folic acid-induced AKI, delayed treatment with Tanshinone IIA, commenced early or late after injury, diminished renal expression of kidney injury markers, reduced apoptosis and improved kidney dysfunction, concomitant with mitigated histologic signs of AKI to CKD transition, including interstitial fibrosis and tubular atrophy, and with an ameliorated inflammatory infiltration in tubulointerstitium and a favored M2-skewed macrophage polarization. Mechanistically, Tanshinone IIA blunted glycogen synthase kinase (GSK)3β overactivity and hyperactivation of its downstream mitogen-activated protein kinases that are centrally implicated in renal fibrogenesis and inflammation. Inhibition of GSK3β is likely a key mechanism mediating the therapeutic activity of Tanshinone IIA, because sodium nitroprusside, a GSK3β activator, largely offset its renoprotective effect. In confirmatory studies, rescue treatment with Tanshinone IIA likewise ameliorated ischemia/reperfusion-induced kidney destruction in mice. Our data suggest that Tanshinone IIA represents a valuable treatment that improves post-AKI kidney salvage via targeting GSK3β. PMID:27857162

  2. Early urinary biomarkers of acute kidney injury in preterm infants.

    Science.gov (United States)

    Hanna, Mina; Brophy, Patrick D; Giannone, Peter J; Joshi, Mandar S; Bauer, John A; RamachandraRao, Satish

    2016-08-01

    Acute kidney injury (AKI) in the neonatal intensive care setting is multifactorial and is associated with significant morbidity and mortality. This study evaluates the utility of novel urinary biomarkers to predict the development and/or severity AKI in preterm infants. We performed a case-control study on a prospective cohort of preterm infants (<32 wk), to compare seven urine biomarkers between 25 infants with AKI and 20 infants without AKI. Infants with AKI had significantly higher neutrophil gelatinase-associated lipocalin (NGAL) (median, control (CTRL) vs. AKI; 0.598 vs. 4.24 µg/ml; P < 0.0001). In contrast, urinary epidermal growth factor (EGF) levels were significantly lower in infants who developed AKI compared to controls (median, CTRL vs. AKI; 0.016 vs. 0.006 µg/ml; P < 0.001). The area under the curve (AUC) for NGAL for prediction of stage I AKI on the day prior to AKI diagnosis (day-1) was 0.91, and for the prediction of stage II/III, AKI was 0.92. Similarly, urine EGF was a predictor of renal injury on day -1 (AUC: 0.97 for stage I and 0.86 for stage II/III AKI). Urinary biomarkers may be useful to predict AKI development prior to changes in serum creatinine (SCr) in preterm infants.

  3. Acute kidney injury complicating bee stings – a review

    Science.gov (United States)

    da Silva, Geraldo Bezerra; Vasconcelos, Adolfo Gomes; Rocha, Amanda Maria Timbó; de Vasconcelos, Vanessa Ribeiro; de Barros, João; Fujishima, Julye Sampaio; Ferreira, Nathália Barros; Barros, Elvino José Guardão; Daher, Elizabeth De Francesco

    2017-01-01

    ABSTRACT Bee stings can cause severe reactions and have caused many victims in the last years. Allergic reactions can be triggered by a single sting and the greater the number of stings, the worse the prognosis. The poisoning effects can be systemic and can eventually cause death. The poison components are melitin, apamin, peptide 401, phospholipase A2, hyaluronidase, histamine, dopamine, and norepinephrine, with melitin being the main lethal component. Acute kidney injury (AKI) can be observed in patients suffering from bee stings and this is due to multiple factors, such as intravascular hemolysis, rhabdomyolysis, hypotension and direct toxicity of the venom components to the renal tubules. Arterial hypotension plays an important role in this type of AKI, leading to ischemic renal lesion. The most commonly identified biopsy finding in these cases is acute tubular necrosis, which can occur due to both, ischemic injury and the nephrotoxicity of venom components. Hemolysis and rhabdomyolysis reported in many cases in the literature, were demonstrated by elevated serum levels of indirect bilirubin and creatine kinase. The severity of AKI seems to be associated with the number of stings, since creatinine levels were higher, in most cases, when there were more than 1,000 stings. The aim of this study is to present an updated review of AKI associated with bee stings, including the currently advised clinical approach. PMID:28591253

  4. Acute kidney injury complicating bee stings - a review.

    Science.gov (United States)

    Silva, Geraldo Bezerra da; Vasconcelos, Adolfo Gomes; Rocha, Amanda Maria Timbó; Vasconcelos, Vanessa Ribeiro de; Barros, João de; Fujishima, Julye Sampaio; Ferreira, Nathália Barros; Barros, Elvino José Guardão; Daher, Elizabeth De Francesco

    2017-06-01

    Bee stings can cause severe reactions and have caused many victims in the last years. Allergic reactions can be triggered by a single sting and the greater the number of stings, the worse the prognosis. The poisoning effects can be systemic and can eventually cause death. The poison components are melitin, apamin, peptide 401, phospholipase A2, hyaluronidase, histamine, dopamine, and norepinephrine, with melitin being the main lethal component. Acute kidney injury (AKI) can be observed in patients suffering from bee stings and this is due to multiple factors, such as intravascular hemolysis, rhabdomyolysis, hypotension and direct toxicity of the venom components to the renal tubules. Arterial hypotension plays an important role in this type of AKI, leading to ischemic renal lesion. The most commonly identified biopsy finding in these cases is acute tubular necrosis, which can occur due to both, ischemic injury and the nephrotoxicity of venom components. Hemolysis and rhabdomyolysis reported in many cases in the literature, were demonstrated by elevated serum levels of indirect bilirubin and creatine kinase. The severity of AKI seems to be associated with the number of stings, since creatinine levels were higher, in most cases, when there were more than 1,000 stings. The aim of this study is to present an updated review of AKI associated with bee stings, including the currently advised clinical approach.

  5. Acute Kidney Injury as a Risk Factor for Delirium and Coma during Critical Illness.

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    Siew, Edward D; Fissell, William H; Tripp, Christina M; Blume, Jeffrey D; Wilson, Matthew D; Clark, Amanda J; Vincz, Andrew J; Ely, E Wesley; Pandharipande, Pratik P; Girard, Timothy D

    2017-06-15

    Acute kidney injury may contribute to distant organ dysfunction. Few studies have examined kidney injury as a risk factor for delirium and coma. To examine whether acute kidney injury is associated with delirium and coma in critically ill adults. In a prospective cohort study of intensive care unit patients with respiratory failure and/or shock, we examined the association between acute kidney injury and daily mental status using multinomial transition models adjusting for demographics, nonrenal organ failure, sepsis, prior mental status, and sedative exposure. Acute kidney injury was characterized daily using the difference between baseline and peak serum creatinine and staged according to Kidney Disease Improving Global Outcomes criteria. Mental status (normal vs. delirium vs. coma) was assessed daily with the Confusion Assessment Method for the ICU and Richmond Agitation-Sedation Scale. Among 466 patients, stage 2 acute kidney injury was a risk factor for delirium (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.07-2.26) and coma (OR, 2.04; 95% CI, 1.25-3.34) as was stage 3 injury (OR for delirium, 2.56; 95% CI, 1.57-4.16) (OR for coma, 3.34; 95% CI, 1.85-6.03). Daily peak serum creatinine (adjusted for baseline) values were also associated with delirium (OR, 1.35; 95% CI, 1.18-1.55) and coma (OR, 1.44; 95% CI, 1.20-1.74). Renal replacement therapy modified the association between stage 3 acute kidney injury and daily peak serum creatinine and both delirium and coma. Acute kidney injury is a risk factor for delirium and coma during critical illness.

  6. Twist2 Is Upregulated in Early Stages of Repair Following Acute Kidney Injury

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    Elizabeth A. Grunz-Borgmann

    2017-02-01

    Full Text Available The aging kidney is a marked by a number of structural and functional changes, including an increased susceptibility to acute kidney injury (AKI. Previous studies from our laboratory have shown that aging male Fischer 344 rats (24 month are more susceptible to apoptosis-mediated injury than young counterparts. In the current studies, we examined the initial injury and early recovery phases of mercuric chloride-induced AKI. Interestingly, the aging kidney had decreased serum creatinine compared to young controls 1 day following mercuric chloride injury, but by day 4, serum creatinine was significantly elevated, suggesting that the aging kidney did not recover from injury. This conclusion is supported by the findings that serum creatinine and kidney injury molecule-1 (Kim-1 gene expression remain elevated compared to young controls at 10 days post-injury. To begin to elucidate mechanism(s underlying dysrepair in the aging kidney, we examined the expression of Twist2, a helix-loop-helix transcription factor that may mediate renal fibrosis. Interestingly, Twist2 gene expression was elevated following injury in both young and aged rats, and Twist2 protein expression is elevated by mercuric chloride in vitro.

  7. A novel therapy to attenuate acute kidney injury and ischemic allograft damage after allogenic kidney transplantation in mice.

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    Faikah Gueler

    Full Text Available Ischemia followed by reperfusion contributes to the initial damage to allografts after kidney transplantation (ktx. In this study we tested the hypothesis that a tetrapeptide EA-230 (AQGV, might improve survival and attenuate loss of kidney function in a mouse model of renal ischemia/reperfusion injury (IRI and ischemia-induced delayed graft function after allogenic kidney transplantation. IRI was induced in male C57Bl/6N mice by transient bilateral renal pedicle clamping for 35 min. Treatment with EA-230 (20-50mg/kg twice daily i.p. for four consecutive days was initiated 24 hours after IRI when acute kidney injury (AKI was already established. The treatment resulted in markedly improved survival in a dose dependent manner. Acute tubular injury two days after IRI was diminished and tubular epithelial cell proliferation was significantly enhanced by EA-230 treatment. Furthermore, CTGF up-regulation, a marker of post-ischemic fibrosis, at four weeks after IRI was significantly less in EA-230 treated renal tissue. To learn more about these effects, we measured renal blood flow (RBF and glomerular filtration rate (GFR at 28 hours after IRI. EA-230 improved both GFR and RBF significantly. Next, EA-230 treatment was tested in a model of ischemia-induced delayed graft function after allogenic kidney transplantation. The recipients were treated with EA-230 (50 mg/kg twice daily i.p. which improved renal function and allograft survival by attenuating ischemic allograft damage. In conclusion, EA-230 is a novel and promising therapeutic agent for treating acute kidney injury and preventing IRI-induced post-transplant ischemic allograft injury. Its beneficial effect is associated with improved renal perfusion after IRI and enhanced regeneration of tubular epithelial cells.

  8. R1 autonomic nervous system in acute kidney injury.

    Science.gov (United States)

    Hering, Dagmara; Winklewski, Pawel J

    2017-02-01

    Acute kidney injury (AKI) is a rapid loss of kidney function resulting in accumulation of end metabolic products and associated abnormalities in fluid, electrolyte and acid-base homeostasis. The pathophysiology of AKI is complex and multifactorial involving numerous vascular, tubular and inflammatory pathways. Neurohumoral activation with heightened activity of the sympathetic nervous system and renin-angiotensin-aldosterone system play a critical role in this scenario. Inflammation and/or local renal ischaemia are underlying mechanisms triggering renal tissue hypoxia and resultant renal microcirculation dysfunction; a common feature of AKI occurring in numerous clinical conditions leading to a high morbidity and mortality rate. The contribution of renal nerves to the pathogenesis of AKI has been extensively demonstrated in a series of experimental models over the past decades. While this has led to better knowledge of the pathogenesis of human AKI, therapeutic approaches to improve patient outcomes are scarce. Restoration of autonomic regulatory function with vagal nerve stimulation resulting in anti-inflammatory effects and modulation of centrally-mediated mechanisms could be of clinical relevance. Evidence from experimental studies suggests that a therapeutic splenic ultrasound approach may prevent AKI via activation of the cholinergic anti-inflammatory pathway. This review briefly summarizes renal nerve anatomy, basic insights into neural control of renal function in the physiological state and the involvement of the autonomic nervous system in the pathophysiology of AKI chiefly due to sepsis, cardiopulmonary bypass and ischaemia/reperfusion experimental model. Finally, potentially preventive experimental pre-clinical approaches for the treatment of AKI aimed at sympathetic inhibition and/or parasympathetic stimulation are presented. © 2016 John Wiley & Sons Australia, Ltd.

  9. Salutary Effects of Cepharanthine against Skeletal Muscle and Kidney Injuries following Limb Ischemia/Reperfusion

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    Ming-Chang Kao

    2015-01-01

    Full Text Available Limb ischemia/reperfusion (I/R causes oxidation and inflammation and subsequently induces muscle and kidney injuries. Cepharanthine, a natural plant alkaloid, possesses anti-inflammatory and antioxidative properties. We elucidated the salutary effects of cepharanthine against muscle and kidney injuries following limb I/R. Adult male rats were randomized to receive I/R or I/R plus cepharanthine. I/R was achieved by applying tourniquet high around each thigh for 3 hours followed by reperfusion for 24 hours. Cepharanthine (10 mg/kg, intraperitoneal was injected immediately before reperfusion. After euthanization, degrees of tissue injury, inflammation, and oxidation were examined. Our data revealed that the I/R group had significant increases in injury biomarker concentrations of muscle (creatine kinase and lactate dehydrogenase and kidney (creatinine, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1. Histological assays revealed moderate muscle and kidney injury characteristics in the I/R group. The I/R group also had significant increases in concentrations of inflammatory molecules (interleukin-6, macrophage inflammatory protein-2, and prostaglandin E2 and reactive nitrogen species (nitric oxide as well as lipid peroxidation (malondialdehyde. Of note, these effects of limb I/R could be mitigated by cepharanthine. These data confirmed that cepharanthine attenuated muscle and kidney injuries induced by limb I/R. The mechanisms may involve its anti-inflammatory and antioxidative capacities.

  10. Acute kidney injury due to tropical infectious diseases and animal venoms: a tale of 2 continents.

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    Burdmann, Emmanuel A; Jha, Vivekanand

    2017-05-01

    South and Southeast Asia and Latin American together comprise 46 countries and are home to approximately 40% of the world population. The sociopolitical and economic heterogeneity, tropical climate, and malady transitions characteristic of the region strongly influence disease behavior and health care delivery. Acute kidney injury epidemiology mirrors these inequalities. In addition to hospital-acquired acute kidney injury in tertiary care centers, these countries face a large preventable burden of community-acquired acute kidney injury secondary to tropical infectious diseases or animal venoms, affecting previously healthy young individuals. This article reviews the epidemiology, clinical picture, prevention, risk factors, and pathophysiology of acute kidney injury associated with tropical diseases (malaria, dengue, leptospirosis, scrub typhus, and yellow fever) and animal venom (snakes, bees, caterpillars, spiders, and scorpions) in tropical regions of Asia and Latin America, and discusses the potential future challenges due to emerging issues. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  11. Acute liver failure and acute kidney injury: Definitions, prognosis, and outcome

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    Włodzimirow, K.A.

    2013-01-01

    The objective of this thesis was to investigate definitions, prognostic indicators and their association with adverse events, mainly mortality for acute liver failure (ALF), acute-on-chronic liver failure (ACLF) and acute kidney injury (AKI).

  12. Antioxidant protection of statins in acute kidney injury induced by sepsis

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    Franciele do Nascimento Santos

    2014-10-01

    Full Text Available Objective Evaluating the effect of preconditioning with simvastatin in acute kidney injury induced by sepsis. Method Male adult Wistar rats were divided into the following groups: SHAM (control; SHAM+Statin (0.5 mg/kg simvastatin, orally; Sepsis (cecal puncture ligation – CPL; Sepsis+Statin. Physiological parameters, peritoneal fluid culture, renal function, oxidative metabolites, severity of acute kidney injury and animal survival were evaluated. Results The treatment with simvastatin in induced sepsis showed elevation of creatinine clearance with attenuation of generation of oxidative metabolites, lower severity of acute kidney injury and reduced mortality. Conclusion This investigation confirmed the renoprotection with antioxidant principle of the simvastatin in acute kidney injury induced by sepsis in an experimental model.

  13. Risk factors for renal injury in children with a solitary functioning kidney.

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    Westland, R.; Kurvers, R.A.; Wijk, J.A. van; Schreuder, M.F.

    2013-01-01

    OBJECTIVE: The hyperfiltration hypothesis implies that children with a solitary functioning kidney are at risk to develop hypertension, proteinuria, and chronic kidney disease. We sought to determine the presenting age of renal injury and identify risk factors for children with a solitary

  14. Acute kidney injury in liver cirrhosis: new definition and application

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    Florence Wong

    2016-12-01

    Full Text Available The traditional diagnostic criteria of renal dysfunction in cirrhosis are a 50% increase in serum creatinine (SCr with a final value above 1.5 mg/dL. This means that patients with milder degrees of renal dysfunction are not being diagnosed, and therefore not offered timely treatment. The International Ascites Club in 2015 adapted the term acute kidney injury (AKI to represent acute renal dysfunction in cirrhosis, and defined it by an increase in SCr of 0.3 mg/dL (26.4 µmoL/L in <48 hours, or a 50% increase in SCr from a baseline within ≤3 months. The severity of AKI is described by stages, with stage 1 represented by these minimal changes, while stages 2 and 3 AKI by 2-fold and 3-fold increases in SCr respectively. Hepatorenal syndrome (HRS, renamed AKI-HRS, is defined by stage 2 or 3 AKI that fulfils all other diagnostic criteria of HRS. Various studies in the past few years have indicated that these new diagnostic criteria are valid in the prediction of prognosis for patients with cirrhosis and AKI. The future in AKI diagnosis may include further refinements such as inclusion of biomarkers that can identify susceptibility for AKI, differentiating the various prototypes of AKI, or track its progression.

  15. Community-acquired acute kidney injury in adults in Africa.

    Science.gov (United States)

    Adu, Dwomoa; Okyere, Perditer; Boima, Vincent; Matekole, Michael; Osafo, Charlotte

    We review recent published data on demographics, causes, diagnoses, treatment, and outcome of acute kidney injury (AKI) in Africa. A review of the incidence, etiology, diagnoses, and treatment of AKI in adults in Africa from studies published between the years 2000 and 2015. The incidence of AKI in hospitalized patients in Africa ranges from 0.3 to 1.9% in adults. Between 70 and 90% of cases of AKI are community acquired. Most patients with AKI are young with a weighted mean age of 41.3 standard deviation (SD) 9.3 years, and a male to female ratio of 1.2 : 1.0. Medical causes account for between 65 and 80% of causes of AKI. This is followed by obstetric causes in 5 - 27% of cases and surgical causes in 2 - 24% of cases. In the reported studies, between 17 and 94% of patients who needed dialysis received this. The mortality of AKI in adults in Africa ranged from 11.5 to 43.5%. Most reported cases of AKI in Africa originate in the community. The low incidence of hospital-acquired AKI is likely to be due to under ascertainment. Most patients with AKI in Africa are young and have a single precipitating cause. Prominent among these are infection, pregnancy complications and nephrotoxins. Early treatment can improve clinical outcomes.

  16. Risk Factors for Acute Kidney Injury in Severe Rhabdomyolysis

    Science.gov (United States)

    Rodríguez, Eva; Soler, María J.; Rap, Oana; Barrios, Clara; Orfila, María A.; Pascual, Julio

    2013-01-01

    Background Acute kidney injury (AKI) is a life-threatening complication of severe rhabdomyolysis. This study was conducted to assess risk factors for AKI and to develop a risk score for early prediction. Methods Retrospective observational cohort study with a 9-year follow-up, carried out in an acute-care teaching-affiliated hospital. A total of 126 patients with severe rhabdomyolysis defined as serum creatine kinase (CK) > 5,000 IU/L fulfilled the inclusion criteria. Univariate and logistic regression analyses were performed to determine risk factors for AKI. Based on the values obtained for each variable, a risk score and prognostic probabilities were estimated to establish the risk for developing AKI. Results The incidence of AKI was 58%. Death during hospitalization was significantly higher among patients with AKI, compared to patients without AKI (19.2% vs 3.6%, p = 0.008). The following variables were independently associated with AKI: peak CK (odds ratio [OR] 4.9, 95%CI 1.4-16.8), hypoalbuminemia (rhabdomyolysis may be useful in clinical practice, particularly to implement early preventive measures. PMID:24367578

  17. Bath salt intoxication causing acute kidney injury requiring hemodialysis.

    Science.gov (United States)

    Regunath, Hariharan; Ariyamuthu, Venkatesh Kumar; Dalal, Pranavkumar; Misra, Madhukar

    2012-10-01

    Traditional bath salts contain a combination of inorganic salts like Epsom salts, table salt, baking soda, sodium metaphosphate, and borax that have cleansing properties. Since 2010, there have been rising concerns about a new type of substance abuse in the name of "bath salts." They are beta-ketone amphetamine analogs and are derivates of cathinone, a naturally occurring amphetamine analog found in the "khat" plant (Catha edulis). Effects reported with intake included increased energy, empathy, openness, and increased libido. Serious adverse effects reported with intoxication included cardiac, psychiatric, and neurological signs and symptoms. Not much is known about the toxicology and metabolism of these compounds. They inhibit monoamine reuptake (dopamine, nor epinephrine, etc.) and act as central nervous system stimulants with high additive and abuse potential because of their clinical and biochemical similarities to effects from use of cocaine, amphetamine, and 3,4-methylenedioxy-N-methylamphetamine. Deaths associated with use of these compounds have also been reported. We report a case of acute kidney injury associated with the use of "bath salt" pills that improved with hemodialysis. © 2012 The Authors. Hemodialysis International © 2012 International Society for Hemodialysis.

  18. Rare acute kidney injury secondary to hypothyroidism-induced rhabdomyolysis.

    Science.gov (United States)

    Cai, Ying; Tang, Lin

    2013-01-01

    Acute kidney injury (AKI) caused by hypothyroidism-induced rhabdomyolysis is a rare and potentially life-threatening syndrome. The aim of this study was to investigate the clinical characteristics of such patients. We retrospectively analyzed five patients treated at the Second Affiliated Hospital of Chongqing Medical University with AKI secondary to hypothyroidism- induced rhabdomyolysis from January 2006 to December 2010. Of the five cases reviewed (4 males, age range of 37 to 62 years), adult primary hypothyroidism was caused by amiodarone (1 case), chronic autoimmune thyroiditis (1 case), and by uncertain etiologies (3 cases). All patients presented with facial and lower extremity edema. Three patients presented with weakness, while two presented with blunted facies and oliguria. Only one patient reported experiencing myalgia and proximal muscle weakness, in addition to fatigue and chills. Creatine kinase, lactate dehydrogenase, and renal function normalized after thyroid hormone replacement, except in two patients who improved through blood purification. Hypothyroidism should be considered in patients presenting with renal impairment associated with rhabdomyolysis. Moreover, further investigation into the etiology of the hypothyroidism is warranted.

  19. Prediction and Prevention of Acute Kidney Injury after Cardiac Surgery

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    Su Rin Shin

    2016-01-01

    Full Text Available The incidence of acute kidney injury after cardiac surgery (CS-AKI ranges from 33% to 94% and is associated with a high incidence of morbidity and mortality. The etiology is suggested to be multifactorial and related to almost all aspects of perioperative management. Numerous studies have reported the risk factors and risk scores and novel biomarkers of AKI have been investigated to facilitate the subclinical diagnosis of AKI. Based on the known independent risk factors, many preventive interventions to reduce the risk of CS-AKI have been tested. However, any single preventive intervention did not show a definite and persistent benefit to reduce the incidence of CS-AKI. Goal-directed therapy has been considered to be a preventive strategy with a substantial level of efficacy. Many pharmacologic agents were tested for any benefit to treat or prevent CS-AKI but the results were conflicting and evidences are still lacking. The present review will summarize the current updated evidences about the risk factors and preventive strategies for CS-AKI.

  20. Kidney Injury Molecule Levels in Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Aslan, Ozgur; Demir, Metin; Koseoglu, Mehmet

    2016-11-01

    This study was designed to determine the diagnostic role of urinary kidney injury molecule (KIM)-1 levels in renal damage in patients with type 2 diabetes mellitus according to the urinary albumin/creatinine ratio. Patients with type 2 diabetes mellitus admitted to different polyclinics in our hospital enrolled in the study and were subdivided into three groups according to albumin/creatinine ratio - normalbuminuric (n: 20); microalbuminuric (n: 20); albuminuric (n: 18) - and compared with the control group. Urine albumin was analyzed using the immunoturbidimetric method (Architect C16000, Abbott Diagnostics). uKIM-1 was determined using a commercially available enzyme-linked immunosorbent assay test kit (USCN Life Science, Hankou, Wuhan, China). One-sample Kolmogorov-Smirnov test, Spearman correlation and Kruskal-Wallis non-parametric tests were performed. Post hoc comparisons were made using Bonferroni-corrected Mann-Whitney U tests. The differences between the controls and normalbuminuric, microalbuminuric and albuminuric groups were highly significant for KIM-1. Positive correlation was found between KIM-1 and urine microalbumin-urine microalbumin/creatinine (r = 0.479 P diabetic nephropathy. J. Clin. Lab. Anal. 00:1-6, 2016. © 2016 Wiley Periodicals, Inc.

  1. Risk factors associated with acute kidney injury in newborns

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    Emad E Ghobrial

    2018-01-01

    Full Text Available Acute kidney injury (AKI in the newborn is a common problem in the neonatal intensive care unit with many underlying factors such as asphyxia, respiratory distress syndrome (RDS, and urogenital anomalies. The aim of this study is to highlight possible risk factors and profile of neonates developing AKI in the Neonatal Intensive Care Unit (NICU of Cairo University Pediatric Hospital. The study was carried out on 90 neonates (30 patients and 60 controls, among neonates admitted to NICU. The study was done over two months, from January 2015 to March 2015. Our study showed that sepsis was detected in 53.3%, prematurity in 46.67%, RDS in 43.3%, congenital heart disease in 20%, and hypoxic-ischemic encephalopathy in 6.67% of patients. Maternal illness and low body temperature were both significant risk factors of AKI in neonates. History of maternal illness, low body temperature, sepsis, prematurity, and respiratory distress can contribute to the development of AKI in neonates.

  2. Hospital Mortality in the United States following Acute Kidney Injury

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    Jeremiah R. Brown

    2016-01-01

    Full Text Available Acute kidney injury (AKI is a common reason for hospital admission and complication of many inpatient procedures. The temporal incidence of AKI and the association of AKI admissions with in-hospital mortality are a growing problem in the world today. In this review, we discuss the epidemiology of AKI and its association with in-hospital mortality in the United States. AKI has been growing at a rate of 14% per year since 2001. However, the in-hospital mortality associated with AKI has been on the decline starting with 21.9% in 2001 to 9.1 in 2011, even though the number of AKI-related in-hospital deaths increased almost twofold from 147,943 to 285,768 deaths. We discuss the importance of the 71% reduction in AKI-related mortality among hospitalized patients in the United States and draw on the discussion of whether or not this is a phenomenon of hospital billing (coding or improvements to the management of AKI.

  3. Acute Kidney Injury and Atypical Features during Pediatric Poststreptococcal Glomerulonephritis

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    Rose M. Ayoob

    2016-01-01

    Full Text Available The most common acute glomerulonephritis in children is poststreptococcal glomerulonephritis (PSGN usually occurring between 3 and 12 years old. Hypertension and gross hematuria are common presenting symptoms. Most PSGN patients do not experience complications, but rapidly progressive glomerulonephritis and hypertensive encephalopathy have been reported. This paper reports 17 patients seen in 1 year for PSGN including 4 with atypical PSGN, at a pediatric tertiary care center. Seventeen children (11 males, mean age of 8 years, were analyzed. Ninety-four percent had elevated serum BUN levels and decreased GFR. Four of the hospitalized patients had complex presentations that included AKI along with positive ANA or ANCAs. Three patients required renal replacement therapy and two were thrombocytopenic. PSGN usually does not occur as a severe nephritis. Over the 12-month study period, 17 cases associated with low serum albumin in 53%, acute kidney injury in 94%, and thrombocytopenia in 18% were treated. The presentation of PSGN may be severe and in a small subset have associations similar to SLE nephritis findings including AKI, positive ANA, and hematological anomalies.

  4. The Development of a Machine Learning Inpatient Acute Kidney Injury Prediction Model.

    Science.gov (United States)

    Koyner, Jay L; Carey, Kyle A; Edelson, Dana P; Churpek, Matthew M

    2018-03-28

    To develop an acute kidney injury risk prediction model using electronic health record data for longitudinal use in hospitalized patients. Observational cohort study. Tertiary, urban, academic medical center from November 2008 to January 2016. All adult inpatients without pre-existing renal failure at admission, defined as first serum creatinine greater than or equal to 3.0 mg/dL, International Classification of Diseases, 9th Edition, code for chronic kidney disease stage 4 or higher or having received renal replacement therapy within 48 hours of first serum creatinine measurement. None. Demographics, vital signs, diagnostics, and interventions were used in a Gradient Boosting Machine algorithm to predict serum creatinine-based Kidney Disease Improving Global Outcomes stage 2 acute kidney injury, with 60% of the data used for derivation and 40% for validation. Area under the receiver operator characteristic curve (AUC) was calculated in the validation cohort, and subgroup analyses were conducted across admission serum creatinine, acute kidney injury severity, and hospital location. Among the 121,158 included patients, 17,482 (14.4%) developed any Kidney Disease Improving Global Outcomes acute kidney injury, with 4,251 (3.5%) developing stage 2. The AUC (95% CI) was 0.90 (0.90-0.90) for predicting stage 2 acute kidney injury within 24 hours and 0.87 (0.87-0.87) within 48 hours. The AUC was 0.96 (0.96-0.96) for receipt of renal replacement therapy (n = 821) in the next 48 hours. Accuracy was similar across hospital settings (ICU, wards, and emergency department) and admitting serum creatinine groupings. At a probability threshold of greater than or equal to 0.022, the algorithm had a sensitivity of 84% and a specificity of 85% for stage 2 acute kidney injury and predicted the development of stage 2 a median of 41 hours (interquartile range, 12-141 hr) prior to the development of stage 2 acute kidney injury. Readily available electronic health record data can be used

  5. Acute kidney injury in symptomatic primary Epstein-Barr virus infectious mononucleosis: Systematic review.

    Science.gov (United States)

    Moretti, Milena; Lava, Sebastiano A G; Zgraggen, Lorenzo; Simonetti, Giacomo D; Kottanattu, Lisa; Bianchetti, Mario G; Milani, Gregorio P

    2017-06-01

    Textbooks and reviews do not mention the association of symptomatic primary Epstein-Barr virus infectious mononucleosis with acute kidney injury in subjects without immunodeficiency or autoimmunity. Stimulated by our experience with two cases, we performed a review of the literature. The literature documents 38 cases (26 male and 12 female individuals ranging in age from 0.3 to 51, median 18 years) of symptomatic primary Epstein-Barr virus infectious mononucleosis complicated by acute kidney injury: 27 acute interstitial nephritides, 1 jaundice-associated nephropathy, 7 myositides and 3 hemolytic uremic syndromes. Acute kidney injury requiring renal replacement therapy was observed in 18 (47%) cases. Acute kidney injury did not resolve in one patient with acute interstitial nephritis. Two patients died because of systemic complications. The remaining 35 cases fully recovered. In individuals with acute symptomatic Epstein-Barr virus infectious mononucleosis, a relevant kidney injury is rare but the outcome potentially fatal. It results from interstitial nephritis, myositis-associated acute kidney injury, hemolytic uremic syndrome or jaundice-associated nephropathy. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Nanoparticle Detection of Urinary Markers for Point-of-Care Diagnosis of Kidney Injury.

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    Hyun Jung Chung

    Full Text Available The high incidence of acute and chronic kidney injury due to various environmental factors such as heavy metals or chemicals has been a major problem in developing countries. However, the diagnosis of kidney injury in these areas can be more challenging due to the lack of highly sensitive and specific techniques that can be applied in point-of-care settings. To address this, we have developed a technique called 'micro-urine nanoparticle detection (μUNPD', that allows the detection of trace amounts of molecular markers in urine. Specifically, this technique utilizes an automated on-chip assay followed by detection with a hand-held device for the read-out. Using the μUNPD technology, the kidney injury markers KIM-1 and Cystatin C were detected down to concentrations of 0.1 ng/ml and 20 ng/ml respectively, which meets the cut-off range required to identify patients with acute or chronic kidney injury. Thus, we show that the μUNPD technology enables point of care and non-invasive detection of kidney injury, and has potential for applications in diagnosing kidney injury with high sensitivity in resource-limited settings.

  7. Acute Kidney Injury: It's not just the 'big' burns.

    Science.gov (United States)

    Kimmel, L A; Wilson, S; Walker, R G; Singer, Y; Cleland, H

    2018-02-01

    Acute Kidney Injury (AKI) complicates the management of at least 25% of patients with severe burns and is associated with long term complications. Most research focuses on the patients with more severe burns, and whether the same factors are associated with the development of AKI in patients with burns between 10 and 19% total body surface area (TBSA) is unknown. The aims of this study were to examine the incidence of, and factors associated with, the development of AKI in patients with %TBSA≥10, as well as the relationship with hospital metrics such as length of stay (LOS). Retrospective medical record review of consecutive burns patients admitted to The Alfred Hospital, the major adult burns centre in Victoria, Australia. Demographic and injury details were recorded. Factors associated with AKI were determined using multiple logistic regression. Between 2010 and June 2014, 300 patients were admitted with burn injury and data on 267 patients was available for analysis. Median age was 54.5 years with 78% being male. Median %TBSA was 15 (IQR 12, 20). The AKI incidence, as measured by the RIFLE criteria, was 22.5%, including 15% (27/184) in patients with %TBSA 10-19. Factors associated with AKI included increasing age and %TBSA (OR 1.05 p<0.001) as well as increased surgeries (p<0.041) and a cardiac comorbidity (p<0.01). All patients with renal comorbidity developed AKI. In the %TBSA 10-19 cohort, only increasing age (OR 1.05 p<0.001) was associated with AKI. After accounting for confounding factors, the probability of discharge from hospital in Non-AKI group was greater than for the AKI patients at all time points (P<0.001). This is the first study to show an association between patients with %TBSA 10-19 and AKI. Given the association between AKI and complications, prospective research is needed to further understand AKI in burns with the aim of risk reduction. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Association of Serious Fall Injuries among United States End Stage Kidney Disease Patients with Access to Kidney Transplantation.

    Science.gov (United States)

    Plantinga, Laura C; Lynch, Raymond J; Patzer, Rachel E; Pastan, Stephen O; Bowling, C Barrett

    2018-04-06

    Serious fall injuries in the setting of ESKD may be associated with poor access to kidney transplant. We explored the burden of serious fall injuries among patients on dialysis and patients on the deceased donor waitlist and the associations of these fall injuries with waitlisting and transplantation. Our analytic cohorts for the outcomes of ( 1 ) waitlisting and ( 2 ) transplantation included United States adults ages 18-80 years old who ( 1 ) initiated dialysis ( n =183,047) and ( 2 ) were waitlisted for the first time ( n =37,752) in 2010-2013. Serious fall injuries were determined by diagnostic codes for falls plus injury (fracture, joint dislocation, or head trauma) in inpatient and emergency department claims; the first serious fall injury after cohort entry was included as a time-varying exposure. Follow-up ended at the specified outcome, death, or the last date of follow-up (September 30, 2014). We used multivariable Cox proportional hazards models to determine the independent associations between serious fall injury and waitlisting or transplantation. Overall, 2-year cumulative incidence of serious fall injury was 6% among patients on incident dialysis; with adjustment, patients who had serious fall injuries were 61% less likely to be waitlisted than patients who did not (hazard ratio, 0.39; 95% confidence interval, 0.35 to 0.44). Among incident waitlisted patients (4% 2-year cumulative incidence), those with serious fall injuries were 29% less likely than their counterparts to be subsequently transplanted (hazard ratio, 0.71; 95% confidence interval, 0.63 to 0.80). Serious fall injuries among United States patients on dialysis are associated with substantially lower likelihood of waitlisting for and receipt of a kidney transplant. Copyright © 2018 by the American Society of Nephrology.

  9. Rhabdomyolysis and Acute Kidney Injury Associated with Hypothyroidism and Statin Therapy

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    Pyoung Ahn

    2013-12-01

    Full Text Available Rhabdomyolysis is a syndrome involving the breakdown of skeletal muscle that causes myoglobin and other intracellular proteins to leak into the circulatory system, resulting in organ injury including acute kidney injury. We report a case of statin-induced rhabdomyolysis and acute kidney injury that developed in a 63-year-old woman with previously undiagnosed hypothyroidism. Untreated hypothyroidism may have caused her hypercholesterolemia requiring statin treatment, and it is postulated that statin-induced muscle injury was aggravated by hypothyroidism resulting in her full-blown rhabdomyolysis. Although this patient was successfully treated with continuous venovenous hemofiltration and L-thyroxin replacement, rhabdomyolysis with acute kidney injury is a potentially life-threatening disorder. Physicians must pay special attention to the possible presence of subclinical hypothyroidism when administering statins in patients with hypercholesterolemia.

  10. Retrospective Evaluation of Milrinone Pharmacokinetics in Children With Kidney Injury.

    Science.gov (United States)

    Gist, Katja M; Mizuno, Tomoyuki; Goldstein, Stuart L; Vinks, Alexander

    2015-12-01

    Milrinone is an inotropic agent with vasodilating properties used in the treatment of ventricular dysfunction. Milrinone is predominantly eliminated by the kidneys and accumulates in the setting of acute kidney injury (AKI). The purpose of this study was to evaluate milrinone pharmacokinetics in children with AKI with or without continuous renal replacement therapy (CRRT). Retrospective collection of milrinone therapeutic drug monitoring data in patients with AKI, including those requiring CRRT, through chart review from January 2008 to March 2014. Pharmacokinetic (PK) data were analyzed by Bayesian estimation using a pediatric population PK model (MW/Pharm). Clearance estimates were allometrically scaled to body weight. Data on 11 patients were available for analysis. Three patients required CRRT. Milrinone concentrations during continuous infusion varied 30-fold and ranged from 44 to 1343 ng/mL. Of the 33 samples obtained in 11 patients, 24 were outside the target range (72.7%), with 16 (48.5%) above and 8 (24.2%) below. Patients with AKI had significantly lower milrinone clearance (4.72 ± 2.26 L/h per 70 kg) compared with published data in patients without AKI. There was large between-patient variability in milrinone clearance (range: 2.91-13.6 L/h per 70 kg). Clearance in patients on CRRT ranged from 2.8 to 7.19 L/h per 70 kg. A significant correlation between milrinone clearance and estimated creatinine clearance was observed (r = 0.70, P = 0.0097). Allometrically scaled milrinone clearance was lower in the youngest patients (younger than 2 years), suggestive of ongoing renal maturation and existing AKI. Pediatric patients with AKI have significantly lower milrinone clearance compared with published data in patients without AKI. Large variability was noted in milrinone concentrations, and they were frequently outside the target range. The large between-patient variability in milrinone concentrations suggests that dosing regimens should be individualized in

  11. Klotho & Activin A in kidney injury Plasma Klotho is maintained in unilateral obstruction despite no upregulation of Klotho biosynthesis in contralateral kidney

    DEFF Research Database (Denmark)

    Nordholm, Anders; Mace, Maria L; Gravesen, Eva

    2018-01-01

    In a new paradigm of etiology related to Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) kidney injury may cause induction of factors in the injured kidney that are released into the circulation and thereby initiate and maintain renal fibrosis and CKD-MBD. Klotho is believed to amelior......In a new paradigm of etiology related to Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) kidney injury may cause induction of factors in the injured kidney that are released into the circulation and thereby initiate and maintain renal fibrosis and CKD-MBD. Klotho is believed...... to ameliorate renal fibrosis and CKD-MBD, while ActivinA might have detrimental effects. The unilateral ureter obstruction (UUO) model is used here to examine this concept by investigating early changes related to renal fibrosis in obstructed kidney, untouched contralateral kidney and vasculature, which might...

  12. Rapamycin protects kidney against ischemia reperfusion injury through recruitment of NKT cells.

    Science.gov (United States)

    Zhang, Chao; Zheng, Long; Li, Long; Wang, Lingyan; Li, Liping; Huang, Shang; Gu, Chenli; Zhang, Lexi; Yang, Cheng; Zhu, Tongyu; Rong, Ruiming

    2014-08-19

    NKT cells play a protective role in ischemia reperfusion (IR) injury, of which the trafficking in the body and recruitment in injured organs can be influenced by immunosuppressive therapy. Therefore, we investigated the effects of rapamycin on kidneys exposed to IR injury in early stage and on trafficking of NKT cells in a murine model. Balb/c mice were subjected to kidney 30 min ischemia followed by 24 h reperfusion. Rapamycin (2.5 ml/kg) was administered by gavage daily, starting 1 day before the operation. Renal function and histological changes were assessed. The proportion of NKT cells in peripheral blood, spleen and kidney was detected by flow cytometry. The chemokines and corresponding receptor involved in NKT cell trafficking were determined by RT-PCR and flow cytometry respectively. Rapamycin significantly improved renal function and ameliorated histological injury. In rapamycin-treated group, the proportion of NKT cells in spleen was significantly decreased but increased in peripheral blood and kidney. In addition, the CXCR3+ NKT cell in the kidney increased remarkably in the rapamycin-treated group. The chemokines, CXCL9 and CXCL10, as the ligands of CXCR3, were also increased in the rapamycin-treated kidney. Rapamycin may recruit NKT cells from spleen to the IR-induced kidney to ameliorate renal IR injury in the early stage.

  13. Nitrite-induced acute kidney injury with secondary hyperparathyroidism: Case report and literature review.

    Science.gov (United States)

    Peng, Tao; Hu, Zhao; Yang, Xiangdong; Gao, Yanxia; Ma, Chengjun

    2018-02-01

    Acute kidney injury (AKI) with hyperparathyroidism caused by nitrite was rare, and renal function and parathyroid hormone (PTH) decreased to normal range after therapy. Acute kidney injury was diagnosed in a 40-year-old male with hyperparathyroidism and cyanosis of his hands and both forearms. The patient ate some recently pickled vegetables, and he experienced nausea, vomiting and diarrhoea without oliguria or anuria; Additionally, his hands and both forearms had a typical blue ash appearance. After admission, the laboratory findings indicated theincreasing serum creatinine (Scr) and parathyroid hormone (PTH). He was diagnosed as acute kidney injury with hyperparathyroidism caused by nitrite. The patient stopped eating the pickled vegetables and was given rehydration, added calories and other supportive therapy without any glucocorticoids. According to his clinical manifestations, laboratory findings and imaging results, the patient was diagnosed with acute kidney injury with secondary hyperparathyroidism. He was given symptomatic supportive care therapy. After one week, the serum creatinine, parathyroid hormone (PTH), hypercalcemia, hyperphosphatemia, proteinuria, and urine red blood cell values decreased to normal range. Nitrite-induced acute kidney injury with secondary hyperparathyroidism was relatively rare. After therapy, the function of the kidney and parathyroid returned to normal. This case suggests that detailed collection of medical history, physical examination and correct symptomatic treatment is very important.

  14. Acute kidney injury due to star fruit ingestion: A case report

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    Mehruba Alam Ananna

    2016-08-01

    Full Text Available Star fruit (Avarrhoa carambola is a fruit from oxalidace family. lt is found in many countries of the world including Bangladesh. But its ingestion or drinking star fruit juice may lead to intoxication especially in patients with chronic kidney disease and manifestations might be neurological or nephrological. lt may also cause acute kidney injury in patients with previously normal renal function. Here we are presenting a case who presented with acute kidney injury after star fruit ingestion with previously unknown renal function impairment. The etiology was confirmed by histopathological exami­nation after doing renal biopsy. This renal function impairment is mainly due to oxalate crystal induce nephropathy which is richly abundant in star fruit. His renal function was improved ·with conservative management. Physicians should be alert to consider the ingestion of star fruit as a cause of acute kidney injury in a patient even in the absence of previous renal function impairment.

  15. Nurses' knowledge to identify early acute kidney injury.

    Science.gov (United States)

    Nascimento, Roseli Aparecida Matheus do; Assunção, Murillo Santucci Cesar; Silva, João Manoel; Amendola, Cristina Prata; Carvalho, Taysa Martindo de; Lima, Emerson Quintino; Lobo, Suzana Margareth Ajeje

    2016-01-01

    To evaluate the knowledgeof nurses on early identification of acute kidney injury (AKI) in intensive care, emergency and hospitalization units. A prospective multi-center study was conducted with 216 nurses, using a questionnaire with 10 questions related to AKI prevention, diagnosis, and treatment. 57.2% of nurses were unable to identify AKI clinical manifestations, 54.6% did not have knowledge of AKI incidence in patients admitted to the ICU, 87.0% of the nurses did not know how to answer as regards the AKI mortality rate in patients admitted to the ICU, 67.1% answered incorrectly that slight increases in serum creatinine do not have an impact on mortality, 66.8% answered incorrectly to the question on AKI prevention measures, 60.4% answered correctly that loop diuretics for preventing AKI is not recommended, 77.6% answered correctly that AKI does not characterize the need for hemodialysis, and 92.5% said they had no knowledge of the Acute Kidney Injury Networkclassification. Nurses do not have enough knowledge to identify early AKI, demonstrating the importance of qualification programs in this field of knowledge. Avaliar o conhecimento do enfermeiro na identificação precoce da Injúria Renal Aguda (IRA) em Unidade de Terapia Intensiva, Unidade de Internação e Emergência. Estudo multicêntrico, prospectivo.Participaram do estudo 216 enfermeiros,por meio de questionário com 10 questões relacionadas à prevenção, ao diagnóstico e ao tratamento da IRA. 57,2% não souberam identificar as manifestações clínicas da IRA, 54,6% não têm conhecimento da incidência de IRA em pacientes internados na UTI, 87,0% dos enfermeiros não souberam responder ao índice de mortalidade de IRA em pacientes internados na UTI, 67,1% responderam incorretamente que aumentos discretos da creatinina sérica não têm impacto na mortalidade, 66,8% responderam incorretamente à questão sobre as medidas de prevenção da IRA, 60,4% acertaram quando responderam que não

  16. Acute kidney injury in stable COPD and at exacerbation

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    Barakat MF

    2015-09-01

    Full Text Available MF Barakat,1 HI McDonald,1 TJ Collier,1 L Smeeth,1 D Nitsch,1 JK Quint1,2 1Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, 2Department of Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College London, London, UK Background: While acute kidney injury (AKI alone is associated with increased mortality, the incidence of hospital admission with AKI among stable and exacerbating COPD patients and the effect of concurrent AKI at COPD exacerbation on mortality is not known.Methods: A total of 189,561 individuals with COPD were identified from the Clinical Practice Research Datalink. Using Poisson and logistic regressions, we explored which factors predicted admission for AKI (identified in Hospital Episode Statistics in this COPD cohort and concomitant AKI at a hospitalization for COPD exacerbation. Using survival analysis, we investigated the effect of concurrent AKI at exacerbation on mortality (n=36,107 and identified confounding factors.Results: The incidence of AKI in the total COPD cohort was 128/100,000 person-years. The prevalence of concomitant AKI at exacerbation was 1.9%, and the mortality rate in patients with AKI at exacerbation was 521/1,000 person-years. Male sex, older age, and lower glomerular filtration rate predicted higher risk of AKI or death. There was a 1.80 fold (95% confidence interval: 1.61, 2.03 increase in adjusted mortality within the first 6 months post COPD exacerbation in patients suffering from AKI and COPD exacerbation compared to those who were AKI free.Conclusion: In comparison to previous studies on general populations and hospitalizations, the incidence and prevalence of AKI is relatively high in COPD patients. Coexisting AKI at exacerbation is prognostic of poor outcome. Keywords: acute renal failure, mortality, emphysema, chronic bronchitis, prognosis

  17. ACUTE KIDNEY INJURY IN PATIENTS WITH CIRRHOSIS- CAUSES AND OUTCOME

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    Amit Hanmant Shejal

    2017-06-01

    Full Text Available BACKGROUND Acute Kidney Injury (AKI is a common complication in patients with cirrhosis leading to high mortality. Creatinine-based criteria for defining AKI are validated in general hospitalised patients, but their application to cirrhotic patients is less certain. This study was undertaken to evaluate current definition of AKI by International Club of Ascites (ICA and assess clinical course of hospitalised cirrhosis patients with AKI and to study the impact of AKI on mortality. MATERIALS AND METHODS We prospectively studied patients with AKI and cirrhosis for a period of 1 year and assessed the association between AKI severity and progression with complications, including death. RESULTS 48 cirrhotic patients with AKI were enrolled in the study period. Mean age of patients was 56.81 ± 9.78 years. The aetiology of cirrhosis included alcohol (52.1%, HBV (2.2%, HCV (4.2%, NASH (27.1% and cryptogenic (14.6%. 13 patients (27.1% had mortality while 35 patients (72.9% survived. 39 patients (81.25% had AKI at admission while 9 patients (18.75% developed later after admission. Patients achieved a peak severity of AKI stage 1, 10.41%; stage 2, 60.41%; and stage 3, 37.5%. The incidence of mortality, increased with severity of AKI in stepwise manner with peak AKI stage 1 has no mortality; stage 2 has 4 (30.76%; stage 3, 9 (69.23%. SIRS was present in 17 patients (35.4% and was significantly associated with mortality. CONCLUSION AKI, as defined by new ICA criteria, in patients with cirrhosis is associated with mortality in a stage-dependent fashion. Early intervention and preventing progression by timely and specific treatment may improve outcomes.

  18. Acute kidney injury in pregnancy-specific disorders

    Directory of Open Access Journals (Sweden)

    J Prakash

    2017-01-01

    Full Text Available The incidence of acute kidney injury in pregnancy (P-AKI has declined significantly over the last three decades in developing countries. However, it is still associated with significant fetomaternal mortality and morbidity. The diagnosis of P-AKI is based on the serum creatinine increase. The usual formulas for estimating glomerular filtration rate (GFR are not validated in this population. The incidence of P-AKI with respect to total AKI cases has decreased in the last three decades from 25% in 1980s to 9% in 2000s at our centre. During the first trimester of gestation, AKI develops most often due to septic abortion or hyperemesis gravidarum. Septic abortion related AKI with respect to total AKI decreased from 9% to 5% in our study. Prevention of unwanted pregnancy and avoidance of septic abortion are keys to eliminate abortion associated AKI in early pregnancy. However, we have not seen AKI on account of hyperemesis gravidarum over a period of 33 years at our center. In the third trimester, the differential diagnosis of AKI in association with pregnancy specific conditions namely preeclampsia/HELLP syndrome, acute fatty liver of pregnancy and thrombotic microangiopathies of pregnancy (P-TMA is more challenging, because these 3 conditions share several clinical features of thrombotic microangiopathy which makes the diagnosis very difficult on clinical grounds. It is imperative to distinguish these conditions to make appropriate therapeutic decisions. Typically, AFLP and HELLP syndrome improve after delivery of the fetus, whereas plasma exchange is the first-line treatment for pregnancy associated thrombotic microangioathies (P-TMA. We observed that preclampsia/eclampsia is the most common cause of AKI in late third trimester and postpartum periods followed by puerperal sepsis and postpartum hemorrhage. Pregnancy-associated thrombotic microangiopathies (aHUS/TTP and AFLP are rare causes of AKI during pregnancy in developing countries.

  19. Acute Kidney Injury in Pregnancy-specific Disorders.

    Science.gov (United States)

    Prakash, J; Ganiger, V C

    2017-01-01

    The incidence of acute kidney injury in pregnancy (P-AKI) has declined significantly over the last three decades in developing countries. However, it is still associated with significant fetomaternal mortality and morbidity. The diagnosis of P-AKI is based on the serum creatinine increase. The usual formulas for estimating glomerular filtration rate (GFR) are not validated in this population. The incidence of P-AKI with respect to total AKI cases has decreased in the last three decades from 25% in 1980s to 9% in 2000s at our centre. During the first trimester of gestation, AKI develops most often due to septic abortion or hyperemesis gravidarum. Septic abortion related AKI with respect to total AKI decreased from 9% to 5% in our study. Prevention of unwanted pregnancy and avoidance of septic abortion are keys to eliminate abortion associated AKI in early pregnancy. However, we have not seen AKI on account of hyperemesis gravidarum over a period of 33 years at our center. In the third trimester, the differential diagnosis of AKI in association with pregnancy specific conditions namely preeclampsia/HELLP syndrome, acute fatty liver of pregnancy and thrombotic microangiopathies of pregnancy (P-TMA) is more challenging, because these 3 conditions share several clinical features of thrombotic microangiopathy which makes the diagnosis very difficult on clinical grounds. It is imperative to distinguish these conditions to make appropriate therapeutic decisions. Typically, AFLP and HELLP syndrome improve after delivery of the fetus, whereas plasma exchange is the first-line treatment for pregnancy associated thrombotic microangioathies (P-TMA). We observed that preclampsia/eclampsia is the most common cause of AKI in late third trimester and postpartum periods followed by puerperal sepsis and postpartum hemorrhage. Pregnancy-associated thrombotic microangiopathies (aHUS/TTP) and AFLP are rare causes of AKI during pregnancy in developing countries.

  20. Allopurinol attenuates acute kidney injury following Bothrops jararaca envenomation.

    Directory of Open Access Journals (Sweden)

    Pedro Henrique França Gois

    2017-11-01

    Full Text Available Snakebites have been recognized as a neglected public health problem in several tropical and subtropical countries. Bothrops snakebites frequently complicate with acute kidney injury (AKI with relevant morbidity and mortality. To date, the only treatment available for Bothrops envenomation is the intravenous administration of antivenom despite its several limitations. Therefore, the study of novel therapies in Bothrops envenomation is compelling. The aim of this study was to evaluate the protective effect of Allopurinol (Allo in an experimental model of Bothrops jararaca venom (BJ-associated AKI. Five groups of Wistar rats were studied: Sham, Allo, BJ, BJ+Allo, BJ+ipAllo. BJ (0.25 mg/kg was intravenously injected during 40'. Saline at same dose and infusion rate was administered to Sham and Allo groups. Allo and BJ+Allo groups received Allo (300 mg/L in the drinking water 7 days prior to Saline or BJ infusion respectively. BJ+ipAllo rats received intraperitoneal Allo (25 mg/Kg 40' after BJ infusion. BJ rats showed markedly reduced glomerular filtration rate (GFR, inulin clearance associated with intense renal vasoconstriction, hemolysis, hemoglobinuria, reduced glutathione and increased systemic and renal markers of nitro-oxidative stress (Nitrotyrosine. Allo ameliorated GFR, renal blood flow (RBF, renal vascular resistance and arterial lactate levels. In addition, Allo was associated with increased serum glutathione as well as reduced levels of plasma and renal Nitrotyrosine. Our data show that Allo attenuated BJ-associated AKI, reduced oxidative stress, improved renal hemodynamics and organ perfusion. It might represent a novel adjuvant approach for Bothrops envenomation, a new use for an old and widely available drug.

  1. Allopurinol attenuates acute kidney injury following Bothrops jararaca envenomation

    Science.gov (United States)

    Martines, Monique Silva; Ferreira, Daniela; Volpini, Rildo; Canale, Daniele; Malaque, Ceila; Crajoinas, Renato; Girardi, Adriana Castello Costa; Massola Shimizu, Maria Heloisa; Seguro, Antonio Carlos

    2017-01-01

    Snakebites have been recognized as a neglected public health problem in several tropical and subtropical countries. Bothrops snakebites frequently complicate with acute kidney injury (AKI) with relevant morbidity and mortality. To date, the only treatment available for Bothrops envenomation is the intravenous administration of antivenom despite its several limitations. Therefore, the study of novel therapies in Bothrops envenomation is compelling. The aim of this study was to evaluate the protective effect of Allopurinol (Allo) in an experimental model of Bothrops jararaca venom (BJ)-associated AKI. Five groups of Wistar rats were studied: Sham, Allo, BJ, BJ+Allo, BJ+ipAllo. BJ (0.25 mg/kg) was intravenously injected during 40’. Saline at same dose and infusion rate was administered to Sham and Allo groups. Allo and BJ+Allo groups received Allo (300 mg/L) in the drinking water 7 days prior to Saline or BJ infusion respectively. BJ+ipAllo rats received intraperitoneal Allo (25 mg/Kg) 40’ after BJ infusion. BJ rats showed markedly reduced glomerular filtration rate (GFR, inulin clearance) associated with intense renal vasoconstriction, hemolysis, hemoglobinuria, reduced glutathione and increased systemic and renal markers of nitro-oxidative stress (Nitrotyrosine). Allo ameliorated GFR, renal blood flow (RBF), renal vascular resistance and arterial lactate levels. In addition, Allo was associated with increased serum glutathione as well as reduced levels of plasma and renal Nitrotyrosine. Our data show that Allo attenuated BJ-associated AKI, reduced oxidative stress, improved renal hemodynamics and organ perfusion. It might represent a novel adjuvant approach for Bothrops envenomation, a new use for an old and widely available drug. PMID:29155815

  2. Long-term kidney outcomes among users of proton pump inhibitors without intervening acute kidney injury.

    Science.gov (United States)

    Xie, Yan; Bowe, Benjamin; Li, Tingting; Xian, Hong; Yan, Yan; Al-Aly, Ziyad

    2017-06-01

    Proton pump inhibitor (PPI) use is associated with an increased risk of acute kidney injury (AKI), incident chronic kidney disease (CKD), and progression to end-stage renal disease (ESRD). PPI-associated CKD is presumed to be mediated by intervening AKI. However, whether PPI use is associated with an increased risk of chronic renal outcomes in the absence of intervening AKI is unknown. To evaluate this we used the Department of Veterans Affairs national databases to build a cohort of 144,032 incident users of acid suppression therapy that included 125,596 PPI and 18,436 Histamine H2 receptor antagonist (H2 blockers) consumers. Over 5 years of follow-up in survival models, cohort participants were censored at the time of AKI occurrence. Compared with incident users of H2 blockers, incident users of PPIs had an increased risk of an estimated glomerular filtration rate (eGFR) under 60 ml/min/1.73m 2 (hazard ratio 1.19; 95% confidence interval 1.15-1.24), incident CKD (1.26; 1.20-1.33), eGFR decline over 30% (1.22; 1.16-1.28), and ESRD or eGFR decline over 50% (1.30; 1.15-1.48). Results were consistent in models that excluded participants with AKI either before chronic renal outcomes, during the time in the cohort, or before cohort entry. The proportion of PPI effect mediated by AKI was 44.7%, 45.47%, 46.00%, and 46.72% for incident eGFR under 60 ml/min/1.73m 2 , incident CKD, eGFR decline over 30%, and ESRD or over 50% decline in eGFR, respectively. Thus, PPI use is associated with increased risk of chronic renal outcomes in the absence of intervening AKI. Hence, reliance on antecedent AKI as warning sign to guard against the risk of CKD among PPI users is not sufficient as a sole mitigation strategy. Published by Elsevier Inc.

  3. Heterozygosity for fibrinogen results in efficient resolution of kidney ischemia reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Amrendra Kumar Ajay

    Full Text Available Fibrinogen (Fg has been recognized to play a central role in coagulation, inflammation and tissue regeneration. Several studies have used Fg deficient mice (Fg(-/- in comparison with heterozygous mice (Fg(+/- to point the proinflammatory role of Fg in diverse pathological conditions and disease states. Although Fg(+/- mice are considered 'normal', plasma Fg is reduced to ~75% of the normal circulating levels present in wild type mice (Fg(+/+. We report that this reduction in Fg protein production in the Fg(+/- mice is enough to protect them from kidney ischemia reperfusion injury (IRI as assessed by tubular injury, kidney dysfunction, necrosis, apoptosis and inflammatory immune cell infiltration. Mechanistically, we observed binding of Fg to ICAM-1 in kidney tissues of Fg(+/+ mice at 24 h following IRI as compared to a complete absence of binding observed in the Fg(+/- and Fg(-/- mice. Raf-1 and ERK were highly activated as evident by significantly higher phosphorylation in the Fg(+/+ kidneys at 24 h following IRI as compared to Fg(+/- and Fg(-/- mice kidneys. On the other hand Cyclin D1 and pRb, indicating higher cell proliferation, were significantly increased in the Fg(+/- and Fg(-/- as compared to Fg(+/+ kidneys. These data suggest that Fg heterozygosity allows maintenance of a critical balance of Fg that enables regression of initial injury and promotes faster resolution of kidney damage.

  4. Subclinical kidney injury before and 1 year after bariatric surgery among adolescents with severe obesity.

    Science.gov (United States)

    Xiao, Nianzhou; Devarajan, Prasad; Inge, Thomas H; Jenkins, Todd M; Bennett, Michael; Mitsnefes, Mark M

    2015-06-01

    To assess subclinical kidney injury in adolescents with severe obesity by measuring biomarkers of early kidney disease and to assess changes in the levels of these biomarkers following bariatric procedures. Twenty-two adolescents undergoing bariatric surgery with no microalbuminuria and normal kidney function were selected. Urinary NGAL, IL-18, and KIM-1 were measured at baseline, 6 and 12 months postoperatively. Biomarker levels were compared to 44 age-gender-matched lean controls. Subjects with obesity had a mean baseline BMI of 48 kg/m(2) that decreased by 34% at 1-year follow-up. Urine NGAL, IL-18, and KIM-1 were significantly elevated in subjects with obesity compared to lean controls at baseline. The obese cohort had a further significant increase in NGAL and KIM-1 at 6 months, followed by decline at 1 year. The overall change in levels of all three biomarkers through 1 year after surgery, however, was not significant compared to baseline. Adolescent severe obesity is associated with increased urinary excretion of novel biomarkers of kidney injury, despite no microalbuminuria or decreased kidney function. This subclinical kidney injury persists 1 year after significant weight loss induced by bariatric surgery, suggesting that close, long-term follow-up of kidney status is warranted in these adolescents. © 2015 The Obesity Society.

  5. Changes in metabolic profiles during acute kidney injury and recovery following ischemia/reperfusion.

    Science.gov (United States)

    Wei, Qingqing; Xiao, Xiao; Fogle, Paul; Dong, Zheng

    2014-01-01

    Changes of metabolism have been implicated in renal ischemia/reperfusion injury (IRI). However, a global analysis of the metabolic changes in renal IRI is lacking and the association of the changes with ischemic kidney injury and subsequent recovery are unclear. In this study, mice were subjected to 25 minutes of bilateral renal IRI followed by 2 hours to 7 days of reperfusion. Kidney injury and subsequent recovery was verified by serum creatinine and blood urea nitrogen measurements. The metabolome of plasma, kidney cortex, and medulla were profiled by the newly developed global metabolomics analysis. Renal IRI induced overall changes of the metabolome in plasma and kidney tissues. The changes started in renal cortex, followed by medulla and plasma. In addition, we identified specific metabolites that may contribute to early renal injury response, perturbed energy metabolism, impaired purine metabolism, impacted osmotic regulation and the induction of inflammation. Some metabolites, such as 3-indoxyl sulfate, were induced at the earliest time point of renal IRI, suggesting the potential of being used as diagnostic biomarkers. There was a notable switch of energy source from glucose to lipids, implicating the importance of appropriate nutrition supply during treatment. In addition, we detected the depressed polyols for osmotic regulation which may contribute to the loss of kidney function. Several pathways involved in inflammation regulation were also induced. Finally, there was a late induction of prostaglandins, suggesting their possible involvement in kidney recovery. In conclusion, this study demonstrates significant changes of metabolome kidney tissues and plasma in renal IRI. The changes in specific metabolites are associated with and may contribute to early injury, shift of energy source, inflammation, and late phase kidney recovery.

  6. Lung-protective mechanical ventilation does not protect against acute kidney injury in patients without lung injury at onset of mechanical ventilation

    NARCIS (Netherlands)

    Cortjens, Bart; Royakkers, Annick A. N. M.; Determann, Rogier M.; van Suijlen, Jeroen D. E.; Kamphuis, Stephan S.; Foppen, Jannetje; de Boer, Anita; Wieland, Cathrien W.; Spronk, Peter E.; Schultz, Marcus J.; Bouman, Catherine S. C.

    2012-01-01

    Introduction: Preclinical and clinical studies suggest that mechanical ventilation contributes to the development of acute kidney injury (AKI), particularly in the setting of lung-injurious ventilator strategies. Objective: To determine whether ventilator settings in critically ill patients without

  7. Evaluation of regenerative capacity after kidney ischemic/reperfustion injury using 99mTc-DMSA

    International Nuclear Information System (INIS)

    Kwak, W. J.; Kim, J. W.; Park, K. M.; Lee, S. W.; Ahn, B. C.; Lee, J. T.; Yoo, J. S.

    2007-01-01

    Acute renal failure can be caused by a reduced renal blood flow induced because of ischemic injury. The damaged kidney can be completely restored in structure and function. 99m Tc-DMSA binds to cortical tubules in kidney and its uptake has been suggested to indicate function of cortical mass. Herein, the generative capacity of kidney after bilateral or unilateral ischemia/reperfusion (I/R) injury was evaluated non-invasively by scintigraphic imaging. Three different animal models were used. One or both kidneys of mice were subjected ischemic for 30 min for unilateral or bilateral I/R model, respectively. In third model, one kidney was excised and the other kidney was subjected ischemic for 30 min to give nephrectomy model. At 1 hr, 1 d, 3 d, 1 w, 2 w, 3 w after reperfusion, 99m Tc-DMSA (27.7 MBq) was injected via tail vein. After 3 hr, the mice were scanned for 30 min with pinhole equipped gamma camera. The ratio of ROI counts of kidney to total counts was calculated. In unilateral I/R mouse, the 99m Tc-DMSA uptake of injured kidney was decreased continuously up to 3 w (13.9 to 7.7%), while uptake in normal kidney is slowly increased. In case of nephrectomy model, 99m Tc-DMSA uptake of injured kidney was rapidly restored within 1 w after I/R operation (8.5 to 30%). Bilateral model showed reduced 99m Tc-DMSA uptake at 1 d, but total uptake in both I/R kidney was also increase up to 30% after 1 w and the uptake was maintained up to 3 w. In unilateral model, the 99m Tc-DMSA uptake of injured kidney kept decreasing up to 3 w while normal kidney showed increased 99m Tc-DMSA uptake. The restoration of I/R kidney was not observed within 3 w. However, in case of animal models which have only I/R kidneys such as bilateral and nephrectomy models, the 99m Tc-DMSA uptake was restored within 1 w and the excised kidney size was also normal in contrast to much smaller I/R kidney of unilateral model

  8. Unilateral Renal Ischemia as a Model of Acute Kidney Injury and Renal Fibrosis in Cats.

    Science.gov (United States)

    Schmiedt, C W; Brainard, B M; Hinson, W; Brown, S A; Brown, C A

    2016-01-01

    The objectives of this study were to define the acute and chronic effects of 1-hour unilateral in vivo renal ischemia on renal function and histology in cats. Twenty-one adult purpose-bred research cats were anesthetized, and 1 kidney underwent renal artery and vein occlusion for 1 hour. Serum creatinine and urea concentrations, urine protein:creatinine ratio, urine-specific gravity, glomerular filtration rate, hematocrit, platelet concentration and function, and white blood cell count were measured at baseline and variable time points after ischemia. Renal histopathology was evaluated on days 3, 6, 12, 21, 42, and 70 postischemia; changes in smooth muscle actin and interstitial collagen were examined. Following ischemia, whole animal glomerular filtration rate was significantly reduced (57% of baseline on day 6; P < .05). At the early time points, the ischemic kidneys exhibited severe acute epithelial necrosis accompanied by evidence of regeneration of tubules predominantly within the corticomedullary junction. At later periods, postischemic kidneys had evidence of tubular atrophy and interstitial inflammation with significantly more smooth muscle actin and interstitial collagen staining and interstitial fibrosis when compared with the contralateral control kidneys. This study characterizes the course of ischemic acute kidney injury in cats and demonstrates that ischemic acute kidney injury triggers chronic fibrosis, interstitial inflammation, and tubular atrophy in feline kidneys. These late changes are typical of those observed in cats with naturally occurring chronic kidney disease. © The Author(s) 2015.

  9. High risk of rhabdomyolysis and acute kidney injury after traumatic limb compartment syndrome.

    Science.gov (United States)

    Tsai, Wei-Hsuan; Huang, Shih-Tsai; Liu, Wen-Chung; Chen, Lee-Wei; Yang, Kuo-Chung; Hsu, Kuei-Chang; Lin, Cheng-Ta; Ho, Yen-Yi

    2015-05-01

    Rhabdomyolysis often occurs after traumatic compartment syndrome, and high morbidity and mortality have been reported with the acute kidney injury that develops subsequently. We focused on the risk factors for rhabdomyolysis and acute kidney injury in patients with traumatic compartment syndrome. We also analyzed the relation between renal function and rhabdomyolysis in these patients. A retrospective chart review was conducted from January 2006 to March 2012. Inpatients with traumatic compartment syndrome were included. We evaluated patients' demographics, history of illicit drugs use or alcohol consumption, mechanism of injury, symptoms, serum creatine kinase levels, and kidney function. A total of 52 patients with a mean age of 40.9 years were included; 23 patients had rhabdomyolysis (44.2%), of which 9 patients developed acute kidney injury (39.1%). Significant predictive factors for rhabdomyolysis were history of illicit drugs or alcohol use (P=0.039; odds ratio, 5.91) and ischemic injury (P=0.005). We found a moderate correlation between serum creatine kinase levels and serum creatinine levels (R=0.57; PRhabdomyolysis was a predisposing factor for acute kidney injury (P=0.011; odds ratio, 8.68). Four patients with rhabdomyolysis required a short period of renal replacement therapy. A high percentage of patients with traumatic compartment syndrome developed rhabdomyolysis (44.2%). Patients with rhabdomyolysis had a higher possibility of developing acute kidney injury (39.1%), and rhabdomyolysis was correlated to renal function. Early diagnosis, frequent monitoring, and aggressive treatment are suggested once compartment syndrome is suspected. The overall prognosis is good with early diagnosis and proper treatment.

  10. Acute Kidney Injury in the Intensive Care Unit

    Directory of Open Access Journals (Sweden)

    Petar Kes

    2010-04-01

    Full Text Available Acute kidney injury (AKI is a common clinical syndrome with a broad aetiological profile. It complicates about 5% of hospital admissions and 30% of admissions to intensive care units (ICU. During last 20 years has been a significant change in the spectrum of severe AKI such that it is no longer mostly a single organ phenomenon but rather a complex multisystem clinical problem. Despite great advances in renal replacement technique (RRT, mortality from AKI, when part of MOF, remains over 50%. The changing nature of AKI requires a new approach using the new advanced technology. Clinicians can provide therapies tailored to time constraints (intermittent, continuous, or extended intermittent, haemodynamic, and metabolic requirements and aimed at molecules of variable molecular weight. Peritoneal dialysis (PD is technically the simplest form of RRT and is still commonly used worldwide. The problems include difficulty in maintaining dialysate flow, peritoneal infection, leakage, protein losses, and restricted ability to clear fluid and uraemic wastes. PD is the preferred treatment modality for AKI in pediatric practice. Patients that are hemodynamically stable can be managed with intermittent hemodyalisis (IHD, whereby relatively short (3 to 4 h dialysis sessions may be performed every day or every other day. Patients who are haemodynamically unstable are best managed using continuous renal replacement therapies (CRRT, which allow for continuous fine-tuning of intravascular volume, easier correction of hypervolemia, better solute removal, more accurately correction of metabolic acidosis, and offers possibilities for unlimited energy support. Recently, “hybrid” or sustained low-efficiency dialysis (SLED was introduced as a method which combines the advantages of IHD with those of CRRT. In this technique, classic dialysis hardware is used at low blood and dialysate flow rates, for prolonged period of time (6 to 12 h/day. SLED offers more haemodynamic

  11. Acute kidney injury aggravated by treatment initiation with apixaban: Another twist of anticoagulant-related nephropathy

    Directory of Open Access Journals (Sweden)

    Sergey V. Brodsky

    2017-12-01

    Full Text Available Anticoagulant-related nephropathy (ARN was initially described in patients on warfarin (as warfarin-related nephropathy and recently in those using dabigatran. Herein, we report clinical history and kidney biopsy findings in a patient on apixaban (Eliquis. Initiation of treatment with apixaban resulted in aggravation of preexisting mild acute kidney injury (AKI. A few days after apixaban therapy, the patient became oligoanuric, and kidney biopsy showed severe acute tubular necrosis with numerous occlusive red blood cell casts. Only one out of 68 glomeruli with open capillary loops had small segmental cellular crescent. Therefore, there was major discrepancy between the degree of glomerular injury and the glomerular hematuria. Considering that the onset of this AKI was associated with apixaban treatment initiation, we propose that this patient had ARN associated with factor Xa inhibitor (apixaban, which has not previously been described. Monitoring of kidney function is recommended after initiation of anticoagulant therapy.

  12. Genistein attenuates ischemia/reperfusion injury in rat kidneys via ...

    African Journals Online (AJOL)

    kidneys via enhancement of antioxidant defense mechanisms: Activation ... Renal function, total oxidant capacity and total antioxidant status in serum were evaluated in the rats. ..... Erel O. Novel automated method to measure total antioxidant ...

  13. Rhabdomyolysis and acute kidney injury in patients with traumatic spinal cord injury

    Science.gov (United States)

    Galeiras, Rita; Mourelo, Mónica; Pértega, Sonia; Lista, Amanda; Ferreiro, Mª Elena; Salvador, Sebastián; Montoto, Antonio; Rodríguez, Antonio

    2016-01-01

    Background: Patients with acute traumatic spinal cord injuries (SCIs) exhibit factors that, in other populations, have been associated with rhabdomyolysis. Purpose: The aim of the study is to determine the incidence of rhabdomyolysis in patients with acute traumatic SCI admitted to the Intensive Care Unit (ICU), as well as the development of secondary acute kidney injury and associated factors. Study Design and Setting: This was an observational, retrospective study. Patient Sample: All adult patients admitted to the ICU with acute traumatic SCI who presented rhabdomyolysis, diagnosed through creatine phosphokinase (CPK) levels >500 IU/L. Outcome Measures: Incidence of rhabdomyolysis and subsequent renal dysfunction was calculated. Materials and Methods: Data about demographic variables, comorbidity, rhabdomyolysis risk factors, and variables involving SCI, severity scores, and laboratory parameters were obtained from clinical records. Multivariate logistic regression was used to identify renal injury risk factors. Results: In 2006–2014, 200 patients with acute SCI were admitted to ICU. Of these, 103 had rhabdomyolysis (incidence = 51.5%; 95% confidence interval [CI]: 44.3%–58.7%). The most typical American Spinal Injury Association classification was A (70.3%). The injury severity score was 30.3 ± 12.1 and sequential organ failure assessment (SOFA) score was 5.6 ± 3.3 points. During their stay, 57 patients (55.3%; 95% CI: 45.2%–65.4%) presented renal dysfunction (creatinine ≥1.2 mg/dL). In the multivariate analysis, variables associated with renal dysfunction were creatinine at admission (odds ratio [OR] = 9.20; P = 0.006) and hemodynamic SOFA score the day following admission (OR = 1.33; P = 0.024). Creatinine was a better predictor of renal dysfunction than the peak CPK value during the rhabdomyolysis (area under the receiver operating characteristic curve: 0.91 vs. 0.63, respectively). Conclusions: Rhabdomyolysis is a frequent condition in patients

  14. From body piercing to acute kidney injury – a case report

    Directory of Open Access Journals (Sweden)

    Irena Wikiera-Magott

    2017-12-01

    Full Text Available Acute kidney injury is an abrupt decline of renal function interfering with the body’s homeostasis. It most commonly occurs in neonates and children treated in intensive care units and undergoing extensive surgical procedures, especially cardiac surgery. Its aetiology is frequently complex, with infectious factors, toxic chemical activity and hydration and electrolyte imbalance occurring simultaneously and aggravating kidney injury. This study reports a case of a 17-year-old female patient in whom acute kidney injury was caused by a combination of factors, including sepsis, adverse effects of analgesic drugs and dehydration. Staphylococcus aureus infection caused by multiple-site piercings performed in a home setting resulted in the development of multiple skin abscesses, myometrial abscesses and a generalised infection. The patient’s condition warranted intensive antibiotic therapy and drainage of the myometrial abscesses. The therapy facilitated eradication of the infection foci and normalising renal function.

  15. Dialysis-Requiring Acute Kidney Injury in Denmark 2000-2012

    DEFF Research Database (Denmark)

    Carlson, Nicholas; Hommel, Kristine; Olesen, Jonas Bjerring

    2016-01-01

    INTRODUCTION: Dialysis-requiring acute kidney injury is a severe illness associated with poor prognosis. However, information pertaining to incidence rates and prevalence of risk factors remains limited in spite of increasing focus. We evaluate time trends of incidence rates and changing patterns...... in prevalence of comorbidities, concurrent medication, and other risk factors in nationwide retrospective cohort study. MATERIALS AND METHODS: All patients with dialysis-requiring acute kidney injury were identified between January 1st 2000 and December 31st 2012. By cross-referencing data from national...... administrative registries, the association of changing patterns in dialysis treatment, comorbidity, concurrent medication and demographics with incidence of dialysis-requiring acute kidney injury was evaluated. RESULTS: A total of 18,561 adult patients with dialysis-requiring AKI were identified between 2000...

  16. Kidney stone matrix proteins ameliorate calcium oxalate monohydrate induced apoptotic injury to renal epithelial cells.

    Science.gov (United States)

    Narula, Shifa; Tandon, Simran; Singh, Shrawan Kumar; Tandon, Chanderdeep

    2016-11-01

    Kidney stone formation is a highly prevalent disease, affecting 8-10% of the human population worldwide. Proteins are the major constituents of human kidney stone's organic matrix and considered to play critical role in the pathogenesis of disease but their mechanism of modulation still needs to be explicated. Therefore, in this study we investigated the effect of human kidney stone matrix proteins on the calcium oxalate monohydrate (COM) mediated cellular injury. The renal epithelial cells (MDCK) were exposed to 200μg/ml COM crystals to induce injury. The effect of proteins isolated from human kidney stone was studied on COM injured cells. The alterations in cell-crystal interactions were examined by phase contrast, polarizing, fluorescence and scanning electron microscopy. Moreover, its effect on the extent of COM induced cell injury, was quantified by flow cytometric analysis. Our study indicated the antilithiatic potential of human kidney stone proteins on COM injured MDCK cells. Flow cytometric analysis and fluorescence imaging ascertained that matrix proteins decreased the extent of apoptotic injury caused by COM crystals on MDCK cells. Moreover, the electron microscopic studies of MDCK cells revealed that matrix proteins caused significant dissolution of COM crystals, indicating cytoprotection against the impact of calcium oxalate injury. The present study gives insights into the mechanism implied by urinary proteins to restrain the pathogenesis of kidney stone disease. This will provide a better understanding of the formation of kidney stones which can be useful for the proper management of the disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Renal sarcoidosis presenting as acute kidney injury with granulomatous interstitial nephritis and vasculitis.

    Science.gov (United States)

    Agrawal, Varun; Crisi, Giovanna M; D'Agati, Vivette D; Freda, Benjamin J

    2012-02-01

    Among the various renal manifestations of sarcoidosis, granulomatous inflammation confined to the tubulointerstitial compartment is the most commonly reported finding. We present the case of a 66-year-old man with acute kidney injury, hypercalcemia, mild restrictive pulmonary disease, and neurologic signs of parietal lobe dysfunction. Kidney biopsy showed diffuse interstitial inflammation with noncaseating granulomas that exhibited the unusual feature of infiltrating the walls of small arteries with destruction of the elastic lamina, consistent with granulomatous vasculitis. The findings of granulomatous interstitial nephritis on kidney biopsy, hypercalcemia, and possible cerebral and pulmonary involvement in the absence of other infectious, drug-induced, or autoimmune causes of granulomatous disease established the diagnosis of sarcoidosis. Pulse methylprednisolone followed by maintenance prednisone therapy led to improvement in kidney function, hypercalcemia, and neurologic symptoms. Vasculocentric granulomatous interstitial nephritis with granulomatous vasculitis is a rare and under-recognized manifestation of renal sarcoidosis. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  18. Serum beta-2 microglobulin levels for predicting acute kidney injury complicating aortic valve replacement.

    Science.gov (United States)

    Zaleska-Kociecka, Marta; Skrobisz, Anna; Wojtkowska, Izabela; Grabowski, Maciej; Dabrowski, Maciej; Kusmierski, Krzysztof; Piotrowska, Katarzyna; Imiela, Jacek; Stepinska, Janina

    2017-10-01

    Acute kidney injury complicating both transcatheter and surgical aortic valve replacement is associated with high rates of morbidity and mortality. The aim of this study was to investigate the role of serum beta 2 (β2) microglobulin, cystatin C and neutrophil gelatinase-associated lipocalin levels in detecting periprocedural acute kidney injury. Eighty consecutive patients who were 70 years of age or older and who were having surgical (n = 40) or transcatheter (n = 40) aortic valve replacement were recruited in a prospective study. The biomarkers were tested before the procedure, 6 times afterwards, at discharge and at a 6-month follow-up visit. The baseline β2-microglobulin level was the strongest predictor of acute kidney injury as a complication of transcatheter aortic valve replacement [odds ratio (OR) 5.277, P = 0.009]. Its level 24 h after the procedure reached the largest area under the curve (AUC) of 0.880 (P regression analysis, the levels of β2-microglobulin and cystatin C 24 h after the procedure were significantly associated with acute kidney injury after transcatheter valve replacement (OR 38.15, P = 0.044; OR 1782, P = 0.019, respectively). In the surgical aortic valve replacement group, the highest AUCs belonged to β2-microglobulin and cystatin C at 24 h (AUC = 0.808, P = 0.003 and AUC = 0.854, P = 0.001, respectively). Their higher values were also associated with acute kidney injury (OR 17.2, P = 0.018; OR 965.6, P = 0.02, respectively). A persistent increase in the postoperative levels of β2-microglobulin following acute kidney injury was associated with the progression of chronic kidney disease for 6 months after both transcatheter (OR 6.56, P = 0.030) and surgical (OR 7.67, P = 0.03) aortic valve replacements. Serum β2-microglobulin had the potential to predict acute kidney injury complicating transcatheter valve replacement and to diagnose it as early as 24 h after both the

  19. Supplementing diet with Manitoba lingonberry juice reduces kidney ischemia-reperfusion injury.

    Science.gov (United States)

    Isaak, Cara K; Wang, Pengqi; Prashar, Suvira; O, Karmin; Brown, Daniel Cw; Debnath, Samir C; Siow, Yaw L

    2017-07-01

    Lingonberry (Vaccinium vitis-idaea L.) contains high levels of anthocyanins which are bioavailable in the kidney and may be protective against ischemia-reperfusion (IR)-induced acute kidney injury. This study investigated the effect of lingonberry juice on the IR-induced stress-activated signalling pathway and inflammatory response in the kidney. Sprague-Dawley rats subjected to kidney IR had significantly impaired kidney function, with increased activation of the JNK signalling pathway and increased inflammatory response, measured using a multiplex panel containing an extensive array of inflammatory biomarkers. In rats fed 1 mL lingonberry juice daily for 3 weeks prior to IR, kidney function was protected and attenuation of inflammatory response and JNK signalling was reflected in the reduction of the measured biomarkers. In vitro results in cultured HK-2 cells confirmed that lingonberry anthocyanins reduced JNK signalling and inflammatory gene expression after IR. This study shows, for the first time, that daily supplementation with lingonberry juice may protect against loss of kidney function induced by IR injury by modulating JNK signalling and inhibiting the subsequent inflammatory response. © 2017 Her Majesty the Queen in Right of Canada. Journal of the Science of Food and Agriculture © 2017 Society of Chemical Industry. © 2017 Her Majesty the Queen in Right of Canada. Journal of the Science of Food and Agriculture © 2017 Society of Chemical Industry.

  20. Acute kidney injury is independently associated with higher mortality after cardiac surgery

    DEFF Research Database (Denmark)

    Kandler, Kristian; Jensen, Mathias E; Nilsson, Jens C

    2014-01-01

    OBJECTIVES: To investigate the incidence of acute kidney injury after cardiac surgery and its association with mortality in a patient population receiving ibuprofen and gentamicin perioperatively. DESIGN: Retrospective study with Cox regression analysis to control for possible preoperative......, intraoperative and postoperative confounders. SETTING: University hospital-based single-center study. PARTICIPANTS: All patients who underwent coronary artery bypass grafting ± valve surgery during 2012. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Acute surgery within 24 hours of coronary angiography.......21-4.51, p = 0.011) and 5.62 (95% CI: 2.42-13.06), psurgery developed AKI in this contemporary cohort. Furthermore, acute kidney injury was an independent...

  1. Application of small RNA sequencing to identify microRNAs in acute kidney injury and fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Pellegrini, Kathryn L. [Department of Medicine, Renal Division, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States); Gerlach, Cory V. [Department of Medicine, Renal Division, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States); Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA (United States); Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Sciences, Harvard Medical School, Boston, MA (United States); Craciun, Florin L.; Ramachandran, Krithika [Department of Medicine, Renal Division, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States); Bijol, Vanesa [Department of Pathology, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States); Kissick, Haydn T. [Department of Surgery, Urology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (United States); Vaidya, Vishal S., E-mail: vvaidya@bwh.harvard.edu [Department of Medicine, Renal Division, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States); Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA (United States); Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Sciences, Harvard Medical School, Boston, MA (United States)

    2016-12-01

    Establishing a microRNA (miRNA) expression profile in affected tissues provides an important foundation for the discovery of miRNAs involved in the development or progression of pathologic conditions. We conducted small RNA sequencing to generate a temporal profile of miRNA expression in the kidneys using a mouse model of folic acid-induced (250 mg/kg i.p.) kidney injury and fibrosis. From the 103 miRNAs that were differentially expressed over the time course (> 2-fold, p < 0.05), we chose to further investigate miR-18a-5p, which is expressed during the acute stage of the injury; miR-132-3p, which is upregulated during transition between acute and fibrotic injury; and miR-146b-5p, which is highly expressed at the peak of fibrosis. Using qRT-PCR, we confirmed the increased expression of these candidate miRNAs in the folic acid model as well as in other established mouse models of acute injury (ischemia/reperfusion injury) and fibrosis (unilateral ureteral obstruction). In situ hybridization confirmed high expression of miR-18a-5p, miR-132-3p and miR-146b-5p throughout the kidney cortex in mice and humans with severe kidney injury or fibrosis. When primary human proximal tubular epithelial cells were treated with model nephrotoxicants such as cadmium chloride (CdCl{sub 2}), arsenic trioxide, aristolochic acid (AA), potassium dichromate (K{sub 2}Cr{sub 2}O{sub 7}) and cisplatin, miRNA-132-3p was upregulated 4.3-fold after AA treatment and 1.5-fold after K{sub 2}Cr{sub 2}O{sub 7} and CdCl{sub 2} treatment. These results demonstrate the application of temporal small RNA sequencing to identify miR-18a, miR-132 and miR-146b as differentially expressed miRNAs during distinct phases of kidney injury and fibrosis progression. - Highlights: • We used small RNA sequencing to identify differentially expressed miRNAs in kidney. • Distinct patterns were found for acute injury and fibrotic stages in the kidney. • Upregulation of miR-18a, -132 and -146b was confirmed in mice

  2. Reduced production of creatinine limits its use as marker of kidney injury in sepsis.

    Science.gov (United States)

    Doi, Kent; Yuen, Peter S T; Eisner, Christoph; Hu, Xuzhen; Leelahavanichkul, Asada; Schnermann, Jürgen; Star, Robert A

    2009-06-01

    Although diagnosis and staging of acute kidney injury uses serum creatinine, acute changes in creatinine lag behind both renal injury and recovery. The risk for mortality increases when acute kidney injury accompanies sepsis; therefore, we sought to explore the limitations of serum creatinine in this setting. In mice, induction of sepsis by cecal ligation and puncture in bilaterally nephrectomized mice increased markers of nonrenal organ injury and serum TNF-alpha. Serum creatinine, however, was significantly lower in septic animals than in animals subjected to bilateral nephrectomy and sham cecal ligation and puncture. Under these conditions treatment with chloroquine decreased nonrenal organ injury markers but paradoxically increased serum creatinine. Sepsis dramatically decreased production of creatinine in nephrectomized mice, without changes in body weight, hematocrit, or extracellular fluid volume. In conclusion, sepsis reduces production of creatinine, which blunts the increase in serum creatinine after sepsis, potentially limiting the early detection of acute kidney injury. This may partially explain why small absolute increases in serum creatinine levels are associated with poor clinical outcomes. These data support the need for new biomarkers that provide better measures of renal injury, especially in patients with sepsis.

  3. The Effects of Dexmedetomidine on Secondary Acute Lung and Kidney Injuries in the Rat Model of Intra-Abdominal Sepsis

    Directory of Open Access Journals (Sweden)

    Uğur Koca

    2013-01-01

    Full Text Available In the present study, the effects of dexmedetomidine on secondary lung and kidney injuries were studied in the rat model of intra-abdominal sepsis by immunohistological and biochemical examinations. We measured serum creatinine, kidney tissue malondialdehide and plasma neutrophil gelatinase-associated lipocalin levels. In order to evaluate tissue injury we determined kidney tissue mononuclear cell infiltration score, alveolar macrophage count, histological kidney and lung injury scores and kidney and lung tissue immunoreactivity scores. We demonstrated that dexmedetomidine attenuates sepsis-induced lung and kidney injuries and apoptosis in the rat model of sepsis. There is still need for comparative studies in order to determine the effects of dexmedetomidine on organ functions in early human sepsis.

  4. Arctigenin: A two-edged sword in ischemia/reperfusion induced acute kidney injury.

    Science.gov (United States)

    Han, Feng; Xia, Xin-Xin; Dou, Meng; Wang, Yu-Xiang; Xue, Wu-Jun; Ding, Xiao-Ming; Zheng, Jin; Ding, Chen-Guang; Tian, Pu-Xun

    2018-04-27

    Arctigenin (ATG) is one of the main active substances in fruit derived from Arctium lappa L. Previous studies have reported that ATG have antitumor, neuroprotective, antioxidant, antifibrosis and anti-inflammatory functions. However, the actions of ATG in kidney with acute injury following ischemia/ reperfusion (I/R) is still uncertain. In our study, mice were subjected to kidney I/R by having the kidney pedicles clamped and administered with vehicle or ATG (1, 3 or 9 mg/kg/d) via oral gavage for 7 consecutive days prior to I/R. Notably, ATG aggravated kidney I/R injury with the concentration increases. Multiple biochemical assays and histological examination showed ATG significantly alleviated the inflammatory response as reflected by a decreased expression of proinflammatory cytokine, TLR4/MyD88, and NF-κB, along with the infiltration of CD68 + macrophage and CD11b + Gr1 + neutrophil in the kidneys. Meanwhile, ATG alleviated I/R-induced oxidative stress proved by increasing kidney manganese superoxide dismutase and glutathione peroxidase activity but reducing levels of malonaldehyde and inducible nitric oxide synthase. On the contrary, apoptosis was significantly increased in kidneys of ATG-treated mice compared with vehicle-treated controls, especially in tubular cells. There were increased numbers of TUNEL positive cells and increased Bcl-2, Bax, cleaved-caspase-3, and cleaved-caspase-9 expression. The current study demonstrates that pretreatment of ATG aggravates I/R induced acute kidney injury by increasing apoptosis of tubular cells despite reducing infiltrating inflammatory cells and proinflammatory cytokine. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  5. Acute Superoxide Radical Scavenging Reduces Blood Pressure but Does Not Influence Kidney Function in Hypertensive Rats with Postischemic Kidney Injury

    Directory of Open Access Journals (Sweden)

    Zoran Miloradović

    2014-01-01

    Full Text Available Acute kidney injury (AKI is associated with significant morbidity and mortality in hypertensive surroundings. We investigated superoxide radical molecules influence on systemic haemodynamic and kidney function in spontaneously hypertensive rats (SHR with induced postischemic AKI. Experiment was performed in anesthetized adult male SHR. The right kidney was removed, and left renal artery was subjected to ischemia by clamping for 40 minutes. The treated group received synthetic superoxide dismutase mimetic TEMPOL in the femoral vein 5 minutes before, during, and 175 minutes after the period of reperfusion, while the control AKI group received the vehicle via the same route. All parameters were measured 24 h after renal reperfusion. TEMPOL treatment significantly decreased mean arterial pressure and total peripheral resistance P<0.05 compared to AKI control. It also increased cardiac output and catalase activity P<0.05. Lipid peroxidation and renal vascular resistance were decreased in TEMPOL P<0.05. Plasma creatinine and kidney morphological parameters were unchanged among TEMPOL treated and control groups. Our study shows that superoxide radicals participate in haemodynamic control, but acute superoxide scavenging is ineffective in glomerular and tubular improvement, probably due to hypertension-induced strong endothelial dysfunction which neutralizes beneficial effects of O2− scavenging.

  6. Markers Which Can Be Used to Determinate Acute Kidney Injury Caused By Shock Wave Lithotripsy

    Directory of Open Access Journals (Sweden)

    Mustafa Aydin

    2014-06-01

    Full Text Available Kidney stone disease is a common and important healt problem. For many years invasive surgical procedures are used for treatment. But, for 30 years, new options have emerged with the use of SWL. At first, clinicians supposed that SWL doesn%u2019t cause any damage to the kidney and other tissues nearby. But this idea has changed today, depending on the clinical experimental studies. By the time, clinical studies have revealed that the method had early and late side effects. Ischemia / reperfusion injury occurs during SWL, because renal blood flow changes during SWL. Thus, free oxygen radicals increases in kidney tissue, total antioxidant capacity decreases and acute kidney injury occurres, as shown in several studies. When the kidney proximal tubule cells are damaged, various molecules (especially glicoproteins are relesed from there. For example, KIM-1, IL-18, IL-6, NGAL, ICAM-1, %u03B22-microglobulin are some of the molecules used in the diagnosis and management of this injury. According to the results of studies, KIM-1 seems as the most useful marker in predicting the renal damage caused by SWL.

  7. T1-mapping for assessment of ischemia-induced acute kidney injury and prediction of chronic kidney disease in mice

    Energy Technology Data Exchange (ETDEWEB)

    Hueper, Katja; Gutberlet, Marcel; Wacker, Frank; Hartung, Dagmar [Hannover Medical School, Department of Radiology, Hannover (Germany); Hannover Medical School, REBIRTH Cluster of Excellence, Hannover (Germany); Peperhove, Matti; Tewes, Susanne; Barrmeyer, Amelie [Hannover Medical School, Department of Radiology, Hannover (Germany); Rong, Song [Hannover Medical School, Department of Nephrology, Hannover (Germany); Zunyi Medical College, Laboratory of Organ Transplantation, Zunyi (China); Gerstenberg, Jessica; Haller, Herman; Gueler, Faikah [Hannover Medical School, Department of Nephrology, Hannover (Germany); Mengel, Michael [University of Alberta, Department of Laboratory Medicine and Pathology, Edmonton (Canada); Meier, Martin [Hannover Medical School, REBIRTH Cluster of Excellence, Hannover (Germany); Hannover Medical School, Institute for Animal Science, Hannover (Germany); Chen, Rongjun [Hannover Medical School, Department of Nephrology, Hannover (Germany); Zhejiang University, The Kidney Disease Center of the First Affiliated Hospital, Hangzhou (China)

    2014-09-15

    To investigate whether T1-mapping allows assessment of acute kidney injury (AKI) and prediction of chronic kidney disease (CKD) in mice. AKI was induced in C57Bl/6N mice by clamping of the right renal pedicle for 35 min (moderate AKI, n = 26) or 45 min (severe AKI, n = 23). Sham animals served as controls (n = 9). Renal histology was assessed in the acute (day 1 + day 7; d1 + d7) and chronic phase (d28) after AKI. Furthermore, longitudinal MRI-examinations (prior to until d28 after surgery) were performed using a 7-Tesla magnet. T1-maps were calculated from a fat-saturated echoplanar inversion recovery sequence, and mean and relative T1-relaxation times were determined. Renal histology showed severe tubular injury at d1 + d7 in both AKI groups, whereas, at d28, only animals with prolonged 45-min ischemia showed persistent signs of AKI. Following both AKI severities T1-values significantly increased and peaked at d7. T1-times in the contralateral kidney without AKI remained stable. At d7 relative T1-values in the outer stripe of the outer medulla were significantly higher after severe than after moderate AKI (138 ± 2 % vs. 121 ± 3 %, p = 0.001). T1-elevation persisted until d28 only after severe AKI. Already at d7 T1 in the outer stripe of the outer medulla correlated with kidney volume loss indicating CKD (r = 0.83). T1-mapping non-invasively detects AKI severity in mice and predicts further outcome. (orig.)

  8. T1-mapping for assessment of ischemia-induced acute kidney injury and prediction of chronic kidney disease in mice

    International Nuclear Information System (INIS)

    Hueper, Katja; Gutberlet, Marcel; Wacker, Frank; Hartung, Dagmar; Peperhove, Matti; Tewes, Susanne; Barrmeyer, Amelie; Rong, Song; Gerstenberg, Jessica; Haller, Herman; Gueler, Faikah; Mengel, Michael; Meier, Martin; Chen, Rongjun

    2014-01-01

    To investigate whether T1-mapping allows assessment of acute kidney injury (AKI) and prediction of chronic kidney disease (CKD) in mice. AKI was induced in C57Bl/6N mice by clamping of the right renal pedicle for 35 min (moderate AKI, n = 26) or 45 min (severe AKI, n = 23). Sham animals served as controls (n = 9). Renal histology was assessed in the acute (day 1 + day 7; d1 + d7) and chronic phase (d28) after AKI. Furthermore, longitudinal MRI-examinations (prior to until d28 after surgery) were performed using a 7-Tesla magnet. T1-maps were calculated from a fat-saturated echoplanar inversion recovery sequence, and mean and relative T1-relaxation times were determined. Renal histology showed severe tubular injury at d1 + d7 in both AKI groups, whereas, at d28, only animals with prolonged 45-min ischemia showed persistent signs of AKI. Following both AKI severities T1-values significantly increased and peaked at d7. T1-times in the contralateral kidney without AKI remained stable. At d7 relative T1-values in the outer stripe of the outer medulla were significantly higher after severe than after moderate AKI (138 ± 2 % vs. 121 ± 3 %, p = 0.001). T1-elevation persisted until d28 only after severe AKI. Already at d7 T1 in the outer stripe of the outer medulla correlated with kidney volume loss indicating CKD (r = 0.83). T1-mapping non-invasively detects AKI severity in mice and predicts further outcome. (orig.)

  9. Prognosis of Acute Kidney Injury and Hepatorenal Syndrome in Patients with Cirrhosis: A Prospective Cohort Study

    Directory of Open Access Journals (Sweden)

    Andrew S. Allegretti

    2015-01-01

    Full Text Available Background/Aims. Acute kidney injury is a common problem for patients with cirrhosis and is associated with poor survival. We aimed to examine the association between type of acute kidney injury and 90-day mortality. Methods. Prospective cohort study at a major US liver transplant center. A nephrologist’s review of the urinary sediment was used in conjunction with the 2007 Ascites Club Criteria to stratify acute kidney injury into four groups: prerenal azotemia, hepatorenal syndrome, acute tubular necrosis, or other. Results. 120 participants with cirrhosis and acute kidney injury were analyzed. Ninety-day mortality was 14/40 (35% with prerenal azotemia, 20/35 (57% with hepatorenal syndrome, 21/36 (58% with acute tubular necrosis, and 1/9 (11% with other (p=0.04 overall. Mortality was the same in hepatorenal syndrome compared to acute tubular necrosis (p=0.99. Mortality was lower in prerenal azotemia compared to hepatorenal syndrome (p=0.05 and acute tubular necrosis (p=0.04. Ten participants (22% were reclassified from hepatorenal syndrome to acute tubular necrosis because of granular casts on urinary sediment. Conclusions. Hepatorenal syndrome and acute tubular necrosis result in similar 90-day mortality. Review of urinary sediment may add important diagnostic information to this population. Multicenter studies are needed to validate these findings and better guide management.

  10. Acute kidney injury in children – not just for the nephrologist

    African Journals Online (AJOL)

    REVIEW. Introduction. The phrase “acute renal failure” has given way to the term “acute ... The staging of AKI is based on the estimated glomerular filtration rate and urine output. AKI from any .... a non-specific predictor of AKI in critically ill children with septic .... KDIGO clinical practice guidelines for acute kidney injury.

  11. A review of oxidative stress in acute kidney injury: protective role of ...

    African Journals Online (AJOL)

    Acute kidney injury (AKI) is the common clinical syndrome which is associated with increased morbidity and mortality. The severity extends from less to more advanced spectrums which link to biological, physical and chemical agents. Oxidative stress (OS)-related AKI has demonstrated the increasing of reactive oxygen ...

  12. Prevalence of Acute Kidney Injury in neonates admitted at a referral ...

    African Journals Online (AJOL)

    Objectives: To determine prevalence of acute kidney injury and associated factors, among neonates admitted at a referral hospital. Design: Cross sectional study conducted 1 May to 31 July 2010. Setting: Harare Central Hospital, Neonatal Unit. Subjects: 270 neonates ≥ 37 weeks gestation admitted within 12 hours of birth.

  13. Acute kidney injury in children with heart failure: any relationship to ...

    African Journals Online (AJOL)

    Materials and Method : Prospective study of cohort of children with heart failure were studied. Heart failure was defined using heart rate for age, respiratory rate for age and tender hepatomegaly. Acute kidney injury was based on absolute serum creatinine level > 0.5 mg/dl on admission. Age, gender, and out come we r e ...

  14. Recurrent episodic acute kidney injury as presenting manifestation of mitochondrial myopathy

    Directory of Open Access Journals (Sweden)

    T P Matthai

    2014-01-01

    Full Text Available Mitochondrial cytopathies (MC are a rare heterogenous group of disorders with frequent multisystem involvement including uncommon renal manifestations. Acute kidney injury (AKI as the primary manifestation of MC is extremely rare. Here, we report a case of recurrent episodic AKI in an adult male who was subsequently diagnosed to have mitochondrial disease.

  15. Clinical and radiological observations in the kidney injury

    International Nuclear Information System (INIS)

    Lee, H. K.; Chung, I. T.; Choi, D. L.; Chung, W. K.; Kim, K. J.

    1981-01-01

    Renal injury resulting from external trauma continue to be common because of the speed and violence of modern transportation. The authors analysis 28 blunt abdominal trauma patients who suspected renal injury from January 1975 to December 1979. The results are based on clinical, physical and radiological examinations especially intravenous urography. The brief results are as follows: 1)Among all 28 patients, 23 cases were male and 5 cases were females. 10 patients were under 15 years old. 2) IVP findings are 8 cases were normal and 20 cases were abnormal. Among abnormal findings, extrarenal hematoma were 11, delayed or incomplete visualization were 4, parenchymal hematoma was 1, and extravasation was 1. 3) In most cases, conservative therapy was done without any significant complication. 4) Intravenous urography is very useful and universal method for diagnosis of renal injury. 5) Also a case reported, uriniferous pseudocyst following operation of renal injury

  16. Different dose-dependent effects of hydrogen sulfide on ischemia-reperfusion induced acute kidney injury in rats

    Directory of Open Access Journals (Sweden)

    Fateme Azizi

    2017-12-01

    Conclusion: Our study demonstrates that different doses of Sodium hydrosulfide (NaHS can play diverse role in renal ischemia reperfusion injury. However, NaHS in the low-doses could protect the kidney from the RIR injury, in a higher dose NaHS exaggerated the renal function by increases plasma creatinine and BUN. Therefore, determining of the therapeutic doses of NaHS may be important in the protection of kidney from the RIR injury.

  17. Hemoglobin A1c Levels Predicts Acute Kidney Injury after Coronary Artery Bypass Surgery in Non-Diabetic Patients

    Directory of Open Access Journals (Sweden)

    Cevdet Ugur Kocogulları

    Full Text Available Abstract INTRODUCTION: Elevated hemoglobin A1c levels in patients with diabetes mellitus have been known as a risk factor for acute kidney injury after coronary artery bypass grafting. However, the relationship between hemoglobin A1c levels in non-diabetics and acute kidney injury is under debate. We aimed to investigate the association of preoperative hemoglobin A1c levels with acute kidney injury in non-diabetic patients undergoing isolated coronary artery bypass grafting. METHODS: 202 non-diabetic patients with normal renal function (serum creatinine <1.4 mg/dl who underwent isolated coronary bypass were analyzed. Hemoglobin A1c level was measured at the baseline examination. Patients were separated into two groups according to preoperative Hemoglobin A1c level. Group 1 consisted of patients with preoperative HbA1c levels of < 5.6% and Group 2 consisted of patients with preoperative HbA1c levels of ≥ 5.6%. Acute kidney injury diagnosis was made by comparing baseline and postoperative serum creatinine to determine the presence of predefined significant change based on the Kidney Disease Improving Global Outcomes (KDIGO definition. RESULTS: Acute kidney injury occurred in 19 (10.5% patients after surgery. The incidence of acute kidney injury was 3.6% in Group 1 and 16.7% in Group 2. Elevated baseline hemoglobin A1c level was found to be associated with acute kidney injury (P=0.0001. None of the patients became hemodialysis dependent. The cut off value for acute kidney injury in our group of patients was 5.75%. CONCLUSION: Our findings suggest that, in non-diabetics, elevated preoperative hemoglobin A1c level may be associated with acute kidney injury in patients undergoing coronary artery bypass grafting. Prospective randomized studies in larger groups are needed to confirm these results.

  18. Experimental study on irradiation injury of the kidneys. II. Cardiovascular changes following renal irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Tomita, S; Fuzikawa, K; Nishimori, I; Tsuda, N; Miyagawa, N [Nagasaki Univ. (Japan). School of Medicine

    1976-09-01

    In order to investigate irradiation injury of the kidney and effect of injured kidney on the whole body, especially cardiovascular changes, a single kidney was extracted from Wistar female rats and only the remaining kidney was irradiated with a great amount of radiation in 4000 R dose experimentally. After seven weeks of irradiation, atrophy and involution of the highest region of the kidney were found. Histologically, fibrous proliferation of interstice accompanied with atrophy of the renal tubule, and slightly increased nuclei and lobulation of the glomerulus were recognized. After 15 weeks of irradiation, atrophy and involution of the whole kidney were found. Histologically, fibrous proliferation of interstice in the kidney accompanied with a high degree of atrophy of the renal tubule, marked increase and lobulation of mesangium ground substance of the glomerulus and mild hypertrophy of arteriole were recognized. Mild degeneration of myocardium was recognized. In the long-term cases passing 29 and 34 weeks after irradiation, blood pressure just before slaughter rose to 250 mmHg. The kidney showed malignant nephrosclerosis-like lesion, and panarteritis was found in the mesentery and peri-pancreatic artery. In the heart, hypertonic myocardosis was recognized. A rise of blood pressure which was observed in this experiment occurred in circulation degenerations resulted from the secondary hypertrophy of the blood vessels accompanied with fibrous proliferation of the interstice which appeared after degeneration of renal tubule. It was thought that panarteritis of cardiovascular system of the whole body, especially mesentery and peri-pancreatic artery, and fibrinoid degeneration of arteriole of the kidney were due to hypertension and angiopathic factors (non-vasopressor extracts from the injured kidney).

  19. Mitochondrial autophagy involving renal injury and aging is modulated by caloric intake in aged rat kidneys.

    Science.gov (United States)

    Cui, Jing; Shi, Suozhu; Sun, Xuefeng; Cai, Guangyan; Cui, Shaoyuan; Hong, Quan; Chen, Xiangmei; Bai, Xue-Yuan

    2013-01-01

    A high-calorie (HC) diet induces renal injury and promotes aging, and calorie restriction (CR) may ameliorate these responses. However, the effects of long-term HC and CR on renal damage and aging have been not fully determined. Autophagy plays a crucial role in removing protein aggregates and damaged organelles to maintain intracellular homeostasis and function. The role of autophagy in HC-induced renal damage is unknown. We evaluated the expression of LC3/Atg8 as a marker of the autophagosome; p62/SQSTM1; polyubiquitin aggregates as markers of autophagy flux; Ambra1, PINK1, Parkin and Bnip3 as markers of mitophagy; 8-hydroxydeoxyguanosine (8-OHdG) as a marker of DNA oxidative damage; and p16 as a marker of organ aging by western blot and immunohistochemical staining in the kidneys of 24-month-old Fischer 344 rats. We also observed mitochondrial structure and autolysosomes by transmission electron microscopy. Expression of the autophagosome formation marker LC3/Atg8 and markers of mitochondrial autophagy (mitophagy) were markedly decreased in the kidneys of the HC group, and markedly increased in CR kidneys. p62/SQSTM1 and polyubiquitin aggregates increased in HC kidneys, and decreased in CR kidneys. Transmission electron microscopy demonstrated that HC kidneys showed severe abnormal mitochondrial morphology with fewer autolysosomes, while CR kidneys exhibited normal mitochondrial morphology with numerous autolysosomes. The level of 8-hydroxydeoxyguanosine was increased in HC kidneys and decreased in CR kidneys. Markers of aging, such as p16 and senescence-associated-galactosidase, were increased significantly in the HC group and decreased significantly in the CR group. The study firstly suggests that HC diet inhibits renal autophagy and aggravates renal oxidative damage and aging, while CR enhances renal autophagy and ameliorates oxidative damage and aging in the kidneys.

  20. Effect of melatonin on kidney cold ischemic preservation injury

    OpenAIRE

    Aslaner, Arif; Gunal, Omer; Turgut, Hamdi Taner; Celik, Erdal; Yildirim, Umran; Demirci, Rojbin Karakoyun; Gunduz, Umut Riza; Calis, Hasan; Dogan, Sami

    2013-01-01

    Melatonin is a potent free radical scavenger of reactive oxygen species, nitric oxide synthase inhibitor and a well-known antioxidant secreted from pineal gland. This hormone has been reported to protect tissue from oxidative damage. In this study, we aim to investigate the effect of melatonin on kidney cold ischemia time when added to preservation solution. Thirty male Wistar albino rats were divided equally into three groups; Ringer Lactate (RL) solution, University of Wisconsin (UW) soluti...

  1. Inhibition of HDAC6 protects against rhabdomyolysis-induced acute kidney injury.

    Science.gov (United States)

    Shi, Yingfeng; Xu, Liuqing; Tang, Jinhua; Fang, Lu; Ma, Shuchen; Ma, Xiaoyan; Nie, Jing; Pi, Xiaoling; Qiu, Andong; Zhuang, Shougang; Liu, Na

    2017-03-01

    Histone deacetylase 6 (HDAC6) inhibition has been reported to protect against ischemic stroke and prolong survival after sepsis in animal models. However, it remains unknown whether HDAC6 inhibition offers a renoprotective effect after acute kidney injury (AKI). In this study, we examined the effect of tubastatin A (TA), a highly selective inhibitor of HDAC6, on AKI in a murine model of glycerol (GL) injection-induced rhabdomyolysis. Following GL injection, the mice developed severe acute tubular injury as indicated by renal dysfunction; expression of neutrophil gelatinase-associated lipocalin (NGAL), an injury marker of renal tubules; and an increase of TdT-mediated dUTP nick-end labeling (TUNEL)-positive tubular cells. These changes were companied by increased HDAC6 expression in the cytoplasm of renal tubular cells. Administration of TA significantly reduced serum creatinine and blood urea nitrogen levels as well as attenuated renal tubular damage in injured kidneys. HDAC6 inhibition also resulted in decreased expression of NGAL, reduced apoptotic cell, and inactivated caspase-3 in the kidney after acute injury. Moreover, injury to the kidney increased phosphorylation of nuclear factor (NF)-κB and expression of multiple cytokines/chemokines including tumor necrotic factor-α and interleukin-6 and monocyte chemoattractant protein-1, as well as macrophage infiltration. Treatment with TA attenuated all those responses. Finally, HDAC6 inhibition reduced the level of oxidative stress by suppressing malondialdehyde (MDA) and preserving expression of superoxide dismutase (SOD) in the injured kidney. Collectively, these data indicate that HDAC6 contributes to the pathogenesis of rhabdomyolysis-induced AKI and suggest that HDAC6 inhibitors have therapeutic potential for AKI treatment. Copyright © 2017 the American Physiological Society.

  2. Stressful life events and acute kidney injury in intensive and semi-intensive care unities.

    Science.gov (United States)

    Diniz, Denise Para; Marques, Daniella Aparecida; Blay, Sérgio Luis; Schor, Nestor

    2012-03-01

    Several studies point out that pathophysiological changes related to stress may influence renal function and are associated with disease onset and evolution. However, we have not found any studies about the influence of stress on renal function and acute kidney injury. To evaluate the association between stressful life events and acute kidney injury diagnosis, specifying the most stressful classes of events for these patients in the past 12 months. Case-control study. The study was carried out at Hospital São Paulo, in Universidade Federal de São Paulo and at Hospital dos Servidores do Estado de São Paulo, in Brazil. Patients with acute kidney injury and no chronic disease, admitted to the intensive or semi-intensive care units were included. Controls included patients in the same intensive care units with other acute diseases, except for the acute kidney injury, and also with no chronic disease. Out of the 579 patients initially identified, 475 answered to the Social Readjustment Rating Scale (SRRS) questionnaire and 398 were paired by age and gender (199 cases and 199 controls). The rate of stressful life events was statistically similar between cases and controls. The logistic regression analysis to detect associated effects of the independent variables to the stressful events showed that: increasing age and economic classes A and B in one of the hospitals (Hospital São Paulo - UNIFESP) increased the chance of a stressful life event (SLE). This study did not show association between the Acute Kidney Injury Group with a higher frequency of stressful life events, but that old age, higher income, and type of clinical center were associated.

  3. Renal Vein Reconstruction for Harvesting Injury in Kidney Transplantation

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    Birkan Bozkurt

    2014-03-01

    Full Text Available Kidney transplantation is the best treatment choice in the end-stage renal disease. In the renal transplantation, renal vein damage or shortness which occurs during cadaveric or living donor nephrectomy causes technical difficulties for surgeons. The lack of the donors already especially cadaveric, the acquirement of the graft, gets very much importance. In this report, it is aimed to share the clinical experiment by which it seen, how anastomosis can become appropriate by using the renal vein which is damaged in the way that anastomosis cannot be done anyway by using cadaveric vena cava graft. The renal vein brought to length for anostomosis which is repaired by using cadaveric vena cava graft, is anastomosed successfully by becoming an end-to-side of the external iliac vein of the recipient. Vascular anastomoses are applied easily in technique. The time of the warm ischemia was under 2 hours and the kidney was functional in the post-operative period. Renal vein trombosis was not observed. The renal vein damage occured during cadaveric or living donor nephrectomy, can be repaired by some methods. In the kidneys in which vein requirement is done, the success rates are rather high although acute tubular necrosis and delayed function can be seen more.

  4. Optical cryoimaging for assessment of radiation-induced injury to rat kidney metabolic state

    Science.gov (United States)

    Mehrvar, Shima; Funding la Cour, Mette; Medhora, Meetha; Camara, Amadou K. S.; Ranji, Mahsa

    2018-02-01

    Objective: This study utilizes fluorescence cryoimaging to quantitatively assess the effect of a high dose of irradiation on rat renal metabolism through redox state. Introduction: Exposure to high doses of irradiation could lead to death, in part, due to renal dysfunction. The kidney is one of the most sensitive organs that exhibit delayed injuries in survivors of acute radiation syndrome. In this study, optical cryoimaging was utilized to examine the potential for renal mitochondrial dysfunction after partial-body irradiation (PBI) and the mitigating effect of lisinopril-treatment, an angiotensin converting enzyme inhibitor that is FDA-approved for other indications. Materials and methods: Rats were exposed to a single dose of 13 Gy leg-out partial body irradiation (PBI, by X-rays). Rats (n = 5/group) received no further treatment, or lisinopril started one week after irradiation and continued at 24 mg/m2 /day. The non-irradiated siblings were used as controls. After 150 days, the rats were sacrificed, and their kidneys harvested and snap frozen in liquid nitrogen for later cryoimaging. The 3D images of metabolic indices (NADH and FAD) were captured, and the redox ratio i.e. NADH/FAD was calculated. The mitochondrial redox state of three groups of rat kidneys were quantified by calculating the volumetric mean of redox ratio images (RR). Results: 3D cryoimaging revealed that in PBI only kidneys, the metabolic marker (RR) decreased significantly by 78% compared to non-irradiated controls. Treatment with lisinopril significantly improved the RR by 93% in groups exposed to PBI. Conclusion: This study aimed at quantifying the level of the mitochondrial redox state of irradiated rat kidneys compared to non-irradiated kidneys (controls) and the efficacy of lisinopril to preserve kidney metabolism after irradiation. PBI oxidized the metabolic state of kidneys and lisinopril mitigated the radiation-induced injury on renal mitochondria.

  5. ROLE OF THE RENAL MICROCIRCULATION IN PROGRESSION OF CHRONIC KIDNEY INJURY IN OBESITY

    Science.gov (United States)

    Chade, Alejandro R.; Hall, John E.

    2016-01-01

    Background Obesity is largely responsible for the growing incidence and prevalence of diabetes, cardiovascular, and renal disease. Current strategies to prevent and treat obesity and its consequences have been insufficient to reverse the ongoing trends. Lifestyle modification or pharmacological therapies often produce modest weight loss which is not sustained and recurrence of obesity is frequently observed, leading to progression of target organ damage in many obese subjects. Therefore, research efforts have focused not only on the factors that regulate energy balance, but also on understanding mechanisms of target organ injury in obesity. Summary and Key message Microvascular disease plays a pivotal role in progressive kidney injury from different etiologies such as hypertension, diabetes, and atherosclerosis, which are all important consequences of chronic obesity. The microvascular networks are anatomical units that are closely adapted to specific functions of nutrition and removal of waste in every organ. Damage of the small vessels in several tissues and organs has been reported in obesity and may increase cardio-renal risk. However, the mechanisms by which obesity and its attendant cardiovascular and metabolic consequences interact to cause renal microvascular injury and chronic kidney disease are still unclear, although substantial progress has been made in recent years. This review addresses potential mechanisms and consequences of obesity-induced renal microvascular injury as well as current treatments that may provide protection of the renal microcirculation and slow progressive kidney injury in obesity. PMID:27771702

  6. Dehydration and malaria augment the risk of developing chronic kidney disease in Sri Lanka.

    Science.gov (United States)

    Siriwardhana, E A R I E; Perera, P A J; Sivakanesan, R; Abeysekara, T; Nugegoda, D B; Jayaweera, J A A S

    2015-01-01

    Chronic kidney disease (CKD) of unknown etiology (CKDu) is a serious health issue in Sri Lanka. One-to-one age and sex-matched two sample comparative study was carried out in the Medawachchiya divisional secretariat area of the North Central Province (NCP) of Sri Lanka, by randomly selecting 100 CKDu patients and 100 age and sex-matched subjects from non-CKDu affected families from the same area. An interviewer-administered questionnaire was used for the collection of data pertaining to occupation, medical history and lifestyle. Data were analyzed using a conditional linear logistic model. Working for >6 h in the field per day, exposure to sun, drinking water only from well, consumption of CKDu. Treatment of water prior to consumption had a significant protective effect against CKDu. Dehydration, history of malaria and drinking untreated well water from are likely contribute to the development of CKD of unknown etiology among the inhabitants of NCP, Sri Lanka.

  7. The role of the uncertainty of measurement of serum creatinine concentrations in the diagnosis of acute kidney injury.

    Science.gov (United States)

    Kin Tekce, Buket; Tekce, Hikmet; Aktas, Gulali; Uyeturk, Ugur

    2016-01-01

    Uncertainty of measurement is the numeric expression of the errors associated with all measurements taken in clinical laboratories. Serum creatinine concentration is the most common diagnostic marker for acute kidney injury. The goal of this study was to determine the effect of the uncertainty of measurement of serum creatinine concentrations on the diagnosis of acute kidney injury. We calculated the uncertainty of measurement of serum creatinine according to the Nordtest Guide. Retrospectively, we identified 289 patients who were evaluated for acute kidney injury. Of the total patient pool, 233 were diagnosed with acute kidney injury using the AKIN classification scheme and then were compared using statistical analysis. We determined nine probabilities of the uncertainty of measurement of serum creatinine concentrations. There was a statistically significant difference in the number of patients diagnosed with acute kidney injury when uncertainty of measurement was taken into consideration (first probability compared to the fifth p = 0.023 and first probability compared to the ninth p = 0.012). We found that the uncertainty of measurement for serum creatinine concentrations was an important factor for correctly diagnosing acute kidney injury. In addition, based on the AKIN classification scheme, minimizing the total allowable error levels for serum creatinine concentrations is necessary for the accurate diagnosis of acute kidney injury by clinicians.

  8. MicroRNA expression data reveals a signature of kidney damage following ischemia reperfusion injury.

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    Michael D Shapiro

    Full Text Available Ischemia reperfusion injury (IRI is a leading cause of acute kidney injury, a common problem worldwide associated with significant morbidity and mortality. We have recently examined the role of microRNAs (miRs in renal IRI using expression profiling. Here we conducted mathematical analyses to determine if differential expression of miRs can be used to define a biomarker of renal IRI. Principal component analysis (PCA was combined with spherical geometry to determine whether samples that underwent renal injury as a result of IRI can be distinguished from controls based on alterations in miR expression using our data set consisting of time series measuring 571 miRs. Using PCA, we examined whether changes in miR expression in the kidney following IRI have a distinct direction when compared to controls based on the trajectory of the first three principal components (PCs for our time series. We then used Monte Carlo methods and spherical geometry to assess the statistical significance of these directions. We hypothesized that if IRI and control samples exhibit distinct directions, then miR expression can be used as a biomarker of injury. Our data reveal that the pattern of miR expression in the kidney following IRI has a distinct direction based on the trajectory of the first three PCs and can be distinguished from changes observed in sham controls. Analyses of samples from immunodeficient mice indicated that the changes in miR expression observed following IRI were lymphocyte independent, and therefore represent a kidney intrinsic response to injury. Together, these data strongly support the notion that IRI results in distinct changes in miR expression that can be used as a biomarker of injury.

  9. Intestinal ischemia-reperfusion injury augments intestinal mucosal injury and bacterial translocation in jaundiced rats.

    Science.gov (United States)

    Yüksek, Yunus Nadi; Kologlu, Murat; Daglar, Gül; Doganay, Mutlu; Dolapci, Istar; Bilgihan, Ayse; Dolapçi, Mete; Kama, Nuri Aydin

    2004-01-01

    The aim of this study was to evaluate local effects and degree of bacterial translocation related with intestinal ischemia-reperfusion injury in a rat obstructive jaundice model. Thirty adult Sprague-Dawley rats (200-250 g) were divided into three groups; including Group 1 (jaundice group), Group 2 (jaundice-ischemia group) and Group 3 (ischemia group). All rats had 2 laparotomies. After experimental interventions, tissue samples for translocation; liver and ileum samples for histopathological examination, 25 cm of small intestine for mucosal myeloperoxidase and malondialdehyde levels and blood samples for biochemical analysis were obtained. Jaundiced rats had increased liver enzyme levels and total and direct bilirubin levels (p<0.05). Intestinal mucosal myeloperoxidase and malondialdehyde levels were found to be high in intestinal ischemia-reperfusion groups (p<0.05). Intestinal mucosal damage was more severe in rats with intestinal ischemia-reperfusion after bile duct ligation (p<0.05). Degree of bacterial translocation was also found to be significantly high in these rats (p<0.05). Intestinal mucosa is disturbed more severely in obstructive jaundice with the development of ischemia and reperfusion. Development of intestinal ischemia-reperfusion in obstructive jaundice increases bacterial translocation.

  10. Impact of acute kidney injury on long-term mortality and progression to chronic kidney disease among critically ill children

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    Najlaa G. Al-Otaibi

    2017-02-01

    Full Text Available Objectives: To determine the 2-year outcome of acute kidney injury (AKI following admission to pediatric critical care units (PICU. Methods: A retrospective cohort study was conducted between January 2012 and December 2013. We followed 131 children admitted to PICU, King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia with a diagnosis of AKI, based on pRIFLE (pediatric risk, injury, failure, loss, and end-stage renal disease, for 2 years. During the study period, 46 children died and 38 of survivors completed the follow-up. Factors affecting long-term progression to chronic kidney disease were also evaluated. Results: The 2-year mortality was more than 40%. The main determinant of the 2-year mortality was the pediatric risk of mortality (PRISM score, which increased the risk of mortality by 6% per each one score (adjusted odds ratio, 1.06: 95% confidence interval: 1.00-1.11. By the end of the 2 years, 33% of survivors had reduction in the glomerular filtration rate and proteinuria, and 73% were hypertensive. Patients with more severe renal impairment at admission, based on the pRIFLE criteria, had higher mortality rate. This association, however, was not independent since it was influenced by baseline disease severity (PRISM score. Conclusion: Large proportion of patients admitted to PICU with AKI either died during the first 2 months of follow-up or developed long-term complications. The severity of AKI, however, was not an independent risk factor for mortality.

  11. Elevated urinary levels of kidney injury molecule-1 among Chinese factory workers exposed to trichloroethylene

    Science.gov (United States)

    Vermeulen, Roel; Huang, Hanlin; Rothman, Nathaniel; Lan, Qing

    2012-01-01

    Epidemiological studies suggest that trichloroethylene (TCE) exposure may be associated with renal cancer. The biological mechanisms involved are not exactly known although nephrotoxicity is believed to play a role. Studies on TCE nephrotoxicity among humans, however, have been largely inconsistent. We studied kidney toxicity in Chinese factory workers exposed to TCE using novel sensitive nephrotoxicity markers. Eighty healthy workers exposed to TCE and 45 comparable unexposed controls were included in the present analyses. Personal TCE exposure measurements were taken over a 2-week period before urine collection. Ninety-six percent of workers were exposed to TCE below the current US Occupational Safety and Health Administration permissible exposure limit (100 ppm 8h TWA), with a mean (SD) of 22.2 (35.9) ppm. Kidney injury molecule-1 (KIM-1) and Pi-glutathione S transferase (GST) alpha were elevated among the exposed subjects as compared with the unexposed controls with a strong exposure-response association between individual estimates of TCE exposure and KIM-1 (P < 0.0001). This is the first report to use a set of sensitive nephrotoxicity markers to study the possible effects of TCE on the kidneys. The findings suggest that at relatively low occupational exposure levels a toxic effect on the kidneys can be observed. This finding supports the biological plausibility of linking TCE exposure and renal cancer. Abbreviations:GSTglutathione-S-transferaseKIM-1kidney injury molecule-1NAGN-acetyl-beta-(d)-glucosaminidaseOVMorganic vapour monitoringTCEtrichloroethyleneVEGFvascular endothelial growth factor. PMID:22665366

  12. Ameliorative effects of pine bark extract on cisplatin-induced acute kidney injury in rats.

    Science.gov (United States)

    Lee, In-Chul; Ko, Je-Won; Park, Sung-Hyeuk; Shin, Na-Rae; Shin, In-Sik; Kim, Yun-Bae; Kim, Jong-Choon

    2017-11-01

    This study investigated the dose-response effects of pine bark extract (PBE, pycnogenol ® ) on oxidative stress-mediated apoptotic changes induced by cisplatin (Csp) in rats. The ameliorating potential of PBE was evaluated after orally administering PBE at doses of 10 or 20 mg/kg for 10 days. Acute kidney injury was induced by a single intraperitoneal injection of Csp at 7 mg/kg on test day 5. Csp treatment caused acute kidney injury manifested by elevated levels of serum blood urea nitrogen (BUN) and creatinine (CRE) with corresponding histopathological changes, including degeneration of tubular epithelial cells, hyaline casts in the tubular lumen, and inflammatory cell infiltration (interstitial nephritis). Csp also induced significant apoptotic changes in renal tubular cells. In addition, Csp treatment induced high levels of oxidative stress, as evidenced by an increased level of malondialdehyde, depletion of the reduced glutathione (GSH) content, and decreased activities of glutathione S-transferase, superoxide dismutase, and catalase in kidney tissues. On the contrary, PBE treatment lowered BUN and CRE levels and effectively attenuated histopathological alterations and apoptotic changes induced by Csp. Additionally, treatment with PBE suppressed lipid peroxidation, prevented depletion of GSH, and enhanced activities of the antioxidant enzymes in kidney tissue. These results indicate that PBE has a cytoprotective effect against oxidative stress-mediated apoptotic changes caused by Csp in the rat kidney, which may be attributed to both increase of antioxidant enzyme activities and inhibition of lipid peroxidation.

  13. Untethering an unusual cause of kidney injury in a teenager with Down syndrome.

    Science.gov (United States)

    Yen, Elizabeth; Miele, Niel F; Barone, Joseph G; Tyagi, Rachana; Weiss, Lynne S

    2014-11-01

    Acute kidney injury (AKI) is characterized by the acute nature and the inability of kidneys to maintain fluid homeostasis as well as adequate electrolyte and acid-base balance, resulting in an accumulation of nitrogenous waste and elevation of serum blood urea nitrogen and creatinine values. Acute kidney injury may be a single isolated event, yet oftentimes, it results from an acute chronic kidney disease. It is critical to seek out the etiology of AKI and to promptly manage the underlying chronic kidney disease to prevent comorbidities and mortality that may ensue. We described a case of a 16-year-old adolescent girl with Down syndrome who presented with AKI and electrolyte aberrance.Abdominal and renal ultrasounds demonstrated a significantly dilated bladder as well as frank hydronephrosis and hydroureter bilaterally. Foley catheter was successful in relieving the obstruction and improving her renal function. However, a magnetic resonance imaging was pursued in light of her chronic constipation and back pain, and it revealed a structural defect (tethered cord) that underlies a chronic process that was highly likely contributory to her AKI. She was managed accordingly with a guarded result and required long-term and close monitoring.

  14. Developing better mouse models to study cisplatin-induced kidney injury.

    Science.gov (United States)

    Sharp, Cierra N; Siskind, Leah J

    2017-10-01

    Cisplatin is a potent chemotherapeutic used for the treatment of many types of cancer. However, its dose-limiting side effect is nephrotoxicity leading to acute kidney injury (AKI). Patients who develop AKI have an increased risk of mortality and are more likely to develop chronic kidney disease (CKD). Unfortunately, there are no therapeutic interventions for the treatment of AKI. It has been suggested that the lack of therapies is due in part to the fact that the established mouse model used to study cisplatin-induced AKI does not recapitulate the cisplatin dosing regimen patients receive. In recent years, work has been done to develop more clinically relevant models of cisplatin-induced kidney injury, with much work focusing on incorporation of multiple low doses of cisplatin administered over a period of weeks. These models can be used to recapitulate the development of CKD after AKI and, by doing so, increase the likelihood of identifying novel therapeutic targets for the treatment of cisplatin-induced kidney injury. Copyright © 2017 the American Physiological Society.

  15. Simvastatin dose and acute kidney injury without concurrent serious muscle injury: A nationwide nested case-control study.

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    Lianne Parkin

    Full Text Available Inconsistent findings from four observational studies suggest that the risk of acute kidney injury (AKI may increase with increasing statin dose or potency, but none of the studies took statin-related severe muscle injury, including rhabdomyolysis, into account. We undertook a nationwide nested case-control study in New Zealand to examine the risk of AKI without concurrent serious muscle injury according to simvastatin dose in two cohorts: people without a history of renal disease and people with non-dialysis dependent chronic kidney disease.A total of 334,710 people aged ≥ 18 years without a history of renal disease (cohort 1 and 5,437 with non-dialysis dependent chronic kidney disease (cohort 2 who initiated simvastatin therapy between 1 January 2006 and 31 December 2013 were identified using national pharmaceutical dispensing and hospital discharge data. Patients who developed AKI without concurrent serious muscle injury during follow-up (cases were ascertained using hospital discharge and mortality data (n = 931 from cohort 1, n = 160 from cohort 2. Up to 10 controls per case, matched by date of birth, sex, and cohort entry date were randomly selected from the relevant cohort using risk set sampling.Relative to current use of 20mg simvastatin daily, the adjusted odds ratios and 95% confidence intervals (95% CI in cohort 1 for current use of 40mg and 80mg were 0.9 (95% CI 0.7-1.2 and 1.3 (95% CI 0.7-2.3, respectively. The adjusted odds ratio for 40mg in cohort 2 was 1.1 (95% CI 0.7-1.9; the numbers taking 80mg were very small and the confidence interval was correspondingly wide.The findings of this study suggest that a relationship between statin dose and AKI may not exist independent of serious muscle injury.

  16. Acute kidney injury due to rhabdomyolysis and renal replacement therapy: a critical review

    Science.gov (United States)

    2014-01-01

    Rhabdomyolysis, a clinical syndrome caused by damage to skeletal muscle and release of its breakdown products into the circulation, can be followed by acute kidney injury (AKI) as a severe complication. The belief that the AKI is triggered by myoglobin as the toxin responsible appears to be oversimplified. Better knowledge of the pathophysiology of rhabdomyolysis and following AKI could widen treatment options, leading to preservation of the kidney: the decision to initiate renal replacement therapy in clinical practice should not be made on the basis of the myoglobin or creatine phosphokinase serum concentrations. PMID:25043142

  17. Dehydration and malaria augment the risk of developing chronic kidney disease in Sri Lanka

    Directory of Open Access Journals (Sweden)

    E. A. R. I. E. Siriwardhana

    2015-01-01

    Full Text Available Chronic kidney disease (CKD of unknown etiology (CKDu is a serious health issue in Sri Lanka. One-to-one age and sex-matched two sample comparative study was carried out in the Medawachchiya divisional secretariat area of the North Central Province (NCP of Sri Lanka, by randomly selecting 100 CKDu patients and 100 age and sex-matched subjects from non-CKDu affected families from the same area. An interviewer-administered questionnaire was used for the collection of data pertaining to occupation, medical history and lifestyle. Data were analyzed using a conditional linear logistic model. Working for >6 h in the field per day, exposure to sun, drinking water only from well, consumption of <3 L of water per day, and having a history of malaria were found to be having significant (P < 0.05 likelihood toward the development of CKDu. Treatment of water prior to consumption had a significant protective effect against CKDu. Dehydration, history of malaria and drinking untreated well water from are likely contribute to the development of CKD of unknown etiology among the inhabitants of NCP, Sri Lanka.

  18. Reduction in podocyte SIRT1 accelerates kidney injury in aging mice.

    Science.gov (United States)

    Chuang, Peter Y; Cai, Weijing; Li, Xuezhu; Fang, Lu; Xu, Jin; Yacoub, Rabi; He, John Cijiang; Lee, Kyung

    2017-09-01

    Both the incidence and prevalence of chronic kidney disease are increasing in the elderly population. Although aging is known to induce kidney injury, the underlying molecular mechanisms remain unclear. Sirtuin 1 (Sirt1), a longevity gene, is known to protect kidney cell injury from various cellular stresses. In previous studies, we showed that the podocyte-specific loss of Sirt1 aggravates diabetic kidney injury. However, the role of Sirt1 in aging-induced podocyte injury is not known. Therefore, in this study we sought to determine the effects of podocyte-specific reduction of Sirt1 in age-induced kidney injury. We employed the inducible podocyte-specific Sirt1 knockdown mice that express shRNA against Sirt1 (Pod-Sirt1 RNAi ) and control mice that express shRNA for luciferase (Pod-Luci RNAi ). We found that reduction of podocyte Sirt1 led to aggravated aging-induced glomerulosclerosis and albuminuria. In addition, urinary level of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative stress, was markedly increased in aged Pod-Sirt1 RNAi mice compared with aged Pod-Luci RNAi mice. Although podocyte-specific markers decreased in aged mice compared with the young controls, the decrease was further exacerbated in aged Pod-Sirt1 RNAi compared with Pod-Luci RNAi mice. Interestingly, expression of cellular senescence markers was significantly higher in the glomeruli of Pod-Sirt1 RNAi mice than Pod-Luci RNAi mice, suggesting that cellular senescence may contribute to podocyte loss in aging kidneys. Finally, we confirmed that Pod-Sirt1 RNAi glomeruli were associated with reduced activation of the transcription factors peroxisome proliferator-activated receptor (PPAR)-α coactivador-1 (PGC1α)/PPARγ, forkhead box O (FOXO)3, FOXO4, and p65 NF-κB, through SIRT1-mediated deacetylation. Together, our data suggest that SIRT1 may be a potential therapeutic target to treat patients with aging-related kidney disease.

  19. Synergistic Interaction of Hypertension and Diabetes in Promoting Kidney Injury and the Role of Endoplasmic Reticulum Stress.

    Science.gov (United States)

    Wang, Zhen; do Carmo, Jussara M; Aberdein, Nicola; Zhou, Xinchun; Williams, Jan M; da Silva, Alexandre A; Hall, John E

    2017-05-01

    Diabetes mellitus and hypertension are major risk factors for chronic kidney injury, together accounting for >70% of end-stage renal disease. In this study, we assessed interactions of hypertension and diabetes mellitus in causing kidney dysfunction and injury and the role of endoplasmic reticulum (ER) stress. Hypertension was induced by aorta constriction (AC) between the renal arteries in 6-month-old male Goto-Kakizaki (GK) type 2 diabetic and control Wistar rats. Fasting plasma glucose averaged 162±11 and 87±2 mg/dL in GK and Wistar rats, respectively. AC produced hypertension in the right kidney (above AC) and near normal blood pressure in the left kidney (below AC), with both kidneys exposed to the same levels of glucose, circulating hormones, and neural influences. After 8 weeks of AC, blood pressure above the AC (and in the right kidney) increased from 109±1 to 152±5 mm Hg in GK rats and from 106±4 to 141±5 mm Hg in Wistar rats. The diabetic-hypertensive right kidneys in GK-AC rats had much greater increases in albumin excretion and histological injury compared with left kidneys (diabetes mellitus only) of GK rats or right kidneys (hypertension only) of Wistar-AC rats. Marked increases in ER stress and oxidative stress indicators were observed in diabetic-hypertensive kidneys of GK-AC rats. Inhibition of ER stress with tauroursodeoxycholic acid for 6 weeks reduced blood pressure (135±4 versus 151±4 mm Hg), albumin excretion, ER and oxidative stress, and glomerular injury, while increasing glomerular filtration rate in hypertensive-diabetic kidneys. These results suggest that diabetes mellitus and hypertension interact synergistically to promote kidney dysfunction and injury via ER stress. © 2017 American Heart Association, Inc.

  20. Autophagy Limits Endotoxemic Acute Kidney Injury and Alters Renal Tubular Epithelial Cell Cytokine Expression.

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    Jeremy S Leventhal

    Full Text Available Sepsis related acute kidney injury (AKI is a common in-hospital complication with a dismal prognosis. Our incomplete understanding of disease pathogenesis has prevented the identification of hypothesis-driven preventive or therapeutic interventions. Increasing evidence in ischemia-reperfusion and nephrotoxic mouse models of AKI support the theory that autophagy protects renal tubular epithelial cells (RTEC from injury. However, the role of RTEC autophagy in septic AKI remains unclear. We observed that lipopolysaccharide (LPS, a mediator of gram-negative bacterial sepsis, induces RTEC autophagy in vivo and in vitro through TLR4-initiated signaling. We modeled septic AKI through intraperitoneal LPS injection in mice in which autophagy-related protein 7 was specifically knocked out in the renal proximal tubules (ATG7KO. Compared to control littermates, ATG7KO mice developed more severe renal dysfunction (24hr BUN 100.1mg/dl +/- 14.8 vs 54.6mg/dl +/- 11.3 and parenchymal injury. After injection with LPS, analysis of kidney lysates identified higher IL-6 expression and increased STAT3 activation in kidney lysates from ATG7KO mice compared to controls. In vitro experiments confirmed an altered response to LPS in RTEC with genetic or pharmacological impairment of autophagy. In conclusion, RTEC autophagy protects against endotoxin induced injury and regulates downstream effects of RTEC TLR4 signaling.

  1. Synergistic impact of acute kidney injury and high level of cervical spinal cord injury on the weaning outcome of patients with acute traumatic cervical spinal cord injury.

    Science.gov (United States)

    Yu, Wen-Kuang; Ko, Hsin-Kuo; Ho, Li-Ing; Wang, Jia-Horng; Kou, Yu Ru

    2015-07-01

    Respiratory neuromuscular impairment severity is known to predict weaning outcome among patients with cervical spinal cord injury; however, the impact of non-neuromuscular complications remains unexplored. This study was to evaluate possible neuromuscular and non-neuromuscular factors that may negatively impact weaning outcome. From September 2002 to October 2012, acute traumatic cervical spinal cord injury patients who had received mechanical ventilation for >48h were enrolled and divided into successful (n=54) and unsuccessful weaning groups (n=19). Various neuromuscular, non-neuromuscular factors and events during the intensive care unit stay were extracted from medical charts and electronic medical records. Variables presenting with a significant difference (pspinal cord injury (C1-3), lower pulse rates, and lower Glasgow Coma Scale score on admission, higher peak blood urea nitrogen, lower trough albumin, and lower trough blood leukocyte counts. Furthermore, unsuccessful weaning patients had a higher incidence of pneumonia, acute respiratory distress syndrome, shock and acute kidney injury during the intensive care unit stay. Multivariate logistic regression analysis revealed acute kidney injury and high level of cervical spinal cord injury were independent risk factors for failure of weaning. Importantly, patients with both risk factors showed a large increase in odds ratio for unsuccessful weaning from mechanical ventilation (pinjury during the intensive care unit stay and high level of cervical spinal injury are two independent risk factors that synergistically work together producing a negative impact on weaning outcome. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Nonpharmacological Strategies to Prevent Contrast-Induced Acute Kidney Injury

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    Paweena Susantitaphong

    2014-01-01

    Full Text Available Contrast-induced AKI (CI-AKI has been one of the leading causes for hospital-acquired AKI and is associated with independent risk for adverse clinical outcomes including morbidity and mortality. The aim of this review is to provide a brief summary of the studies that focus on nonpharmacological strategies to prevent CI-AKI, including routine identification of at-risk patients, use of appropriate hydration regimens, withdrawal of nephrotoxic drugs, selection of low-osmolar contrast media or isoosmolar contrast media, and using the minimum volume of contrast media as possible. There is no need to schedule dialysis in relation to injection of contrast media or injection of contrast agent in relation to dialysis program. Hemodialysis cannot protect the poorly functioning kidney against CI-AKI.

  3. Severe acute dehydration in a desert rodent elicits a transcriptional response that effectively prevents kidney injury.

    Science.gov (United States)

    MacManes, Matthew David

    2017-08-01

    Animals living in desert environments are forced to survive despite severe heat, intense solar radiation, and both acute and chronic dehydration. These animals have evolved phenotypes that effectively address these environmental stressors. To begin to understand the ways in which the desert-adapted rodent Peromyscus eremicus survives, reproductively mature adults were subjected to 72 h of water deprivation, during which they lost, on average, 23% of their body weight. The animals reacted via a series of changes in the kidney, which included modulating expression of genes responsible for reducing the rate of transcription and maintaining water and salt balance. Extracellular matrix turnover appeared to be decreased, and apoptosis was limited. In contrast to the canonical human response, serum creatinine and other biomarkers of kidney injury were not elevated, suggesting that changes in gene expression related to acute dehydration may effectively prohibit widespread kidney damage in the cactus mouse. Copyright © 2017 the American Physiological Society.

  4. Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin as prognostic markers in idiopathic membranous nephropathy

    NARCIS (Netherlands)

    Maas, Rutger J. H.; van den Brand, Jan A. J. G.; Waanders, Femke; Meijer, Esther; van Goor, Harry; Peters, Hilde P.; Hofstra, Julia M.; Wetzels, Jack F. M.

    Background: Urinary excretion of alpha-1-microglobulin and beta-2-microglobulin reflects tubular damage and predicts outcome in patients with idiopathic membranous nephropathy with reasonable accuracy. Urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin are novel

  5. Assessment of cisplatin-induced kidney injury using an integrated rodent platform

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yafei [Global Safety Assessment, AstraZeneca R and D Waltham, MA 02451 (United States); Brott, David [Patient Safety, AstraZeneca R and D Wilmington, DE 19850 (United States); Luo, Wenli [Discovery Statistics, AstraZeneca R and D Waltham, MA 02451 (United States); Gangl, Eric [DMPK, AstraZeneca R and D Waltham, MA 02451 (United States); Kamendi, Harriet; Barthlow, Herbert; Lengel, David; Fikes, James; Kinter, Lewis [Global Safety Assessment, AstraZeneca R and D Waltham, MA 02451 (United States); Valentin, Jean-Pierre [Global Safety Assessment, AstraZeneca R and D Alderley Park, Macclesfield, SK10 4TG (United Kingdom); Bialecki, Russell, E-mail: russell.bialecki@astrazeneca.com [Global Safety Assessment, AstraZeneca R and D Waltham, MA 02451 (United States)

    2013-05-01

    Current diagnosis of drug-induced kidney injury (DIKI) primarily relies on detection of elevated plasma creatinine (Cr) or blood urea nitrogen (BUN) levels; however, both are indices of overall kidney function and changes are delayed with respect to onset of nephron injury. Our aim was to investigate whether early changes in new urinary DIKI biomarkers predict plasma Cr, BUN, renal hemodynamic and kidney morphological changes associated with kidney injury following a single dose of cisplatin (CDDP) using an integrated platform in rodent. Conscious surgically prepared male Han Wistar rats were given a single intraperitoneal dose of CDDP (15 mg/kg). Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), urinalysis, DIKI biomarkers, CDDP pharmacokinetics, blood pressures, heart rate, body temperature and electroencephalogram (EEG) were measured in the same vehicle- or CDDP-treated animals over 72 h. Plasma chemistry (including Cr and BUN) and renal tissues were examined at study termination. Cisplatin caused progressive reductions of GFR, ERPF, heart rate and body temperature from day 1 (0–24 h). DIKI biomarkers including alpha-glutathione S-transferase (α-GST) significantly increased as early as 6 h post-dose, which preceded significant declines of GFR and ERPF (24 h), increased plasma Cr and BUN (72 h), and associated with renal acute tubular necrosis at 72 h post-dose. The present study adds to the current understanding of CDDP action by demonstrating that early increases in urinary excretion of α-GST predict DIKI risk following acute exposure to CDDP in rats, before changes in traditional DIKI markers are evident. - Highlights: ► CDDP causes direct damage to kidneys without affecting EEG or CVS function. ► α-GST and albumin detect DIKI earlier when compared with traditional indices. ► Integrated “cardiovascular-EEG-renal” model to better understand DIKI mechanisms ► Promotes 3R's principles in drug discovery and development.

  6. The potential use of biomarkers in predicting contrast-induced acute kidney injury

    Directory of Open Access Journals (Sweden)

    Andreucci M

    2016-09-01

    Full Text Available Michele Andreucci,1 Teresa Faga,1 Eleonora Riccio,2 Massimo Sabbatini,2 Antonio Pisani,2 Ashour Michael,1 1Department of Health Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, 2Department of Public Health, University of Naples Federico II, Naples, Italy Abstract: Contrast-induced acute kidney injury (CI-AKI is a problem associated with the use of iodinated contrast media, causing kidney dysfunction in patients with preexisting renal failure. It accounts for 12% of all hospital-acquired kidney failure and increases the length of hospitalization, a situation that is worsening with increasing numbers of patients with comorbidities, including those requiring cardiovascular interventional procedures. So far, its diagnosis has relied upon the rise in creatinine levels, which is a late marker of kidney damage and is believed to be inadequate. Therefore, there is an urgent need for biomarkers that can detect CI-AKI sooner and more reliably. In recent years, many new biomarkers have been characterized for AKI, and these are discussed particularly with their use in known CI-AKI models and studies and include neutrophil gelatinase-associated lipocalin, cystatin C (Cys-C, kidney injury molecule-1, interleukin-18, N-acetyl-β-d-glucosaminidase, and L-type fatty acid-binding protein (L-FABP. The potential of miRNA and metabolomic technology is also mentioned. Early detection of CI-AKI may lead to early intervention and therefore improve patient outcome, and in future any one or a combination of several of these markers together with development in technology for their analysis may prove effective in this respect. Keywords: radiocontrast media, acute renal failure, markers, renal injury

  7. Assessment of cisplatin-induced kidney injury using an integrated rodent platform

    International Nuclear Information System (INIS)

    Chen, Yafei; Brott, David; Luo, Wenli; Gangl, Eric; Kamendi, Harriet; Barthlow, Herbert; Lengel, David; Fikes, James; Kinter, Lewis; Valentin, Jean-Pierre; Bialecki, Russell

    2013-01-01

    Current diagnosis of drug-induced kidney injury (DIKI) primarily relies on detection of elevated plasma creatinine (Cr) or blood urea nitrogen (BUN) levels; however, both are indices of overall kidney function and changes are delayed with respect to onset of nephron injury. Our aim was to investigate whether early changes in new urinary DIKI biomarkers predict plasma Cr, BUN, renal hemodynamic and kidney morphological changes associated with kidney injury following a single dose of cisplatin (CDDP) using an integrated platform in rodent. Conscious surgically prepared male Han Wistar rats were given a single intraperitoneal dose of CDDP (15 mg/kg). Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), urinalysis, DIKI biomarkers, CDDP pharmacokinetics, blood pressures, heart rate, body temperature and electroencephalogram (EEG) were measured in the same vehicle- or CDDP-treated animals over 72 h. Plasma chemistry (including Cr and BUN) and renal tissues were examined at study termination. Cisplatin caused progressive reductions of GFR, ERPF, heart rate and body temperature from day 1 (0–24 h). DIKI biomarkers including alpha-glutathione S-transferase (α-GST) significantly increased as early as 6 h post-dose, which preceded significant declines of GFR and ERPF (24 h), increased plasma Cr and BUN (72 h), and associated with renal acute tubular necrosis at 72 h post-dose. The present study adds to the current understanding of CDDP action by demonstrating that early increases in urinary excretion of α-GST predict DIKI risk following acute exposure to CDDP in rats, before changes in traditional DIKI markers are evident. - Highlights: ► CDDP causes direct damage to kidneys without affecting EEG or CVS function. ► α-GST and albumin detect DIKI earlier when compared with traditional indices. ► Integrated “cardiovascular-EEG-renal” model to better understand DIKI mechanisms ► Promotes 3R's principles in drug discovery and development

  8. Single-dose-dexketoprofen-induced acute kidney injury due to massive rhabdomyolysis.

    Science.gov (United States)

    Sav, Tansu; Unal, Aydin; Erden, Abdulsamet; Gunal, Ali Ihsan

    2012-10-01

    A 70-year-old male patient was admitted complaining of weakness and pain in his arms and lower limbs. His serum creatine kinase and serum creatinine were markedly elevated (36,248 IU/L and 2.8 mg/dL, respectively). He had taken dexketoprofen trometamol because of a common cold, which had developed the previous night. Acute kidney injury caused by dexketoprofen-induced rhabdomyolysis was diagnosed by ruling out other possible causes, such as dermato/polymyositis, myxedema, brucellosis, and hepatitis. Dexketoprofen administration was stopped. As diuresis did not restore spontaneously, the patient was treated with I.V. alkaline solutions and mannitol. Hemodialysis was performed because of anuria and severe metabolic acidosis. The patient's renal function later recovered. In conclusion, dexketoprofen may be a potential risk factor for acute kidney injury and rhabdomyolysis.

  9. Acute Kidney Injury Complicated Epstein-Barr Virus Infection in Infancy

    Directory of Open Access Journals (Sweden)

    Gamze Ozgurhan

    2015-01-01

    Full Text Available Infectious mononucleosis is an acute lymphoproliferative disorder caused by the Epstein-Barr virus (EBV and seen most commonly in children and young adults. Clinical presentation of the disease is characterized by fever, tonsillopharyngitis, lymphadenopathy, and hepatosplenomegaly, whereas serological findings of this benign disorder include positive heterophilic antibody formation (transient increase in heterophilic antibodies and prominence of hematological lymphocytosis of more than 10% of atypical lymphocytes. An EBV infection is usually asymptomatic in childhood, but acute kidney injury can be a rare complication during its course. Most cases recover from the disease completely. Early recognition of EBV infection and estimation of its complication are important for its prognosis. In light of previous literature, we discuss the case evaluated as an EBV infection complicated by acute kidney injury in early childhood and results of tubulointerstitial nephritis shown on a renal biopsy that was later diagnosed as an EBV infection by serological examination.

  10. Loxosceles gaucho venom-induced acute kidney injury--in vivo and in vitro studies.

    Directory of Open Access Journals (Sweden)

    Rui V Lucato

    Full Text Available BACKGROUND: Accidents caused by Loxosceles spider may cause severe systemic reactions, including acute kidney injury (AKI. There are few experimental studies assessing Loxosceles venom effects on kidney function in vivo. METHODOLOGY/PRINCIPAL FINDINGS: In order to test Loxosceles gaucho venom (LV nephrotoxicity and to assess some of the possible mechanisms of renal injury, rats were studied up to 60 minutes after LV 0.24 mg/kg or saline IV injection (control. LV caused a sharp and significant drop in glomerular filtration rate, renal blood flow and urinary output and increased renal vascular resistance, without changing blood pressure. Venom infusion increased significantly serum creatine kinase and aspartate aminotransferase. In the LV group renal histology analysis found acute epithelial tubular cells degenerative changes, presence of cell debris and detached epithelial cells in tubular lumen without glomerular or vascular changes. Immunohistochemistry disclosed renal deposition of myoglobin and hemoglobin. LV did not cause injury to a suspension of fresh proximal tubules isolated from rats. CONCLUSIONS/SIGNIFICANCE: Loxosceles gaucho venom injection caused early AKI, which occurred without blood pressure variation. Changes in glomerular function occurred likely due to renal vasoconstriction and rhabdomyolysis. Direct nephrotoxicity could not be demonstrated in vitro. The development of a consistent model of Loxosceles venom-induced AKI and a better understanding of the mechanisms involved in the renal injury may allow more efficient ways to prevent or attenuate the systemic injury after Loxosceles bite.

  11. Protective effects of Tribulus terrestris L extract against acute kidney injury induced by reperfusion injury in rats.

    Science.gov (United States)

    Najafi, Houshang; Firouzifar, Mohammad Reza; Shafaat, Omid; Changizi Ashtiyani, Saeed; Hosseini, Nasser

    2014-07-01

    This study aimed to investigate the protective effect of aerial parts of the Tribulus terrestris L extract on acute kidney injury (AKI) induced by ischemia for 30 minutes and reperfusion for 24 hours in rats. Ten male Sprague-Dawley rats in the AKI and 10 in the Tribulus terrestris groups received the extract solvent and extract of the plant (11 mg/kg), respectively, for 13 days (oral administration). On day 14, ischemia for 30 minutes and reperfusion for 24 hours were induced on the rats. In the last 6 hours of the reperfusion period (24 hours), urine samples were collected in metabolic cages. At the end of this period, blood samples were also taken to determine plasma urea nitrogen, creatinine, and electrolyte concentrations. The kidney tissues were collected for measuring the level of oxidative stress and histological studies. They were compared with the sham operation group and a control group with normal diet and no operation. In the Tribulus terrestris group, the increase in plasma creatinine and urea nitrogen concentrations was significantly less following reperfusion, and their values reached the same level as that in the sham group. Creatinine clearance and urine osmolarity in the Tribulus terrestris group was higher in comparison with the AKI group, whereas sodium absolute excretion, fractional excretion of potassium, oxidative stress, and cellular damages were less. Oral administration of Tribulus terrestris extract for 2 weeks can decrease kidney functional disturbance, oxidative stress, and cellular damages following reperfusion injury in rats.

  12. Unusual presentations of acute kidney injury and neurologic complications due to snake bite

    Directory of Open Access Journals (Sweden)

    Hamid Noshad

    2015-06-01

    Full Text Available Introduction: Vascularity of kidneys is very high, so these organs are potentially susceptible to be affected with toxins including snake venom. Hypersensitivity to snake venous could cause some neurological problem. Case Report: We present a 14-year-old boy with acute kidney injury (AKI due to snake bite. After a few days, kidney failure with hematuria was developed. His serum creatinine level rose to 3 mg/dl and following 2 weeks gradually and decreased to normal level without any special treatment except for anti-venom, which was not prescribed inappropriate time (this type of AKI is not reported previously. He had seizure attacks, which were according to magnetic resonance imaging due to posterior reversible encephalopathy syndrome (PRES (This neurologic complication has been seen in other kidney injuries but up to now it was not reported in snake bite victims. Conclusion: Sanke venom could cause PRES due to AKI and seizure could be one of the most important complications in snake bite.

  13. Increased susceptibility to structural acute kidney injury in a mouse model of presymptomatic cardiomyopathy.

    Science.gov (United States)

    Pleasant, LaTawnya; Ma, Qing; Devarajan, Mahima; Parameswaran, Priyanka; Drake, Keri; Siroky, Brian; Shay-Winkler, Kritton; Robbins, Jeffrey; Devarajan, Prasad

    2017-09-01

    The early events that signal renal dysfunction in presymptomatic heart failure are unclear. We tested the hypothesis that functional and mechanistic changes occur in the kidney that precede the development of symptomatic heart failure. We employed a transgenic mouse model with cardiomyocyte-specific overexpression of mutant α-B-crystallin that develops slowly progressive cardiomyopathy. Presymptomatic transgenic mice displayed an increase in serum creatinine (1.17 ± 0.34 vs. wild type 0.65 ± 0.16 mg/dl, P kidneys exhibited a twofold upregulation of the Ren1 gene, marked overexpression of renin protein in the tubules, and a worsened response to ischemia-reperfusion injury based on serum creatinine (2.77 ± 0.66 in transgenic mice vs. 2.01 ± 0.58 mg/dl in wild type, P kidney that occur in early presymptomatic heart failure, which increase the susceptibility to subsequent acute kidney injury. Copyright © 2017 the American Physiological Society.

  14. A mouse model of alcoholic liver fibrosis-associated acute kidney injury identifies key molecular pathways

    International Nuclear Information System (INIS)

    Furuya, Shinji; Chappell, Grace A.; Iwata, Yasuhiro; Uehara, Takeki; Kato, Yuki; Kono, Hiroshi; Bataller, Ramon; Rusyn, Ivan

    2016-01-01

    Clinical data strongly indicate that acute kidney injury (AKI) is a critical complication in alcoholic hepatitis, an acute-on-chronic form of liver failure in patients with advanced alcoholic fibrosis. Development of targeted therapies for AKI in this setting is hampered by the lack of an animal model. To enable research into molecular drivers and novel therapies for fibrosis- and alcohol-associated AKI, we aimed to combine carbon tetrachloride (CCl 4 )-induced fibrosis with chronic intra-gastric alcohol feeding. Male C57BL/6J mice were administered a low dose of CCl 4 (0.2 ml/kg 2 × week/6 weeks) followed by alcohol intragastrically (up to 25 g/kg/day for 3 weeks) and with continued CCl 4 . We observed that combined treatment with CCl 4 and alcohol resulted in severe liver injury, more pronounced than using each treatment alone. Importantly, severe kidney injury was evident only in the combined treatment group. This mouse model reproduced distinct pathological features consistent with AKI in human alcoholic hepatitis. Transcriptomic analysis of kidneys revealed profound effects in the combined treatment group, with enrichment for damage-associated pathways, such as apoptosis, inflammation, immune-response and hypoxia. Interestingly, Havcr1 and Lcn2, biomarkers of AKI, were markedly up-regulated. Overall, this study established a novel mouse model of fibrosis- and alcohol-associated AKI and identified key mechanistic pathways. - Highlights: • Acute kidney injury (AKI) is a critical complication in alcoholic hepatitis • We developed a novel mouse model of fibrosis- and alcohol-associated AKI • This model reproduces key molecular and pathological features of human AKI • This animal model can help identify new targeted therapies for alcoholic hepatitis

  15. A mouse model of alcoholic liver fibrosis-associated acute kidney injury identifies key molecular pathways

    Energy Technology Data Exchange (ETDEWEB)

    Furuya, Shinji; Chappell, Grace A.; Iwata, Yasuhiro [Department of Veterinary Integrative Biosciences, Texas A& M University, College Station, TX (United States); Uehara, Takeki; Kato, Yuki [Laboratory of Veterinary Pathology, Osaka Prefecture University, Osaka (Japan); Kono, Hiroshi [First Department of Surgery, University of Yamanashi, Yamanashi (Japan); Bataller, Ramon [Division of Gastroenterology & Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, NC (United States); Rusyn, Ivan, E-mail: irusyn@tamu.edu [Department of Veterinary Integrative Biosciences, Texas A& M University, College Station, TX (United States)

    2016-11-01

    Clinical data strongly indicate that acute kidney injury (AKI) is a critical complication in alcoholic hepatitis, an acute-on-chronic form of liver failure in patients with advanced alcoholic fibrosis. Development of targeted therapies for AKI in this setting is hampered by the lack of an animal model. To enable research into molecular drivers and novel therapies for fibrosis- and alcohol-associated AKI, we aimed to combine carbon tetrachloride (CCl{sub 4})-induced fibrosis with chronic intra-gastric alcohol feeding. Male C57BL/6J mice were administered a low dose of CCl{sub 4} (0.2 ml/kg 2 × week/6 weeks) followed by alcohol intragastrically (up to 25 g/kg/day for 3 weeks) and with continued CCl{sub 4}. We observed that combined treatment with CCl{sub 4} and alcohol resulted in severe liver injury, more pronounced than using each treatment alone. Importantly, severe kidney injury was evident only in the combined treatment group. This mouse model reproduced distinct pathological features consistent with AKI in human alcoholic hepatitis. Transcriptomic analysis of kidneys revealed profound effects in the combined treatment group, with enrichment for damage-associated pathways, such as apoptosis, inflammation, immune-response and hypoxia. Interestingly, Havcr1 and Lcn2, biomarkers of AKI, were markedly up-regulated. Overall, this study established a novel mouse model of fibrosis- and alcohol-associated AKI and identified key mechanistic pathways. - Highlights: • Acute kidney injury (AKI) is a critical complication in alcoholic hepatitis • We developed a novel mouse model of fibrosis- and alcohol-associated AKI • This model reproduces key molecular and pathological features of human AKI • This animal model can help identify new targeted therapies for alcoholic hepatitis.

  16. Urine NGAL Predicts Severity of Acute Kidney Injury After Cardiac Surgery: A Prospective Study

    OpenAIRE

    Bennett, Michael; Dent, Catherine L.; Ma, Qing; Dastrala, Sudha; Grenier, Frank; Workman, Ryan; Syed, Hina; Ali, Salman; Barasch, Jonathan; Devarajan, Prasad

    2008-01-01

    Background and objectives: The authors have previously shown that urine neutrophil gelatinase-associated lipocalin (NGAL), measured by a research ELISA, is an early predictive biomarker of acute kidney injury (AKI) after cardiopulmonary bypass (CPB). In this study, whether an NGAL immunoassay developed for a standardized clinical platform (ARCHITECT analyzer®, Abbott Diagnostics Division, Abbott Laboratories, Abbott Park, IL) can predict AKI after CPB was tested.

  17. Cystatin C as an early marker of acute kidney injury in septic shock.

    Science.gov (United States)

    Ortuño-Andériz, F; Cabello-Clotet, N; Vidart-Simón, N; Postigo-Hernández, C; Domingo-Marín, S; Sánchez-García, M

    2015-03-01

    To describe the utility of determining plasma cystatinC concentrations in the diagnosis of acute incident kidney injury in septic shock. Prospective series of 50 patients with septic shock and plasma creatinine levels <2mg/dL hospitalized in an intensive care unit. Clinical and laboratory follow-ups were conducted, with measurements of cystatinC, urea and plasma creatinine levels from the diagnosis of septic shock to 5days later. The severity of the septic shock was assessed with the RIFLE scale. Twenty patients (40%) developed acute kidney injury: 8 (16%) were categorized as RIFLE-R, 5 (10%) as RIFLE-I and 7 (14%) as RIFLE-F. All patients categorized as RIFLE-F required extracorporeal renal clearance. Eighteen (36%) patients died, 8 (20%) of whom had developed acute kidney injury in their evolution. There was poor correlation between plasma creatinine and cystatin C levels (r=.501; P=.001), which disappeared upon reaching any degree of renal impairment on the RIFLE scale. CystatinC levels increased earlier and were better able to identify patients who would develop serious renal function impairment (RIFLE-F) than creatinine and urea levels. The initial cystatinC levels were related to mortality at 30days (OR=1.16; 95%CI: 03-.85). For patients who developed acute septic kidney injury, the plasma cystatinC levels increased before the classical markers of renal function. CystatinC also constitutes a severity biomarker that correlates with progression to RIFLE-F, the need for extrarenal clearance and, ultimately, mortality. This precocity could be useful for starting measures that prevent the progression of renal dysfunction. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  18. Aspirin-triggered resolvin D1 down-regulates inflammatory responses and protects against endotoxin-induced acute kidney injury

    International Nuclear Information System (INIS)

    Chen, Jiao; Shetty, Sreerama; Zhang, Ping; Gao, Rong; Hu, Yuxin; Wang, Shuxia; Li, Zhenyu; Fu, Jian

    2014-01-01

    The presence of endotoxin in blood can lead to acute kidney injury (AKI) and septic shock. Resolvins, the endogenous lipid mediators derived from docosahexaenoic acid, have been reported to exhibit potent anti-inflammatory action. Using a mouse model of lipopolysaccharide (LPS)-induced AKI, we investigated the effects of aspirin-triggered resolvin D1 (AT-RvD1) on inflammatory kidney injury. Administration of AT-RvD1 1 h after LPS challenge protected the mice from kidney injury as indicated by the measurements of blood urea nitrogen, serum creatinine, and morphological alterations associated with tubular damage. The protective effects were evidenced by decreased neutrophil infiltration in the kidney indicating reduction in inflammation. AT-RvD1 treatment restored kidney cell junction protein claudin-4 expression, which was otherwise reduced after LPS challenge. AT-RvD1 treatment inhibited endotoxin-induced NF-κB activation and suppressed LPS-induced ICAM-1 and VCAM-1 expression in the kidney. Moreover, AT-RvD1 treatment markedly decreased LPS-induced IL-6 level in the kidney and blocked IL-6-mediated signaling including STAT3 and ERK phosphorylation. Our findings demonstrate that AT-RvD1 is a potent anti-inflammatory mediator in LPS-induced kidney injury, and AT-RvD1 has therapeutic potential against AKI during endotoxemia

  19. Aspirin-triggered resolvin D1 down-regulates inflammatory responses and protects against endotoxin-induced acute kidney injury

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Jiao [Center for Research on Environmental Disease, University of Kentucky, Lexington, KY 40536 (United States); Shetty, Sreerama [Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, TX 75708 (United States); Zhang, Ping [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041 (China); Gao, Rong; Hu, Yuxin [Center for Research on Environmental Disease, University of Kentucky, Lexington, KY 40536 (United States); Wang, Shuxia [Graduate Center for Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Li, Zhenyu [Division of Cardiovascular Medicine, University of Kentucky, Lexington, KY 40536 (United States); Fu, Jian, E-mail: jian.fu@uky.edu [Center for Research on Environmental Disease, University of Kentucky, Lexington, KY 40536 (United States); Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States)

    2014-06-01

    The presence of endotoxin in blood can lead to acute kidney injury (AKI) and septic shock. Resolvins, the endogenous lipid mediators derived from docosahexaenoic acid, have been reported to exhibit potent anti-inflammatory action. Using a mouse model of lipopolysaccharide (LPS)-induced AKI, we investigated the effects of aspirin-triggered resolvin D1 (AT-RvD1) on inflammatory kidney injury. Administration of AT-RvD1 1 h after LPS challenge protected the mice from kidney injury as indicated by the measurements of blood urea nitrogen, serum creatinine, and morphological alterations associated with tubular damage. The protective effects were evidenced by decreased neutrophil infiltration in the kidney indicating reduction in inflammation. AT-RvD1 treatment restored kidney cell junction protein claudin-4 expression, which was otherwise reduced after LPS challenge. AT-RvD1 treatment inhibited endotoxin-induced NF-κB activation and suppressed LPS-induced ICAM-1 and VCAM-1 expression in the kidney. Moreover, AT-RvD1 treatment markedly decreased LPS-induced IL-6 level in the kidney and blocked IL-6-mediated signaling including STAT3 and ERK phosphorylation. Our findings demonstrate that AT-RvD1 is a potent anti-inflammatory mediator in LPS-induced kidney injury, and AT-RvD1 has therapeutic potential against AKI during endotoxemia.

  20. Depletion of kidney CD11c+ F4/80+ cells impairs the recovery process in ischaemia/reperfusion-induced acute kidney injury.

    Science.gov (United States)

    Kim, Myung-Gyu; Boo, Chang Su; Ko, Yoon Sook; Lee, Hee Young; Cho, Won Yong; Kim, Hyoung Kyu; Jo, Sang-Kyung

    2010-09-01

    Recent studies provided evidence of the potential role of CD11c(+) F4/80(+) dendritic subset in mediating injury and repair. The purpose of this study was to examine the role of kidney CD11c(+) F4/80(+) dendritic subset in the recovery phase of ischaemia/reperfusion injury (IRI). Following ischaemia/reperfusion (I/R), liposome clodronate or phosphate buffered saline (PBS) was administered, and on day 7 biochemical and histologic kidney damage was assessed. Activation and depletion of CD11c(+) F4/80(+) dendritic subset were confirmed by flow cytometry. Isolation of kidney CD11c(+) cells on days 1 and 7 with in vitro culture for measuring cytokines was performed to define functional characteristics of these cells, and adoptive transfer of CD11c(+) cells was also done. Following kidney IRI, the percentage of CD11c(+) F4/80(+) kidney dendritic cell subset that co-expresses maturation marker increased. Liposome clodronate injection after I/R resulted in preferential depletion of CD11c(+) F4/80(+) kidney dendritic subset, and depletion of these cells was associated with persistent kidney injury, more apoptosis, inflammation and impaired tubular cell proliferation. CD11c(+) F4/80(+) cell depletion was also associated with higher tissue levels of pro-inflammatory cytokines and lower level of IL-10, indicating the persistence of inflammatory milieu. Isolated kidney CD11c(+) cells on day 7 showed different phenotype with increased production of IL-10 compared with those on day 1. Adoptive transfer of CD11c(+) cells partially reversed impaired tissue recovery. Our results suggest that kidney CD11c(+) F4/80(+) dendritic subset might contribute to the recovery process by dynamic phenotypic change from pro-inflammatory to anti-inflammatory with modulation of immune response.

  1. Star fruit toxicity: a cause of both acute kidney injury and chronic kidney disease: a report of two cases.

    Science.gov (United States)

    Abeysekera, R A; Wijetunge, S; Nanayakkara, N; Wazil, A W M; Ratnatunga, N V I; Jayalath, T; Medagama, A

    2015-12-17

    Star fruit (Averrhoa carambola) is commonly consumed as a herbal remedy for various ailments in tropical countries. However, the dangers associated with consumption of star fruit are not commonly known. Although star fruit induced oxalate nephrotoxicity in those with existing renal impairment is well documented, reports on its effect on those with normal renal function are infrequent. We report two unique clinical presentation patterns of star fruit nephrotoxicity following consumption of the fruit as a remedy for diabetes mellitus-the first, in a patient with normal renal function and the second case which we believe is the first reported case of chronic kidney disease (CKD) due to prolonged and excessive consumption of star fruits. The first patient is a 56-year-old female diabetic patient who had normal renal function prior to developing acute kidney injury (AKI) after consuming large amount of star fruit juice at once. The second patient, a 60-year-old male, also diabetic presented with acute on chronic renal failure following ingestion of a significant number of star fruits in a short duration with a background history of regular star fruit consumption over the past 2-3 years. Both had histologically confirmed oxalate induced renal injury. The former had histological features of acute tubulo-interstitial disease whilst the latter had acute-on-chronic interstitial disease; neither had histological evidence of diabetic nephropathy. Both recovered over 2 weeks without the need for haemodialysis. These cases illustrate the importance of obtaining the patient's detailed history with respect to ingestion of herbs, traditional medication and health foods such as star fruits especially in AKI or CKD of unknown cause.

  2. [Star fruit as a cause of acute kidney injury].

    Science.gov (United States)

    Scaranello, Karilla Lany; Alvares, Valeria Regina de Cristo; Carneiro, Daniely Maria Queiroz; Barros, Flávio Henrique Soares; Gentil, Thais Marques Sanches; Thomaz, Myriam José; Pereira, Benedito Jorge; Pereira, Mariana Batista; Leme, Graziella Malzoni; Diz, Mary Carla Esteves; Laranja, Sandra Maria Rodrigues

    2014-01-01

    The star fruit belongs to the family Oxalidacea, species Averrhoa carambola. It is rich in minerals, vitamin A, C, B complex vitamins and oxalic acid. Recent studies show that the toxicity of the fruit differs between the patients and may be explained by single biological responses, age, and the intake quantity of the neurotoxin in each fruit in addition to glomerular filtration rate given by each patient. Additionally, the nephrotoxicity caused by the fruit is dose-dependent and may lead to the deposition of crystals of calcium oxalate intratubular, as well as by direct injury to the renal tubular epithelium, leading to apoptosis of the same. We report the case of a patient who after ingestion of the juice and fresh fruit, developed acute renal failure requiring dialysis, evolving with favourable outcome and recovery of renal function.

  3. Assessment of acute kidney injury with T1 mapping MRI following solid organ transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Peperhove, Matti; Vo Chieu, Van Dai; Gutberlet, Marcel; Hartung, Dagmar; Tewes, Susanne; Wacker, Frank; Hueper, Katja [Hannover Medical School, Diagnostic and Interventional Radiology, Hannover (Germany); Jang, Mi-Sun; Gwinner, Wilfried; Haller, Hermann; Gueler, Faikah [Nephrology, Hannover Medical School, Hannover (Germany); Warnecke, Gregor; Fegbeutel, Christiane; Haverich, Axel [Hannover Medical School, Cardiothoracic, Transplantation and Vascular Surgery, Hannover (Germany); Lehner, Frank [Hannover Medical School, General, Abdominal and Transplant Surgery, Hannover (Germany); Braesen, Jan Hinrich [Pathology, Hannover Medical School, Hannover (Germany)

    2018-01-15

    To evaluate T1 mapping as a non-invasive, functional MRI biomarker in patients shortly after solid organ transplantation to detect acute postsurgical kidney damage and to correlate T1 times with renal function. 101 patients within 2 weeks after solid organ transplantation (49 kidney transplantation, 52 lung transplantation) and 14 healthy volunteers were examined by MRI between July 2012 and April 2015 using the modified Look-Locker inversion recovery (MOLLI) sequence. T1 times in renal cortex and medulla and the corticomedullary difference were compared between groups using one-way ANOVA adjusted for multiple comparison with the Tukey test, and T1 times were correlated with renal function using Pearson's correlation. Compared to healthy volunteers T1 times were significantly increased after solid organ transplantation in the renal cortex (healthy volunteers 987 ± 102 ms; kidney transplantation 1299 ± 101 ms, p < 0.001; lung transplantation 1058 ± 96 ms, p < 0.05) and to a lesser extent in the renal medulla. Accordingly, the corticomedullary difference was diminished shortly after solid organ transplantation. T1 changes were more pronounced following kidney compared to lung transplantation, were associated with the stage of renal impairment and significantly correlated with renal function. T1 mapping may be helpful for early non-invasive assessment of acute kidney injury and renal pathology following major surgery such as solid organ transplantation. (orig.)

  4. Assessment of acute kidney injury with T1 mapping MRI following solid organ transplantation

    International Nuclear Information System (INIS)

    Peperhove, Matti; Vo Chieu, Van Dai; Gutberlet, Marcel; Hartung, Dagmar; Tewes, Susanne; Wacker, Frank; Hueper, Katja; Jang, Mi-Sun; Gwinner, Wilfried; Haller, Hermann; Gueler, Faikah; Warnecke, Gregor; Fegbeutel, Christiane; Haverich, Axel; Lehner, Frank; Braesen, Jan Hinrich

    2018-01-01

    To evaluate T1 mapping as a non-invasive, functional MRI biomarker in patients shortly after solid organ transplantation to detect acute postsurgical kidney damage and to correlate T1 times with renal function. 101 patients within 2 weeks after solid organ transplantation (49 kidney transplantation, 52 lung transplantation) and 14 healthy volunteers were examined by MRI between July 2012 and April 2015 using the modified Look-Locker inversion recovery (MOLLI) sequence. T1 times in renal cortex and medulla and the corticomedullary difference were compared between groups using one-way ANOVA adjusted for multiple comparison with the Tukey test, and T1 times were correlated with renal function using Pearson's correlation. Compared to healthy volunteers T1 times were significantly increased after solid organ transplantation in the renal cortex (healthy volunteers 987 ± 102 ms; kidney transplantation 1299 ± 101 ms, p < 0.001; lung transplantation 1058 ± 96 ms, p < 0.05) and to a lesser extent in the renal medulla. Accordingly, the corticomedullary difference was diminished shortly after solid organ transplantation. T1 changes were more pronounced following kidney compared to lung transplantation, were associated with the stage of renal impairment and significantly correlated with renal function. T1 mapping may be helpful for early non-invasive assessment of acute kidney injury and renal pathology following major surgery such as solid organ transplantation. (orig.)

  5. Environmental exposure to arsenic and chromium in children is associated with kidney injury molecule-1

    International Nuclear Information System (INIS)

    Cárdenas-González, M.; Osorio-Yáñez, C.; Gaspar-Ramírez, O.; Pavković, M.; Ochoa-Martínez, A.; López-Ventura, D.

    2016-01-01

    Environmental hazards from natural or anthropological sources are widespread, especially in the north-central region of Mexico. Children represent a susceptible population due to their unique routes of exposure and special vulnerabilities. In this study we evaluated the association of exposure to environmental kidney toxicants with kidney injury biomarkers in children living in San Luis Potosi (SLP), Mexico. A cross-sectional study was conducted with 83 children (5–12 years of age) residents of Villa de Reyes, SLP. Exposure to arsenic, cadmium, chromium, fluoride and lead was assessed in urine, blood and drinking water samples. Almost all tap and well water samples had levels of arsenic (81.5%) and fluoride (100%) above the permissible levels recommended by the World Health Organization. Mean urine arsenic (45.6 ppb) and chromium (61.7 ppb) were higher than the biological exposure index, a reference value in occupational settings. Using multivariate adjusted models, we found a dose-dependent association between kidney injury molecule-1 (KIM-1) across chromium exposure tertiles [(T1: reference, T2: 467 pg/mL; T3: 615 pg/mL) (p-trend=0.001)]. Chromium upper tertile was also associated with higher urinary miR-200c (500 copies/μl) and miR-423 (189 copies/μL). Arsenic upper tertile was also associated with higher urinary KIM-1 (372 pg/mL). Other kidney injury/functional biomarkers such as serum creatinine, glomerular filtration rate, albuminuria, neutrophil gelatinase-associated lipocalin and miR-21 did not show any association with arsenic, chromium or any of the other toxicants evaluated. We conclude that KIM-1 might serve as a sensitive biomarker to screen children for kidney damage induced by environmental toxic agents. - Highlights: • Children living in Mexico had exceedingly high arsenic and chromium exposure. • Arsenic and chromium exposure was significantly associated with urinary KIM-1. • KIM-1 might serve as a sensitive biomarker to evaluate kidney

  6. Environmental exposure to arsenic and chromium in children is associated with kidney injury molecule-1

    Energy Technology Data Exchange (ETDEWEB)

    Cárdenas-González, M. [Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Sciences, Harvard Medical School, Boston, MA (United States); Osorio-Yáñez, C. [Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (United States); Gaspar-Ramírez, O. [Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, Unidad Noreste (CIATEJ), Nuevo Leon (Mexico); Pavković, M. [Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Sciences, Harvard Medical School, Boston, MA (United States); Renal Division, Department of Medicine, Brigham and Women' s Hospital, Boston, MA (United States); Ochoa-Martínez, A. [Laboratorio de Toxicología Molecular, Centro de Investigación Aplicada en Ambiente y Salud (CIAAS), Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología (CIACYT), Universidad Autónoma de San Luis Potosí, San Luis Potosí (Mexico); López-Ventura, D. [Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), México City (Mexico); and others

    2016-10-15

    Environmental hazards from natural or anthropological sources are widespread, especially in the north-central region of Mexico. Children represent a susceptible population due to their unique routes of exposure and special vulnerabilities. In this study we evaluated the association of exposure to environmental kidney toxicants with kidney injury biomarkers in children living in San Luis Potosi (SLP), Mexico. A cross-sectional study was conducted with 83 children (5–12 years of age) residents of Villa de Reyes, SLP. Exposure to arsenic, cadmium, chromium, fluoride and lead was assessed in urine, blood and drinking water samples. Almost all tap and well water samples had levels of arsenic (81.5%) and fluoride (100%) above the permissible levels recommended by the World Health Organization. Mean urine arsenic (45.6 ppb) and chromium (61.7 ppb) were higher than the biological exposure index, a reference value in occupational settings. Using multivariate adjusted models, we found a dose-dependent association between kidney injury molecule-1 (KIM-1) across chromium exposure tertiles [(T1: reference, T2: 467 pg/mL; T3: 615 pg/mL) (p-trend=0.001)]. Chromium upper tertile was also associated with higher urinary miR-200c (500 copies/μl) and miR-423 (189 copies/μL). Arsenic upper tertile was also associated with higher urinary KIM-1 (372 pg/mL). Other kidney injury/functional biomarkers such as serum creatinine, glomerular filtration rate, albuminuria, neutrophil gelatinase-associated lipocalin and miR-21 did not show any association with arsenic, chromium or any of the other toxicants evaluated. We conclude that KIM-1 might serve as a sensitive biomarker to screen children for kidney damage induced by environmental toxic agents. - Highlights: • Children living in Mexico had exceedingly high arsenic and chromium exposure. • Arsenic and chromium exposure was significantly associated with urinary KIM-1. • KIM-1 might serve as a sensitive biomarker to evaluate kidney

  7. Early rise in postoperative creatinine for identification of acute kidney injury after cardiac surgery.

    Science.gov (United States)

    Karkouti, Keyvan; Rao, Vivek; Chan, Christopher T; Wijeysundera, Duminda N

    2017-08-01

    Acute kidney injury (AKI) is a potentially serious complication of cardiac surgery. Treatment strategies are unlikely to prove efficacious unless patients are identified and treated soon after the onset of injury. In this observational study, we determined and validated the ability of an early rise in postoperative serum creatinine to identify patients who suffer AKI during cardiac surgery. The relationship between an early rise in creatinine (immediate postoperative / preoperative creatinine) and AKI (> 50% increase in creatinine by postoperative calendar days 1or 2) was determined by logistic regression modelling. Existing databases were used for model development (n = 4,820; one institution) and validation (n = 6,553; 12 institutions). Acute kidney injury occurred in 9.1% (n = 437) and 9.8% (n = 645) of patients in the development and validation sets, respectively. An early rise in creatinine was related to AKI (P 1.30 (n = 127), the sensitivity, specificity, positive, and negative predictive values for AKI in the development set were 20% (95% CI, 16 to 24), 99% (95% CI, 99 to 99), 68% (95% CI, 59 to 76), and 93% (95% CI, 92 to 93), respectively. In patients undergoing cardiac surgery with cardiopulmonary bypass, an early rise in postoperative creatinine is a useful marker for the early identification of AKI patients. This could allow inclusion of such patients in clinical trials of promising therapeutic strategies that need to be initiated soon after the onset of injury.

  8. Clinical significance of NGAL and KIM-1 for acute kidney injury in patients with scrub typhus.

    Directory of Open Access Journals (Sweden)

    In O Sun

    Full Text Available The aim of this study is to investigate the clinical significance of neutrophil gelatinase-associated lipocalin (NGAL and kidney injury molecule-1 (KIM-1 for acute kidney injury (AKI in patients with scrub typhus.From 2014 to 2015, 145 patients were diagnosed with scrub typhus. Of these, we enrolled 138 patients who were followed up until renal recovery or for at least 3 months. We measured serum and urine NGAL and KIM-1 levels and evaluated prognostic factors affecting scrub typhus-associated AKI.Of the 138 patients, 25 had scrub typhus-associated AKI. The incidence of AKI was 18.1%; of which 11.6%, 4.3%, and 2.2% were classified as risk, injury, and failure, respectively, according to RIFLE criteria. Compared with patients in the non-AKI group, patients in the AKI group were older and showed higher total leukocyte counts and hypoalbuminemia or one or more comorbidities such as hypertension (72% vs 33%, p<0.01, diabetes (40% vs 14%, p<0.01, or chronic kidney disease (32% vs 1%, p<0.01. In addition, serum NGAL values (404± 269 vs 116± 78 ng/mL, P<0.001, KIM-1 values (0.80± 0.52 vs 0.33± 0.68 ng/mL, P<0.001, urine NGAL/creatinine values (371± 672 vs 27± 39 ng/mg, P<0.001 and urine KIM-1/creatinine values (4.04± 2.43 vs 2.38± 1.89 ng/mg, P<0.001 were higher in the AKI group than in the non-AKI group. By multivariate logistic regression, serum NGAL and the presence of chronic kidney disease were significant predictors of AKI.Serum NGAL might be an additive predictor for scrub typhus-associated AKI.

  9. Emerging Biomarkers and Metabolomics for Assessing Toxic Nephropathy and Acute Kidney Injury (AKI in Neonatology

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    M. Mussap

    2014-01-01

    Full Text Available Identification of novel drug-induced toxic nephropathy and acute kidney injury (AKI biomarkers has been designated as a top priority by the American Society of Nephrology. Increasing knowledge in the science of biology and medicine is leading to the discovery of still more new biomarkers and of their roles in molecular pathways triggered by physiological and pathological conditions. Concomitantly, the development of the so-called “omics” allows the progressive clinical utilization of a multitude of information, from those related to the human genome (genomics and proteome (proteomics, including the emerging epigenomics, to those related to metabolites (metabolomics. In preterm newborns, one of the most important factors causing the pathogenesis and the progression of AKI is the interaction between the individual genetic code, the environment, the gestational age, and the disease. By analyzing a small urine sample, metabolomics allows to identify instantly any change in phenotype, including changes due to genetic modifications. The role of liquid chromatography-mass spectrometry (LC-MS, proton nuclear magnetic resonance (1H NMR, and other emerging technologies is strategic, contributing basically to the sudden development of new biochemical and molecular tests. Urine neutrophil gelatinase-associated lipocalin (uNGAL and kidney injury molecule-1 (KIM-1 are closely correlated with the severity of kidney injury, representing noninvasive sensitive surrogate biomarkers for diagnosing, monitoring, and quantifying kidney damage. To become routine tests, uNGAL and KIM-1 should be carefully tested in multicenter clinical trials and should be measured in biological fluids by robust, standardized analytical methods.

  10. Oxidative stress caused by activation of NADPH oxidase 4 promotes contrast-induced acute kidney injury.

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    Bo Young Jeong

    Full Text Available Contrast-induced acute kidney injury (CIAKI is a leading cause of acute kidney injury following radiographic procedures. Intrarenal oxidative stress plays a critical role in CIAKI. Nicotinamide adenine dinucleotide 3-phosphate (NADPH oxidases (Noxs are important sources of reactive oxygen species (ROS. Among the various types of Noxs, Nox4 is expressed predominantly in the kidney in rodents. Here, we evaluated the role of Nox4 and benefit of Nox4 inhibition on CIAKI using in vivo and in vitro models. HK-2 cells were treated with iohexol, with or without Nox4 knockdown, or the most specific Nox1/4 inhibitor (GKT137831. Effects of Nox4 inhibition on CIAKI mice were examined. Expression of Nox4 in HK-2 cells was significantly increased following iohexol exposure. Silencing of Nox4 rescued the production of ROS, downregulated pro-inflammatory markers (particularly phospho-p38 implicated in CIAKI, and reduced Bax and caspase 3/7 activity, which resulted in increased cellular survival in iohexol-treated HK-2 cells. Pretreatment with GKT137831 replicated these effects by decreasing levels of phospho-p38. In a CIAKI mouse model, even though the improvement of plasma blood urea nitrogen was unclear, pretreatment with GKT137831 resulted in preserved structure, reduced expression of 8-hydroxy-2'-deoxyguanosine (8OHdG and kidney injury molecule-1 (KIM-1, and reduced number of TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. These results suggest Nox4 as a key source of reactive oxygen species responsible for CIAKI and provide a novel potential option for prevention of CIAKI.

  11. Immobilisation-induced hypercalcemia following spinal cord injury affecting the kidney function in two young native Greenlanders

    DEFF Research Database (Denmark)

    Linstow, Michael V; Biering-Sørensen, Fin

    2017-01-01

    INTRODUCTION: Immobilisation-induced hypercalcemia following SCI affecting the kidney function, is a rare but potentially serious condition. We report immobilisation-induced hypercalcemia affecting the kidney function in two young native Greenlanders with spinal cord injury (SCI). CASE...... PRESENTATIONS: Two 15- and 24-year-old male native Greenlanders, both with traumatic C5 SCI were admitted to our spinal cord unit. They were non-smokers without history of daily alcohol intake pre- or immediately post-injury. No physical demanding activities pre-injury. Due to complaints of nausea/vomiting 10...... the last 20 years our spinal cord unit has only experienced immobilisation-induced hypercalcemia following SCI affecting the kidney function in two young male native Greenlanders. This finding of immobilisation-induced hypercalcemia following SCI affecting the kidney function in two young native...

  12. Urine Biochemistry in the Early Postoperative Period after Cardiac Surgery: Role in Acute Kidney Injury Monitoring

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    Alexandre Toledo Maciel

    2013-01-01

    Full Text Available We have recently suggested that sequential urine electrolyte measurement in critically ill patients may be useful in monitoring kidney function. Cardiac surgery is one of the leading causes of acute kidney injury (AKI in the intensive care unit (ICU. In this paper, we describe the sequential behavior of urine electrolytes in three patients in the early (first 60 hours postoperative period after cardiac surgery according to AKI status: no AKI, transient AKI, and persistent AKI. We have found that the patient with no AKI had stable and high concentrations of sodium (NaU and chloride (ClU in sequential spot samples of urine. AKI development was characterized in the other two patients by decreases in NaU and ClU, which have started early after ICU admission. Transient AKI was marked by also transient and less severe decreases in NaU and ClU. Persistent AKI was marked by the less favorable clinical course with abrupt and prolonged declines in NaU and ClU values. These electrolytes in urine had a behavior like a “mirror image” in comparison with that of serum creatinine. We suggest that sequential urine electrolytes are useful in monitoring acute kidney injury development in the early postoperative period after cardiac surgery.

  13. Protective Activity of Dendropanax Morbifera Against Cisplatin-Induced Acute Kidney Injury

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    Eun-Sun Kim

    2015-01-01

    Full Text Available Background/Aims: Drug-induced acute kidney injury (AKI has been a severe threat to hospitalized patients, raising the urgent needs to develop strategies to reduce AKI. We investigated the protective activity of Dendropanax morbifera (DP, a medicinal plant which has been widely used to treat infectious and pain diseases, on acute kidney injury (AKI using cisplatin-induced nephropathic models. Methods: Both in vitro renal tubular cells (NRK-52E and in vivo rat models were used to demonstrate the nephroprotective effect of DP. Results: Methanolic extract from DP significantly reduced cisplatin-induced toxicity in renal tubular cells. Through successive liquid extraction, the extract of DP was separated into n-hexane, CHCl3, EtOAc, n-BuOH, and H2O fractions. Among these, the CHCl3 fraction (DPCF was found to be most potent. The protective activity of DPCF was found to be mediated through anti-oxidant, mitochondrial protective, and anti-apoptotic activities. In in vivo rat models of AKI, treatment with DPCF significantly reversed the cisplatin-induced increase in blood urea nitrogen and serum creatinine and histopathologic damage, recovered the level of anti-oxidant enzymes, and inhibited renal apoptosis. Conclusion: We demonstrated that DP extracts decreased cisplatin-induced renal toxicity, indicating its potential to ameliorate drug-associated acute kidney damage.

  14. Cystatin C in the diagnostics of acute kidney injury after heart transplantation

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    A. G. Strokov

    2017-01-01

    Full Text Available Aim. To examine the assumption that significant concentrations of cystatin C in urine are the manifestation of the tubular necrosis and, respectively, the severity of kidney damage after heart transplantation (HTx.Materials and methods. In this study we evaluated 33 heart recipients (6 women and 27 men, aged from 24 to 68 years old who had risk factors of acute kidney injury: serum creatinine level >113 μmol/l and/or mechanical circulatory support requirement (20 patients, in 14 cases before HTx. Cystatin C concentration in serum and in urine was measured by DyaSis particle-enhanced immunoturbidimetric assay test «Cystatin C FS».Results. Recipients were divided into two groups according to the levels of cystatinuria. In the group with the significant (more than 0.18 mg/l urinary cystatin C concentrations the requirement of renal replacement therapy (RRT was 2.5-fold higher, and the mean duration of RRT was more than 10-fold longer. In 2 patients with the significant cystatinuria acute kidney injury (AKI has transformed into end-stage renal disease (ESRD.Conclusion. Due to data obtained we may suppose that significant concentrations of cystatin C in urine are the marker of the tubular necrosis with the prolonged RRT requirement. Further studies are needed to justify this relationship.

  15. Andrographolide protects against cigarette smoke-induced oxidative lung injury via augmentation of Nrf2 activity

    Science.gov (United States)

    Guan, SP; Tee, W; Ng, DSW; Chan, TK; Peh, HY; Ho, WE; Cheng, C; Mak, JC; Wong, WSF

    2013-01-01

    Background and Purpose Cigarette smoke is a major cause for chronic obstructive pulmonary disease (COPD). Andrographolide is an active biomolecule isolated from the plant Andrographis paniculata. Andrographolide has been shown to activate nuclear factor erythroid-2-related factor 2 (Nrf2), a redox-sensitive antioxidant transcription factor. As Nrf2 activity is reduced in COPD, we hypothesize that andrographolide may have therapeutic value for COPD. Experimental Approach Andrographolide was given i.p. to BALB/c mice daily 2 h before 4% cigarette smoke exposure for 1 h over five consecutive days. Bronchoalveolar lavage fluid and lungs were collected for analyses of cytokines, oxidative damage markers and antioxidant activities. BEAS-2B bronchial epithelial cells were exposed to cigarette smoke extract (CSE) and used to study the antioxidant mechanism of action of andrographolide. Key Results Andrographolide suppressed cigarette smoke-induced increases in lavage fluid cell counts; levels of IL-1β, MCP-1, IP-10 and KC; and levels of oxidative biomarkers 8-isoprostane, 8-OHdG and 3-nitrotyrosine in a dose-dependent manner. Andrographolide promoted inductions of glutathione peroxidase (GPx) and glutathione reductase (GR) activities in lungs from cigarette smoke-exposed mice. In BEAS-2B cells, andrographolide markedly increased nuclear Nrf2 accumulation, promoted binding to antioxidant response element (ARE) and total cellular glutathione level in response to CSE. Andrographolide up-regulated ARE-regulated gene targets including glutamate-cysteine ligase catalytic (GCLC) subunit, GCL modifier (GCLM) subunit, GPx, GR and heme oxygenase-1 in BEAS-2B cells in response to CSE. Conclusions Andrographolide possesses antioxidative properties against cigarette smoke-induced lung injury probably via augmentation of Nrf2 activity and may have therapeutic potential for treating COPD. PMID:23146110

  16. Ulinastatin Protects against Acute Kidney Injury in Infant Piglets Model Undergoing Surgery on Hypothermic Low-Flow Cardiopulmonary Bypass.

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    Xiaocou Wang

    Full Text Available Infants are more vulnerable to kidney injuries induced by inflammatory response syndrome and ischemia-reperfusion injury following cardiopulmonary bypass especially with prolonged hypothermic low-flow (HLF. This study aims to evaluate the protective role of ulinastatin, an anti-inflammatory agent, against acute kidney injuries in infant piglets model undergoing surgery on HLF cardiopulmonary bypass.Eighteen general-type infant piglets were randomly separated into the ulinastatin group (Group U, n = 6, the control group (Group C, n = 6, and the sham operation group (Group S, n = 6, and anaesthetized. The groups U and C received following experimental procedure: median thoracotomy, routine CPB and HLF, and finally weaned from CPB. The group S only underwent sham median thoracotomy. Ulinastatin at a dose of 5,000 units/kg body weight and a certain volume of saline were administrated to animals of the groups U and C at the beginning of CPB and at aortic declamping, respectively. Venous blood samples were collected at 3 different time points: after anesthesia induction in all experimental groups, 5 minutes, and 120 minutes after CPB in the Groups U and C. Markers for inflammation and acute kidney injury were tested in the collected plasma. N-acetyl-β-D-glucosaminidase (NAG from urine, markers of oxidative stress injury and TUNEL-positive cells in kidney tissues were also detected.The expressions of plasma inflammatory markers and acute kidney injury markers increased both in Group U and Group C at 5 min and 120 min after CPB. Also, numbers of TUNEL-positive cells and oxidative stress markers in kidney rose in both groups. At the time point of 120-min after CPB, compared with the Group C, some plasma inflammatory and acute kidney injury markers as well as TUNEL-positive cells and oxidative stress markers in kidney were significantly reduced in the Group U. Histologic analyses showed that HLF promoted acute tubular necrosis and dilatation

  17. Milrinone Dosing Issues in Critically Ill Children With Kidney Injury: A Review.

    Science.gov (United States)

    Gist, Katja M; Goldstein, Stuart L; Joy, Melanie S; Vinks, Alexander A

    2016-02-01

    Milrinone is an inotropic drug used in a variety of clinical settings in adults and children. The efficacy of milrinone in pediatric low-cardiac output syndrome after cardiac surgery is reported. Its primary route of removal from the body is through the kidney as unchanged drug in the urine. Milrinone is not known to be efficiently removed by extracorporeal dialytic therapies and thus has the potential to cause serious adverse effects and potentially worsens renal function in patients experiencing acute kidney injury (AKI). AKI is an important public health issue that is associated with increased morbidity, mortality, and cost. It is a known risk factor for the development of chronic kidney disease. There are no specific therapies to mitigate AKI once it has developed, and interventions are focused on supportive care and dose adjustment of medications. Estimating glomerular filtration rate based on height and serum creatinine is the most commonly used clinical method for assessing kidney function and modification of medication doses. The purpose of this review is to discuss our current understanding of milrinone pharmacokinetics and pharmacodynamics in children with AKI and to describe the potential use of urinary biomarkers to guide therapeutic decision making for milrinone dosing.

  18. Using acute kidney injury severity and scoring systems to predict outcome in patients with burn injury

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    George Kuo

    2016-12-01

    Conclusion: Our results revealed that AKI stage has considerable discriminative power for predicting mortality. Compared with other prognostic models, AKI stage is easier to use to assess outcome in patients with severe burn injury.

  19. Clinical significance of NGAL and KIM-1 for acute kidney injury in patients with scrub typhus.

    Science.gov (United States)

    Sun, In O; Shin, Sung Hye; Cho, A Young; Yoon, Hyun Ju; Chang, Mi Yok; Lee, Kwang Young

    2017-01-01

    The aim of this study is to investigate the clinical significance of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) for acute kidney injury (AKI) in patients with scrub typhus. From 2014 to 2015, 145 patients were diagnosed with scrub typhus. Of these, we enrolled 138 patients who were followed up until renal recovery or for at least 3 months. We measured serum and urine NGAL and KIM-1 levels and evaluated prognostic factors affecting scrub typhus-associated AKI. Of the 138 patients, 25 had scrub typhus-associated AKI. The incidence of AKI was 18.1%; of which 11.6%, 4.3%, and 2.2% were classified as risk, injury, and failure, respectively, according to RIFLE criteria. Compared with patients in the non-AKI group, patients in the AKI group were older and showed higher total leukocyte counts and hypoalbuminemia or one or more comorbidities such as hypertension (72% vs 33%, pscrub typhus-associated AKI.

  20. The role of fluid overload in the prediction of outcome in acute kidney injury.

    Science.gov (United States)

    Selewski, David T; Goldstein, Stuart L

    2018-01-01

    Our understanding of the epidemiology and the impact of acute kidney injury (AKI) and fluid overload on outcomes has improved significantly over the past several decades. Fluid overload occurs commonly in critically ill children with and without associated AKI. Researchers in pediatric AKI have been at the forefront of describing the impact of fluid overload on outcomes in a variety of populations. A full understanding of this topic is important as fluid overload represents a potentially modifiable risk factor and a target for intervention. In this state-of-the-art review, we comprehensively describe the definition of fluid overload, the impact of fluid overload on kidney function, the impact of fluid overload on the diagnosis of AKI, the association of fluid overload with outcomes, the targeted therapy of fluid overload, and the impact of the timing of renal replacement therapy on outcomes.

  1. Herbal and dietary supplements related to diarrhea and acute kidney injury: a case report.

    Science.gov (United States)

    Wanitsriphinyo, Suphamat; Tangkiatkumjai, Mayuree

    2017-03-01

    Background There is very little evidence relating to the association of herbal medicine with diarrhea and the development of acute kidney injury (AKI). This study reports a case of diarrhea-induced AKI, possibly related to an individual ingesting copious amounts of homemade mixed fruit and herb puree. Case presentation A 45-year-old Thai man with diabetes had diarrhea for 2 days, as a result of taking high amounts of a puree made up of eight mixed fruits and herbs over a 3-day period. He developed dehydration and stage 2 AKI, with a doubling of his serum creatinine. He had been receiving enalapril, as a prescribed medication, over one year. After he stopped taking both the puree and enalapril, and received fluid replacement therapy, within a week his serum creatinine had gradually decreased. The combination of puree, enalapril and AKI may also have induced hyperkalemia in this patient. Furthermore, the patient developed hyperphosphatemia due to his worsening kidney function, exacerbated by regularly taking some dietary supplements containing high levels of phosphate. His serum levels of potassium and phosphate returned to normal within a week, once the patient stopped both the puree and all dietary supplements, and had begun receiving treatment for hyperkalemia. Results The mixed fruit and herb puree taken by this man may have led to his diarrhea due to its effect; particularly if the patient was taking a high concentration of such a drink. Both the puree and enalapril are likely to attenuate the progression of kidney function. The causal relationship between the puree and AKI was probable (5 scores) assessed by the modified Naranjo algorithm. This is the first case report, as far as the authors are aware, relating the drinking of a mixed fruit and herbal puree to diarrhea and AKI in a patient with diabetes. Conclusions This case can alert health care providers to the possibility that herbal medicine could induce diarrhea and develop acute kidney injury.

  2. Nicotine protects kidney from renal ischemia/reperfusion injury through the cholinergic anti-inflammatory pathway.

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    Claude Sadis

    Full Text Available Kidney ischemia/reperfusion injury (I/R is characterized by renal dysfunction and tubular damages resulting from an early activation of innate immunity. Recently, nicotine administration has been shown to be a powerful inhibitor of a variety of innate immune responses, including LPS-induced toxaemia. This cholinergic anti-inflammatory pathway acts via the alpha7 nicotinic acetylcholine receptor (alpha7nAChR. Herein, we tested the potential protective effect of nicotine administration in a mouse model of renal I/R injury induced by bilateral clamping of kidney arteries. Renal function, tubular damages and inflammatory response were compared between control animals and mice receiving nicotine at the time of ischemia. Nicotine pretreatment protected mice from renal dysfunction in a dose-dependent manner and through the alpha7nAChR, as attested by the absence of protection in alpha7nAChR-deficient mice. Additionally, nicotine significantly reduced tubular damages, prevented neutrophil infiltration and decreased productions of the CXC-chemokine KC, TNF-alpha and the proinflammatory high-mobility group box 1 protein. Reduced tubular damage in nicotine pre-treated mice was associated with a decrease in tubular cell apoptosis and proliferative response as attested by the reduction of caspase-3 and Ki67 positive cells, respectively. All together, these data highlight that nicotine exerts a protective anti-inflammatory effect during kidney I/R through the cholinergic alpha7nAChR pathway. In addition, this could provide an opportunity to overcome the effect of surgical cholinergic denervation during kidney transplantation.

  3. Urine Levels of Defensin α1 Reflect Kidney Injury in Leptospirosis Patients

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    Haorile Chagan-Yasutan

    2016-09-01

    Full Text Available Leptospirosis is a zoonotic disease whose severe forms are often accompanied by kidney dysfunction. In the present study, urinary markers were studied for potential prediction of disease severity. Urine samples from 135 patients with or without leptospirosis at San Lazaro Hospital, the Philippines, were analyzed. Urine levels of defensin α1 (uDA1 were compared with those of neutrophil gelatinase-associated lipocalin (uNGAL and N-acetyl-β-d-glucosidase (uNAG. Serum creatinine (Cr was used as a marker of kidney injury. The levels of uDA1/Cr, uNGAL/Cr, and uNAG/Cr were positive in 46%, 90%, and 80% of leptospirosis patients, and 69%, 70%, and 70% of non-leptospirosis patients, respectively. In leptospirosis patients, the correlation of uDA1/Cr, uNGAL/Cr and uNAG/Cr levels with serum Cr were r = 0.3 (p < 0.01, r = 0.29 (p < 0.01, and r = 0.02 (p = 0.81, respectively. uDA1/Cr levels were correlated with uNGAL/Cr levels (r = 0.49, p < 0.01 and uNAG/Cr levels (r = 0.47, p < 0.0001 in leptospirosis patients. These findings suggest that uDA1, uNGAL, and uNAG were elevated in leptospirosis patients and reflected various types of kidney damage. uDA1 and uNGAL can be used to track kidney injury in leptospirosis patients because of their correlation with the serum Cr level.

  4. Acute kidney failure

    Science.gov (United States)

    ... Renal failure - acute; ARF; Kidney injury - acute Images Kidney anatomy References Devarajan P. Biomarkers for assessment of renal function during acute kidney injury. In: Alpern RJ, Moe OW, Caplan M, ...

  5. Andrographolide induced acute kidney injury: analysis of 26 cases reported in Chinese Literature.

    Science.gov (United States)

    Zhang, Wu-Xing; Zhang, Zhi-Min; Zhang, Zhi-Qiang; Wang, Yang; Zhou, Wei

    2014-01-01

    Some Chinese herbs have been known for their kidney toxicity. Andrographolide, the primary component of a traditional medicinal herb, Andrographis paniculata, is widely used in China for the treatment of upper and lower respiratory tract infection, and dysentery etc. The aim of the study was to identify and summarize any case of kidney injury attributed to its use in the Chinese literature. A systemic analysis of the Chinese literature from January 1978 to August 2013 was conducted of case reports of andrographolide induced acute kidney injury (AKI). We identified 26 cases of andrographolide induced AKI (22 males and four females), with an average age of 31.3 years (range: 21 months to 47 years). 100-750 mg (58% 500 mg) of andrographolide was administered in 100-500 mL 5% glucose solution or normal saline by intravenous drip once a day. The adverse event appeared after one to six doses (19 [73.1%] patients got only one dose; cumulative dose 690 ± 670 mg) of andrographolide was given, or 0-96 h (median 1 h) after andrographolide was given. The symptoms included flank pain in 23 cases (88.5%), decreased urine volume in five cases (19.2%), and nausea or vomiting in six cases (23.1%). Laboratory tests showed maximum creatinine 352.8 ± 184.1 (158-889) μmol/L and blood urea nitrogen 12.1 ± 7.6 (4.0-40.6) mmol/L. Urine analysis showed proteinuria in 10 (38.5%) cases and occult blood in eight (30.8%) cases. Kidney biopsy was carried out in two cases and both revealed acute tubular necrosis. Management of this adverse event included withdrawal of the culprit drug, conservative therapy, and renal replacement therapy (six cases, 23.1%). All the patients recovered and were discharged with a normal or close to normal serum creatinine. Their average length of hospital stay was 12.1 ± 4.8 days. Acute kidney injury may occur shortly after intravenous infusion of andrographolide, with symptoms including flank pain, decreased urine output, and

  6. Bardoxolone methyl (BARD) ameliorates aristolochic acid (AA)-induced acute kidney injury through Nrf2 pathway.

    Science.gov (United States)

    Wu, Juan; Liu, Xinhui; Fan, Jinjin; Chen, Wenfang; Wang, Juan; Zeng, Youjia; Feng, Xiaorang; Yu, Xueqing; Yang, Xiao

    2014-04-06

    Bardoxolone methyl (BARD) is an antioxidant modulator that acts through induction of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. This study aimed to investigate the role of BARD in protecting kidneys from aristolochic acid (AA)-induced acute kidney injury (AKI). Male C57BL/6 mice received intraperitoneal (i.p.) injections of aristolochic acid I (AAI) (5mg/kg/day) for 5 days to produce acute AA nephropathy (AAN) model. BARD (10mg/kg/day, i.p.) was applied for 7 consecutive days, starting 2 days prior to AAI administration. The mice in the AA group showed AKI as evidenced by worsening kidney function evaluated by blood urea nitrogen (BUN) and serum creatinine (SCr) levels, and severe tubulointerstitial injury marked by massive tubule necrosis in kidney tissues. BARD significantly reduced BUN and SCr levels which were elevated by AAI. Additionally, AAI-induced histopathological renal damage was ameliorated by BARD. Furthermore, the expression of Nrf2 was reduced, and its repressor Kelch-like ECH-associated protein 1 (Keap1) was increased significantly, whereas heme oxygenase-1 (HO-1) was upregulated and NAD(P)H quinone oxidoreductase-1 (NQO1) was barely increased in the cytoplasm of tubules in kidneys after treatment with AAI. BARD significantly upregulated renal Nrf2, NQO1 and HO-1 expression and downregulated Keap1 expression compared with those in the AA group. Moreover, it was found that Nrf2 was expressed both in the cytoplasm and nuclear of glomeruli and tubules, whereas NQO1 and HO-1 were localized in the cytoplasm of tubules only. In conclusion, AA-induced acute renal injury was associated with impaired Nrf2 activation and expression of its downstream target genes in renal tissues. BARD prevented renal damage induced by AAI, and this renoprotective effect may be exerted by activating the Nrf2 signaling pathway and increasing expression of the downstream target genes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. Estimated glomerular filtration rate is an early biomarker of cardiac surgery-associated acute kidney injury.

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    Candela-Toha, Ángel; Pardo, María Carmen; Pérez, Teresa; Muriel, Alfonso; Zamora, Javier

    2018-04-20

    and objective Acute kidney injury (AKI) diagnosis is still based on serum creatinine and diuresis. However, increases in creatinine are typically delayed 48h or longer after injury. Our aim was to determine the utility of routine postoperative renal function blood tests, to predict AKI one or 2days in advance in a cohort of cardiac surgery patients. Using a prospective database, we selected a sample of patients who had undergone major cardiac surgery between January 2002 and December 2013. The ability of the parameters to predict AKI was based on Acute Kidney Injury Network serum creatinine criteria. A cohort of 3,962 cases was divided into 2groups of similar size, one being exploratory and the other a validation sample. The exploratory group was used to show primary objectives and the validation group to confirm results. The ability to predict AKI of several kidney function parameters measured in routine postoperative blood tests, was measured with time-dependent ROC curves. The primary endpoint was time from measurement to AKI diagnosis. AKI developed in 610 (30.8%) and 623 (31.4%) patients in the exploratory and validation samples, respectively. Estimated glomerular filtration rate using the MDRD-4 equation showed the best AKI prediction capacity, with values for the AUC ROC curves between 0.700 and 0.946. We obtained different cut-off values for estimated glomerular filtration rate depending on the degree of AKI severity and on the time elapsed between surgery and parameter measurement. Results were confirmed in the validation sample. Postoperative estimated glomerular filtration rate using the MDRD-4 equation showed good ability to predict AKI following cardiac surgery one or 2days in advance. Copyright © 2018 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  8. Development and validation of electronic surveillance tool for acute kidney injury: A retrospective analysis.

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    Ahmed, Adil; Vairavan, Srinivasan; Akhoundi, Abbasali; Wilson, Gregory; Chiofolo, Caitlyn; Chbat, Nicolas; Cartin-Ceba, Rodrigo; Li, Guangxi; Kashani, Kianoush

    2015-10-01

    Timely detection of acute kidney injury (AKI) facilitates prevention of its progress and potentially therapeutic interventions. The study objective is to develop and validate an electronic surveillance tool (AKI sniffer) to detect AKI in 2 independent retrospective cohorts of intensive care unit (ICU) patients. The primary aim is to compare the sensitivity, specificity, and positive and negative predictive values of AKI sniffer performance against a reference standard. This study is conducted in the ICUs of a tertiary care center. The derivation cohort study subjects were Olmsted County, MN, residents admitted to all Mayo Clinic ICUs from July 1, 2010, through December 31, 2010, and the validation cohort study subjects were all patients admitted to a Mayo Clinic, Rochester, campus medical/surgical ICU on January 12, 2010, through March 23, 2010. All included records were reviewed by 2 independent investigators who adjudicated AKI using the Acute Kidney Injury Network criteria; disagreements were resolved by a third reviewer. This constituted the reference standard. An electronic algorithm was developed; its precision and reliability were assessed in comparison with the reference standard in 2 separate cohorts, derivation and validation. Of 1466 screened patients, a total of 944 patients were included in the study: 482 for derivation and 462 for validation. Compared with the reference standard in the validation cohort, the sensitivity and specificity of the AKI sniffer were 88% and 96%, respectively. The Cohen κ (95% confidence interval) agreement between the electronic and the reference standard was 0.84 (0.78-0.89) and 0.85 (0.80-0.90) in the derivation and validation cohorts. Acute kidney injury can reliably and accurately be detected electronically in ICU patients. The presented method is applicable for both clinical (decision support) and research (enrollment for clinical trials) settings. Prospective validation is required. Copyright © 2015 Elsevier Inc. All

  9. Acute kidney injury after near drowning: The way from the beach to hemodialysis.

    Science.gov (United States)

    Alp, Alper; Akdam, Hakan; Meteoğlu, İbrahim; Ünsal, Alparslan; Akar, Harun; Yeniçerioğlu, Yavuz

    2016-01-01

    Acute kidney injury (AKI) occurs in many different situations and may have a variable prognosis influenced by clinical setting, underlying cause, and comorbidity. This is important because of the high mortality and morbidity risk affecting many people around the world. Near-drowning related AKI requiring hemodialysis is very seldom reported in literature. Although cardiovascular and respiratory disorders are more frequently seen after this entity, we aimed to emphasize this rare but dangerous complication in near-drowning patients. © 2015 International Society for Hemodialysis.

  10. Acute Kidney Injury and Rhabdomyolysis as an Initial Presentation of Hashimoto’s Thyroiditis

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    Deephak Swaminath

    2013-03-01

    Full Text Available The myopathy associated with hypothyroidism is usually mild and causes myalgia,stiffness, fatigability, and muscle weakness. Severe forms of myopathy, such as rhabdomyolysiswith acute kidney injury (AKI, have rarely been reported in hypothyroidpatients. We describe a young patient who presented with generalized body aches,cramps, and abdominal pain with vomiting after physical exercise. His laboratory studiesdemonstrated that he had rhabdomyolysis and AKI secondary to hypothyroidism;both resolved with thyroid hormone replacement. Hypothyroidism should be consideredin the differential diagnosis of rhabdomyolysis when common causes are excluded.

  11. Everolimus-associated acute kidney injury in patients with metastatic breast cancer

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    A Chandra

    2017-01-01

    Full Text Available Recently, everolimus (Evl has been introduced in the management of hormone receptor-positive metastatic breast cancer, in combination with aromatase inhibitors. Evl-induced acute kidney injury has hitherto been described in other malignancies, especially renal cell cancer, but only once before in a patient with breast cancer. We describe two cases of Evl-associated nephrotoxicity in patients with breast cancer, one of whom underwent a renal biopsy showing acute tubular necrosis. Both our patients improved after withdrawal of the offending agent and have normal renal functions on follow-up.

  12. Urinary apolipoprotein M as a biomarker of acute kidney injury in children undergoing heart surgery

    DEFF Research Database (Denmark)

    Svarrer, Eva Martha Madsen; Andersen, Henrik Ørbæk; Helvind, Morten

    2016-01-01

    AIM: To investigate whether apoM is excreted in urine of children undergoing heart surgery and the potential of apoM as early biomarker of acute kidney injury (AKI). MATERIALS & METHODS: Urine was collected in children undergoing heart surgery. ApoM was measured with ELISA. U-apoM was characterized.......018). Sensitivity was 0.71 and specificity was 0.68 at a cutoff level at 1.45 nmol/l. CONCLUSION: ApoM is excreted in the urine of children after cardiac surgery. Its potential as biomarker of AKI deserves exploration....

  13. Acute kidney injury and disseminated intravascular coagulation due to mercuric chloride poisoning

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    J Dhanapriya

    2016-01-01

    Full Text Available Mercury is a toxic heavy metal and occurs in organic and inorganic forms. Inorganic mercury includes elemental mercury and mercury salts. Mercury salts are usually white powder or crystals, and widely used in indigenous medicines and folk remedies in Asia. Inorganic mercury poisoning causes acute kidney injury (AKI and gastrointestinal manifestations and can be life-threatening. We describe a case with unknown substance poisoning who developed AKI and disseminated intravascular coagulation (DIC. Renal biopsy showed acute tubular necrosis. Later, the consumed substance was proven to be mercuric chloride. His renal failure improved over time, and his creatinine normalized after 2 months.

  14. Acute kidney injury associated with ingestion of star fruit: Acute oxalate nephropathy.

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    Barman, A K; Goel, R; Sharma, M; Mahanta, P J

    2016-01-01

    Starfruit ( Averrhoa carambola ) and its juice are popular in the Indian subcontinent as an indigenous medicine. Oxalate concentration in this fruit and it's freshly prepared juice is very high. We present a report of patients presenting with acute kidney injury due to oxalate nephropathy admitted in a single center. All patients had history of ingesting star fruit. Patients became symptomatic after 10-12 h of eating and main symptoms were pain abdomen and decrease in urine output. Three patients needed hemodialysis. All improved with complete renal recovery. Taking star fruit in large amount on an empty stomach and in a dehydrated state is a risk factor for nephrotoxicity.

  15. Role of cytosolic NADP+-dependent isocitrate dehydrogenase in ischemia-reperfusion injury in mouse kidney.

    Science.gov (United States)

    Kim, Jinu; Kim, Ki Young; Jang, Hee-Seong; Yoshida, Takumi; Tsuchiya, Ken; Nitta, Kosaku; Park, Jeen-Woo; Bonventre, Joseph V; Park, Kwon Moo

    2009-03-01

    Cytosolic NADP+-dependent isocitrate dehydrogenase (IDPc) synthesizes reduced NADP (NADPH), which is an essential cofactor for the generation of reduced glutathione (GSH), the most abundant and important antioxidant in mammalian cells. We investigated the role of IDPc in kidney ischemia-reperfusion (I/R) in mice. The activity and expression of IDPc were highest in the cortex, modest in the outer medulla, and lowest in the inner medulla. NADPH levels were greatest in the cortex. IDPc expression in the S1 and S2 segments of proximal tubules was higher than in the S3 segment, which is much more susceptible to I/R. IDPc protein was also highly expressed in the mitochondrion-rich intercalated cells of the collecting duct. IDPc activity was 10- to 30-fold higher than the activity of glucose-6-phosphate dehydrogenase, another producer of cytosolic NADPH, in various kidney regions. This study identifies that IDPc may be the primary source of NADPH in the kidney. I/R significantly reduced IDPc expression and activity and NADPH production and increased the ratio of oxidized glutathione to total glutathione [GSSG/(GSH+GSSG)], resulting in kidney dysfunction, tubular cell damage, and lipid peroxidation. In LLC-PK(1) cells, upregulation of IDPc by IDPc gene transfer protected the cells against hydrogen peroxide, enhancing NADPH production, inhibiting the increase of GSSG/(GSH+GSSG), and reducing lipid peroxidation. IDPc downregulation by small interference RNA treatment presented results contrasting with the upregulation. In conclusion, these results demonstrate that IDPc is expressed differentially along tubules in patterns that may contribute to differences in susceptibility to injury, is a major enzyme in cytosolic NADPH generation in kidney, and is downregulated with I/R.

  16. Role of TRPV1 channels in ischemia/reperfusion-induced acute kidney injury.

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    Lan Chen

    Full Text Available OBJECTIVES: Transient receptor potential vanilloid 1 (TRPV1 -positive sensory nerves are widely distributed in the kidney, suggesting that TRPV1-mediated action may participate in the regulation of renal function under pathophysiological conditions. Stimulation of TRPV1 channels protects against ischemia/reperfusion (I/R-induced acute kidney injury (AKI. However, it is unknown whether inhibition of these channels is detrimental in AKI or not. We tested the role of TRPV1 channels in I/R-induced AKI by modulating these channels with capsaicin (TRPV1 agonist, capsazepine (TRPV1 antagonist and using Trpv1-/- mice. METHODS AND RESULTS: Anesthetized C57BL/6 mice were subjected to 25 min of renal ischemia and 24 hrs of reperfusion. Mice were pretreated with capsaicin (0.3 mg/kg body weight or capsazepine (50 mg/kg body weight. Capsaicin ameliorated the outcome of AKI, as measured by serum creatinine levels, tubular damage,neutrophil gelatinase-associated lipocalin (NGAL abundance and Ly-6B.2 positive polymorphonuclear inflammatory cells in injured kidneys. Neither capsazepine nor deficiency of TRPV1 did deteriorate renal function or histology after AKI. Measurements of endovanilloids in kidney tissue indicate that 20-hydroxyeicosatetraeonic acid (20-HETE or epoxyeicosatrienoic acids (EETs are unlikely involved in the beneficial effects of capsaicin on I/R-induced AKI. CONCLUSIONS: Activation of TRPV1 channels ameliorates I/R-induced AKI, but inhibition of these channels does not affect the outcome of AKI. Our results may have clinical implications for long-term safety of renal denervation to treat resistant hypertension in man, with respect to the function of primary sensory nerves in the response of the kidney to ischemic stimuli.

  17. Conservative management of a grade V injury to an ectopic pelvic kidney following blunt trauma to the lower abdomen: a case report

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    Becker Adam M

    2010-07-01

    Full Text Available Abstract Introduction Ectopic pelvic kidneys represent an anatomic variant that remains clinically asymptomatic in most patients. While there is some literature to suggest that ectopic kidneys may be more predisposed to blunt trauma injuries, there are few examples to guide the management of these injuries. To our knowledge, we present the first case of a grade V renal injury to an ectopic pelvic kidney managed successfully with conservative measures. Case Presentation We present a case of grade V renal injury to an ectopic pelvic kidney in a 21 year-old African-American male. The clinical and radiographic findings are presented, along with the patient's conservative hospital course. Conclusion We suggest that management of grade V renal injuries to ectopic pelvic kidneys can be treated similarly to that of kidneys in normal anatomic position. Conservative measures may be considered in properly selected patients.

  18. Validating the utilisation of venous bicarbonate as a predictor of acute kidney injury in crush syndrome from sjambok injuries

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    David Lee Skinner

    2017-05-01

    Full Text Available Background. Crush injury secondary to sjambok beatings is a well-described phenomenon in southern Africa. Owing to a number of factors, it can result in acute kidney injury (AKI. In 1992, Muckart et al. described a risk stratification system using venous bicarbonate (VB that can be used in the management of these patients. Objective. To validate this score in the modern era of AKI risk stratification. Methods. A retrospective study was performed on a local trauma database from June 2010 to December 2012. All patients with crush injury from sjambok/blunt instrument beatings were included in the analysis. VB was compared with the Kidney Disease Improving Global Outcomes scoring system for AKI. Serum base excess (BE and creatine kinase were also examined as biomarkers. The endpoints were the need for renal replacement therapy (RRT and mortality. Results. Three hundred and ten patients were included. The overall mortality rate was 1.9%, 14.8% of patients had AKI, and 3.9% required RRT. Both VB and BE performed well in RRT prediction, with areas under the receiver operating characteristic curve of 0.847 (95% confidence interval (CI 0.756 - 0.938; p<0.001 and 0.871 (95% CI 0.795 - 0.947; p<0.001, respectively. The sensitivity and specificity of BE were 83.3% and 80.2% at an optimal cut-point of –7.25 mmol/L, while those of VB were 83.3% and 79.5% at an optimal cut-point of 18.85 mmol/L. VB was significantly different across the AKI risk groups (p<0.001, in keeping with the original Muckart risk stratification system. Conclusion. The risk stratification score using VB is valid and should continue to be used as a tool in the management of patients with sjambok injuries. BE performs well in predicting the need for RRT, with a value of <–7.25 mmol/L indicating severe injury.

  19. Rhabdomyolysis among critically ill combat casualties: Associations with acute kidney injury and mortality.

    Science.gov (United States)

    Stewart, Ian J; Faulk, Tarra I; Sosnov, Jonathan A; Clemens, Michael S; Elterman, Joel; Ross, James D; Howard, Jeffrey T; Fang, Raymond; Zonies, David H; Chung, Kevin K

    2016-03-01

    Rhabdomyolysis has been associated with poor outcomes in patients with traumatic injury, especially in the setting of acute kidney injury (AKI). However, rhabdomyolysis has not been systematically examined in a large cohort of combat casualties injured in the wars in Iraq and Afghanistan. We conducted a retrospective study of casualties injured during combat operations in Iraq and Afghanistan who were initially admitted to the intensive care unit from February 1, 2002, to February 1, 2011. Information on age, sex, Abbreviated Injury Scale (AIS) score, Injury Severity Score (ISS), mechanism of injury, shock index, creatine kinase, and serum creatinine were collected. These variables were examined via multivariate logistic and Cox regression analyses to determine factors independently associated with rhabdomyolysis, AKI, and death. Of 6,011 admissions identified, a total of 2,109 patients met inclusion criteria and were included for analysis. Rhabdomyolysis, defined as creatine kinase greater than 5,000 U/L, was present in 656 subjects (31.1%). Risk factors for rhabdomyolysis identified on multivariable analysis included injuries to the abdomen and extremities, increased ISS, male sex, explosive mechanism of injury, and shock index greater than 0.9. After adjustment, patients with rhabdomyolysis had a greater than twofold increase in the odds of AKI. In the analysis for mortality, rhabdomyolysis was significantly associated with death until AKI was added, at which point it lost statistical significance. We found that rhabdomyolysis is associated with the development of AKI in combat casualties. While rhabdomyolysis was strongly associated with mortality on the univariate model and in conjunction with both ISS and age, it was not associated with mortality after the inclusion of AKI. This suggests that the effect of rhabdomyolysis on mortality may be mediated by AKI. Prognostic and epidemiologic study, level III.

  20. Acute kidney injury in the newborn: the role of the perinatal pathologist

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    Daniela Fanni

    2014-06-01

    Full Text Available Neonatal acute kidney injury (AKI, that becomes acute renal failure (when renal replacement is needed, represents a common clinical problem in critically ill infants admitted to neonatal intensive care unit (NICU centers. This article is aimed at reviewing the most important histological renal changes generally considered typical of AKI, useful to confirm, at morphological level, the structural and cell lesions responsible for the clinical picture. In the first part a simple schematic approach to the elementary lesions of the developing kidney will be proposed, aimed to decipher the renal lesions. In the second part, the typical lesions of AKI in the neonate will be presented and discussed. In the final part, we’ll prospect the necessity for a more accurate microscopic analysis of the kidney in every neonate undergoing asphyxia or sepsis, in order to reveal subtle renal changes that might allow a pathological diagnosis of AKI even in newborns in which the clinical and laboratory pictures were not representative of a severe kidney damage. Finally, the role of the clinical-pathological discussion between the pathologist and the neonatologist will be underlined, in order to reach a final diagnosis, based on the clinical history, the laboratory findings, and the histological lesions. In this article, the role of the pathologist in the evaluation of a neonatal kidney in a newborn with the clinical diagnosis of AKI is described, with particular attention to the differences existing between the preterm and the at term kidney, focusing on the differentiation between developmental changes occurring in the kidney in the perinatal period and the histological lesions induced by pathological events occurring around birth. Proceedings of the International Course on Perinatal Pathology (part of the 10th International Workshop on Neonatology · October 22nd-25th, 2014 · Cagliari (Italy · October 25th, 2014 · The role of the clinical pathological

  1. Clinical analysis of cause, treatment and prognosis in acute kidney injury patients.

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    Fan Yang

    Full Text Available Acute kidney injury (AKI is characterized by an abrupt decline in renal function, resulting in an inability to secrete waste products and maintain electrolyte and water balance, and is associated with high risks of morbidity and mortality. This study retrospectively analyzed clinical data, treatment, and prognosis of 271 hospitalized patients (172 males and 99 females diagnosed with AKI from December, 2008 to December, 2011. In addition, this study explored the association between the cause of AKI and prognosis, severity and treatment of AKI. The severity of AKI was classified according to the Acute Kidney Injury Network (AKIN criteria. Renal recovery was defined as a decrease in a serum creatinine level to the normal value. Prerenal, renal, and postrenal causes accounted for 36.5% (99 patients, 46.5% (126 patients and 17.0% (46 patients, respectively, of the incidence of AKI. Conservative, surgical, and renal replacement treatments were given to 180 (66.4%, 30 (11.1% and 61 patients (22.5%, respectively. The overall recovery rate was 21.0%, and the mortality rate was 19.6%. Levels of Cl(-, Na(+ and carbon dioxide combining power decreased with increasing severity of AKI. Cause and treatment were significantly associated with AKI prognosis. Likewise, the severity of AKI was significantly associated with cause, treatment and prognosis. Multivariate logistic regression analysis found that respiratory injury and multiple organ dysfunction syndrome (MODS were associated with AKI patient death. Cause, treatment and AKIN stage are associated with the prognosis of AKI. Respiratory injury and MODS are prognostic factors for death of AKI patients.

  2. Impact of real-time electronic alerting of acute kidney injury on therapeutic intervention and progression of RIFLE class.

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    Colpaert, Kirsten; Hoste, Eric A; Steurbaut, Kristof; Benoit, Dominique; Van Hoecke, Sofie; De Turck, Filip; Decruyenaere, Johan

    2012-04-01

    To evaluate whether a real-time electronic alert system or "AKI sniffer," which is based on the RIFLE classification criteria (Risk, Injury and Failure), would have an impact on therapeutic interventions and acute kidney injury progression. Prospective intervention study. Surgical and medical intensive care unit in a tertiary care hospital. A total of 951 patients having in total 1,079 admission episodes were admitted during the study period (prealert control group: 227, alert group: 616, and postalert control group: 236). Three study phases were compared: A 1.5-month prealert control phase in which physicians were blinded for the acute kidney injury sniffer and a 3-month intervention phase with real-time alerting of worsening RIFLE class through the Digital Enhanced Cordless Technology telephone system followed by a second 1.5-month postalert control phase. A total of 2593 acute kidney injury alerts were recorded with a balanced distribution over all study phases. Most acute kidney injury alerts were RIFLE class risk (59.8%) followed by RIFLE class injury (34.1%) and failure (6.1%). A higher percentage of patients in the alert group received therapeutic intervention within 60 mins after the acute kidney injury alert (28.7% in alert group vs. 7.9% and 10.4% in the pre- and postalert control groups, respectively, p μ .001). In the alert group, more patients received fluid therapy (23.0% vs. 4.9% and 9.2%, p μ .01), diuretics (4.2% vs. 2.6% and 0.8%, p μ .001), or vasopressors (3.9% vs. 1.1% and 0.8%, p μ .001). Furthermore, these patients had a shorter time to intervention (p μ .001). A higher proportion of patients in the alert group showed return to a baseline kidney function within 8 hrs after an acute kidney injury alert "from normal to risk" compared with patients in the control group (p = .048). The real-time alerting of every worsening RIFLE class by the acute kidney injury sniffer increased the number and timeliness of early therapeutic interventions

  3. Over-diuresis or cardiac tamponade? An unusual case of acute kidney injury and early closure

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    Gurkeerat Singh

    2016-04-01

    Full Text Available An 84-year-old man with hypertension and a history of deep venous thrombosis (on warfarin was admitted with shortness of breath presumed to be due to congestive heart failure. Echocardiogram performed the following day showed a low-normal ejection fraction with signs of elevated right-sided pressures but was otherwise normal. He improved with diuretic therapy but after a few days was found to be hypotensive with a concomitant rise in creatinine with decreased urine output. This was felt to be secondary to over-diuresis but he did not respond to small boluses of intravenous fluids as his kidney function continued to worsen and hypotension persisted. He was transferred to the intermediate care unit where a rapid, bedside ultrasound revealed a new, moderate-sized pericardial effusion with tamponade physiology. Pericardiocentesis, with removal of 750 cc of frank blood, led to dramatic improvement in blood pressure, kidney function, and urine output. Here, we demonstrate the utility of point-of-care ultrasound in a community hospital setting where urgent echocardiogram is not routinely available. We also report acute kidney injury due to pericardial tamponade reversed with therapeutic pericardiocentesis.

  4. Taurine decreased uric acid levels in hyperuricemic rats and alleviated kidney injury.

    Science.gov (United States)

    Feng, Ying; Sun, Fang; Gao, Yongchao; Yang, Jiancheng; Wu, Gaofeng; Lin, Shumei; Hu, Jianmin

    2017-07-29

    Hyperuricemia can lead to direct kidney damage. Taurine participates in several renal physiological processes and has been shown as a renoprotective agent. It has been reported that taurine could reduce uric acid levels in diabetic rats, but to date there was no research on the effects of taurine on hyperuricemic rats with kidney injury. In present study, hyperuricemic rat models were induced by intragastric administration of adenine and ethambutol hydrochloride for 10 days, and taurine (1% or 2%) were added in the drinking water 7 days in advance for consecutively 17 days. The results showed that taurine alleviated renal morphological and pathological changes as well as kidney dysfunction in hyperuricemic rats. Taurine could efficiently decrease the elevated xanthine oxidase activities in hyperuricemic rats, indicating its effect on the regulation of uric acid formation. The reabsorption and secretion of uric acid are dependent on a number of urate transporters. Expressions of three urate transporters were significantly down-regulated in hyperuricemic rats, while taurine prevented the decrease of mRNA and protein expression levels of these urate transporters. The results indicate that taurine might play a role in the regulation of renal uric acid excretion. Therefore, taurine could be a promising agent for the treatment of hyperuricemia. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Prevention and Therapy of Acute Kidney Injury in the Developing World

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    Vijay Kher

    2017-07-01

    Full Text Available Timely recognition of patients at risk or with possible acute kidney injury (AKI is essential for early intervention to minimize further damage and improve outcome. Initial management of patients with suspected and persistent AKI should include thorough clinical assessment of all patients with AKI to identify reversible factors, including fluid volume status, potential nephrotoxins, and an assessment of the underlying health of the kidney. Based on these assessments, early interventions to provide appropriate and adequate fluid resuscitation while avoiding fluid overload, removal of nephrotoxins, and adjustment of drug doses according to the level of kidney function derangement are important. The judicious use of diuretics for fluid overload and/or in cardiac decompensated patients and introduction of early enteral nutritional support need to be considered to improve outcomes in AKI. Although these basic principles are well recognized, their application in clinical practice in low resource settings is often limited due to lack of education, availability of resources, and lack of trained personnel, which limits access to care. We report the consensus recommendations of the 18th Acute Dialysis Quality Initiative meeting in Hyderabad, India, on strategies to evaluate patients with suspected AKI and initiate measures for prevention and management to improve outcomes, particularly in low resource settings. These recomendations provide a framework for caregivers, who are often primary care physicians, nurses, and other allied healthcare personnel, to manage patients with AKI in resource poor countries.

  6. Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin as prognostic markers in idiopathic membranous nephropathy.

    Science.gov (United States)

    Maas, Rutger Jh; van den Brand, Jan Ajg; Waanders, Femke; Meijer, Esther; Goor van, Harry; Peters, Hilde P; Hofstra, Julia M; Wetzels, Jack Fm

    2016-01-01

    Urinary excretion of alpha-1-microglobulin and beta-2-microglobulin reflects tubular damage and predicts outcome in patients with idiopathic membranous nephropathy with reasonable accuracy. Urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin are novel biomarkers of tubular damage. We investigated if these markers could improve prediction of outcome in idiopathic membranous nephropathy. We measured kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin in urine samples from patients with idiopathic membranous nephropathy, who had nephrotic proteinuria and normal renal function. Excretion of alpha-1-microglobulin and beta-2-microglobulin had been measured previously. Progression was defined as a serum creatinine rise >30%, a rise in serum creatinine to an absolute value of ≥135 µmol/L, or a clinical decision to start immunosuppressive therapy. Remission was defined as proteinuria 50% reduction from baseline. Sixty-nine patients were included. Median follow-up was 35 months (interquartile range 18-63 months). Progression occurred in 30 patients (44%), and spontaneous remission in 36 (52%). Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin excretion rates were significantly correlated with each other, and with alpha-1-microglobulin and beta-2-microglobulin. The areas under the receiver operating characteristic curves for progression were 0.75 (0.62-0.87) for kidney injury molecule-1 and 0.74 (0.62-0.87) for neutrophil gelatinase-associated lipocalin. In multivariate analysis with either alpha-1-microglobulin and beta-2-microglobulin, kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin did not independently predict outcome. Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin excretion rates correlated with excretion rates of other tubular damage markers and predicted outcome in patients with idiopathic membranous nephropathy. They did not add prognostic value

  7. Long-term Stability of Urinary Biomarkers of Acute Kidney Injury in Children.

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    Schuh, Meredith P; Nehus, Edward; Ma, Qing; Haffner, Christopher; Bennett, Michael; Krawczeski, Catherine D; Devarajan, Prasad

    2016-01-01

    Recent meta-analyses support the utility of urinary biomarkers for the diagnosis and prognosis of acute kidney injury. It is critical to establish optimal sample handling conditions for short-term processing and long-term urinary storage prior to widespread clinical deployment and meaningful use in prospective clinical trials. Prospective study. 80 children (median age, 1.1 [IQR, 0.5-4.2] years) undergoing cardiac surgery with cardiopulmonary bypass at our center. 50% of patients had acute kidney injury (defined as ≥50% increase in serum creatinine from baseline). We tested the effect on biomarker concentrations of short-term urine storage in ambient, refrigerator, and freezer conditions. We also tested the effects of multiple freeze-thaw cycles, as well as prolonged storage for 5 years. Urine concentrations of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), and interleukin 18 (IL-18). All biomarkers were measured using commercially available kits. All 3 biomarkers were stable in urine stored at 4°C for 24 hours, but showed significant degradation (5.6%-10.1% from baseline) when stored at 25°C. All 3 biomarkers showed only a small although significant decrease in concentration (0.77%-2.9% from baseline) after 3 freeze-thaw cycles. Similarly, all 3 biomarkers displayed only a small but significant decrease in concentration (0.84%-3.2%) after storage for 5 years. Only the 3 most widely studied biomarkers were tested. Protease inhibitors were not evaluated. Short-term storage of urine samples for measurement of NGAL, KIM-1, and IL-18 may be performed at 4°C for up to 24 hours, but not at room temperature. These urinary biomarkers are stable at -80°C for up to 5 years of storage. Our results are reassuring for the deployment of these assays as biomarkers in clinical practice, as well as in prospective clinical studies requiring long-term urine storage. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier

  8. Albumin administration is associated with acute kidney injury in cardiac surgery: a propensity score analysis.

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    Frenette, Anne Julie; Bouchard, Josée; Bernier, Pascaline; Charbonneau, Annie; Nguyen, Long Thanh; Rioux, Jean-Philippe; Troyanov, Stéphan; Williamson, David R

    2014-11-14

    The risk of acute kidney injury (AKI) with the use of albumin-containing fluids compared to starches in the surgical intensive care setting remains uncertain. We evaluated the adjusted risk of AKI associated with colloids following cardiac surgery. We performed a retrospective cohort study of patients undergoing on-pump cardiac surgery in a tertiary care center from 2008 to 2010. We assessed crystalloid and colloid administration until 36 hours after surgery. AKI was defined by the RIFLE (risk, injury, failure, loss and end-stage kidney disease) risk and Acute Kidney Injury Network (AKIN) stage 1 serum creatinine criterion within 96 hours after surgery. Our cohort included 984 patients with a baseline glomerular filtration rate of 72 ± 19 ml/min/1.73 m(2). Twenty-three percent had a reduced left ventricular ejection fraction (LVEF), thirty-one percent were diabetics and twenty-three percent underwent heart valve surgery. The incidence of AKI was 5.3% based on RIFLE risk and 12.0% based on the AKIN criterion. AKI was associated with a reduced LVEF, diuretic use, anemia, heart valve surgery, duration of extracorporeal circulation, hemodynamic instability and the use of albumin, pentastarch 10% and transfusions. There was an important dose-dependent AKI risk associated with the administration of albumin, which also paralleled a higher prevalence of concomitant risk factors for AKI. To address any indication bias, we derived a propensity score predicting the likelihood to receive albumin and matched 141 cases to 141 controls with a similar risk profile. In this analysis, albumin was associated with an increased AKI risk (RIFLE risk: 12% versus 5%, P = 0.03; AKIN stage 1: 28% versus 13%, P = 0.002). We repeated this methodology in patients without postoperative hemodynamic instability and still identified an association between the use of albumin and AKI. Albumin administration was associated with a dose-dependent risk of AKI and remained significant using a propensity

  9. Does hypokalemia contribute to acute kidney injury in chronic laxative abuse?

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    Eun-Young Lee

    2015-06-01

    Full Text Available Prolonged hypokalemia from chronic laxative abuse is recognized as the cause of chronic tubulointerstitial disease, known as “hypokalemic nephropathy,” but it is not clear whether it contributes to acute kidney injury (AKI. A 42-year-old woman with a history of chronic kidney disease as a result of chronic laxative abuse from a purging type of anorexia nervosa (AN-P, developed an anuric AKI requiring hemodialysis and a mild AKI 2 months later. Both episodes of AKI involved severe to moderate hypokalemia (1.2 and 2.7 mmol/L, respectively, volume depletion, and mild rhabdomyolysis. The histologic findings of the first AKI revealed the remnants of acute tubular necrosis with advanced chronic tubulointerstitial nephritis and ischemic glomerular injury. Along with these observations, the intertwined relationship among precipitants of recurrent AKI in AN-P is discussed, and then we postulate a contributory role of hypokalemia involved in the pathophysiology of the renal ischemia-induced AKI.

  10. Optical Spectroscopy Approach for the Predictive Assessment of Kidney Functional Recovery Following Ischemic Injury

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    Raman, R N; Pivetti, C D; Rubenchik, A M; Matthews, D L; Troppmann, C; Demos, S G

    2010-02-11

    Tissue that has undergone significant yet unknown amount of ischemic injury is frequently encountered in organ transplantation and trauma clinics. With no reliable real-time method of assessing the degree of injury incurred in tissue, surgeons generally rely on visual observation which is subjective. In this work, we investigate the use of optical spectroscopy methods as a potentially more reliable approach. Previous work by various groups was strongly suggestive that tissue autofluorescence from NADH obtained under UV excitation is sensitive to metabolic response changes. To test and expand upon this concept, we monitored autofluorescence and light scattering intensities of injured vs. uninjured rat kidneys via multimodal imaging under 355 nm, 325 nm, and 266 nm excitation as well as scattering under 500 nm illumination. 355 nm excitation was used to probe mainly NADH, a metabolite, while 266 nm excitation was used to probe mainly tryptophan to correct for non-metabolic signal artifacts. The ratio of autofluorescence intensities derived under these two excitation wavelengths was calculated and its temporal profile was fit to a relaxation model. Time constants were extracted, and longer time constants were associated with kidney dysfunction. Analysis of both the autofluorescence and light scattering images suggests that changes in microstructure tissue morphology, blood absorption spectral characteristics, and pH contribute to the behavior of the observed signal which may be used to obtain tissue functional information and offer predictive capability.

  11. Smad signaling pathway in pathogenesis of kidney injury induced by calcium oxalate stone in rats

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    Fan Zhang

    2016-10-01

    Full Text Available Objective: To investigate the involvement of Smad signaling pathway in the pathogenesis of kidney injury induced by calcium oxalate stone in rats to provide a reference for clinical treatment. Methods: Clean SD rats were randomly divided into 3 group, namely the control group, model group and pirfenidone group. Ethylene glycol + αhydroxy vitamin D3 was used as a stone-inducing agent to replicate the renal calcium oxalate stone model. Rats in the pirfenidone group were treated with pirfenidone intragastric administration. The serum Cr, BUN and 24-hour oxalate and calcium in renal tissues were assayed. The expressions of Bax/ Bcl2 protein, Caspase3 protein, TGFβ, Smad1, Smad2 and Smad3 proteins were detected by the fluorescent quantitation PCR method. Results: Compared with the rats of the control group, the results showed that the levels of serum BUN, Cr and 24-hour oxalate in rats of the model group were increased greatly, Bax and Caspase3 mRNA also increased while the level of Bcl2 decreased significantly, and the expressions of TGFβ, Smad1, Smad2 and Smad3 proteins increased distinctly as well (P<0.01. These abnormal parameters could be normalized effectively by pirfenidone. Conclusions: Activated TGFβ/Smad signaling pathway is involved in the pathogenesis of kidney injury induced by calcium oxalate stone in rats.

  12. Secreted Factors from Bone Marrow Stromal Cells Upregulate IL-10 and Reverse Acute Kidney Injury

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    Jack M. Milwid

    2012-01-01

    Full Text Available Acute kidney injury is a devastating syndrome that afflicts over 2,000,000 people in the US per year, with an associated mortality of greater than 70% in severe cases. Unfortunately, standard-of-care treatments are not sufficient for modifying the course of disease. Many groups have explored the use of bone marrow stromal cells (BMSCs for the treatment of AKI because BMSCs have been shown to possess unique anti-inflammatory, cytoprotective, and regenerative properties in vitro and in vivo. It is yet unresolved whether the primary mechanisms controlling BMSC therapy in AKI depend on direct cell infusion, or whether BMSC-secreted factors alone are sufficient for mitigating the injury. Here we show that BMSC-secreted factors are capable of providing a survival benefit to rats subjected to cisplatin-induced AKI. We observed that when BMSC-conditioned medium (BMSC-CM is administered intravenously, it prevents tubular apoptosis and necrosis and ameliorates AKI. In addition, we observed that BMSC-CM causes IL-10 upregulation in treated animals, which is important to animal survival and protection of the kidney. In all, these results demonstrate that BMSC-secreted factors are capable of providing support without cell transplantation, and the IL-10 increase seen in BMSC-CM-treated animals correlates with attenuation of severe AKI.

  13. Optical spectroscopy approach for the predictive assessment of kidney functional recovery following ischemic injury

    Science.gov (United States)

    Raman, Rajesh N.; Pivetti, Christopher D.; Rubenchik, Alexander M.; Matthews, Dennis L.; Troppmann, Christoph; Demos, Stavros G.

    2010-02-01

    Tissue that has undergone significant yet unknown amount of ischemic injury is frequently encountered in organ transplantation and trauma clinics. With no reliable real-time method of assessing the degree of injury incurred in tissue, surgeons generally rely on visual observation which is subjective. In this work, we investigate the use of optical spectroscopy methods as a potentially more reliable approach. Previous work by various groups was strongly suggestive that tissue autofluorescence from NADH obtained under UV excitation is sensitive to metabolic response changes. To test and expand upon this concept, we monitored autofluorescence and light scattering intensities of injured vs. uninjured rat kidneys via multimodal imaging under 355 nm, 325 nm, and 266 nm excitation as well as scattering under 500 nm illumination. 355 nm excitation was used to probe mainly NADH, a metabolite, while 266 nm excitation was used to probe mainly tryptophan to correct for non-metabolic signal artifacts. The ratio of autofluorescence intensities derived under these two excitation wavelengths was calculated and its temporal profile was fit to a relaxation model. Time constants were extracted, and longer time constants were associated with kidney dysfunction. Analysis of both the autofluorescence and light scattering images suggests that changes in microstructure tissue morphology, blood absorption spectral characteristics, and pH contribute to the behavior of the observed signal which may be used to obtain tissue functional information and offer predictive capability.

  14. Factors associated with mortality in a population with acute kidney injury undergoing hemodialysis in Peru

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    Percy Herrera-Añazco

    Full Text Available Abstract Introduction: Patients with acute kidney injury (AKI in developing countries are described in a profile of young age, with less comorbidities, with unifactorial, and with a lower mortality compared to patients in developed countries. Objective: To assess mortality in patients with acute kidney injury undergoing hemodialysis (HD and its associated factors in a developing country setting. Methods: Retrospective study. Demographic, clinical, and mortality variables were collected from patients who presented AKI and underwent HD between January 2014 and December 2015 at a national reference hospital in Lima, Peru. Risk ratios (RR and 95% confidence intervals (95%CI were estimated through Poisson regressions. Results: Data from 72 patients with AKI that underwent HD were analyzed, 66.7% of them were 8.9 mg/dL. The adjusted analysis showed that having had a creatinine level of > 8.9 mg/dL, compared to a creatinine level of < 5.2 mg/dL at the time of initiating HD, was associated with 74% less probability of death. Conclusion: Four out of every ten AKI patients undergoing HD die. Higher levels of creatinine were associated with lower probability of mortality.

  15. The Phenotypic Fate of Bone Marrow-Derived Stem Cells in Acute Kidney Injury

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    Guowei Feng

    2013-11-01

    Full Text Available Background: Despite increasing attention on the role of bone marrow derived stem cells in repair or rejuvenation of tissues and organs, cellular mechanisms of such cell-based therapy remain poorly understood. Methods: We reconstituted hematopoiesis in recipient C57BL/6J mice by transplanting syngeneic GFP+ bone marrow (BM cells. Subsequently, the recipients received subcutaneous injection of granulocyte-colony stimulating factor (G-CSF and were subjected to acute renal ischemic injury. Flow cytometry and immunostaining were performed at various time points to assess engraftment and phenotype of BM derived stem cells. Results: Administration of G-CSF increased the release of BM derived stem cells into circulation and enhanced the ensuing recruitment of BM derived stem cells into injured kidney. During the second month post injury, migrated BM derived stem cells lost hematopoietic phenotype (CD45 but maintained the expression of other markers (Sca-1, CD133 and CD44, suggesting their potential of transdifferentiation into renal stem cells. Moreover, G-CSF treatment enhanced the phenotypic conversion. Conclusion: Our work depicted a time-course dependent transition of phenotypic characteristics of BM derived stem cells, demonstrated the existence of BM derived stem cells in damaged kidney and revealed the effects of G-CSF on cell transdifferentiation.

  16. Are Urinary Tubular Injury Markers Useful in Chronic Kidney Disease? A Systematic Review and Meta Analysis.

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    Zhou, Le-Ting; Lv, Lin-Li; Pan, Ming-Ming; Cao, Yu-Han; Liu, Hong; Feng, Ye; Ni, Hai-Feng; Liu, Bi-Cheng

    2016-01-01

    Adverse outcome of chronic kidney disease, such as end stage renal disease, is a significant burden on personal health and healthcare costs. Urinary tubular injury markers, such as NGAL, KIM-1 and NAG, could provide useful prognostic value for the early identification of high-risk patients. However, discrepancies between recent large prospective studies have resulted in controversy regarding the potential clinical value of these markers. Therefore, we conducted the first meta-analysis to provide a more persuasive argument to this debate. In the current meta-analysis, based on ten prospective studies involving 29366 participants, we evaluated the role of urinary tubular injury markers (NGAL, KIM-1 and NAG) in predicting clinical outcomes including CKD stage 3, end stage renal disease and mortality. The prognostic values of these biomarkers were estimated using relative risks and 95% confidence interval in adjusted models. All risk estimates were normalized to those of 1 standard deviation increase in log-scale concentrations to minimize heterogeneity. Fixed-effects models were adopted to combine risk estimates. The quality of the research and between-study heterogeneity were evaluated. The level of research evidence was identified according to the GRADE profiler. uNGAL was identified as an independent risk predictor of ESRD (pooled adjusted relative risk: 1.40[1.21 to 1.61], pchronic kidney disease. A borderline significance of uKIM-1 in predicting CKD stage 3 independently in the community-based population was observed (pooled adjusted relative risk: 1.13[1.00 to 1.27], p = 0.057). Only the prognostic value of uNGAL for ESRD was supported by a grade B level of evidence. The concentration of uNGAL can be used in practice as an independent predictor of end stage renal disease among patients with chronic kidney disease, but it may be not useful in predicting disease progression to CKD stage 3 among community-based population.

  17. Definition, Management, and Outcomes of Acute Kidney Injury: An International Survey of Nephrologists.

    Science.gov (United States)

    Farooq, Umar; Tober, Aaron; Chinchilli, Vernon; Reeves, W Brian; Ghahramani, Nasrollah

    2017-12-01

    Acute kidney injury (AKI) is a complex disease burdened by uncertainties of definition, management strategies, and prognosis. This study explores the relationship between demographic characteristics of nephrologists and their perceptions about the definition, management, and follow-up of AKI. We developed a Web-based survey, the International Survey on Acute Kidney Injury (ISAKI), consisting of 29 items in 4 categories: (1) demographic and practice characteristics, (2) definition of AKI, (3) management of renal replacement therapy (RRT) in AKI, and (4) sequelae of AKI. A multivariable stepwise logistic regression model was used to examine relationships between the dependent variables and the demographic characteristics of the respondents. Responses from 743 nephrologists from 90 countries were analyzed. The majority (60%) of respondents reported using RIFLE and/or AKIN criteria regularly to define AKI, although US nephrologists were less likely to do so (OR: 0.58; 95% CI: 0.42-0.85). The most common initial RRT modality was intermittent hemodialysis (63.5%), followed by continuous RRT (23.8%). Faculty affiliation was associated with a higher likelihood of using a dialysis schedule of ≥4 times a week (OR: 1.75; 95% CI: 1.20-2.55). The respondents believed that a single episode of AKI increases the likelihood of development of chronic kidney disease (CKD) (55%), subsequent AKI (36%), and rapid progression of preexisting CKD (87%). US nephrologists were less likely to recommend follow-up after resolution of AKI (OR: 0.15; 95% CI: 0.07-0.33). Our findings highlight the need for a widely accepted consensus definition of AKI, a uniform approach to management, and improved follow-up after resolution of AKI episodes.

  18. Measurement of renal blood flow by phase-contrast magnetic resonance imaging during septic acute kidney injury: a pilot investigation.

    Science.gov (United States)

    Prowle, John R; Molan, Maurice P; Hornsey, Emma; Bellomo, Rinaldo

    2012-06-01

    In septic patients, decreased renal perfusion is considered to play a major role in the pathogenesis of acute kidney injury. However, the accurate measurement of renal blood flow in such patients is problematic and invasive. We sought to overcome such obstacles by measuring renal blood flow in septic patients with acute kidney injury using cine phase-contrast magnetic resonance imaging. Pilot observational study. University-affiliated general adult intensive care unit. Ten adult patients with established septic acute kidney injury and 11 normal volunteers. Cine phase-contrast magnetic resonance imaging measurement of renal blood flow and cardiac output. The median age of the study patients was 62.5 yrs and eight were male. At the time of magnetic resonance imaging, eight patients were mechanically ventilated, nine were on continuous hemofiltration, and five required vasopressors. Cine phase-contrast magnetic resonance imaging examinations were carried out without complication. Median renal blood flow was 482 mL/min (range 335-1137) in septic acute kidney injury and 1260 mL/min (range 791-1750) in healthy controls (p = .003). Renal blood flow indexed to body surface area was 244 mL/min/m2 (range 165-662) in septic acute kidney injury and 525 mL/min/m2 (range 438-869) in controls (p = .004). In patients with septic acute kidney injury, median cardiac index was 3.5 L/min/m2 (range 1.6-8.7), and median renal fraction of cardiac output was only 7.1% (range 4.4-10.8). There was no rank correlation between renal blood flow index and creatinine clearance in patients with septic acute kidney injury (r = .26, p = .45). Cine phase-contrast magnetic resonance imaging can be used to noninvasively and safely assess renal perfusion during critical illness in man. Near-simultaneous accurate measurement of cardiac output enables organ blood flow to be assessed in the context of the global circulation. Renal blood flow seems consistently reduced as a fraction of cardiac output in

  19. Acute Kidney Injury and Risk of Incident Heart Failure Among US Veterans.

    Science.gov (United States)

    Bansal, Nisha; Matheny, Michael E; Greevy, Robert A; Eden, Svetlana K; Perkins, Amy M; Parr, Sharidan K; Fly, James; Abdel-Kader, Khaled; Himmelfarb, Jonathan; Hung, Adriana M; Speroff, Theodore; Ikizler, T Alp; Siew, Edward D

    2018-02-01

    Acute kidney injury (AKI) is common and associated with poor outcomes. Heart failure is a leading cause of cardiovascular disease among patients with chronic kidney disease. The relationship between AKI and heart failure remains unknown and may identify a novel mechanistic link between kidney and cardiovascular disease. Observational study. We studied a national cohort of 300,868 hospitalized US veterans (2004-2011) without a history of heart failure. AKI was the predictor and was defined as a 0.3-mg/dL or 50% increase in serum creatinine concentration from baseline to the peak hospital value. Patients with and without AKI were matched (1:1) on 28 in- and outpatient covariates using optimal Mahalanobis distance matching. Incident heart failure was defined as 1 or more hospitalization or 2 or more outpatient visits with a diagnosis of heart failure within 2 years through 2013. There were 150,434 matched pairs in the study. Patients with and without AKI during the index hospitalization were well matched, with a median preadmission estimated glomerular filtration rate of 69mL/min/1.73m 2 . The overall incidence rate of heart failure was 27.8 (95% CI, 19.3-39.9) per 1,000 person-years. The incidence rate was higher in those with compared with those without AKI: 30.8 (95% CI, 21.8-43.5) and 24.9 (95% CI, 16.9-36.5) per 1,000 person-years, respectively. In multivariable models, AKI was associated with 23% increased risk for incident heart failure (HR, 1.23; 95% CI, 1.19-1.27). Study population was primarily men, reflecting patients seen at Veterans Affairs hospitals. AKI is an independent risk factor for incident heart failure. Future studies to identify underlying mechanisms and modifiable risk factors are needed. Copyright © 2017 National Kidney Foundation, Inc. All rights reserved.

  20. Superantigens are critical for Staphylococcus aureus Infective endocarditis, sepsis, and acute kidney injury.

    Science.gov (United States)

    Salgado-Pabón, Wilmara; Breshears, Laura; Spaulding, Adam R; Merriman, Joseph A; Stach, Christopher S; Horswill, Alexander R; Peterson, Marnie L; Schlievert, Patrick M

    2013-08-20

    Infective endocarditis and kidney infections are serious complications of Staphylococcus aureus sepsis. We investigated the role of superantigens (SAgs) in the development of lethal sepsis, infective endocarditis, and kidney infections. SAgs cause toxic shock syndrome, but it is unclear if SAgs contribute to infective endocarditis and kidney infections secondary to sepsis. We show in the methicillin-resistant S. aureus strain MW2 that lethal sepsis, infective endocarditis, and kidney infections in rabbits are critically dependent on high-level SAgs. In contrast, the isogenic strain lacking staphylococcal enterotoxin C (SEC), the major SAg in this strain, is attenuated in virulence, while complementation restores disease production. SAgs' role in infective endocarditis appears to be both superantigenicity and direct endothelial cell stimulation. Maintenance of elevated blood pressure by fluid therapy significantly protects from infective endocarditis, possibly through preventing bacterial accumulation on valves and increased SAg elimination. These data should facilitate better methods to manage these serious illnesses. The Centers for Disease Control and Prevention reported in 2007 that Staphylococcus aureus is the most significant cause of serious infectious diseases in the United States (R. M. Klevens, M. A. Morrison, J. Nadle, S. Petit, K. Gershman, et al., JAMA 298:1763-1771, 2007). Among these infections are sepsis, infective endocarditis, and acute kidney injury. Infective endocarditis occurs in 30 to 60% of patients with S. aureus bacteremia and carries a mortality rate of 40 to 50%. Over the past decades, infective endocarditis outcomes have not improved, and infection rates are steadily increasing (D. H. Bor, S. Woolhandler, R. Nardin, J. Brusch, D. U. Himmelstein, PLoS One 8:e60033, 2013). There is little understanding of the S. aureus virulence factors that are key for infective endocarditis development and kidney abscess formation. We demonstrate that

  1. Acute kidney injury in a shepherd with severe malaria: a case report

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    Boushab BM

    2016-10-01

    Full Text Available Boushab Mohamed Boushab,1 Fatim-Zahra Fall-Malick,2 Mamoudou Savadogo,3 Leonardo Kishi Basco,4 1Department of Internal Medicine, Aïoun Regional Hospital, Hodh El Gharbi, Mauritania; 2National Institute of Hepatology-Virology in Nouakchott, School of Medicine, Nouakchott, Mauritania; 3Department of Infectious Diseases, University Teaching Hospital Yalgado Ouédrago, Ouagadougou, Burkina Faso; 4Research Unit of Infectious and Tropical Diseases, Institut de Recherche pour le Développement (Research Institute for Development, Aix-Marseille University, Marseille, France Abstract: Malaria is one of the main reasons for outpatient consultation and hospitalization in Mauritania. Although four Plasmodium species, ie, Plasmodium (P. falciparum, P. vivax, P. malariae, and P. ovale, cause malaria in Mauritania, recent data on their frequency is ­lacking. Since infections with P. falciparum generally result in serious disease, their identification is important. We report a case of oliguric renal injury associated with malaria in a 65-year-old shepherd. Clinical manifestations included anemia, oliguria, and elevated creatinine and urea. The rapid diagnostic test for malaria and microscopic examination of blood smears were positive for P. falciparum. On the basis of this, the patient was diagnosed as having acute kidney injury as a complication of severe malaria. The patient was treated for malaria with intravenous quinine for 4 days, followed by 3 days of oral treatment. Volume expansion, antipyretic treatment, and diuretics were administered. He also had two rounds of dialysis after which he partially recovered renal function. This outcome is not always the rule. Prognosis depends much on early diagnosis and appropriate supportive treatment. Keywords: malaria, oliguric kidney injury, shepherd, quinine, dialysis

  2. Predicting renal recovery after liver transplant with severe pretransplant subacute kidney injury: The impact of warm ischemia time.

    Science.gov (United States)

    Laskey, Heather L; Schomaker, Nathan; Hung, Kenneth W; Asrani, Sumeet K; Jennings, Linda; Nydam, Trevor L; Gralla, Jane; Wiseman, Alex; Rosen, Hugo R; Biggins, Scott W

    2016-08-01

    Identifying which liver transplantation (LT) candidates with severe kidney injury will have a full recovery of renal function after liver transplantation alone (LTA) is difficult. Avoiding unnecessary simultaneous liver-kidney transplantation (SLKT) can optimize the use of scarce kidney grafts. Incorrect predictions of spontaneous renal recovery after LTA can lead to increased morbidity and mortality. We retrospectively analyzed all LTA patients at our institution from February 2002 to February 2013 (n = 583) and identified a cohort with severe subacute renal injury (n = 40; creatinine <2 mg/dL in the 14-89 days prior to LTA and not on renal replacement therapy [RRT] yet, ≥2 mg/dL within 14 days of LTA and/or on RRT). Of 40 LTA recipients, 26 (65%) had renal recovery and 14 (35%) did not. The median (interquartile range) warm ischemia time (WIT) in recipients with and without renal recovery after LTA was 31 minutes (24-46 minutes) and 39 minutes (34-49 minutes; P = 0.02), respectively. Adjusting for the severity of the subacute kidney injury with either Acute Kidney Injury Network or Risk, Injury, Failure, Loss, and End-Stage Kidney Disease criteria, increasing WIT was associated with lack of renal recovery (serum creatinine <2 mg/dL after LTA, not on RRT), with an odds ratio (OR) of 1.08 (1.01-1.16; P = 0.03) and 1.09 (1.01-1.17; P = 0.02), respectively. For each minute of increased WIT, there was an 8%-9% increase in the risk of lack of renal recovery after LTA. In a separate cohort of 98 LTA recipients with subacute kidney injury, we confirmed the association of WIT and lack of renal recovery (OR, 1.04; P = 0.04). In LT candidates with severe subacute renal injury, operative measures to minimize WIT may improve renal recovery potentially avoiding RRT and the need for subsequent kidney transplant. Liver Transplantation 22 1085-1091 2016 AASLD. © 2016 American Association for the Study of Liver Diseases.

  3. ET-1 deletion from endothelial cells protects the kidney during the extension phase of ischemia/reperfusion injury

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    Arfian, Nur [Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Emoto, Noriaki, E-mail: emoto@med.kobe-u.ac.jp [Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Department of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe (Japan); Vignon-Zellweger, Nicolas; Nakayama, Kazuhiko; Yagi, Keiko [Department of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe (Japan); Hirata, Ken-ichi [Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Ischemia/reperfusion injury (IRI) induced increased endothelin-1 (ET-1) expression. Black-Right-Pointing-Pointer IRI was accompanied by tubular injury and remodeling of renal arteries. Black-Right-Pointing-Pointer IRI increased oxidative stress and inflammation. Black-Right-Pointing-Pointer Genetic suppression of ET-1 in endothelial cells attenuates IRI in the kidney. Black-Right-Pointing-Pointer The mechanisms include the inhibition of oxidative stress and inflammation. -- Abstract: Background: The prognosis of patients after acute kidney injury (AKI) is poor and treatment is limited. AKI is mainly caused by renal ischemia/reperfusion injury (IRI). During the extension phase of IRI, endothelial damage may participate in ischemia and inflammation. Endothelin-1 (ET-1) which is mostly secreted by endothelial cells is an important actor of IRI, particularly through its strong vasoconstrictive properties. We aimed to analyze the specific role of ET-1 from the endothelial cells in AKI. Methods: We used mice lacking ET-1 in the vascular endothelial cells (VEETKO). We induced IRI in VEETKO mice and wild type controls by clamping both kidneys for 30 min. Sham operated mice were used as controls. Mice were sacrificed one day after IRI in order to investigate the extension phase of IRI. Kidney function was assessed based on serum creatinine concentration. Levels of expression of ET-1, its receptor ET{sub A}, protein kinase C, eNOS, E-Cadherin and inflammation markers were evaluated by real time PCR or western blot. Tubular injury was scored on periodic acid Schiff stained kidney preparations. Lumen and wall area of small intrarenal arteries were measured on kidney slices stained for alpha smooth muscle cell actin. Oxidative stress, macrophage infiltration and cell proliferation was evaluated on slices stained for 8-hydroxy-2 Prime -deoxyguanosine, F4/80 and PCNA, respectively. Results: IRI induced kidney failure and increased ET-1 and

  4. Evaluation of kidney repair capacity using 99mTc-DMSA in ischemia/reperfusion injury models.

    Science.gov (United States)

    Kwak, Wonjung; Jang, Hee-Seong; Belay, Takele; Kim, Jinu; Ha, Yeong Su; Lee, Sang Woo; Ahn, Byeong-Cheol; Lee, Jaetae; Park, Kwon Moo; Yoo, Jeongsoo

    2011-03-04

    Quantitative (99m)Tc-DMSA renal uptake was studied in different renal ischemia/reperfusion (I/R) mice models for the assessment of renal repair capacity. Mice models of nephrectomy, uni- and bi-lateral I/R together with sham-operated mice were established. At 1h, 1d, 4d, 1, 2 and 3 wk after I/R, (99m)Tc-DMSA (27.7 ± 1.3 MBq) was injected via tail vein and after 3h post-injection, the mice were scanned for 30 min with pinhole equipped gamma camera. Higher uptake of (99m)Tc-DMSA was measured in normal kidneys of uni-lateral I/R model and nephrectomized kidney I/R model at 3 wk post-surgery. Comparing the restoration capacities of the affected kidneys of nephrectomy, uni- and bi-lateral I/R models, higher repair capacity was observed in the nephrectomized model followed by bi-lateral then uni-lateral models. The normal kidney may retard the restoration of damaged kidney in uni-lateral I/R model. Moreover, 3 wk after Uni-I/R, the size of injured kidney was significantly smaller than non-ischemic contralateral and sham operated kidneys, while nephrectomy I/R kidneys were significantly enlarged compared to all others at 3 wk post-surgery. Very strong correlation between (99m)Tc-DMSA uptake and weight of dissected kidneys in I/R models was observed. Consistent with (99m)Tc-DMSA uptake results, all histological results indicate that kidney recovery after injury is correlated with the amount of intact tubules and kidney sizes. In summary, our study showed good potentials of (99m)Tc-DMSA scan as a promising non-invasive method for evaluation of kidney restoration after I/R injuries. Interestingly, mice with Bi-I/R injury showed faster repair capacity than those with uni-I/R. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Assessment of Worldwide Acute Kidney injury Epidemiology in Neonates (AWAKEN: Design of a Retrospective Cohort Study

    Directory of Open Access Journals (Sweden)

    Jennifer Garcia Jetton

    2016-07-01

    Full Text Available INTRODUCTION: Acute kidney injury (AKI affects ~30% of hospitalized neonates. Critical to advancing our understanding of neonatal AKI is collaborative research among neonatologists and nephrologists. The Neonatal Kidney Collaborative (NKC is an international, multidisciplinary group dedicated to investigating neonatal AKI. The AWAKEN study (Assessment of Worldwide Acute Kidney injury Epidemiology in Neonates was designed to describe the epidemiology of neonatal AKI, validate the definition of neonatal AKI, identify primary risk factors for neonatal AKI, and investigate the contribution of fluid management to AKI events and short term outcomes. METHODS and ANALYSIS: The NKC was established with at least one pediatric nephrologist and neonatologist from 24 institutions from 4 countries (USA, Canada, Australia, India. A Steering Committee and four subcommittees were created. The database subcommittee oversaw the development of the web-based database (MediData Rave™ that captured all NICU admissions from 1/1/14-3/31/14. Inclusion and exclusion criteria were applied to eliminate babies with a low likelihood of AKI. Data collection includes: 1 baseline demographic information; 2 daily physiologic parameters and care received during the first week of life; 3 weekly snapshots; 4 discharge information including growth parameters, final diagnoses, discharge medications and need for renal replacement therapy; and 5 all serum creatinine values. ETHICS and DISSEMINATION: AWAKEN was proposed as human subjects research. The study design allowed for a waiver of informed consent/parental permission. NKC investigators will disseminate data through peer-reviewed publications and educational conferences. DISCUSSION: The purpose of this publication is to describe the formation of the NKC, the establishment of the AWAKEN cohort and database, future directions and a few lessons learned. The AWAKEN database includes ~325 unique variables and >4 million discrete data

  6. Urinary protein profiles in ketorolac-associated acute kidney injury in patients undergoing orthopedic day surgery

    Directory of Open Access Journals (Sweden)

    Mariano F

    2017-09-01

    Full Text Available Filippo Mariano,1 Chiara Cogno,1 Fulvia Giaretta,2,3 Ilaria Deambrosis,2,3 Simona Pozza,4 Maurizio Berardino,5 Giuseppe Massazza,6 Luigi Biancone1,3 1Department of General and Specialist Medicine, Nephrology, Dialysis and Transplantation Unit, City of Health and Science, CTO Hospital, Turin, 2Department of General and Specialist Medicine, Laboratory of Nephrology and Immunopathology, City of Health and Science, Molinette Hospital, Turin, 3Department of Medical Sciences, University of Turin, Turin, 4Department of Radiology and Radiotherapy, CTO Radiology, City of Health and Science, CTO Hospital, Turin, 5Department of Anesthesiology and Intensive Care, Anesthesiology and Intensive Care 5, City of Health and Science, CTO Hospital, Turin, 6Department of Orthopedics and Traumatology, Week Hospital Unit, City of Health and Science, CTO Hospital, and University of Turin, Turin, Italy Background: Parenteral administration of ketorolac is very effective in controlling postoperative pain for orthopedic surgery. Ketorolac can induce clinically relevant renal alterations in elderly patients, whereas its short course is considered safe for young adults with normal preoperative renal function. In this study, of a cohort of young adults undergoing elective orthopedic day surgery, we sought cases complicated by readmission due to acute kidney injury (AKI.Patients and methods: Among 1397 young adults, aged 18–32 years who were admitted to undergo orthopedic day surgery from 2013 to 2015, four patients (0.29%, three males/one female treated in postprocedure with ketorolac (from 60 to 90 mg/day for 1–2 days were readmitted for suspected severe AKI. We evaluated functional outcome, urinary protein profiles and kidney biopsy (1 patient.Results: After day surgery discharge, they experienced gastrointestinal disturbances, flank pain and fever. Readmitted on post-surgery days 3–4, they presented with oliguric AKI (creatinine range 158.4–466.4 µmol/L and

  7. Ambulatory Care after Acute Kidney Injury: An Opportunity to Improve Patient Outcomes

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    Samuel A. Silver

    2015-10-01

    Full Text Available Purpose of review: Acute kidney injury (AKI is an increasingly common problem among hospitalized patients. Patients who survive an AKI-associated hospitalization are at higher risk of de novo and worsening chronic kidney disease, end-stage kidney disease, cardiovascular disease, and death. For hospitalized patients with dialysis-requiring AKI, outpatient follow-up with a nephrologist within 90 days of hospital discharge has been associated with enhanced survival. However, most patients who survive an AKI episode do not receive any follow-up nephrology care. This narrative review describes the experience of two new clinical programs to care for AKI patients after hospital discharge: the Acute Kidney Injury Follow-up Clinic for adults (St. Michael's Hospital and University Health Network, Toronto, Canada and the AKI Survivor Clinic for children (Cincinnati Children's Hospital, USA. Sources of information: MEDLINE, PubMed, ISI Web of Science Findings: These two ambulatory clinics have been in existence for close to two (adult and four (pediatric years, and were developed separately and independently in different populations and health systems. The components of both clinics are described, including the target population, referral process, medical interventions, patient education activities, and follow-up schedule. Common elements include targeting patients with KDIGO stage 2 or 3 AKI, regular audits of the inpatient nephrology census to track eligible patients, medication reconciliation, and education on the long-term consequences of AKI. Limitations: Despite the theoretical benefits of post-AKI follow-up and the clinic components described, there is no high quality evidence to prove that the interventions implemented in these clinics will reduce morbidity or mortality. Therefore, we also present a plan to evaluate the adult AKI Follow-up Clinic in order to determine if it can improve clinical outcomes compared to patients with AKI who do not

  8. Injuria renal aguda en la sepsis grave Acute kidney injury in severe sepsis

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    Hernán Trimarchi

    2009-06-01

    Full Text Available La sepsis afecta al 40% de los pacientes críticos, siendo su mortalidad de aproximadamente un 30% en el caso de la sepsis grave, y de 75% con injuria renal aguda, la cual sucede en el 20-51% de los casos. Se realizó un estudio prospectivo, observacional, longitudinal, en 80 pacientes sépticos graves en el lapso de 1 año para determinar el desarrollo de injuria renal aguda y su relación con la mortalidad; correlacionar antecedentes clínicos y variaciones del laboratorio con la mortalidad; determinar la tasa de mortalidad de la sepsis grave; relacionar óbito y foco séptico primario; evaluar la predictibilidad de mortalidad según niveles de creatinina de ingreso y sus variaciones finales. Se definieron dos grupos: Obito (n = 25 y No-óbito (n = 55. Analizados según la creatinina de ingreso, 39 tenían valores normales de creatinina (10 óbitos y 41 la presentaban elevada (15 óbitos; según la creatinina de egreso, 48 presentaron creatinina normal y fallecieron 7, mientras que 32 tenían daño renal agudo, de los cuales 18 fallecieron. De los 25 pacientes fallecidos, el 72% presentaron daño renal. De éstos, 7 pacientes vivos y 2 fallecidos requirieron hemodiálisis. El foco primario más frecuente fue el respiratorio (26.4%. El desarrollo de daño renal es un alto predictor de mortalidad en la sepsis, independientemente de los valores iniciales de creatinina. Edad más avanzada, hipertensión arterial, score APACHE más elevado, anemia más grave, hipoalbuminemia, hiperfosfatemia e hiperkalemia se asociaron a mayor mortalidad. La mortalidad global fue 31.3%. La imposibilidad de identificar el foco séptico primario se asoció a mayor mortalidad. El foco respiratorio se relacionó a mayor riesgo de requerir hemodiálisis.Sepsis affects 40% of critically ill patients, with a reported mortality of approximately 30% in severe sepsis, raising to 75% when acute kidney injury ensues, which occurs in about 20-51% of cases. The present study

  9. Rhabdomyolysis-Induced Acute Kidney Injury Under Hypoxia and Deprivation of Food and Water

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    Jingwen Wang

    2013-10-01

    Full Text Available Background: To investigate the renal pathophysiologyin rhabdomyolysis-induced acute kidney injury (AKI in rats under hypoxia and deprivation of food and water (HDFW, thus broadening the knowledge about rhabdomyolysis-induced AKI in massive earthquake. Methods: Male Wistar rats weighing 200-230g were randomized into control, rhabdomyolysis (R, HDFW and rhabdomyolysis in combination with HDFW (R/HDFW group. Experimental rhabdomyolysis rat model was established through clamping hind limb muscles, HDFW model rats were kept in 10% hypoxic chamber unavailable to food and water. At 1, 3, 5, 7, 9, 11d after treatment, serum creatinine (Scr level, renal index, renal structural changes and cell apoptosis were analyzed. Results: After R, HDFW, R/HDFW treatment, the animals showed significantly higher Scr levels than the control group. Renal index in R and R/HDFW groups elevated remarkably compared with that in control and HDFW group. The results of histopathology, ultra-structure and apoptosis assay suggested that rhabdomyolysis caused renal tubular injury, HDFW treatment resulted in renal vascular dilation, tissue congestion and tubular cell damage. In addition, more severe renal lesion appeared in R/HDFW. Conclusions: We conclude that the association of experimental rhabdomyolysis with HDFW results in a different functional and histological pattern. The rhabdomyolysis-HDFW combination causes more severe renal injury.

  10. Clinical Impact of Speed Variability to Identify Ultramarathon Runners at Risk for Acute Kidney Injury.

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    Sen-Kuang Hou

    Full Text Available Ultramarathon is a high endurance exercise associated with a wide range of exercise-related problems, such as acute kidney injury (AKI. Early recognition of individuals at risk of AKI during ultramarathon event is critical for implementing preventative strategies.To investigate the impact of speed variability to identify the exercise-related acute kidney injury anticipatively in ultramarathon event.This is a prospective, observational study using data from a 100 km ultramarathon in Taipei, Taiwan. The distance of entire ultramarathon race was divided into 10 splits. The mean and variability of speed, which was determined by the coefficient of variation (CV in each 10 km-split (25 laps of 400 m oval track were calculated for enrolled runners. Baseline characteristics and biochemical data were collected completely 1 week before, immediately post-race, and one day after race. The main outcome was the development of AKI, defined as Stage II or III according to the Acute Kidney Injury Network (AKIN criteria. Multivariate analysis was performed to determine the independent association between variables and AKI development.26 ultramarathon runners were analyzed in the study. The overall incidence of AKI (in all Stages was 84.6% (22 in 26 runners. Among these 22 runners, 18 runners were determined as Stage I, 4 runners (15.4% were determined as Stage II, and none was in Stage III. The covariates of BMI (25.22 ± 2.02 vs. 22.55 ± 1.96, p = 0.02, uric acid (6.88 ± 1.47 vs. 5.62 ± 0.86, p = 0.024, and CV of speed in specific 10-km splits (from secondary 10 km-split (10th - 20th km-split to 60th - 70th km-split were significantly different between runners with or without AKI (Stage II in univariate analysis and showed discrimination ability in ROC curve. In the following multivariate analysis, only CV of speed in 40th - 50th km-split continued to show a significant association to the development of AKI (Stage II (p = 0.032.The development of exercise

  11. [Augmented reality for image guided therapy (ARIGT) of kidney tumor during nephron sparing surgery (NSS): animal model and clinical approach].

    Science.gov (United States)

    Drewniak, Tomasz; Rzepecki, Maciej; Juszczak, Kajetan; Kwiatek, Wojciech; Bielecki, Jakub; Zieliński, Krzysztof; Ruta, Andrzej; Czekierda, Łukasz; Moczulskis, Zbigniew

    2011-01-01

    The main problem in nephron sparing surgery (NSS) is to preserve renal tumors oncological purity during the removal of the tumor with a margin of macroscopically unchanged kidney tissue while keeping the largest possible amount of normal parenchyma of the operated kidney. The development of imaging techniques, in particular IGT (Image Guided Therapy) allows precise imaging of the surgical field and, therefore, is essential in improving the effectiveness of NSS (increase of nephron sparing with the optimal radicality). The aim of this study was to develop a method of the three-dimensional (3D) imaging of the kidney tumor and its lodge in the operated kidney using 3D laser scanner during NSS procedure. Additionally, the animal model of visualization was developed. The porcine kidney model was used to test the set built up with HD cameras and linear laser scanner connected to a laptop with graphic software (David Laser Scanner, Germany) showing the surface of the kidney and the lodge after removal the chunk of renal parenchyma. Additionally, the visualization and reconstruction was performed on animal porcine model. Moreover, 5 patients (3 women, 2 men) aged from 37 to 68 years (mean 56), diagnosed with kidney tumors in CT scans with a diameter of 3.7-6.9 cm (mean 4.9) were operated in our Department this year, scanning the surface during the treatment with the kidney tumor and kidney tumor after it is removed with a margin of renal tissue. In one case, the lodge of removed tumor was scanned. Dimensions in 3D reconstruction images of laser scans in the study of animal model and the images obtained intraoperatively were compared with the dimensions evaluated during preoperative CT scans, intraoperative measurements. Three-dimensional imaging laser scanner operating field loge resected tumor and the tumor on the kidney of animal models and during NSS treatments for patients with kidney tumors is possible in real time with an accuracy of -2 mm do +9 mm (+/- 3 mm). The

  12. Community-Acquired Acute Kidney Injury: A Nationwide Survey in China.

    Science.gov (United States)

    Wang, Yafang; Wang, Jinwei; Su, Tao; Qu, Zhen; Zhao, Minghui; Yang, Li

    2017-05-01

    This study aimed to describe the burden of community-acquired acute kidney injury (AKI) in China based on a nationwide survey about AKI. Cross-sectional and retrospective study. A national sample of 2,223,230 hospitalized adult patients from 44 academic/local hospitals in Mainland China was used. AKI was defined according to the 2012 KDIGO AKI creatinine criteria or an increase or decrease in serum creatinine level of 50% during the hospital stay. Community-acquired AKI was identified when a patient had AKI that could be defined at hospital admission. The rate, cause, recognition, and treatment of community-acquired AKI were stratified according to hospital type, latitude, and economic development of the regions in which the patients were admitted. All-cause in-hospital mortality and recovery of kidney function at hospital discharge. 4,136 patients with community-acquired AKI were identified during the 2 single-month snapshots (January 2013 and July 2013). Of these, 2,020 (48.8%) had cases related to decreased kidney perfusion; 1,111 (26.9%), to intrinsic kidney disease; and 499 (12.1%), to urinary tract obstruction. In the north versus the south, more patients were exposed to nephrotoxins or had urinary tract obstructions. 536 (13.0%) patients with community-acquired AKI had indications for renal replacement therapy (RRT), but only 347 (64.7%) of them received RRT. Rates of timely diagnosis and appropriate use of RRT were higher in regions with higher per capita gross domestic product. All-cause in-hospital mortality was 7.3% (295 of 4,068). Delayed AKI recognition and being located in northern China were independent risk factors for in-hospital mortality, and referral to nephrology providers was an independent protective factor. Possible misclassification of AKI and community-acquired AKI due to nonstandard definitions and missing data for serum creatinine. The features of community-acquired AKI varied substantially in different regions of China and were closely

  13. Acute kidney injury in liver transplant candidates : A position paper on behalf of the Liver Intensive Care Group of Europe

    NARCIS (Netherlands)

    Angeli, Paolo; Bezinover, Dimitri; Biancofiore, Gianni; Bienholz, Anja; Findlay, James; Paugam Burtz, Catherine; Reyntjens, Koen; Sakai, Tetsuro; Saner, Fuat H; Tomescu, Dana; Wagener, Gebhard; Weiss, Emmanuel

    INTRODUCTION: Acute kidney injury is associated with high mortality in the perioperative period of liver transplantation. The aim of this position paper was to provide an up-to-date overview with special emphases on diagnosis, risk factors, and treatment. EVIDENCE ACQUISITION: The Liver Intensive

  14. A comparison of early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury

    DEFF Research Database (Denmark)

    Karvellas, Constantine J; Farhat, Maha R; Sajjad, Imran

    2011-01-01

    Introduction: Our aim was to investigate the impact of early versus late initiation of renal replacement therapy (RRT) on clinical outcomes in critically ill patients with acute kidney injury (AKI). Methods: Systematic review and meta-analysis were used in this study. PUBMED, EMBASE, SCOPUS, Web ...

  15. A Meta-analysis of the Association of Estimated GFR, Albuminuria, Diabetes Mellitus, and Hypertension With Acute Kidney Injury

    NARCIS (Netherlands)

    James, Matthew T.; Grams, Morgan E.; Woodward, Mark; Elley, C. Raina; Green, Jamie A.; Wheeler, David C.; de Jong, Paul; Gansevoort, Ron T.; Levey, Andrew S.; Warnock, David G.; Sarnak, Mark J.; de Zeeuw, Dick; Bakker, Stephan J. L.; van der Harst, Pim; Heerspink, Hiddo J.

    2015-01-01

    Background: Diabetes mellitus and hypertension are risk factors for acute kidney injury (AKI). Whether estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (ACR) remain risk factors for AKI in the presence and absence of these conditions is uncertain. Study Design:

  16. Human mesenchymal stem cells alter macrophage phenotype and promote regeneration via homing to the kidney following ischemia-reperfusion injury

    NARCIS (Netherlands)

    Wise, Andrea F; Williams, Timothy M; Kiewiet, Mensiena B G; Payne, Natalie L; Siatskas, Christopher; Samuel, Chrishan S; Ricardo, Sharon D

    2014-01-01

    Mesenchymal stem cells (MSCs) ameliorate injury and accelerate repair in many organs, including the kidney, although the reparative mechanisms and interaction with macrophages have not been elucidated. This study investigated the reparative potential of human bone marrow-derived MSCs and traced

  17. N-octanoyl dopamine treatment exerts renoprotective properties in acute kidney injury but not in renal allograft recipients

    NARCIS (Netherlands)

    Klotz, Sarah; Pallavi, Prama; Tsagogiorgas, Charalambos; Zimmer, Fabian; Zoellner, Frank G.; Binzen, Uta; Greffrath, Wolfgang; Treede, Rolf-Detlef; Walter, Jakob; Harmsen, Martin C.; Kraemer, Bernhard K.; Hafner, Mathias; Yard, Benito A.; Hoeger, Simone

    N-octanoyl dopamine (NOD) treatment improves renal function when applied to brain dead donors and in the setting of warm ischaemia-induced acute kidney injury (AKI). Because it also activates transient receptor potential vanilloid type 1 (TRPV1) channels, we first assessed if NOD conveys its

  18. National Guidelines «Acute Kidney Injury: Basic Principles of the Diagnosis, Prevention and Treatment (2015» Part I

    Directory of Open Access Journals (Sweden)

    A.V. Smirnov

    2016-04-01

    Full Text Available The main problems of acute kidney injury (AKI are considered. The necessity of introduction of the AKI concept into the practice of national health care is justified. Specific recommendations for the diagnosis, monitoring, prevention and treatment of this dangerous condition are given.

  19. Peritoneal dialysis vs. haemodialysis in the management of paediatric acute kidney injury in Kano, Nigeria: a cost analysis.

    Science.gov (United States)

    Obiagwu, Patience N; Abdu, Aliyu

    2015-01-01

    To determine the cost of the dialytic management of paediatric acute kidney injury in a low-income country. All children under the age of 15 years, who had either peritoneal dialysis or haemodialysis for acute kidney injury in Aminu Kano Teaching Hospital over a 1-year period, were studied. The average cost of each dialysis modality was estimated. Of 20 children, who had dialysis for acute kidney injury, 12 (60%) had haemodialysis and 8 (40%) had peritoneal dialysis. The mean cost for haemodialysis exceeded that of peritoneal dialysis ($363.33 vs. $311.66, t = 1.04, P = 0.313) with the mean cost of consumables significantly accounting for most of the cost variation ($248.49 vs. $164.73, t = 2.91, P = 0.009). Mean costs of nephrologist visit and nursing were not found to be significant. Peritoneal dialysis is the less costly alternative for managing acute kidney injury in children in our environment. © 2014 John Wiley & Sons Ltd.

  20. Nuclear DNA as Predictor of Acute Kidney Injury in Patients Undergoing Coronary Artery Bypass Graft: A Pilot Study.

    Science.gov (United States)

    Likhvantsev, Valery V; Landoni, Giovanni; Grebenchikov, Oleg A; Skripkin, Yuri V; Zabelina, Tatiana S; Zinovkina, Liudmila A; Prikhodko, Anastasia S; Lomivorotov, Vladimir V; Zinovkin, Roman A

    2017-12-01

    To measure the release of plasma nuclear deoxyribonucleic acid (DNA) and to assess the relationship between nuclear DNA level and acute kidney injury occurrence in patients undergoing cardiac surgery. Cardiovascular anesthesiology and intensive care unit of a large tertiary-care university hospital. Prospective observational study. Fifty adult patients undergoing cardiac surgery. Nuclear DNA concentration was measured in the plasma. The relationship between the level of nuclear DNA and the incidence of acute kidney injury after coronary artery bypass grafting was investigated. Cardiac surgery leads to significant increase in plasma nuclear DNA with peak levels 12 hours after surgery (median [interquartile range] 7.0 [9.6-22.5] µg/mL). No difference was observed between off-pump and on-pump surgical techniques. Nuclear DNA was the only predictor of acute kidney injury between baseline and early postoperative risk factors. The authors found an increase of nuclear DNA in the plasma of patients who had undergone coronary artery bypass grafting, with a peak after 12 hours and an association of nuclear DNA with postoperative acute kidney injury. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. A model-specific role of microRNA-223 as a mediator of kidney injury during experimental sepsis.

    Science.gov (United States)

    Colbert, James F; Ford, Joshay A; Haeger, Sarah M; Yang, Yimu; Dailey, Kyrie L; Allison, Kristen C; Neudecker, Viola; Evans, Christopher M; Richardson, Vanessa L; Brodsky, Kelley S; Faubel, Sarah; Eltzschig, Holger K; Schmidt, Eric P; Ginde, Adit A

    2017-08-01

    Sepsis outcomes are heavily dependent on the development of septic organ injury, but no interventions exist to interrupt or reverse this process. microRNA-223 (miR-223) is known to be involved in both inflammatory gene regulation and host-pathogen interactions key to the pathogenesis of sepsis. The goal of this study was to determine the role of miR-223 as a mediator of septic kidney injury. Using miR-223 knockout mice and multiple models of experimental sepsis, we found that miR-223 differentially influences acute kidney injury (AKI) based on the model used. In the absence of miR-223, mice demonstrated exaggerated AKI in sterile models of sepsis (LPS injection) and attenuated AKI in a live-infection model of sepsis (cecal ligation and puncture). We demonstrated that miR-223 expression is induced in kidney homogenate after cecal ligation and puncture, but not after LPS or fecal slurry injection. We investigated additional potential mechanistic explanations including differences in peritoneal bacterial clearance and host stool virulence. Our findings highlight the complex role of miR-223 in the pathogenesis of septic kidney injury, as well as the importance of differences in experimental sepsis models and their consequent translational applicability. Copyright © 2017 the American Physiological Society.

  2. Blood transfusion improves renal oxygenation and renal function in sepsis-induced acute kidney injury in rats

    NARCIS (Netherlands)

    L. Zafrani (Lara); B. Ergin (Bulent); Kapucu, A. (Aysegul); C. Ince (Can)

    2016-01-01

    textabstractBackground: The effects of blood transfusion on renal microcirculation during sepsis are unknown. This study aimed to investigate the effect of blood transfusion on renal microvascular oxygenation and renal function during sepsis-induced acute kidney injury. Methods: Twenty-seven Wistar

  3. Blood transfusion improves renal oxygenation and renal function in sepsis-induced acute kidney injury in rats

    NARCIS (Netherlands)

    Zafrani, Lara; Ergin, Bulent; Kapucu, Aysegul; Ince, Can

    2016-01-01

    The effects of blood transfusion on renal microcirculation during sepsis are unknown. This study aimed to investigate the effect of blood transfusion on renal microvascular oxygenation and renal function during sepsis-induced acute kidney injury. Twenty-seven Wistar albino rats were randomized into

  4. Timing of renal replacement therapy and clinical outcomes in critically ill patients with severe acute kidney injury

    NARCIS (Netherlands)

    Bagshaw, Sean M.; Uchino, Shigehiko; Bellomo, Rinaldo; Morimatsu, Hiroshi; Morgera, Stanislao; Schetz, Miet; Tan, Ian; Bouman, Catherine; Macedo, Ettiene; Gibney, Noel; Tolwani, Ashita; Oudemans-van Straaten, Heleen M.; Ronco, Claudio; Kellum, John A.; French, Craig; Mulder, John; Pinder, Mary; Roberts, Brigit; Botha, John; Mudholkar, Pradeen; Holt, Andrew; Hunt, Tamara; Honoré, Patrick Maurice; Clerbaux, Gaetan; Schetz, Miet Maria; Wilmer, Alexander; Yu, Luis; Macedo, Ettiene V.; Laranja, Sandra Maria; Rodrigues, Cassio José; Suassuna, José Hermógenes Rocco; Ruzany, Frederico; Campos, Bruno; Leblanc, Martine; Senécal, Lynne; Gibney, R. T. Noel; Johnston, Curtis; Brindley, Peter; Tan, Ian K. S.; Chen, Hui De; Wan, Li; Rokyta, Richard; Krouzecky, Ales; Neumayer, Hans-Helmut; Detlef, Kindgen-Milles; Mueller, Eckhard; Tsiora, Vicky; Sombolos, Kostas; Mustafa, Iqbal; Suranadi, Iwayan; Bar-Lavie, Yaron; Nakhoul, Farid; Ceriani, Roberto; Bortone, Franco; Zamperetti, Nereo; Pappalardo, Federico; Marino, Giovanni; Calabrese, Prospero; Monaco, Francesco; Liverani, Chiara; Clementi, Stefano; Coltrinari, Rosanna; Marini, Benedetto; Fuke, Nobuo; Miyazawa, Masaaki; Katayama, Hiroshi; Kurasako, Toshiaki; Hirasaw, Hiroyuki; Oda, Shigeto; Tanigawa, Koichi; Tanaka, Keiichi; Oudemans-van Straaten, Helena Maria; de Pont, Anne-Cornelie J. M.; Bugge, Jan Frederik; Riddervold, Fridtjov; Nilsen, Paul Age; Julsrud, Joar; Teixeira e Costa, Fernando; Marcelino, Paulo; Serra, Isabel Maria; Yaroustovsky, Mike; Grigoriyanc, Rachik; Lee, Kang Hoe; Loo, Shi; Singh, Kulgit; Barrachina, Ferran; Llorens, Julio; Sanchez-Izquierdo-Riera, Jose Angel; Toral-Vazquez, Darío; Wizelius, Ivar; Hermansson, Dan; Gaspert, Tomislav; Maggiorini, Marco; Davenport, Andrew; Lombardi, Raúl; Llopart, Teresita; Venkataraman, Ramesh; Kellum, John; Murray, Patrick; Trevino, Sharon; Benjamin, Ernest; Hufanda, Jerry; Paganini, Emil; Warnock, David; Guirguis, Nabil

    2009-01-01

    The aim of this study is to evaluate the relationship between timing of renal replacement therapy (RRT) in severe acute kidney injury and clinical outcomes. This was a prospective multicenter observational study conducted at 54 intensive care units (ICUs) in 23 countries enrolling 1238 patients.

  5. A comparison of observed versus estimated baseline creatinine for determination of RIFLE class in patients with acute kidney injury

    NARCIS (Netherlands)

    Bagshaw, Sean M.; Uchino, Shigehiko; Cruz, Dinna; Bellomo, Rinaldo; Morimatsu, Hiroshi; Morgera, Stanislao; Schetz, Miet; Tan, Ian; Bouman, Catherine; Macedo, Etienne; Gibney, Noel; Tolwani, Ashita; Oudemans-van Straaten, Heleen M.; Ronco, Claudio; Kellum, John A.; French, Craig; Mulder, John; Pinder, Mary; Roberts, Brigit; Botha, John; Mudholkar, Pradeen; Holt, Andrew; Hunt, Tamara; Honoré, Patrick Maurice; Clerbaux, Gaetan; Schetz, Miet Maria; Wilmer, Alexander; Yu, Luis; Macedo, Ettiene V.; Laranja, Sandra Maria; Rodrigues, Cassio José; Suassuna, José Hermógenes Rocco; Ruzany, Frederico; Campos, Bruno; Leblanc, Martine; Senécal, Lynne; Gibney, R. T. Noel; Johnston, Curtis; Brindley, Peter; Tan, Ian K. S.; Chen, Hui De; Wan, Li; Rokyta, Richard; Krouzecky, Ales; Neumayer, Hans-Helmut; Detlef, Kindgen-Milles; Mueller, Eckhard; Tsiora, Vicky; Sombolos, Kostas; Mustafa, Iqbal; Suranadi, Iwayan; Bar-Lavie, Yaron; Nakhoul, Farid; Ceriani, Roberto; Bortone, Franco; Zamperetti, Nereo; Pappalardo, Federico; Marino, Giovanni; Calabrese, Prospero; Monaco, Francesco; Liverani, Chiara; Clementi, Stefano; Coltrinari, Rosanna; Marini, Benedetto; Fuke, Nobuo; Miyazawa, Masaaki; Katayama, Hiroshi; Kurasako, Toshiaki; Hirasawa, Hiroyuki; Oda, Shigeto; Tanigawa, Koichi; Tanaka, Keiichi; Oudemans-van Straaten, Helena Maria; de Pont, Anne-Cornelie J. M.; Bugge, Jan Frederik; Riddervold, Fridtjov; Nilsen, Paul Age; Julsrud, Joar; Teixeira e Costa, Fernando; Marcelino, Paulo; Serra, Isabel Maria; Yaroustovsky, Mike; Grigoriyanc, Rachik; Lee, Kang Hoe; Loo, Shi; Singh, Kulgit; Barrachina, Ferran; Llorens, Julio; Sanchez-Izquierdo-Riera, Jose Angel; Toral-Vazquez, Darío; Wizelius, Ivar; Hermansson, Dan; Gaspert, Tomislav; Maggiorini, Marco; Davenport, Andrew; Lombardi, Raúl; Llopart, Teresita; Venkataraman, Ramesh; Kellum, John; Murray, Patrick; Trevino, Sharon; Benjamin, Ernest; Hufanda, Jerry; Paganini, Emil; Warnock, David; Guirguis, Nabil

    2009-01-01

    The RIFLE classification scheme for acute kidney injury (AKI) is based on relative changes in serum creatinine (SCr) and on urine output. The SCr criteria, therefore, require a pre-morbid baseline value. When unknown, current recommendations are to estimate a baseline SCr by the MDRD equation.

  6. A case of severe acute kidney injury by near-drowning.

    Science.gov (United States)

    Seong, Eun Young; Rhee, Harin; Lee, Naria; Lee, Sung Jun; Song, Sang Heon; Lee, Dong Won; Lee, Soo Bong; Sol, Mee Young; Kwak, Ihm Soo

    2012-02-01

    Acute kidney injury (AKI) secondary to near-drowning is rarely described and poorly understood. Only few cases of severe isolated AKI resulting from near-drowning exist in the literature. We report a case of near-drowning who developed to isolated AKI due to acute tubular necrosis (ATN) requiring dialysis. A 21-yr-old man who recovered from near-drowning in freshwater 3 days earlier was admitted to our hospital with anuria and elevated level of serum creatinine. He needed five sessions of hemodialysis and then renal function recovered spontaneously. Renal biopsy confirmed ATN. We review the existing literature on near-drowning-induced AKI and discuss the possible pathogenesis.

  7. First presentation of Addison's disease as hyperkalaemia in acute kidney injury.

    Science.gov (United States)

    Maki, Sara; Kramarz, Caroline; Maria Heister, Paula; Pasha, Kamran

    2016-05-11

    Addison's disease is a rare endocrine disorder that frequently presents with non-specific symptoms, but may deteriorate rapidly into life-threatening Addisonian crisis if left untreated. Diagnosis can be difficult in patients without a suggestive medical history. We describe a case of a 37-year-old man who was admitted with acute kidney injury and hyperkalaemia, resistant to treatment with insulin/dextrose and calcium gluconate. On clinical examination, he was found to be hyperpigmented; a subsequent random serum cortisol of 49 nmol/L affirmed the preliminary diagnosis of Addison's disease. The patient's hyperkalaemia improved on treatment with hydrocortisone, and a follow-up morning adrenocorticotropic hormone of 1051 ng/L confirmed the diagnosis. 2016 BMJ Publishing Group Ltd.

  8. Forced fluid removal in intensive care patients with acute kidney injury

    DEFF Research Database (Denmark)

    Berthelsen, R E; Perner, A; Jensen, A K

    2018-01-01

    /or continuous renal replacement therapy aiming at net negative fluid balance > 1 mL/kg ideal body weight/hour until cumulative fluid balance calculated from ICU admission reached less than 1000 mL. RESULTS: After 20 months, we stopped the trial prematurely due to a low inclusion rate with 23 (2%) included...... patients out of the 1144 screened. Despite the reduced sample size, we observed a marked reduction in cumulative fluid balance 5 days after randomisation (mean difference -5814 mL, 95% CI -2063 to -9565, P = .003) with forced fluid removal compared to standard care. While the trial was underpowered...... for clinical endpoints, no point estimates suggested harm from forced fluid removal. CONCLUSIONS: Forced fluid removal aiming at 1 mL/kg ideal body weight/hour may be an effective treatment of fluid accumulation in ICU patients with acute kidney injury. A definitive trial using our inclusion criteria seems...

  9. Autophagy sequesters damaged lysosomes to control lysosomal biogenesis and kidney injury.

    Science.gov (United States)

    Maejima, Ikuko; Takahashi, Atsushi; Omori, Hiroko; Kimura, Tomonori; Takabatake, Yoshitsugu; Saitoh, Tatsuya; Yamamoto, Akitsugu; Hamasaki, Maho; Noda, Takeshi; Isaka, Yoshitaka; Yoshimori, Tamotsu

    2013-08-28

    Diverse causes, including pathogenic invasion or the uptake of mineral crystals such as silica and monosodium urate (MSU), threaten cells with lysosomal rupture, which can lead to oxidative stress, inflammation, and apoptosis or necrosis. Here, we demonstrate that lysosomes are selectively sequestered by autophagy, when damaged by MSU, silica, or the lysosomotropic reagent L-Leucyl-L-leucine methyl ester (LLOMe). Autophagic machinery is recruited only on damaged lysosomes, which are then engulfed by autophagosomes. In an autophagy-dependent manner, low pH and degradation capacity of damaged lysosomes are recovered. Under conditions of lysosomal damage, loss of autophagy causes inhibition of lysosomal biogenesis in vitro and deterioration of acute kidney injury in vivo. Thus, we propose that sequestration of damaged lysosomes by autophagy is indispensable for cellular and tissue homeostasis.

  10. Acute Kidney Injury Recognition in Low- and Middle-Income Countries

    Directory of Open Access Journals (Sweden)

    Jorge Cerdá

    2017-07-01

    Full Text Available Acute kidney injury (AKI is increasingly common around the world. Because of the low availability of effective therapies and resource limitations, early preventive and therapeutic measures are essential to decrease morbidity, mortality, and cost. Timely recognition and diagnosis of AKI requires a heightened degree of suspicion in the appropriate clinical and environmental context. In low- and middle-income countries (LMICs, early detection is impaired by limited resources and low awareness. In this article, we report the consensus recommendations of the 18th Acute Dialysis Quality Initiative meeting in Hyderabad, India, on how to improve recognition of AKI. We expect these recommendations will lead to an earlier and more accurate diagnosis of AKI, and improved research to promote a better understanding of the epidemiology, etiology, and histopathology of AKI in LMICs.

  11. Arterial pressure during cardiopulmonary bypass is not associated with acute kidney injury

    DEFF Research Database (Denmark)

    Kandler, K; Jensen, M E; Nilsson, J C

    2015-01-01

    BACKGROUND: Acute kidney injury (AKI) after cardiac surgery is common and is associated with increased mortality. We wanted to investigate if the arterial pressure or the use of norepinephrine during cardiopulmonary bypass were associated with AKI. METHODS: A retrospective analysis of patients who...... underwent coronary artery bypass grafting with or without concomitant procedures was conducted. AKI was defined using the RIFLE criteria. Data on arterial pressure and use of norepinephrine during cardiopulmonary bypass were entered in a binary logistic regression model to control for possible perioperative...... and in higher amounts, during cardiopulmonary bypass, in patients who developed AKI. These differences in arterial pressures and use of norepinephrine between the groups were not found to be significant when entered in the binary logistic regression model. CONCLUSION: No independent relationship between...

  12. High cut-off membranes in acute kidney injury and continuous renal replacement therapy.

    Science.gov (United States)

    Ricci, Zaccaria; Romagnoli, Stefano; Ronco, Claudio

    2017-11-24

    Innovation in continuous renal replacement therapies (CRRT) utilized to treat acute kidney injury (AKI) and sepsis, has brought new machines and techniques. Part of these new advances are due to the availability of innovative biomaterials and the construction of membranes with larger pores and wide distribution of pore sizes. This includes the creation of a new generation of high cut-off membranes whose utilization in clinical practice is promising for the wide spectrum of solutes that are removed during extracorporeal therapies.However, the enlargement of pore diameters brings some loss of albumin during treatment and this effect is still under evaluation, since there is a possibility that this is detrimental for the patient. A thorough review of the available clinical literature is reported in this paper with a reappraisal of the potential application of these new technologies.

  13. Heart block and acute kidney injury due to hyperparathyroidism-induced hypercalcemic crisis.

    Science.gov (United States)

    Brown, Taylor C; Healy, James M; McDonald, Mary J; Hansson, Joni H; Quinn, Courtney E

    2014-12-01

    We describe a patient who presented with multi-system organ failure due to extreme hypercalcemia (serum calcium 19.8 mg/dL), resulting from primary hyperparathyroidism. He was found to have a 4.8 cm solitary atypical parathyroid adenoma. His course was complicated by complete heart block, acute kidney injury, and significant neurocognitive disturbances. Relevant literature was reviewed and discussed. Hyperparathyroidism-induced hypercalcemic crisis (HIHC) is a rare presentation of primary hyperparathyroidism and only a small minority of these patients develop significant cardiac and renal complications. In cases of HIHC, a multidisciplinary effort can facilitate rapid treatment of life-threatening hypercalcemia and definitive treatment by surgical resection. As such, temporary transvenous cardiac pacing and renal replacement therapy can provide a life-saving bridge to definitive parathyroidectomy in cases of HIHC.

  14. Testing Danegaptide Effects on Kidney Function after Ischemia/Reperfusion Injury in a New Porcine Two Week Model.

    Directory of Open Access Journals (Sweden)

    Chris Amdisen

    Full Text Available Ischemia/reperfusion injury (I/R-I is a leading cause of acute kidney injury (AKI and is associated with increased mortality. Danegaptide is a selective modifier of the gap junction protein connexion 43. It has cytoprotective as well as anti-arrhythmic properties and has been shown to reduce the size of myocardial infarct in pigs. The aim of this study was to investigate the ischemia-protective effect of Danegaptide in a porcine renal I/R-I model with two weeks follow up.Unilateral renal I/R-I was induced in pigs by clamping the left renal artery over a two hour period. The model allowed examination of renal blood flow by magnetic resonance imaging (MRI and the measurement of single kidney GFR two weeks after injury. Eleven animals were randomized to Danegaptide-infusion while nine animals received placebo. Kidney histology and urinary neutrophil gelatinase-associated lipocalin (NGAL excretion were included as markers of AKI.Unilateral kidney I/R-I resulted in an immediate ~50% GFR reduction, associated with a four-fold increase in urinary NGAL-excretion. Fourteen days after I/R-I, the total GFR was ~75% of baseline with a significantly lower GFR in the injured left kidney compared to the right kidney. No differences in GFR were observed between the treated and non-treated animals immediately after I/R-I or at Day 14. Furthermore, no differences were observed in the urinary excretion of NGAL, renal blood flow or other markers of renal function.As expected this porcine renal I/R-I model was associated with reduced GFR two weeks after injury. Danegaptide did not improve renal function after I/R-I.

  15. Experimental chronic kidney disease attenuates ischemia-reperfusion injury in an ex vivo rat lung model.

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    Chung-Kan Peng

    Full Text Available Lung ischemia reperfusion injury (LIRI is one of important complications following lung transplant and cardiopulmonary bypass. Although patients on hemodialysis are still excluded as lung transplant donors because of the possible effects of renal failure on the lungs, increased organ demand has led us to evaluate the influence of chronic kidney disease (CKD on LIRI. A CKD model was induced by feeding Sprague-Dawley rats an adenine-rich (0.75% diet for 2, 4 and 6 weeks, and an isolated rat lung in situ model was used to evaluate ischemia reperfusion (IR-induced acute lung injury. The clinicopathological parameters of LIRI, including pulmonary edema, lipid peroxidation, histopathological changes, immunohistochemistry changes, chemokine CXCL1, inducible nitric oxide synthase (iNOS, proinflammatory and anti-inflammatory cytokines, heat shock protein expression, and nuclear factor-κB (NF-κB activation were determined. Our results indicated that adenine-fed rats developed CKD as characterized by increased blood urea nitrogen and creatinine levels and the deposition of crystals in the renal tubules and interstitium. IR induced a significant increase in the pulmonary arterial pressure, lung edema, lung injury scores, the expression of CXCL1 mRNA, iNOS level, and protein concentration of the bronchial alveolar lavage fluid (BALF. The tumor necrosis factor-α levels in the BALF and perfusate; the interleukin-10 level in the perfusate; and the malondialdehyde levels in the lung tissue and perfusate were also significantly increased by LIRI. Counterintuitively, adenine-induced CKD significantly attenuated the severity of lung injury induced by IR. CKD rats exhibited increased heat shock protein 70 expression and decreased activation of NF-κB signaling. In conclusion, adenine-induced CKD attenuated LIRI by inhibiting the NF-κB pathway.

  16. Acute Kidney Injury in Patients on SGLT2 Inhibitors: A Propensity-Matched Analysis.

    Science.gov (United States)

    Nadkarni, Girish N; Ferrandino, Rocco; Chang, Alexander; Surapaneni, Aditya; Chauhan, Kinsuk; Poojary, Priti; Saha, Aparna; Ferket, Bart; Grams, Morgan E; Coca, Steven G

    2017-11-01

    Sodium-glucose cotransporter-2 (SGLT2) inhibitors are new medications that improve cardiovascular and renal outcomes in patients with type 2 diabetes (T2D). However, the Food and Drug Administration has issued alerts regarding increased acute kidney injury (AKI) risk with canagliflozin and dapagliflozin. We aimed to assess the real-world risk of AKI in new SGLT2 inhibitor users in two large health care utilization cohorts of patients with T2D. We used longitudinal data from the Mount Sinai chronic kidney disease registry and the Geisinger Health System cohort. We selected SGLT inhibitor users and nonusers (patients with T2D without SGLT2 inhibitor prescription). We determined AKI by the KDIGO (Kidney Disease: Improving Global Outcomes) definition (AKI KDIGO ). We performed 1:1 nearest-neighbor propensity matching and calculated unadjusted hazard ratios (HRs) and adjusted HRs (aHRs; accounting for covariates poorly balanced) for AKI in primary and sensitivity analyses. We identified 377 SGLT2 inhibitor users and 377 nonusers in the Mount Sinai cohort, of whom 3.8 and 9.7%, respectively, had an AKI KDIGO event over a median follow-up time of 14 months. The unadjusted hazards of AKI KDIGO were 60% lower in users (HR 0.4 [95% CI 0.2-0.7]; P = 0.01), which was unchanged (aHR 0.4 [95% CI 0.2-0.7]; P = 0.004) postadjustment. Similarly, we identified 1,207 SGLT2 inhibitor users and 1,207 nonusers in the Geisinger cohort, of whom 2.2 and 4.6% had an AKI KDIGO event. AKI KDIGO unadjusted hazards were lower in users (HR 0.5 [95% CI 0.3-0.8]; P SGLT2 inhibitor use in patients with T2D in two large health systems. © 2017 by the American Diabetes Association.

  17. Renal ultrasound provides low utility in evaluating cardiac surgery associated acute kidney injury.

    Science.gov (United States)

    Young, Allen; Crawford, Todd; Pierre, Alejandro Suarez; Trent Magruder, J; Fraser, Charles; Conte, John; Whitman, Glenn; Sciortino, Christopher

    2017-09-02

    Renal ultrasonography is part of the algorithm in assessing acute kidney injury (AKI). The purpose of this study was to assess the clinical utility of renal US in postoperative cardiac patients who develop AKI. We conducted a retrospective study of 90 postoperative cardiac surgery patients at a single institution from 1/19/2010 to 3/19/2016 who underwent renal US for AKI. We reviewed provider documentation to determine whether renal US changed management. We defined change as: administration of crystalloid or colloid, addition of inotropic or vasopressor, or procedural interventions on the renal system. Mean age of study patients was 68 ± 13 years. 48/90 patients (53.3%) had pre-existing chronic kidney disease of varying severity. 48 patients (53.3%) had normal renal US with incidental findings and 31 patients (34.4%) had US evidence of medical kidney disease. 10 patients (11.1%) had limited US results due to poor visualization and 1 patient (1.1%) had mild right-sided hydronephrosis. No patients were found to have obstructive uropathy or renal artery stenosis. Clinical management was altered in only 4/90 patients (4.4%), which included 3 patients that received a fluid bolus and 1 patient that received a fluid bolus and inotropes. No vascular or urologic procedures resulted from US findings. Although renal ultrasound is often utilized in the work-up of AKI, our study shows that renal US provides little benefit in managing postoperative cardiac patients. This diagnostic modality should be scrutinized rather than viewed as a universal measure in the cardiac surgery population.

  18. A Direct Comparison between Norepinephrine and Phenylephrine for Augmenting Spinal Cord Perfusion in a Porcine Model of Spinal Cord Injury.

    Science.gov (United States)

    Streijger, Femke; So, Kitty; Manouchehri, Neda; Gheorghe, Ana; Okon, Elena B; Chan, Ryan M; Ng, Benjamin; Shortt, Katelyn; Sekhon, Mypinder S; Griesdale, Donald E; Kwon, Brian K

    2018-03-28

    Current clinical guidelines recommend elevating the mean arterial blood pressure (MAP) to increase spinal cord perfusion in patients with acute spinal cord injury (SCI). This is typically achieved with vasopressors such as norepinephrine (NE) and phenylephrine (PE). These drugs differ in their pharmacological properties and potentially have different effects on spinal cord blood flow (SCBF), oxygenation (PO 2 ), and downstream metabolism after injury. Using a porcine model of thoracic SCI, we evaluated how these vasopressors influenced intraparenchymal SCBF, PO 2 , hydrostatic pressure, and metabolism within the spinal cord adjacent to the injury site. Yorkshire pigs underwent a contusion/compression SCI at T10 and were randomized to receive either NE or PE for MAP elevation of 20 mm Hg, or no MAP augmentation. Prior to injury, a combined SCBF/PO 2 sensor, a pressure sensor, and a microdialysis probe were inserted into the spinal cord adjacent to T10 at two locations: a "proximal" site and a "distal" site, 2 mm and 22 mm from the SCI, respectively. At the proximal site, NE and PE resulted in little improvement in SCBF during cord compression. Following decompression, NE resulted in increased SCBF and PO 2 , whereas decreased levels were observed for PE. However, both NE and PE were associated with a gradual decrease in the lactate to pyruvate (L/P) ratio after decompression. PE was associated with greater hemorrhage through the injury site than that in control animals. Combined, our results suggest that NE promotes better restoration of blood flow and oxygenation than PE in the traumatically injured spinal cord, thus providing a physiological rationale for selecting NE over PE in the hemodynamic management of acute SCI.

  19. Metabolic acidosis as a risk factor for the development of acute kidney injury and hospital mortality.

    Science.gov (United States)

    Hu, Jiachang; Wang, Yimei; Geng, Xuemei; Chen, Rongyi; Xu, Xialian; Zhang, Xiaoyan; Lin, Jing; Teng, Jie; Ding, Xiaoqiang

    2017-05-01

    Metabolic acidosis has been proved to be a risk factor for the progression of chronic kidney disease, but its relation to acute kidney injury (AKI) has not been investigated. In general, a diagnosis of metabolic acidosis is based on arterial blood gas (ABG) analysis, but the diagnostic role of carbon dioxide combining power (CO 2 CP) in the venous blood may also be valuable to non-respiratory patients. This retrospective study included all adult non-respiratory patients admitted consecutively to our hospital between October 01, 2014 and September 30, 2015. A total of 71,089 non-respiratory patients were included, and only 4,873 patients were evaluated by ABG analysis at admission. In patients with ABG, acidosis, metabolic acidosis, decreased HCO 3 - and hypocapnia at admission was associated with the development of AKI, while acidosis and hypocapnia were independent predictors of hospital mortality. Among non-respiratory patients, decreased CO 2 CP at admission was an independent risk factor for AKI and hospital mortality. ROC curves indicated that CO 2 CP was a reasonable biomarker to exclude metabolic acidosis, dual and triple acid-base disturbances. The effect sizes of decreased CO 2 CP on AKI and hospital mortality varied according to age and different underlying diseases. Metabolic acidosis is an independent risk factor for the development of AKI and hospital mortality. In non-respiratory patient, decreased CO 2 CP is also an independent contributor to AKI and mortality and can be used as an indicator of metabolic acidosis.

  20. Urine neutrophil gelatinase-associated lipocalin (NGAL as a biomarker for acute canine kidney injury

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    Lee Ya-Jane

    2012-12-01

    Full Text Available Abstract Background Biomarkers for the early prediction of canine acute kidney injury (AKI are clinically important. Recently, neutrophil gelatinase-associated lipocalin (NGAL was found to be a sensitive biomarker for the prediction of human AKI at a very early stage and the development of AKI after surgery. However, NGAL has not yet been studied with respect to dog kidney diseases. The application of NGAL canine AKI was investigated in this study. Results The canine NGAL gene was successfully cloned and expressed. Polyclonal antibodies against canine NGAL were generated and used to develop an ELISA for measuring NGAL protein in serum and urine samples that were collected from 39 dogs at different time points after surgery. AKI was defined by the standard method, namely a serum creatinine increase of greater than or equal to 26.5 μmol/L from baseline within 48 h. At 12 h after surgery, compared to the group without AKI (12 dogs, the NGAL level in the urine of seven dogs with AKI was significantly increased (median 178.4 pg/mL vs. 88.0 pg/mL, and this difference was sustained to 72 h. Conclusion As the increase in NGAL occurred much earlier than the increase in serum creatinine, urine NGAL seems to be able to serve as a sensitive and specific biomarker for the prediction of AKI in dogs.

  1. Inverse association between serum creatinine and mortality in acute kidney injury.

    Science.gov (United States)

    de Souza, Sergio Pinto; Matos, Rodrigo Santos; Barros, Luisa Leite; Rocha, Paulo Novis

    2014-01-01

    Sepsis is a leading precipitant of Acute Kidney Injury (AKI) in intensive care unit (ICU) patients, and is associated with a high mortality rate. We aimed to evaluate the risk factors for dialysis and mortality in a cohort of AKI patients of predominantly septic etiology. Adult patients from an ICU for whom nephrology consultation was requested were included. End-stage chronic renal failure and kidney transplant patients were excluded. 114 patients were followed. Most had sepsis (84%), AKIN stage 3 (69%) and oliguria (62%) at first consultation. Dialysis was performed in 66% and overall mortality was 70%. Median serum creatinine in survivors and non-survivors was 3.95 mg/dl (2.63 - 5.28) and 2.75 mg/dl (1.81 - 3.69), respectively. In the multivariable models, oliguria and serum urea were positively associated with dialysis; otherwise, a lower serum creatinine at first consultation was independently associated with higher mortality. In a cohort of septic AKI, oliguria and serum urea were the main indications for dialysis. We also described an inverse association between serum creatinine and mortality. Potential explanations for this finding include: delay in diagnosis, fluid overload with hemodilution of serum creatinine or poor nutritional status. This finding may also help to explain the low discriminative power of general severity scores - that assign higher risks to higher creatinine levels - in septic AKI patients.

  2. [Clinical characteristic of patients with acute kidney injury complicated severe cardio-vascular diseases].

    Science.gov (United States)

    Wróbel, Paweł; Wyrwicz-Zielińska, Grażyna; Krzysztonek-Weber, Izabela; Sułowicz, Władysław

    2016-01-01

    Patients with cardiovascular diseases are a group of increased risk of acute kidney injury (AKI). Mortality in this group of patients with AKI, especially treated in intensive care units, is very high. The aim of this study was to evaluate the clinical characteristic of patients with AKI complicated severe cardiovascular diseases. Retrospective evaluation of 246 questionnaire of patients with AKI in the course of severe cardiovascular diseases treated in the wards of nephrological profile from the malopolska and podkarpackie voivodships in the years 2000-2011 was performed. The group of patients consisted of 157 men and 89 women, with mean age 67.9 ± 14.8 years. The most common cause of AKI were: acute decompensated heart failure--24 (9.8%), chronic decompensated heart failure--94 (38.2%), cardiac arrest--29 (11.8%), myocardial infarction--48 (19.5%), CABG--12 (4.9%), cardiac valve implantation--14 (5.7), heart transplantation--4 (1.6%) and aortic aneurysm--21 (8.5%). Age distribution of patients with AKI revealed that most numerous group had 71-80 years. The most of patients (95.9%) with AKI were treated with hemodialysis. The mortality rate in the study group was very high (69.5%). Recovery of renal function was observed in 39 (27.3%) of patients. Signs of kidney disease before AKI was noted in 116 (47.2%) of patients. Patients with severe cardiovascular complications and AKI had high mortality rate instead of performed hemodialysis treatment.

  3. Acute kidney injury and hyperbilirubinemia in a young male after ingestion of Tribulus terrestris.

    Science.gov (United States)

    Ryan, Margaret; Lazar, Ira; Nadasdy, Gyongyi M; Nadasdy, Tibor; Satoskar, Anjali A

    2015-03-01

    Acute tubular necrosis (ATN), especially from toxic injury is frequently accompanied by tubular casts and crystals. Myeloma casts, myoglobin, red blood cell and granular casts are well described. However, bile casts in tubules are rarely seen. We describe a case of Tribulus terrestris toxicity in a young healthy male, presenting with severe hyperbilirubinemia followed by acute renal failure and bile containing casts in the tubules. Tribulus terrestris is an herb often used by athletes as a nutritional supplement for performance enhancement. Although it is thought to be relatively safe, serious side effects have been reported before. Our aim is to increase awareness of the potential toxicities of performance enhancing herbal medications. These are often sold over-the-counter and therefore casually used, especially by young healthy individuals. Beneficial effects are controversial. Under-reporting by patients and infrequent documentation by health-care providers can delay diagnosis. We elaborately describe the kidney biopsy findings in Tribulus terrestris toxicity, and also provide a concise overview of the spectrum of tubular casts and their staining patterns, found in various kidney diseases.

  4. Clinical Course of Acute Kidney Injury in Elderly Individuals Above 80 Years

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    Isabell Funk

    2016-12-01

    Full Text Available Background/Aims: Aging is associated with renal function decline and elderly patients are more vulnerable to acute kidney injury (AKI. The causes and prognosis of AKI according to new KDIGO definition that broadened the diagnosis and included more patients without dialysis dependence have not yet been compared between younger and elderly patients. Methods: In a retrospective analysis all patients with AKI admitted to a tertiary care Nephrology department (N=424 were included. Individuals were stratified by age (≤80 years, >80 years. Primary end-point was death or dialysis dependence at hospital discharge, secondary analyses addressed the need for dialysis, creatinine at discharge, mortality, and length of stay. Results: The distribution of AKI causes was different between the age groups. Circulatory AKI was the most important cause in both groups; however, septic or toxic AKI contributed relevantly in younger patients. Nevertheless, the number of patients reaching the primary end-point was similar (younger, 20.4%; older, 18.0%; OR 1.17, 95%CI, 0.703-1.948. While mortality tended to be higher in the older population, none of the secondary analyses indicated worse outcome for the older patients. Conclusion: The prognosis of AKI in elderly patients is not necessarily worse than in middle aged individuals. Nevertheless, older patients may be particularly vulnerable to circulatory or ischemic insults of the kidneys.

  5. Inverse association between serum creatinine and mortality in acute kidney injury

    Directory of Open Access Journals (Sweden)

    Sergio Pinto de Souza

    2014-12-01

    Full Text Available Introduction: Sepsis is a leading precipitant of Acute Kidney Injury (AKI in intensive care unit (ICU patients, and is associated with a high mortality rate. Objective: We aimed to evaluate the risk factors for dialysis and mortality in a cohort of AKI patients of predominantly septic etiology. Methods: Adult patients from an ICU for whom nephrology consultation was requested were included. End-stage chronic renal failure and kidney transplant patients were excluded. Results: 114 patients were followed. Most had sepsis (84%, AKIN stage 3 (69% and oliguria (62% at first consultation. Dialysis was performed in 66% and overall mortality was 70%. Median serum creatinine in survivors and non-survivors was 3.95 mg/dl (2.63 - 5.28 and 2.75 mg/dl (1.81 - 3.69, respectively. In the multivariable models, oliguria and serum urea were positively associated with dialysis; otherwise, a lower serum creatinine at first consultation was independently associated with higher mortality. Conclusion: In a cohort of septic AKI, oliguria and serum urea were the main indications for dialysis. We also described an inverse association between serum creatinine and mortality. Potential explanations for this finding include: delay in diagnosis, fluid overload with hemodilution of serum creatinine or poor nutritional status. This finding may also help to explain the low discriminative power of general severity scores - that assign higher risks to higher creatinine levels - in septic AKI patients.

  6. INTRA-ABDOMINAL HYPERTENSION AS A RISK FACTOR FOR ACUTE KIDNEY INJURY IN CRITICALLY ILL PATIENTS

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    Sreelatha

    2016-05-01

    Full Text Available BACKGROUND AND AIMS Increased intra-abdominal pressure (IAP, also referred to as intra-abdominal hypertension (IAH, affects organ function in critically ill patients. The prevalence of IAH is between 32% - 65% in intensive care units. Normal IAP is ≈ 5–7 mmHg. According to WSACS definition, IAH = IAP ≥12 mmHg and is divided into 4 grades. They are Grade I (12-15 mmHg, Grade II (16-20 mmHg, Grade III (21-25 mmHg, Grade IV (>25 mmHg. Transvesical measurement of IAP currently is the most popular technique. Several systems with or without the need for electronic equipment are available that allow IAP measurement. The aim is to study the incidence of IAH in critically ill patients, to assess the risk factors for development of IAH, to study the role of IAH as a risk factor for Acute Kidney Injury (AKI, to assess the role of IAH as a risk factor for increased (Intensive Care Unit ICU mortality. SUBJECTS AND METHODS This is a prospective observational study. Study period was six months. The study included 52 patients admitted to Medical ICU in Government Medical College, Kozhikode, Kerala. RESULTS AND CONCLUSION There was a very high incidence of intra-abdominal hypertension in critically ill patients. IAH was significantly associated with risk factors like sepsis, mechanical ventilation, pancreatitis, capillary leak, ascites, cumulative fluid balance and cirrhosis. IAH is an independent risk factor for development of acute kidney injury. IAH is an independent predictor of mortality in critically ill patients.

  7. Acute kidney injury and edaravone in acute ischemic stroke: the Fukuoka Stroke Registry.

    Science.gov (United States)

    Kamouchi, Masahiro; Sakai, Hironori; Kiyohara, Yutaka; Minematsu, Kazuo; Hayashi, Kunihiko; Kitazono, Takanari

    2013-11-01

    A free radical scavenger, edaravone, which has been used for the treatment of ischemic stroke, was reported to cause acute kidney injury (AKI) as a fatal adverse event. The aim of the present study was to clarify whether edaravone is associated with AKI in patients with acute ischemic stroke. From the Fukuoka Stroke Registry database, 5689 consecutive patients with acute ischemic stroke who were hospitalized within 24 hours of the onset of symptoms were included in this study. A logistic regression analysis for the Fukuoka Stroke Registry cohort was done to identify the predictors for AKI. A propensity score-matched nested case-control study was also performed to elucidate any association between AKI and edaravone. Acute kidney injury occurred in 128 of 5689 patients (2.2%) with acute ischemic stroke. A multivariate analysis revealed that the stroke subtype, the basal serum creatinine level, and the presence of infectious complications on admission were each predictors of developing AKI. In contrast, a free radical scavenger, edaravone, reduced the risk of developing AKI (multivariate-adjusted odds ratio [OR] .45, 95% confidence interval [CI] .30-.67). Propensity score-matched case-control study confirmed that edaravone use was negatively associated with AKI (propensity score-adjusted OR .46, 95% CI .29-.74). Although AKI has a significant impact on the clinical outcome of hospital inpatients, edaravone has a protective effect against the development of AKI in patients with acute ischemic stroke. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  8. Two acute kidney injury risk scores for critically ill cancer patients undergoing non-cardiac surgery.

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    Xing, Xue-Zhong; Wang, Hai-Jun; Huang, Chu-Lin; Yang, Quan-Hui; Qu, Shi-Ning; Zhang, Hao; Wang, Hao; Gao, Yong; Xiao, Qing-Ling; Sun, Ke-Lin

    2012-01-01

    Several risk scoures have been used in predicting acute kidney injury (AKI) of patients undergoing general or specific operations such as cardiac surgery. This study aimed to evaluate the use of two AKI risk scores in patients who underwent non-cardiac surgery but required intensive care. The clinical data of patients who had been admitted to ICU during the first 24 hours of ICU stay between September 2009 and August 2010 at the Cancer Institute, Chinese Academy of Medical Sciences & Peking Union Medical College were retrospectively collected and analyzed. AKI was diagnosed based on the acute kidney injury network (AKIN) criteria. Two AKI risk scores were calculated: Kheterpal and Abelha factors. The incidence of AKI was 10.3%. Patients who developed AKI had a increased ICU mortality of 10.9% vs. 1.0% and an in-hospital mortality of 13.0 vs. 1.5%, compared with those without AKI. There was a significant difference between the classification of Kheterpal's AKI risk scores and the occurrence of AKI (PAbelha's AKI risk scores and the occurrence of AKI (P=0.499). Receiver operating characteristic curves demonstrated an area under the curve of 0.655±0.043 (P=0.001, 95% confidence interval: 0.571-0.739) for Kheterpal's AKI risk score and 0.507±0.044 (P=0.879, 95% confidence interval: 0.422-0.592) for Abelha's AKI risk score. Kheterpal's AKI risk scores are more accurate than Abelha's AKI risk scores in predicting the occurrence of AKI in patients undergoing non-cardiac surgery with moderate predictive capability.

  9. Urinary biomarkers TIMP-2 and IGFBP7 early predict acute kidney injury after major surgery.

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    Ivan Gocze

    Full Text Available To assess the ability of the urinary biomarkers IGFBP7 (insulin-like growth factor-binding protein 7 and TIMP-2 (tissue inhibitor of metalloproteinase 2 to early predict acute kidney injury (AKI in high-risk surgical patients.Postoperative AKI is associated with an increase in short and long-term mortality. Using IGFBP7 and TIMP-2 for early detection of cellular kidney injury, thus allowing the early initiation of renal protection measures, may represent a new concept of evaluating renal function.In this prospective study, urinary [TIMP-2]×[IGFBP7] was measured in surgical patients at high risk for AKI. A predefined cut-off value of [TIMP-2]×[IGFBP7] >0.3 was used for assessing diagnostic accuracy. Perioperative characteristics were evaluated, and ROC analyses as well as logistic regression models of risk assessment were calculated with and without a [TIMP-2]×[IGFBP7] test.107 patients were included in the study, of whom 45 (42% developed AKI. The highest median values of biomarker were detected in septic, transplant and patients after hepatic surgery (1.24 vs 0.45 vs 0.47 ng/l²/1000. The area under receiving operating characteristic curve (AUC for the risk of any AKI was 0.85, for early use of RRT 0.83 and for 28-day mortality 0.77. In a multivariable model with established perioperative risk factors, the [TIMP-2]×[IGFBP7] test was the strongest predictor of AKI and significantly improved the risk assessment (p<0.001.Urinary [TIMP-2]×[IGFBP7] test sufficiently detect patients with risk of AKI after major non-cardiac surgery. Due to its rapid responsiveness it extends the time frame for intervention to prevent development of AKI.

  10. Cardiac-surgery associated acute kidney injury requiring renal replacement therapy. A Spanish retrospective case-cohort study

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    Garcia-Fernandez Nuria

    2009-09-01

    Full Text Available Abstract Background Acute kidney injury is among the most serious complications after cardiac surgery and is associated with an impaired outcome. Multiple factors may concur in the development of this disease. Moreover, severe renal failure requiring renal replacement therapy (RRT presents a high mortality rate. Consequently, we studied a Spanish cohort of patients to assess the risk factors for RRT in cardiac surgery-associated acute kidney injury (CSA-AKI. Methods A retrospective case-cohort study in 24 Spanish hospitals. All cases of RRT after cardiac surgery in 2007 were matched in a crude ratio of 1:4 consecutive patients based on age, sex, treated in the same year, at the same hospital and by the same group of surgeons. Results We analyzed the data from 864 patients enrolled in 2007. In multivariate analysis, severe acute kidney injury requiring postoperative RRT was significantly associated with the following variables: lower glomerular filtration rates, less basal haemoglobin, lower left ventricular ejection fraction, diabetes, prior diuretic treatment, urgent surgery, longer aortic cross clamp times, intraoperative administration of aprotinin, and increased number of packed red blood cells (PRBC transfused. When we conducted a propensity analysis using best-matched of 137 available pairs of patients, prior diuretic treatment, longer aortic cross clamp times and number of PRBC transfused were significantly associated with CSA-AKI. Patients requiring RRT needed longer hospital stays, and suffered higher mortality rates. Conclusion Cardiac-surgery associated acute kidney injury requiring RRT is associated with worse outcomes. For this reason, modifiable risk factors should be optimised and higher risk patients for acute kidney injury should be identified before undertaking cardiac surgery.

  11. Long-term follow-up of patients after acute kidney injury: patterns of renal functional recovery.

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    Etienne Macedo

    Full Text Available BACKGROUND AND OBJECTIVES: Patients who survive acute kidney injury (AKI, especially those with partial renal recovery, present a higher long-term mortality risk. However, there is no consensus on the best time to assess renal function after an episode of acute kidney injury or agreement on the definition of renal recovery. In addition, only limited data regarding predictors of recovery are available. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: From 1984 to 2009, 84 adult survivors of acute kidney injury were followed by the same nephrologist (RCRMA for a median time of 4.1 years. Patients were seen at least once each year after discharge until end stage renal disease (ESRD or death. In each consultation serum creatinine was measured and glomerular filtration rate estimated. Renal recovery was defined as a glomerular filtration rate value ≥60 mL/min/1.73 m2. A multiple logistic regression was performed to evaluate factors independently associated with renal recovery. RESULTS: The median length of follow-up was 50 months (30-90 months. All patients had stabilized their glomerular filtration rates by 18 months and 83% of them stabilized earlier: up to 12 months. Renal recovery occurred in 16 patients (19% at discharge and in 54 (64% by 18 months. Six patients died and four patients progressed to ESRD during the follow up period. Age (OR 1.09, p<0.0001 and serum creatinine at hospital discharge (OR 2.48, p = 0.007 were independent factors associated with non renal recovery. The acute kidney injury severity, evaluated by peak serum creatinine and need for dialysis, was not associated with non renal recovery. CONCLUSIONS: Renal recovery must be evaluated no earlier than one year after an acute kidney injury episode. Nephrology referral should be considered mainly for older patients and those with elevated serum creatinine at hospital discharge.

  12. Ginger extract diminishes chronic fructose consumption-induced kidney injury through suppression of renal overexpression of proinflammatory cytokines in rats.

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    Yang, Ming; Liu, Changjin; Jiang, Jian; Zuo, Guowei; Lin, Xuemei; Yamahara, Johji; Wang, Jianwei; Li, Yuhao

    2014-05-27

    The metabolic syndrome is associated with an increased risk of development and progression of chronic kidney disease. Renal inflammation is well known to play an important role in the initiation and progression of tubulointerstitial injury of the kidneys. Ginger, one of the most commonly used spices and medicinal plants, has been demonstrated to improve diet-induced metabolic abnormalities. However, the efficacy of ginger on the metabolic syndrome-associated kidney injury remains unknown. This study aimed to investigate the impact of ginger on fructose consumption-induced adverse effects in the kidneys. The fructose control rats were treated with 10% fructose in drinking water over 5 weeks. The fructose consumption in ginger-treated rats was adjusted to match that of fructose control group. The ethanolic extract of ginger was co-administered (once daily by oral gavage). The indexes of lipid and glucose homeostasis were determined enzymatically, by ELISA and/or histologically. Gene expression was analyzed by Real-Time PCR. In addition to improve hyperinsulinemia and hypertriglyceridemia, supplement with ginger extract (50 mg/kg) attenuated liquid fructose-induced kidney injury as characterized by focal cast formation, slough and dilation of tubular epithelial cells in the cortex of the kidneys in rats. Furthermore, ginger also diminished excessive renal interstitial collagen deposit. By Real-Time PCR, renal gene expression profiles revealed that ginger suppressed fructose-stimulated monocyte chemoattractant protein-1 and its receptor chemokine (C-C motif) receptor-2. In accord, overexpression of two important macrophage accumulation markers CD68 and F4/80 was downregulated. Moreover, overexpressed tumor necrosis factor-alpha, interleukin-6, transforming growth factor-beta1 and plasminogen activator inhibitor (PAI)-1 were downregulated. Ginger treatment also restored the downregulated ratio of urokinase-type plasminogen activator to PAI-1. The present results

  13. Livolin Forte Ameliorates Cadmium-Induced Kidney Injury in Wistar Rats

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    Akomolafe Rufus O.

    2016-06-01

    Full Text Available The kidney, which is an integral part of the drug excretion system, was reported as one of the targets of cadmium toxicity. Early events of cadmium toxicity in the cell include a decrease in cell membrane fluidity, breakdown of its integrity, and impairment of its repair mechanisms. Phosphatidylcholine and vitamin E have a marked fluidizing effect on cellular membranes. We hypothesized that Livolin forte (LIV could attenuate kidney damage induced by cadmium in rats. Twenty-five adult male Wistar rats were divided into five groups of five rats each: group I (control group received 0.3 ml/kg/day of propylene glycol for six weeks; group II was given 5 mg/kg/day of cadmium (Cd i.p for 5 consecutive days; group III rats were treated in a similar way as group II but were allowed a recovery period of 4 weeks; group IV was treated with LIV (5.2 mg/kg/day for a period of 4 weeks after inducing renal injury with Cd similarly to group II; and group V was allowed a recovery period of 2 weeks after a 4-week LIV treatment (5.2 mg/kg/day following Cd administration. A significant increase in plasma creatinine, urea, uric acid, and TBARS were observed in groups II and III compared to the control rats. Significant reductions in total protein, glucose, and GSH activity were also recorded. The urine concentrations of creatinine, urea, and uric acid in groups II and III were significantly lower than the control group. Th is finding was accompanied by a significant decrease in creatinine and urea clearance. Post-treatment with LIV caused significant decreases in plasma creatinine, urea, uric acid, and TBARS. Significant increases in total protein, glucose, and GSH activity of groups IV and V were observed compared to group II. A significant increase in urine concentrations of creatinine, urea, and uric acid and significant decreases in total protein, glucose, and GSH activity were observed in groups IV and V compared to group II. Photomicrographs of the rat kidneys

  14. Renal blood flow, fractional excretion of sodium and acute kidney injury: time for a new paradigm?

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    Prowle, John; Bagshaw, Sean M; Bellomo, Rinaldo

    2012-12-01

    Global renal blood flow is considered pivotal to renal function. Decreased global renal blood flow (decreased perfusion) is further considered the major mechanism of reduced glomerular filtration rate responsible for the development of acute kidney injury (AKI) in critically ill patients. Additionally, urinary biochemical tests are widely taught to allow the differential diagnosis of prerenal (functional) AKI and intrinsic [structural AKI (so-called acute tubular necrosis)]. In this review we will examine recent evidence regarding these two key clinical paradigms. Recent animal experiments and clinical studies in humans using cine-phase contrast magnetic resonance technology are not consistent with the decreased perfusion paradigm. They suggest instead that changes in the intra-renal circulation including modification in efferent arteriolar function and intra-renal shunting are much more likely to be responsible for AKI, especially in sepsis. Similarly, recent human studies indicate the urinary biochemistry has limited diagnostic or prognostic ability and is dissociated form biomarker and microscopic evidence of tubular injury. Intra-renal microcirculatory changes are likely more important than changes in global blood flow in the development of AKI. Urinary biochemistry is not a clinically useful diagnostic or prognostic tool in critically ill patients at risk of or with AKI.

  15. Ureteral stents increase risk of postoperative acute kidney injury following colorectal surgery.

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    Hassinger, Taryn E; Mehaffey, J Hunter; Mullen, Matthew G; Michaels, Alex D; Elwood, Nathan R; Levi, Shoshana T; Hedrick, Traci L; Friel, Charles M

    2018-07-01

    Ureteral stents are commonly placed before colorectal resection to assist in identification of ureters and prevent injury. Acute kidney injury (AKI) is a common cause of morbidity and increased cost following colorectal surgery. Although previously associated with reflex anuria, prophylactic stents have not been found to increase AKI. We sought to determine the impact of ureteral stents on the incidence of AKI following colorectal surgery. All patients undergoing colon or rectal resection at a single institution between 2005 and 2015 were reviewed using American College of Surgeons National Surgical Quality Improvement Program dataset. AKI was defined as a rise in serum creatinine to ≥ 1.5 times the preoperative value. Univariate and multivariate regression analyses were performed to identify independent predictors of AKI. 2910 patients underwent colorectal resection. Prophylactic ureteral stents were placed in 129 patients (4.6%). Postoperative AKI occurred in 335 (11.5%) patients during their hospitalization. The stent group demonstrated increased AKI incidence (32.6% vs. 10.5%; p colorectal surgery including age, procedure duration, and ureteral stent placement. Prophylactic ureteral stents independently increased AKI risk when placed prior to colorectal surgery. These data demonstrate increased morbidity and hospital costs related to usage of stents in colorectal surgery, indicating that placement should be limited to patients with highest potential benefit.

  16. The description of a method for accurately estimating creatinine clearance in acute kidney injury.

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    Mellas, John

    2016-05-01

    Acute kidney injury (AKI) is a common and serious condition encountered in hospitalized patients. The severity of kidney injury is defined by the RIFLE, AKIN, and KDIGO criteria which attempt to establish the degree of renal impairment. The KDIGO guidelines state that the creatinine clearance should be measured whenever possible in AKI and that the serum creatinine concentration and creatinine clearance remain the best clinical indicators of renal function. Neither the RIFLE, AKIN, nor KDIGO criteria estimate actual creatinine clearance. Furthermore there are no accepted methods for accurately estimating creatinine clearance (K) in AKI. The present study describes a unique method for estimating K in AKI using urine creatinine excretion over an established time interval (E), an estimate of creatinine production over the same time interval (P), and the estimated static glomerular filtration rate (sGFR), at time zero, utilizing the CKD-EPI formula. Using these variables estimated creatinine clearance (Ke)=E/P * sGFR. The method was tested for validity using simulated patients where actual creatinine clearance (Ka) was compared to Ke in several patients, both male and female, and of various ages, body weights, and degrees of renal impairment. These measurements were made at several serum creatinine concentrations in an attempt to determine the accuracy of this method in the non-steady state. In addition E/P and Ke was calculated in hospitalized patients, with AKI, and seen in nephrology consultation by the author. In these patients the accuracy of the method was determined by looking at the following metrics; E/P>1, E/P1 and 0.907 (0.841, 0.973) for 0.95 ml/min accurately predicted the ability to terminate renal replacement therapy in AKI. Include the need to measure urine volume accurately. Furthermore the precision of the method requires accurate estimates of sGFR, while a reasonable measure of P is crucial to estimating Ke. The present study provides the

  17. Effect of Renin-Angiotensin-Aidosterone System Inhibition, Dietary Sodium Restriction, and/or Diuretics on Urinary Kidney Injury Molecule 1 Excretion in Nondiabetic Proteinuric Kidney Disease : A Post Hoc Analysis of a Randomized Controlled Trial

    NARCIS (Netherlands)

    Waanders, Femke; Vaidya, Vishal S.; van Goor, Harry; Leuvenink, Henri; Damman, Kevin; Hamming, Inge; Bonventre, Joseph V.; Vogt, Liffert; Navis, Gerjan

    Background: Tubulointerstitial damage plays an important role in chronic kidney disease (CKD) with proteinuria. Urinary kidney injury molecule 1 (KIM-1) reflects tubular KIM-1 and is considered a sensitive biomarker for early tubular damage. We hypothesized that a decrease in proteinuria by using

  18. The experimental investigation of fibrinolytic system under the influence of flocalin in conditions of acute hypoxic kidney injury

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    A. I. Gozhenko

    2017-08-01

    Full Text Available In the experiments on rats subjected to acute hypoxic histochemical nephropathy, caused by sodium nitrite and 2,4-dinitrophenol, fibrinolytic activities of blood plasma, urine, renal cortex, medulla, and papilla after treatment with flocalin – the activator of KATP channels, were studied­. It was shown that in the conditions of acute kidney hypoxic injury flocalin administration resulted in the increase and essential restoration of fibrinolysis in blood plasma diminished under hypoxia, which was due to the growth of non-enzymatic fibrinolysis, whereas in urine and renal medulla the appreciable increase of enzymatic fibrinolytic activity took place. Moreover, the treatment of hypoxic nephropathy animals by flocalin resulted in the marked restoration of kidney ion regulatory and protein excretory functions that proves the positive influence of KATP channels activation on the one of the biochemical mechanisms of acute kidney injury as well as the protective effect of flocalin in relation to tubular cells of nephron. The obtained results testify to the beneficial effects of KATP channels activation in the conditions of acute hypoxic kidneys injury.

  19. Developing an intervention to prevent acute kidney injury: using the Plan, Do, Study, Act (PDSA) service improvement approach.

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    Byrne, Jo; Xu, Gang; Carr, Sue

    2015-03-01

    In the UK, recent National Institute for Health and Care Excellence guidelines for acute kidney injury point to the need for interventions to help prevent this condition. Effective medicines management is of prime importance in reducing the risk of AKI. Part of this challenge is to increase patients' awareness of their medicines and the possible need to temporarily withhold certain medications when acutely unwell. The objectives were to use a service improvement approach (the Plan, Do, Study, Act cycle) to develop an intervention and to evaluate current delivery of acute kidney injury management and to test and generate new ideas relating to patients' needs. A postal feedback form sent to a random sample of over 200 patients with chronic kidney disease. The feedback form collected information on: what patients know about acute kidney injury and managing medicines; where patients get their information from; whether patients want more information and where from; and what patients feel about self-managing their medicines. Completed feedback forms were received from 113 participants. Of these, 92% said they had received no advice, 77% of respondents wanted more advice but only 17% said they would feel comfortable to stop their own medication without medical consent. The PDSA cycle offered a very useful framework to evaluate the current service delivery and to test and generate new ideas for the development of an AKI intervention. Our findings highlighted that the current service is limited and more robust research is needed. © 2014 European Dialysis and Transplant Nurses Association/European Renal Care Association.

  20. [Gene transfer-induced human heme oxygenase-1 over-expression protects kidney from ischemia-reperfusion injury in rats].

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    Lü, Jin-xing; Yan, Chun-yin; Pu, Jin-xian; Hou, Jian-quan; Yuan, He-xing; Ping, Ji-gen

    2010-12-14

    To study the protection of gene transfer-induced human heme oxygenase-1 over-expression against renal ischemia reperfusion injury in rats. The model of kidney ischemia-reperfusion injury was established with Sprague-Dawley rats. In the therapy group (n=18), the left kidney was perfused and preserved with Ad-hHO-1 at 2.5×10(9) pfu/1.0 ml after flushed with 0-4°C HC-A organ storage solution via donor renal aorta. The rats in control groups were perfused with 0.9% saline solution (n=12) or the vector carrying no interest gene Ad-EGFP 2.5×10(9) pfu/1.0 ml (n=18) instead of Ad-hHO-1. BUN and Cr in serum were measured by slide chemical methods. The kidney samples of rats were harvested for assay of histology, immunohistochemistry and quantification of HO enzymatic activity. Apoptosis cells in the kidney were measured by TUNEL. Ad-hHO-1 via donor renal aorta could transfect renal cells of rats effectively, enzymatic activity of HO in treated group [(1.62±0.07) nmol×mg(-1)×min(-1)] is higher than in control groups treated with saline solution team [(1.27±0.07) nmol×mg(-1)×min(-1)] and vector EGFP team [(1.22±0.06) nmol×mg(-1)×min(-1)] (PhHO-1 expressed hHO-1 in kidneys at a high level. Corresponding to this, the level of BUN and Cr, as well as the number of apoptosis cells, were decreased, and the damage in histology by HE staining was ameliorated. Over-expression of human HO-1 can protect the kidney from ischemia/reperfusion injury in rats.

  1. Aag-initiated base excision repair promotes ischemia reperfusion injury in liver, brain, and kidney.

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    Ebrahimkhani, Mohammad R; Daneshmand, Ali; Mazumder, Aprotim; Allocca, Mariacarmela; Calvo, Jennifer A; Abolhassani, Nona; Jhun, Iny; Muthupalani, Sureshkumar; Ayata, Cenk; Samson, Leona D

    2014-11-11

    Inflammation is accompanied by the release of highly reactive oxygen and nitrogen species (RONS) that damage DNA, among other cellular molecules. Base excision repair (BER) is initiated by DNA glycosylases and is crucial in repairing RONS-induced DNA damage; the alkyladenine DNA glycosylase (Aag/Mpg) excises several DNA base lesions induced by the inflammation-associated RONS release that accompanies ischemia reperfusion (I/R). Using mouse I/R models we demonstrate that Aag(-/-) mice are significantly protected against, rather than sensitized to, I/R injury, and that such protection is observed across three different organs. Following I/R in liver, kidney, and brain, Aag(-/-) mice display decreased hepatocyte death, cerebral infarction, and renal injury relative to wild-type. We infer that in wild-type mice, Aag excises damaged DNA bases to generate potentially toxic abasic sites that in turn generate highly toxic DNA strand breaks that trigger poly(ADP-ribose) polymerase (Parp) hyperactivation, cellular bioenergetics failure, and necrosis; indeed, steady-state levels of abasic sites and nuclear PAR polymers were significantly more elevated in wild-type vs. Aag(-/-) liver after I/R. This increase in PAR polymers was accompanied by depletion of intracellular NAD and ATP levels plus the translocation and extracellular release of the high-mobility group box 1 (Hmgb1) nuclear protein, activating the sterile inflammatory response. We thus demonstrate the detrimental effects of Aag-initiated BER during I/R and sterile inflammation, and present a novel target for controlling I/R-induced injury.

  2. Post-traumatic acute kidney injury: a cross-sectional study of trauma patients.

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    Lai, Wei-Hung; Rau, Cheng-Shyuan; Wu, Shao-Chun; Chen, Yi-Chun; Kuo, Pao-Jen; Hsu, Shiun-Yuan; Hsieh, Ching-Hua; Hsieh, Hsiao-Yun

    2016-11-22

    The causes of post-traumatic acute kidney injury (AKI) are multifactorial, and shock associated with major trauma has been proposed to result in inadequate renal perfusion and subsequent AKI in trauma patients. This study aimed to investigate the true incidence and clinical presentation of post-traumatic AKI in hospitalized adult patients and its association with shock at a Level I trauma center. Detailed data of 78 trauma patients with AKI and 14,504 patients without AKI between January 1, 2009 and December 31, 2014 were retrieved from the Trauma Registry System. Patients with direct renal trauma were excluded from this study. Two-sided Fisher's exact or Pearson's chi-square tests were used to compare categorical data, unpaired Student's t-test was used to analyze normally distributed continuous data, and Mann-Whitney's U test was used to compare non-normally distributed data. Propensity score matching with a 1:1 ratio with logistic regression was used to evaluate the effect of shock on AKI. Patients with AKI presented with significantly older age, higher incidence rates of pre-existing comorbidities, higher odds of associated injures (subdural hematoma, intracerebral hematoma, intra-abdominal injury, and hepatic injury), and higher injury severity than patients without AKI. In addition, patients with AKI had a longer hospital stay (18.3 days vs. 9.8 days, respectively; P < 0.001) and intensive care unit (ICU) stay (18.8 days vs. 8.6 days, respectively; P < 0. 001), higher proportion of admission into the ICU (57.7% vs. 19.0%, respectively; P < 0.001), and a higher odds ratio (OR) of short-term mortality (OR 39.0; 95% confidence interval, 24.59-61.82; P < 0.001). However, logistic regression analysis of well-matched pairs after propensity score matching did not show a significant influence of shock on the occurrence of AKI. We believe that early and aggressive resuscitation, to avoid prolonged untreated shock, may help to prevent the occurrence

  3. Aging has small effects on initial ischemic acute kidney injury development despite changing intrarenal immunologic micromilieu in mice.

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    Jang, Hye Ryoun; Park, Ji Hyeon; Kwon, Ghee Young; Park, Jae Berm; Lee, Jung Eun; Kim, Dae Joong; Kim, Yoon-Goo; Kim, Sung Joo; Oh, Ha Young; Huh, Wooseong

    2016-02-15

    Inflammatory process mediated by innate and adaptive immune systems is a major pathogenic mechanism of renal ischemia-reperfusion injury (IRI). There are concerns that organ recipients may be at increased risk of developing IRI after receiving kidneys from elder donors. To reveal the effects of aging on the development of renal IRI, we compared the immunologic micromilieu of normal and postischemic kidneys from mice of three different ages (9 wk, 6 mo, and 12 mo). There was a higher number of total T cells, especially effector memory CD4/CD8 T cells, and regulatory T cells in the normal kidneys of old mice. On day 2 after IRI, the proportion of necrotic tubules and renal functional changes were comparable between groups although old mice had a higher proportion of damaged tubule compared with young mice. More T cells, but less B cells, trafficked into the postischemic kidneys of old mice. The infiltration of NK T cells was similar across the groups. Macrophages and neutrophils were comparable between groups in both normal kidneys and postischemic kidneys. The intrarenal expressions of TNF-α and VEGF were decreased in normal and postischemic kidneys of aged mice. These mixed effects of aging on lymphocytes and cytokines/chemokines were not different between the two groups of old mice. Our study demonstrates that aging alters the intrarenal micromilieu but has small effects on the development of initial renal injury after IRI. Further study investigating aging-dependent differences in the repair process of renal IRI may be required. Copyright © 2016 the American Physiological Society.

  4. Hyperuricemia Induces Wnt5a/Ror2 Gene Expression, Epithelial–Mesenchymal Transition, and Kidney Tubular Injury in Mice

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    Wiwit Ananda Wahyu Setyaningsih

    2018-03-01

    Full Text Available Background: Hyperuricemia contributes to kidney injury, characterized by tubular injury with epithelial–mesenchymal transition (EMT. Wnt5a/Ror2 signaling drives EMT in many kidney pathologies. This study sought to evaluate the involvement of Wnt5a/Ror2 in hyperuricemia-induced EMT in kidney tubular injury. Methods: A hyperuricemia model was performed in male Swiss background mice (3 months old, 30–40 g with daily intraperitoneal injections of 125 mg/kg body weight (BW of uric acid. The mice were terminated on day 7 (UA7, n=5 and on day 14 (UA14, n=5. Allopurinol groups (UAl7 and UAl14, each n=5 were added with oral 50 mg/kg BW of allopurinol treatment. The serum uric acid level was quantified, and tubular injury was assessed based on PAS staining. Reverse transcriptase-PCR was done to quantify Wnt5a, Ror2, E-cadherin, and vimentin expressions. IHC staining was done for E-cadherin and collagen I. We used the Shapiro–Wilk for normality testing and one-way ANOVA for variance analysis with a P<0.05 as significance level using SPSS 22 software. Results: The hyperuricemia groups had a higher uric acid level, which was associated with a higher tubular injury score. Meanwhile, the allopurinol groups had a significantly lower uric acid level and tubular injury than the uric acid groups. Reverse transcriptase-PCR revealed downregulation of the E-cadherin expression. While vimentin and collagen I expression are upregulated, which was associated with a higher Wnt5a expression. However, the allopurinol groups had reverse results. Immunostaining revealed a reduction in E-cadherin staining in the epithelial cells and collagen I positive staining in the epithelial cells and the interstitial areas. Conclusion: Hyperuricemia induced tubular injury, which might have been mediated by EMT through the activation of Wnt5a.

  5. Deletion of Rac1GTPase in the Myeloid Lineage Protects against Inflammation-Mediated Kidney Injury in Mice.

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    Miki Nagase

    Full Text Available Macrophage-mediated inflammation has been implicated in various kidney diseases. We previously reported that Rac1, a Rho family small GTP-binding protein, was overactivated in several chronic kidney disease models, and that Rac1 inhibitors ameliorated renal injury, in part via inhibition of inflammation, but the detailed mechanisms have not been clarified. In the present study, we examined whether Rac1 in macrophages effects cytokine production and the inflammatory mechanisms contributing to kidney derangement. Myeloid-selective Rac1 flox control (M-Rac1 FC and knockout (M-Rac1 KO mice were generated using the cre-loxP system. Renal function under basal conditions did not differ between M-Rac1 FC and KO mice. Accordingly, lipopolysaccharide (LPS-evoked kidney injury model was created. LPS elevated blood urea nitrogen and serum creatinine, enhanced expressions of kidney injury biomarkers, Kim-1 and Ngal, and promoted tubular injury in M-Rac1 FC mice. By contrast, deletion of myeloid Rac1 almost completely prevented the LPS-mediated renal impairment. LPS triggered a marked induction of macrophage-derived inflammatory cytokines, IL-6 and TNFα, in M-Rac1 FC mice, which was accompanied by Rac1 activation, stimulation of reduced nicotinamide-adenine dinucleotide phosphate (NADPH oxidase, and reactive oxygen species overproduction. These changes were inhibited in M-Rac1 KO mice. LPS evoked F4/80-positive macrophages accumulation in the kidney, which was not affected by myeloid Rac1 deficiency. We further tested the role of Rac1 signaling in cytokine production using macrophage cell line, RAW264.7. Exposure to LPS increased IL-6 and TNFα mRNA expression. The LPS-driven cytokine induction was dose-dependently blocked by the Rac1 inhibitor EHT1864, NADPH oxidase inhibitor diphenyleneiodonium, and NF-κB inhibitor BAY11-7082. In conclusion, genetic ablation of Rac1 in the myeloid lineage protected against LPS-induced renal inflammation and injury, by

  6. Evaluation of Temporal Changes in Urine-based Metabolomic and Kidney Injury Markers to Detect Compound Induced Acute Kidney Tubular Toxicity in Beagle Dogs.

    Science.gov (United States)

    Wagoner, M P; Yang, Y; McDuffie, J E; Klapczynski, M; Buck, W; Cheatham, L; Eisinger, D; Sace, F; Lynch, K M; Sonee, M; Ma, J-Y; Chen, Y; Marshall, K; Damour, M; Stephen, L; Dragan, Y P; Fikes, J; Snook, S; Kinter, L B

    2017-01-01

    Urinary protein biomarkers and metabolomic markers have been leveraged to detect acute Drug Induced Kidney Injury (DIKI) in rats; however, the utility of these indicators to enable early detection of DIKI in canine models has not been well documented. Therefore, we evaluated temporal changes in biomarkers and metabolites in urine from male and female beagle dogs. Gentamicin- induced kidney lesions in male dogs were characterized by moderate to severe tubular epithelial cell degeneration/necrosis, epithelial cell regeneration and dilation; and a unique urinebased metabolomic fingerprint. These metabolite changes included time and treatment-dependent increases in lactate, taurine, glucose, lactate, alanine, and citrate as well as 9 other known metabolites. As early as 3 days post dose, gentamicin induced increases in urinary albumin, clusterin, neutrophil gelatinase associated protein (NGAL) and total protein concentrations. Urinary albumin, clusterin, and NGAL showed earlier and more robust elevations than traditional kidney safety biomarkers, blood urea nitrogen and serum creatinine. Elevations in urinary kidney injury molecule 1 (KIM-1) were less reliable for detection of gentamicin nephrotoxicity in dogs based on values generated utilizing multiple first-generation, canine-specific KIM-1 immunoassays. The metabolic fingerprint was further evaluated in male and female dogs that received Compound A which induced slightly reversible renal tubular alterations characterized as degeneration/necrosis and concurrent significant increases in urinary taurine amongst other markers. These data support further investigations to demonstrate the value of urinary metabolites, albumin, clusterin, NGAL and taurine as promising markers to enable early detection of DIKI in dogs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Foliar injury response of petunia and kidney bean to simultaneous and alternate exposures to ozone and PAN

    Energy Technology Data Exchange (ETDEWEB)

    Nouchi, I.; Mayumi, H.; Yamazoe, F.

    1984-01-01

    Petunia at about 6 weeks old and kidney bean at two growing stages (6-7 days old and 16-18 days old) were exposed separately to O/sub 3/ (0-0.40 ppm) and PAN (0-0.25 ppm) for 4 h and to the mixture for the same time. In addition, petunia was exposed to O/sub 3/ (0.10-0.40 ppm) and then PAN (0.010-0.040 ppm) for 4 h, respectively. Foliar injury of petunia and kidney bean in exposures to the mixtures of O/sub 3/ and PAN was significantly smaller than that induced by each oxidant, with the exception of PAN injury on young leaves of 16-18 day-old kidney bean. The percentage of foliar injury caused by either of the mixed pollutants decreased with an increase of the concentration of the other oxidant, and was found to approximate a logarithmic function of the combined pollutant concentrations expressed as O/sub 3/ minum PAN or vice versa. Alternate exposures caused no additive or synergistic injuries. 23 references, 3 figures, 6 tables.

  8. Foliar injury response of petunia and kidney bean to simultaneous and alternate exposures to ozone and pan

    Science.gov (United States)

    Nouchi, Isamu; Mayumi, Hirokazu; Yamazoe, Fumio

    Petunia at about 6 weeks old and kidney bean at two growing stages (6-7 days old and 16-18 days old) were exposed separately to O 3, (0-0.40 ppm) and PAN (0-0.25 ppm) for 4 h and to the mixture for the same time. In addition, petunia was exposed to O, (0.10-0.40 ppm) and then PAN (0.010-0.040 ppm) for 4 h, respectively. Foliar injury of petunia and kidney bean in exposures to the mixtures of O 3 and PAN was significantly smaller than that induced by each oxidant, with the exception of PAN injury on young leaves of 16-18 day-old kidney bean. The percentage of foliar injury caused by either of the mixed pollutants decreased with an increase of the concentration of the other oxidant, and was found to approximate a logarithmic function of the combined pollutant concentrations expressed as O 3, minum PAN or vice versa. Alternate exposures caused no additive or synergistic injuries.

  9. Non-invasive detection of the early phase of kidney injury by photoacoustic/computed tomography imaging

    Science.gov (United States)

    Pan, Wanma; Peng, Wen; Ning, Fengling; Zhang, Yu; Zhang, Yunfei; Wang, Yinhang; Xie, Weiyi; Zhang, Jing; Xin, Hong; Li, Cong; Zhang, Xuemei

    2018-06-01

    The early diagnosis of kidney diseases, which can remarkably impair the quality of life and are costly, has encountered great difficulties. Therefore, the development of methods for early diagnosis has great clinical significance. In this study, we used an emerging technique of photoacoustic (PA) imaging, which has relatively high spatial resolution and good imaging depth. Two kinds of PA gold nanoparticle (GNP)-based bioprobes were developed based on their superior photo detectability, size controllability and biocompatibility. The kidney injury mouse model was developed by unilateral ureteral obstruction for 96 h and the release of obstruction model). Giving 3.5 and 5.5 nm bioprobes by tail vein injection, we found that the 5.5 nm probe could be detected in the bladder in the model group, but not in the control group. These results were confirmed by computed tomography imaging. Furthermore, the model group did not show changes in the blood biochemical indices (BUN and Scr) and histologic examination. The 5.5 nm GNPs were found to be the critical point for early diagnosis of kidney injury. This new method was faster and more sensitive and accurate for the detection of renal injury, compared with conventional methods, and can be used for the development of a PA GNP-based bioprobe for diagnosing renal injury.

  10. Urinary Neutrophil Gelatinase-Associated Lipocalin as a Predictor of Acute Kidney Injury, Severe Kidney Injury, and the Need for Renal Replacement Therapy in the Intensive Care Unit

    Directory of Open Access Journals (Sweden)

    Fatma I. Albeladi

    2017-07-01

    Full Text Available Background: Recent attempts were made to identify early indicators of acute kidney injury (AKI in order to accelerate treatment and hopefully improve outcomes. This study aims to assess the value of urinary neutrophil gelatinase-associated lipocalin (uNGAL as a predictor of AKI, severe AKI, and the need for renal replacement therapy (RRT. Methods: We conducted a prospective study and included adults admitted to our intensive care unit (ICU at King Abdulaziz University Hospital (KAUH, between May 2012 and June 2013, who had at least 1 major risk factor for AKI. They were followed up throughout their hospital stay to identify which potential characteristics predicted any of the above 3 outcomes. We collected information on patients’ age and gender, the Acute Physiology And Chronic Health Evaluation, version II (APACHE II score, the Sepsis-Related Organ Failure Assessment (SOFA score, serum creatinine and cystatin C levels, and uNGAL. We compared ICU patients who presented with any of the 3 outcomes with others who did not. Results: We included 75 patients, and among those 21 developed AKI, 18 severe AKI, and 17 required RRT. Bivariate analysis revealed intergroup differences for almost all clinical variables (e.g., patients with AKI vs. patients without AKI; while multivariate analysis identified mean arterial pressure as the only predictor for AKI (p < 0.001 and the SOFA score (p = 0.04 as the only predictor for severe AKI. For RRT, day 1 maximum uNGAL was the stronger predictor (p < 0.001 when compared to admission diagnosis (p = 0.014. Day 1 and day 2 maximum uNGAL levels were good and excellent predictors for future RRT, but only fair to good predictors for AKI and severe AKI. Conclusions: Maximum urine levels of uNGAL measured over the first and second 24 h of an ICU admission were highly accurate predictors of the future need for RRT, however less accurate at detecting early and severe AKI.

  11. Neuroprotective effects of scutellarin against hypoxic-ischemic-induced cerebral injury via augmentation of antioxidant defense capacity.

    Science.gov (United States)

    Guo, Hong; Hu, Li-Min; Wang, Shao-Xia; Wang, Yu-Lin; Shi, Fang; Li, Hui; Liu, Yang; Kang, Li-Yuan; Gao, Xiu-Mei

    2011-12-31

    An increasing number of studies has indicated that hypoxic-ischemic-induced cerebral injury is partly mediated via oxidative stress. Recent researches have focused on searching for drug and herbal manipulations to protect against hypoxic-ischemic-induced oxidative cell damage. Scutellarin is a flavonoid derived from the Erigeron breviscapus (vant.) and has been reported to exhibit neuroprotective properties. However, its precise mechanism, particularly its antioxidation mechanism, remains elusive. In the present study, we investigated the neuroprotective effects of scutellarin on middle cerebral artery occlusion (MCAO)-induced brain damage in rats, and oxygen-glucose deprivation (OGD)-induced toxicity in primary culture of rat cortical neurons. In vivo, intraperitoneal injections of scutellarin (20 and 60 mg/kg) improved the neurological score and diminished the percentage of brain infarct volume. At the same time, scutellarin significantly increased superoxide dismutase (SOD), catalase (CAT) activities and glutathione (GSH) level in ischemic brain tissues, enhancing endogenous antioxidant activity. Moreover, pretreatment of scutellarin (25, 50 and 100 μM) protected neurons against lethal stimuli, decreased the percentage of apoptotic cells and inhibited reactive oxygen species (ROS) generation in OGD-induced primary cortical neurons in vitro. These results suggest that the preventive and therapeutic potential of scutellarin in cerebral injury patients is, at least in part, ascribed to augmentation of cellular antioxidant defense capacity.

  12. CD147/basigin reflects renal dysfunction in patients with acute kidney injury.

    Science.gov (United States)

    Nagaya, Hiroshi; Kosugi, Tomoki; Maeda-Hori, Mayuko; Maeda, Kayaho; Sato, Yuka; Kojima, Hiroshi; Hayashi, Hiroki; Kato, Noritoshi; Ishimoto, Takuji; Sato, Waichi; Yuzawa, Yukio; Matsuo, Seiichi; Kadomatsu, Kenji; Maruyama, Shoichi

    2014-10-01

    Acute tubular necrosis (ATN) describes a form of intrinsic acute kidney injury (AKI) that results from persistent hypoperfusion and subsequent activation of the immune system. A glycosylated transmembrane protein, CD147/basigin, is involved in the pathogenesis of renal ischemia and fibrosis. The present study investigated whether CD147 can reflect pathological features and renal dysfunction in patients with AKI. Plasma and spot urine samples were collected from 24 patients (12 controls and 12 with ATN) who underwent renal biopsy between 2008 and 2012. In another study, patients undergoing open surgery to treat abdominal aortic aneurysms (AAAs) were enrolled in 2004. We collected urine and plasma samples from seven patients with AKI and 33 patients without AKI, respectively. In these experiments, plasma and urinary CD147, and urinary L-fatty acid-binding protein (L-FABP) levels were measured, and the former expression in kidneys was examined by immunostaining. In biopsy tissues of ATN with severe histological features, CD147 induction was strikingly present in inflammatory cells such as macrophages and lymphocytes in the injured interstitium, but not in damaged tubules representing atrophy. Both plasma and urinary CD147 levels were strikingly increased in ATN patients; both values showed greater correlations with renal dysfunction compared to urinary L-FABP. In patients who had undergone open AAA surgery, urinary and plasma CD147 values in AKI patients were significantly higher than in non-AKI patients at post-operative day 1, similar to the profile of urinary L-FABP. CD147 was prominent in its ability to detect AKI and may allow the start of preemptive medication.

  13. Evaluation of estimated creatinine clearance before steady state in acute kidney injury by creatinine kinetics.

    Science.gov (United States)

    Yashiro, Masatomo; Ochiai, Miyuki; Fujisawa, Nao; Kadoya, Yuko; Kamata, Tadashi

    2012-08-01

    A simple method to calculate estimated creatinine clearance using two serum creatinine concentration (Cr) values in acute kidney injury (AKI) was developed (eCrCl-AKI). We aimed to evaluate its accuracy and to clarify its contribution to the classification of AKI. We validated the errors in eCrCl-AKI in a simulation study after various reductions in creatinine clearance (CrCl) at various levels of chronic kidney disease (CKD). We compared the eCrCl-AKI-based classification of RIFLE criteria with the Cr-based classification or that proposed by Waikar and Bonventre. The regression equations of eCrCl-AKI on time were determined and Cr values were reconstructed by creatinine kinetics substituting CrCl with eCrCl-AKI in actual patients. Most errors in eCrCl-AKI were relatively small (from -13.6 to +7.9%) with the exception of two Cr values that straddled the changing trend of Cr. The classification according to RIFLE criteria based on Cr was unstable and did not enable adequate classification, especially in milder reductions of CrCl with advanced CKD. The classification based on eCrCl-AKI was stable and enabled adequate classification. There were good agreements between measured Cr and reconstructed Cr with eCrCl-AKI. The regression equations of eCrCl-AKI revealed changes of renal function that were unexpected only from fluctuations of Cr. eCrCl-AKI can provide relatively accurate estimates for fluctuating CrCl. eCrCl-AKI enables more stable and earlier classification of AKI than Cr, at least in the simulation study. The more widespread use of eCrCl-AKI in actual clinical settings of AKI is necessary to evaluate this formula.

  14. Acute kidney injury in Hemiscorpius lepturus scorpion stung children: Risk factors and clinical features

    Directory of Open Access Journals (Sweden)

    Ehsan Valavi

    2016-01-01

    Full Text Available Acute kidney injury (AKI is frequently seen in Hemiscorpius lepturus scorpion stung children. We have previously reported several victims with hemolytic uremic syndrome (HUS and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 deficiency. Hence, we conducted this study to identify predictive factors and clinical features of AKI in H. lepturus scorpion stung patients. We included all 215 H. lepturus scorpion stung children with no previous renal diseases in two groups (with and without AKI and compared them based on their clinical and laboratory findings. AKI was found in 27.4% of patients, they were significantly younger and with lower body weight (P = 0.006, P = 0.011, respectively. There was a significant difference between groups with and without AKI in findings such as fever (P = 0.003, hypertension (P <0.001, hemolytic anemia (P <0.001, thrombocytopenia (P <0.001, massive proteinuria (P <0.001, hemoglobinuria (P <0.001, pyuria (P <0.001, and hematuria (P = 0.004. HUS was in 5.5% and disseminated intravascular coagulation in 14.6% which had a significant association with AKI (P <0.001.There were several independent predictors for AKI in a multivariate regression model including thrombocytopenia (P = 0.002, pyuria (P = 0.01, proteinuria (P =0.01, and fever (P = 0.02. Hemodialysis was performed in four patients but kidney function improved in all patients and there was no findings of renal impairment after three months follow-up. We found several predictors for AKI in children following H. lepturus scorpion sting including younger age, delay in receiving medical care, pigmenturia, microangiopathic hemolytic anemia, proteinuria, and pyuria.

  15. Incidence, predictive factors, and clinical outcomes of acute kidney injury after gastric surgery for gastric cancer.

    Directory of Open Access Journals (Sweden)

    Chang Seong Kim

    Full Text Available BACKGROUND: Postoperative acute kidney injury (AKI, a serious surgical complication, is common after cardiac surgery; however, reports on AKI after noncardiac surgery are limited. We sought to determine the incidence and predictive factors of AKI after gastric surgery for gastric cancer and its effects on the clinical outcomes. METHODS: We conducted a retrospective study of 4718 patients with normal renal function who underwent partial or total gastrectomy for gastric cancer between June 2002 and December 2011. Postoperative AKI was defined by serum creatinine change, as per the Kidney Disease Improving Global Outcomes guideline. RESULTS: Of the 4718 patients, 679 (14.4% developed AKI. Length of hospital stay, intensive care unit admission rates, and in-hospital mortality rate (3.5% versus 0.2% were significantly higher in patients with AKI than in those without. AKI was also associated with requirement of renal replacement therapy. Multivariate analysis revealed that male gender; hypertension; chronic obstructive pulmonary disease; hypoalbuminemia (<4 g/dl; use of diuretics, vasopressors, and contrast agents; and packed red blood cell transfusion were independent predictors for AKI after gastric surgery. Postoperative AKI and vasopressor use entailed a high risk of 3-month mortality after multiple adjustments. CONCLUSIONS: AKI was common after gastric surgery for gastric cancer and associated with adverse outcomes. We identified several factors associated with postoperative AKI; recognition of these predictive factors may help reduce the incidence of AKI after gastric surgery. Furthermore, postoperative AKI in patients with gastric cancer is an important risk factor for short-term mortality.

  16. Deficiencies in education and experience in the management of acute kidney injury among Malawian healthcare workers.

    Science.gov (United States)

    Evans, R; Rudd, P; Hemmila, U; Dobbie, H; Dreyer, G

    2015-09-01

    Acute kidney injury (AKI) is a common but under-recognised disease process, which carries a high risk of mortality or chronic complications, such as chronic kidney disease and other organ dysfunction. Management of AKI, however, is suboptimal, both in developed settings and in Malawi. This is partly because of deficiencies in AKI education and training. To establish current levels of AKI education in a range of healthcare workers in Malawi. An AKI symposium was held in Blantyre in March 2015. Delegates were asked to complete a survey at the start of the symposium to assess their clinical experience and education in the management of AKI. From 100 delegates, 89 nurses, clinical officers, and physicians, originating from 11 different districts, responded to the survey. Twenty-two percent of healthcare workers (including 28% of district workers of the various cadres and 31% of nurses) had never received teaching on any aspect of renal disease, and 50% (including 63% of district workers and 61% of nurses) had never received teaching specifically on AKI. Forty-four percent did not feel confident managing AKI, and 98% wanted more support managing patients with renal disease. Thirty-four percent (including 55% of district workers) were unaware that haemodialysis was available at Queen Elizabeth Central Hospital (QECH) for the treatment of AKI and 53% (74% of district workers) were unaware that peritoneal dialysis was available for the treatment of AKI in children. Only 33% had ever referred a patient with AKI to QECH. There are deficiencies in education about, and clinical experience in, the management of AKI among Malawian healthcare workers, in addition to limited awareness of the renal service available at QECH. Urgent action is required to address these issues in order to prevent morbidity and mortality from AKI in Malawi.

  17. 4-Phenylbutyrate inhibits tunicamycin-induced acute kidney injury via CHOP/GADD153 repression.

    Directory of Open Access Journals (Sweden)

    Rachel E Carlisle

    Full Text Available Different forms of acute kidney injury (AKI have been associated with endoplasmic reticulum (ER stress; these include AKI caused by acetaminophen, antibiotics, cisplatin, and radiocontrast. Tunicamycin (TM is a nucleoside antibiotic known to induce ER stress and is a commonly used inducer of AKI. 4-phenylbutyrate (4-PBA is an FDA approved substance used in children who suffer from urea cycle disorders. 4-PBA acts as an ER stress inhibitor by aiding in protein folding at the molecular level and preventing misfolded protein aggregation. The main objective of this study was to determine if 4-PBA could protect from AKI induced by ER stress, as typified by the TM-model, and what mechanism(s of 4-PBA's action were responsible for protection. C57BL/6 mice were treated with saline, TM or TM plus 4-PBA. 4-PBA partially protected the anatomic segment most susceptible to damage, the outer medullary stripe, from TM-induced AKI. In vitro work showed that 4-PBA protected human proximal tubular cells from apoptosis and TM-induced CHOP expression, an ER stress inducible proapoptotic gene. Further, immunofluorescent staining in the animal model found similar protection by 4-PBA from CHOP nuclear translocation in the tubular epithelium of the medulla. This was accompanied by a reduction in apoptosis and GRP78 expression. CHOP(-/- mice were protected from TM-induced AKI. The protective effects of 4-PBA extended to the ultrastructural integrity of proximal tubule cells in the outer medulla. When taken together, these results indicate that 4-PBA acts as an ER stress inhibitor, to partially protect the kidney from TM-induced AKI through the repression of ER stress-induced CHOP expression.

  18. Preliminary Study on J-Resolved NMR Method Usability for Toxic Kidney's Injury Assessment.

    Science.gov (United States)

    Doskocz, Marek; Marchewka, Zofia; Jeż, Magdalena; Passowicz-Muszyńska, Ewa; Długosz, Anna

    2015-01-01

    Nowadays, the Nuclear Magnetic Resonance (NMR) techniques are tested for metabolomic urine profile in order to detect early damage of kidney. The purpose of this investigation was the initial assessment of two-dimensional J-resolved NMR urine spectra analysis usability for early kidney injuries detection. The amino acids (AA) and acids profile change after the exposure to nephrotoxic agent (the cisplatin infusion) was examined. The material was the urine of patients with non-small-cell lung cancer, treated with cisplatin in Pulmonology and Lung Cancers Clinic in Wrocław. The urine of healthy volunteers was also examined. The identification of metabolites in urine was based on two-dimensional JRES signals in spectra, described in Human Metabolites Database (HMD). The molar concentration of metabolites was calculated from the volume under the signals. The analysis was focused on amino acids and organic acids (lactid acid and pyruvic acid) profiles. Any specific amino acids were identified after cisplatin infusion in comparison to the state before infusion. However, the differences in concentration were observed over 2-fold increase in valine, isoleucine and leucine, over 3-fold in alanine. Also, the concentration of pyruvic and lactic acids increased significantly (p≤0.05, p≤0.01). There were no specific amino acids identified in response to the infusion of cisplatin; however, some changes in the concentrations of amino acids and other small molecules were found. The analysis of two-dimensional JRES spectra showed an increase of alanine, leucine, isoleucine and valine concentration after the application of cisplatin. It seems that it is worth developing the JRES method based on special computer program.

  19. Significant Acute Kidney Injury Due to Non-steroidal Anti-inflammatory Drugs: Inpatient Setting

    Directory of Open Access Journals (Sweden)

    Mehul Dixit

    2010-04-01

    Full Text Available In the United States non-steroidal anti-inflammatory drugs (NSAID are freely available over-the-counter. Because of the adverse effects on the kidneys and the popularity of these drugs, unregulated use of NSAIDs is an under recognized and potentially dangerous problem. Fifteen inpatients, mean age of 15.2 ± 2.3 years (five males, 10 females, were referred to nephrology for acute kidney injury. All patients admitted to taking ibuprofen and six also consumed naproxen. None of the patients had underlying renal diseases at the time of admission. Nine patients had proteinuria and 12 had hematuria (including one with gross hematuria. One patient had nephrotic syndrome but the condition resolved spontaneously without steroids and has remained in remission for four years. Two patients required dialysis. Only one of the dialyzed patients required steroid therapy for recovery of renal function. The mean duration of hospitalization was 7.4 ± 5.5 days. The serum creatinine peaked at 4.09 ± 4.24 (range 1.2-15.3 mg/dL. All patients recovered renal function with normalization of serum creatinine to 0.71 ± 0.15 mg/dL. The estimated GFR (glomerular filtration rate at peak of renal failure was 38.2 ± 20.5 mL/min but did improve to a baseline of 134 ± 26.2 mL/min (range 89-177, p < 0.01. However, the duration from onset to normalization of serum creatinine was 37 ± 42 days indicating that majority of patients had abnormal renal function for a prolonged period. In conclusion, NSAIDs pose a significant risk of renal failure for significant duration and as an entity may be under recognized.

  20. N-acetylcysteine ameliorates contrast‑induced kidney injury in rats with unilateral hydronephrosis.

    Science.gov (United States)

    Xia, Qiang; Liu, Chunxiao; Zheng, Xia

    2018-02-01

    The aim of the present study was to investigate the protective effects of N‑acetylcysteine (NAC) on contrast‑induced acute kidney injury in rats with unilateral hyronephrosis. Eighty‑two male Sprague Dawley rats were randomized to undergo sham operation (n=14) or unilateral ureteral obstruction (UUO) (n=68). After 3 weeks, the UUO animals were randomized to three groups: NAC gastric perfusion, UUO+iohexol+NAC (n=24); normal saline perfusion, UUO+iohexol (n=24); and controls, UUO (n=20). After 3 days, UUO+iohexol+NAC and UUO+iohexol rats were injected with iohexol. One day after contrast, half of the rats were sacrificed to assess the pathological changes to the kidneys, serum creatinine, serum neutrophil gelatinase‑associated lipocalin (NGAL), renal cell apoptosis rate and expression of apoptosis regulators Bcl‑2/Bax. The remaining rats underwent obstruction relief and were analyzed 3 weeks later. Compared with the controls, serum NGAL levels were high in UUO+iohexol rats 1 day following injection and 3 weeks after obstruction relief, but UUO+iohexol+NAC rats exhibited lower serum NGAL levels compared with UUO+iohexol rats (all Pmodeling, UUO+iohexol rats exhibited a significantly higher apoptosis rate of renal tubular cells, higher expression of Bax mRNA, and lower ratio of Bcl‑2/Bax (all Prelief, UUO+iohexol+NAC rats exhibited a lower apoptosis rate, lower Bax mRNA expression, higher expression of Bcl‑2 mRNA and higher ratio of Bcl‑2/Bax (all P<0.05) compared with day 1 following drug administration. The prophylactic use of NAC reduced the apoptotic rate of renal tubular cells following contrast exposition, which was accompanied by changes in the expression of Bcl‑2/Bax mRNA.

  1. Usefulness of polyetheretherketone (PEEK) cage with plate augmentation for anterior arthrodesis in traumatic cervical spine injury.

    Science.gov (United States)

    Song, Kyung-Jin; Choi, Byung-Wan; Kim, Gyu-Hyung; Song, Ji-Hun

    2010-01-01

    Even though many clinical reports about cages have been documented in patients with degenerative disorders, reports were scarce for traumatic injury cases, and those cases using metal cages were restricted to only one-level injury. To evaluate the usefulness of polyetheretherketone (PEEK) cage and plate construction in anterior interbody fusions (AIF) for traumatic cervical spine injuries by analyzing radiographic changes and clinical outcomes. Retrospective study. Fifty-eight patients (91 levels) underwent cage and plate construction for treatment of traumatic cervical spine injury. The fusion rate, fusion time, changes of Cobb angle, subsidence rate, and adjacent level changes were assessed as a radiographic outcome. Clinical analysis includes the recovery rate on the American Spinal Injury Association (ASIA) impairment scale and the presence of the complications. We evaluated 58 patients (91 levels) who underwent surgery and had at least 24 months in follow-up study. Radiographic evaluation included the assessment of interbody fusion rate, fusion time, changes of Cobb angle, subsidence rate, and adjacent level changes. Clinical assessment was done by analyzing recovery state of ASIA impairment scale from preoperative period to the last follow-up and by evaluating complications. Fifty-four cases showed bony fusion within 3 months after the surgery. The mean Cobb angle between the vertebral bodies was 2.54 degrees before operation, 9.13 degrees after operation, and 8.39 degrees at the latest follow-up. The mean intervertebral disc height was increased by 3.01 mm after the operation, but the mean height was 2.17 mm shorter at the last follow-up than after postoperation. In terms of clinical results, five Grade A cases and one Grade B case as assessed by the ASIA impairment scale were unchanged until the last follow-up. Twenty-three cases of Grade C, 16 cases of Grade D, and 13 cases of Grade E improved to seven cases, 26 cases, and 19 cases, respectively. Three

  2. Hypoxia-induced pulmonary arterial hypertension augments lung injury and airway reactivity caused by ozone exposure

    Energy Technology Data Exchange (ETDEWEB)

    Zychowski, Katherine E.; Lucas, Selita N.; Sanchez, Bethany; Herbert, Guy; Campen, Matthew J., E-mail: mcampen@salud.unm.edu

    2016-08-15

    Ozone (O{sub 3})-related cardiorespiratory effects are a growing public health concern. Ground level O{sub 3} can exacerbate pre-existing respiratory conditions; however, research regarding therapeutic interventions to reduce O{sub 3}-induced lung injury is limited. In patients with chronic obstructive pulmonary disease, hypoxia-associated pulmonary hypertension (HPH) is a frequent comorbidity that is difficult to treat clinically, yet associated with increased mortality and frequency of exacerbations. In this study, we hypothesized that established HPH would confer vulnerability to acute O{sub 3} pulmonary toxicity. Additionally, we tested whether improvement of pulmonary endothelial barrier integrity via rho-kinase inhibition could mitigate pulmonary inflammation and injury. To determine if O{sub 3} exacerbated HPH, male C57BL/6 mice were subject to either 3 weeks continuous normoxia (20.9% O{sub 2}) or hypoxia (10.0% O{sub 2}), followed by a 4-h exposure to either 1 ppm O{sub 3} or filtered air (FA). As an additional experimental intervention fasudil (20 mg/kg) was administered intraperitoneally prior to and after O{sub 3} exposures. As expected, hypoxia significantly increased right ventricular pressure and hypertrophy. O{sub 3} exposure in normoxic mice caused lung inflammation but not injury, as indicated by increased cellularity and edema in the lung. However, in hypoxic mice, O{sub 3} exposure led to increased inflammation and edema, along with a profound increase in airway hyperresponsiveness to methacholine. Fasudil administration resulted in reduced O{sub 3}-induced lung injury via the enhancement of pulmonary endothelial barrier integrity. These results indicate that increased pulmonary vascular pressure may enhance lung injury, inflammation and edema when exposed to pollutants, and that enhancement of pulmonary endothelial barrier integrity may alleviate such vulnerability. - Highlights: • Environmental exposures can exacerbate chronic obstructive

  3. Hypoxia-induced pulmonary arterial hypertension augments lung injury and airway reactivity caused by ozone exposure

    International Nuclear Information System (INIS)

    Zychowski, Katherine E.; Lucas, Selita N.; Sanchez, Bethany; Herbert, Guy; Campen, Matthew J.

    2016-01-01

    Ozone (O 3 )-related cardiorespiratory effects are a growing public health concern. Ground level O 3 can exacerbate pre-existing respiratory conditions; however, research regarding therapeutic interventions to reduce O 3 -induced lung injury is limited. In patients with chronic obstructive pulmonary disease, hypoxia-associated pulmonary hypertension (HPH) is a frequent comorbidity that is difficult to treat clinically, yet associated with increased mortality and frequency of exacerbations. In this study, we hypothesized that established HPH would confer vulnerability to acute O 3 pulmonary toxicity. Additionally, we tested whether improvement of pulmonary endothelial barrier integrity via rho-kinase inhibition could mitigate pulmonary inflammation and injury. To determine if O 3 exacerbated HPH, male C57BL/6 mice were subject to either 3 weeks continuous normoxia (20.9% O 2 ) or hypoxia (10.0% O 2 ), followed by a 4-h exposure to either 1 ppm O 3 or filtered air (FA). As an additional experimental intervention fasudil (20 mg/kg) was administered intraperitoneally prior to and after O 3 exposures. As expected, hypoxia significantly increased right ventricular pressure and hypertrophy. O 3 exposure in normoxic mice caused lung inflammation but not injury, as indicated by increased cellularity and edema in the lung. However, in hypoxic mice, O 3 exposure led to increased inflammation and edema, along with a profound increase in airway hyperresponsiveness to methacholine. Fasudil administration resulted in reduced O 3 -induced lung injury via the enhancement of pulmonary endothelial barrier integrity. These results indicate that increased pulmonary vascular pressure may enhance lung injury, inflammation and edema when exposed to pollutants, and that enhancement of pulmonary endothelial barrier integrity may alleviate such vulnerability. - Highlights: • Environmental exposures can exacerbate chronic obstructive pulmonary disease (COPD). • It is unknown if comorbid

  4. CD4 T cell knockout does not protect against kidney injury and worsens cancer.

    Science.gov (United States)

    Ravichandran, Kameswaran; Wang, Qian; Ozkok, Abdullah; Jani, Alkesh; Li, Howard; He, Zhibin; Ljubanovic, Danica; Weiser-Evans, Mary C; Nemenoff, Raphael A; Edelstein, Charles L

    2016-04-01

    Most previous studies of cisplatin-induced acute kidney injury (AKI) have been in models of acute, high-dose cisplatin administration that leads to mortality in non-tumor-bearing mice. The aim of the study was to determine whether CD4 T cell knockout protects against AKI and cancer in a clinically relevant model of low-dose cisplatin-induced AKI in mice with cancer. Kidney function, serum neutrophil gelatinase-associated lipocalin (NGAL), acute tubular necrosis (ATN), and tubular apoptosis score were the same in wild-type and CD4 -/- mice with AKI. The lack of protection against AKI in CD4 -/- mice was associated with an increase in extracellular signal-regulated kinase (ERK), p38, CXCL1, and TNF-α, mediators of AKI and fibrosis, in both cisplatin-treated CD4 -/- mice and wild-type mice. The lack of protection was independent of the presence of cancer or not. Tumor size was double, and cisplatin had an impaired therapeutic effect on the tumors in CD4 -/- vs. wild-type mice. Mice depleted of CD4 T cells using the GK1.5 antibody were not protected against AKI and had larger tumors and lesser response to cisplatin. In summary, in a clinically relevant model of cisplatin-induced AKI in mice with cancer, (1) CD4 -/- mice were not protected against AKI; (2) ERK, p38, CXCL1, and TNF-α, known mediators of AKI, and interstitial fibrosis were increased in CD4 -/- kidneys; and (3) CD4 -/- mice had faster tumor growth and an impaired therapeutic effect of cisplatin on the tumors. The data warns against the use of CD4 T cell inhibition to attenuate cisplatin-induced AKI in patients with cancer. A clinically relevant low-dose cisplatin model of AKI in mice with cancer was used. CD4 -/- mice were not functionally or histologically protected against AKI. CD4 -/- mice had faster tumor growth. CD4 -/- mice had an impaired therapeutic effect of cisplatin on the tumors. Mice depleted of CD4 T cells were not protected against AKI and had larger tumors.

  5. Pharmacogenomic Variants May Influence the Urinary Excretion of Novel Kidney Injury Biomarkers in Patients Receiving Cisplatin

    Science.gov (United States)

    Chang, Cara; Hu, Yichun; Hogan, Susan L.; Mercke, Nickie; Gomez, Madeleine; O’Bryant, Cindy; Bowles, Daniel W.; George, Blessy; Wen, Xia; Aleksunes, Lauren M.; Joy, Melanie S.

    2017-01-01

    Nephrotoxicity is a dose limiting side effect associated with the use of cisplatin in the treatment of solid tumors. The degree of nephrotoxicity is dictated by the selective accumulation of cisplatin in renal tubule cells due to: (1) uptake by organic cation transporter 2 (OCT2) and copper transporter 1 (CTR1); (2) metabolism by glutathione S-transferases (GSTs) and γ-glutamyltransferase 1 (GGT1); and (3) efflux by multidrug resistance-associated protein 2 (MRP2) and multidrug and toxin extrusion protein 1 (MATE1). The purpose of this study was to determine the significance of single nucleotide polymorphisms that regulate the expression and function of transporters and metabolism genes implicated in development of acute kidney injury (AKI) in cisplatin treated patients. Changes in the kidney function were assessed using novel urinary protein biomarkers and traditional markers. Genotyping was conducted by the QuantStudio 12K Flex Real-Time PCR System using a custom open array chip with metabolism, transport, and transcription factor polymorphisms of interest to cisplatin disposition and toxicity. Traditional and novel biomarker assays for kidney toxicity were assessed for differences according to genotype by ANOVA. Allele and genotype frequencies were determined based on Caucasian population frequencies. The polymorphisms rs596881 (SLC22A2/OCT2), and rs12686377 and rs7851395 (SLC31A1/CTR1) were associated with renoprotection and maintenance of estimated glomerular filtration rate (eGFR). Polymorphisms in SLC22A2/OCT2, SLC31A1/CTRI, SLC47A1/MATE1, ABCC2/MRP2, and GSTP1 were significantly associated with increases in the urinary excretion of novel AKI biomarkers: KIM-1, TFF3, MCP1, NGAL, clusterin, cystatin C, and calbindin. Knowledge concerning which genotypes in drug transporters are associated with cisplatin-induced nephrotoxicity may help to identify at-risk patients and initiate strategies, such as using lower or fractionated cisplatin doses or avoiding

  6. Analysis of spatiotemporal metabolomic dynamics for sensitively monitoring biological alterations in cisplatin-induced acute kidney injury.

    Science.gov (United States)

    Irie, Miho; Hayakawa, Eisuke; Fujimura, Yoshinori; Honda, Youhei; Setoyama, Daiki; Wariishi, Hiroyuki; Hyodo, Fuminori; Miura, Daisuke

    2018-01-29

    Clinical application of the major anticancer drug, cisplatin, is limited by severe side effects, especially acute kidney injury (AKI) caused by nephrotoxicity. The detailed metabolic mechanism is still largely unknown. Here, we used an integrated technique combining mass spectrometry imaging (MSI) and liquid chromatography-mass spectrometry (LC-MS) to visualize the diverse spatiotemporal metabolic dynamics in the mouse kidney after cisplatin dosing. Biological responses to cisplatin was more sensitively detected within 24 h as a metabolic alteration, which is much earlier than possible with the conventional clinical chemistry method of blood urea nitrogen (BUN) measurement. Region-specific changes (e.g., medulla and cortex) in metabolites related to DNA damage and energy generation were observed over the 72-h exposure period. Therefore, this metabolomics approach may become a novel strategy for elucidating early renal responses to cisplatin, prior to the detection of kidney damage evaluated by conventional method. Copyright © 2018. Published by Elsevier Inc.

  7. Breast Regression Protein-39/Chitinase 3-Like 1 Promotes Renal Fibrosis after Kidney Injury via Activation of Myofibroblasts.

    Science.gov (United States)

    Montgomery, Tinika A; Xu, Leyuan; Mason, Sherene; Chinnadurai, Amirtha; Lee, Chun Geun; Elias, Jack A; Cantley, Lloyd G

    2017-11-01

    The normal response to kidney injury includes a robust inflammatory infiltrate of PMNs and macrophages. We previously showed that the small secreted protein breast regression protein-39 (BRP-39), also known as chitinase 3-like 1 (CHI3L1) and encoded by the Chi3l1 gene, is expressed at high levels by macrophages during the early stages of kidney repair and promotes tubular cell survival via IL-13 receptor α 2 (IL13R α 2)-mediated signaling. Here, we investigated the role of BRP-39 in profibrotic responses after AKI. In wild-type mice, failure to resolve tubular injury after unilateral ischemia-reperfusion injury (U-IRI) led to sustained low-level Chi3l1 mRNA expression by renal cells and promoted macrophage persistence and severe interstitial fibrosis. Analysis of macrophages isolated from wild-type kidneys 14 days after U-IRI revealed high-level expression of the profibrotic BRP-39 receptor Ptgdr2 / Crth2 and expression of the profibrotic markers Lgals3 , Pdgfb , Egf , and Tgfb In comparison, injured kidneys from mice lacking BRP-39 had significantly fewer macrophages, reduced expression of profibrotic growth factors, and decreased accumulation of extracellular matrix. BRP-39 depletion did not affect myofibroblast accumulation but did attenuate myofibroblast expression of Col1a1 , Col3a1 , and Fn1 Together, these results identify BRP-39 as an important activator of macrophage-myofibroblast crosstalk and profibrotic signaling in the setting of maladaptive kidney repair. Copyright © 2017 by the American Society of Nephrology.

  8. Blood Pressure Lowering and Safety Improvements With Liver Angiotensinogen Inhibition in Models of Hypertension and Kidney Injury.

    Science.gov (United States)

    Mullick, Adam E; Yeh, Steve T; Graham, Mark J; Engelhardt, Jeffery A; Prakash, Thazha P; Crooke, Rosanne M

    2017-09-01

    Uncontrolled hypertension is an important contributor to cardiovascular disease. Despite the armamentarium of antihypertensive treatments, there remains a need for novel agents effective in individuals who cannot reach acceptable blood pressure levels. Inhibitors targeting the renin-angiotensin-aldosterone system (RAAS) are widely used but may not optimally inhibit RAAS and demonstrate an acceptable safety profile. Experiments were conducted to characterize a series of AGT (angiotensinogen) antisense oligonucleotides (ASOs) and compare their efficacy and tolerability to traditional RAAS blockade. AGT ASOs which target multiple systemic sites of AGT versus an N-acetylgalactosamine-conjugated AGT ASO that targets the liver were compared with captopril and losartan. Spontaneously hypertensive rats fed an 8% NaCl diet, a model of malignant hypertension resistant to standard RAAS inhibitors, demonstrated robust and durable blood pressure reductions with AGT ASO treatments, which was not observed with standard RAAS blockade. Studies in rat models of acute kidney injury produced by salt deprivation revealed kidney injury with ASO treatment that reduced kidney-expressed AGT, but not in animals treated with the N-acetylgalactosamine AGT ASO despite comparable plasma AGT reductions. Administration of either captopril or losartan also produced acute kidney injury during salt deprivation. Thus, intrarenal RAAS derived from kidney AGT, and inhibited by the standard of care, contributes to the maintenance of renal function during severe RAAS challenge. Such improvements in efficacy and tolerability by a liver-selective AGT inhibitor could be desirable in individuals not at their blood pressure goal with existing RAAS blockade. © 2017 American Heart Association, Inc.

  9. A Case of Mushroom Poisoning with Russula subnigricans: Development of Rhabdomyolysis, Acute Kidney Injury, Cardiogenic Shock, and Death.

    Science.gov (United States)

    Cho, Jong Tae; Han, Jin Hyung

    2016-07-01

    Mushroom exposures are increasing worldwide. The incidence and fatality of mushroom poisoning are reported to be increasing. Several new syndromes in mushroom poisoning have been described. Rhabdomyolytic mushroom poisoning is one of new syndromes. Russula subnigricans mushroom can cause delayed-onset rhabdomyolysis with acute kidney injury in the severely poisoned patient. There are few reports on the toxicity of R. subnigricans. This report represents the first record of R. subnigricans poisoning with rhabdomyolysis in Korea, describing a 51-year-old man who suffered from rhabdomyolysis, acute kidney injury, severe hypocalcemia, respiratory failure, ventricular tachycardia, cardiogenic shock, and death. Mushroom poisoning should be considered in the evaluation of rhabdomyolysis of unknown cause. Furthermore, R. subnigricans should be considered in the mushroom poisoning with rhabdomyolysis.

  10. Relationships between cerebral autoregulation and markers of kidney and liver injury in neonatal encephalopathy and therapeutic hypothermia.

    Science.gov (United States)

    Lee, J K; Perin, J; Parkinson, C; O'Connor, M; Gilmore, M M; Reyes, M; Armstrong, J; Jennings, J M; Northington, F J; Chavez-Valdez, R

    2017-08-01

    We studied whether cerebral blood pressure autoregulation and kidney and liver injuries are associated in neonatal encephalopathy (NE). We monitored autoregulation of 75 newborns who received hypothermia for NE in the neonatal intensive care unit to identify the mean arterial blood pressure with optimized autoregulation (MAP OPT ). Autoregulation parameters and creatinine, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were analyzed using adjusted regression models. Greater time with blood pressure within MAP OPT during hypothermia was associated with lower creatinine in girls. Blood pressure below MAP OPT related to higher ALT and AST during normothermia in all neonates and boys. The opposite occurred in rewarming when more time with blood pressure above MAP OPT related to higher AST. Blood pressures that optimize cerebral autoregulation may support the kidneys. Blood pressures below MAP OPT and liver injury during normothermia are associated. The relationship between MAP OPT and AST during rewarming requires further study.

  11. Mesenchymal stem cells ameliorate rhabdomyolysis-induced acute kidney injury via the activation of M2 macrophages

    Science.gov (United States)

    2014-01-01

    Introduction The mortality of rhabdomyolysis-induced acute kidney injury (AKI) is still high, as there is no effective therapy. It has been shown that bone marrow-derived mesenchymal stem cells (MSCs) can induce M2 macrophages, which mediate MSC protection in other experimental inflammation-related organ injury. This study was designed to investigate the protective effects of macrophage activation in MSC therapy of rhabdomyolysis-induced AKI. Methods MSCs were injected into glycerol-induced rhabdomyolysis mice. Renal injury was evaluated using the serum creatinine, urea nitrogen, renal pathology and acute tubular necrosis score. The distribution of MSCs was detected using two-photon fluorescence confocal imaging. Immunofluorescence of anti-F4/80 and anti-CD206 was performed to determine macrophages and M2 macrophages in the tissues of the kidney, and M2 macrophage infiltration was also evaluated using western blotting analyses. After depletion of macrophages using clodronate liposomes at the phase of kidney repair, renal injury was re-evaluated. RAW 264.7 macrophages were incubated with lipopolysaccharide and co-cultured with MSCs and subsequently visualised using immunofluorescence staining and flow cytometry analysis. Finally, disparate phenotype macrophages, including normal macrophages (M0), lipopolysaccharide-stimulated macrophages (M1), and MSC-co-cultured macrophages (M2), were infused into mice with AKI, which were pre-treated with liposomal clodronate. Results In vivo infusion of MSCs protected AKI mice from renal function impairment and severe tubular injury, which was accompanied by a time-dependent increase in CD206-positive M2 macrophage infiltration. In addition, depleting macrophages with clodronate delayed restoration of AKI. In vitro, macrophages co-cultured with MSCs acquired an anti-inflammatory M2 phenotype, which was characterised by an increased expression of CD206 and the secretory cytokine interleukin (IL)-10. The concentrations of IL-10, IL

  12. Structural Injury after Lithium Treatment in Human and Rat Kidney involves Glycogen Synthase Kinase-3β Positive Epithelium

    DEFF Research Database (Denmark)

    Kjærsgaard, Gitte; Madsen, Kirsten; Marcussen, Niels

    2011-01-01

    Lithium is reabsorbed by distal nephron segments in sodium depleted states. It was hypothesized that lithium causes permanent injury to the developing kidney particularly in the sodium-retaining phase around weaning through entry into epithelial cells of the distal nephron and inhibition of glyco....... Lithium causes proliferation, structural injury and increases inactive pGSK-3β abundance in these segments. The data are compatible with epithelial entry of lithium and a causal role for GSK-3β in postnatal developing cortical collecting duct epithelium....

  13. Blood transfusion improves renal oxygenation and renal function in sepsis-induced acute kidney injury in rats.

    Science.gov (United States)

    Zafrani, Lara; Ergin, Bulent; Kapucu, Aysegul; Ince, Can

    2016-12-20

    The effects of blood transfusion on renal microcirculation during sepsis are unknown. This study aimed to investigate the effect of blood transfusion on renal microvascular oxygenation and renal function during sepsis-induced acute kidney injury. Twenty-seven Wistar albino rats were randomized into four groups: a sham group (n = 6), a lipopolysaccharide (LPS) group (n = 7), a LPS group that received fluid resuscitation (n = 7), and a LPS group that received blood transfusion (n = 7). The mean arterial blood pressure, renal blood flow, and renal microvascular oxygenation within the kidney cortex were recorded. Acute kidney injury was assessed using the serum creatinine levels, metabolic cost, and histopathological lesions. Nitrosative stress (expression of endothelial (eNOS) and inducible nitric oxide synthase (iNOS)) within the kidney was assessed by immunohistochemistry. Hemoglobin levels, pH, serum lactate levels, and liver enzymes were measured. Fluid resuscitation and blood transfusion both significantly improved the mean arterial pressure and renal blood flow after LPS infusion. Renal microvascular oxygenation, serum creatinine levels, and tubular damage significantly improved in the LPS group that received blood transfusion compared to the group that received fluids. Moreover, the renal expression of eNOS was markedly suppressed under endotoxin challenge. Blood transfusion, but not fluid resuscitation, was able to restore the renal expression of eNOS. However, there were no significant differences in lactic acidosis or liver function between the two groups. Blood transfusion significantly improved renal function in endotoxemic rats. The specific beneficial effect of blood transfusion on the kidney could have been mediated in part by the improvements in renal microvascular oxygenation and sepsis-induced endothelial dysfunction via the restoration of eNOS expression within the kidney.

  14. Hydrogen sulfide in posthemorrhagic shock mesenteric lymph drainage alleviates kidney injury in rats

    Energy Technology Data Exchange (ETDEWEB)

    Han, B.; Zhao, Z.G.; Zhang, L.M.; Li, S.G.; Niu, C.Y. [Institute of Microcirculation, Hebei North University, Hebei Zhangjiakou (China)

    2015-04-28

    Posthemorrhagic shock mesenteric lymph (PHSML) is a key factor in multiple organ injury following hemorrhagic shock. We investigated the role of hydrogen sulfide (H{sub 2}S) in PHSML drainage in alleviating acute kidney injury (AKI) by administering D,L-propargylglycine (PPG) and sodium hydrosulfide hydrate (NaHS) to 12 specific pathogen-free male Wistar rats with PHSML drainage. A hemorrhagic shock model was established in 4 experimental groups: shock, shock+drainage, shock+drainage+PPG (45 mg/kg, 0.5 h prehemorrhage), and shock+drainage+NaHS (28 µmol/kg, 0.5 h prehemorrhage). Fluid resuscitation was performed after 1 h of hypotension, and PHMSL was drained in the last three groups for 3 h after resuscitation. Renal function and histomorphology were assessed along with levels of H{sub 2}S, cystathionine-γ-lyase (CSE), Toll-like receptor 4 (TLR4), interleukin (IL)-10, IL-12, and tumor necrosis factor (TNF)-α in renal tissue. Hemorrhagic shock induced AKI with increased urea and creatinine levels in plasma and higher H{sub 2}S, CSE, TLR4, IL-10, IL-12, and TNF-α levels in renal tissue. PHSML drainage significantly reduced urea, creatinine, H{sub 2}S, CSE, and TNF-α but not TLR4, IL-10, or IL-12. PPG decreased creatinine, H{sub 2}S, IL-10, and TNF-α levels, but this effect was reversed by NaHS administration. In conclusion, PHSML drainage alleviated AKI following hemorrhagic shock by preventing increases in H{sub 2}S and H{sub 2}S-mediated inflammation.

  15. Creatinine as predictor value of mortality and acute kidney injury in rhabdomyolysis.

    Science.gov (United States)

    Baeza-Trinidad, R; Brea-Hernando, A; Morera-Rodriguez, S; Brito-Diaz, Y; Sanchez-Hernandez, S; El Bikri, L; Ramalle-Gomara, E; Garcia-Alvarez, J L

    2015-11-01

    Rhabdomyolysis (RB) is a syndrome characterised by decomposition of skeletal muscle that could be life threatening, so the identification of biomarkers of its severity could help us in its treatment. Creatine kinase (CK) is usually taken as a reference in patients with RB in order to stratify prognosis, however that is not probably the most effective parameter. The present study was designed to analyse the specific features and mortality of patients with RB and the relation between creatinine, CK and mortality. Retrospective cohort analysis among patients admitted to San Pedro Hospital in Logroño (Spain) with RB (CK levels higher than 2000 U/L) diagnosed since 1 January 2009 until 31 December 2; 013 522 patients with RB patients diagnosed of RB were collected. The aetiology and the analytical feature (creatinine, CK, calcium, phosphorus, pH and bicarbonate), as well as 30-year mortality, were investigated. Among the 522 patients, there were 138 deaths. Four patients required renal replacement therapy. The most common cause of RB was trauma (29%). Infectious aetiology had the highest mortality (41.2%). The median CK was 3451 u/L (interquartile range 3348), and the mean creatinine at admission was 132.6 umol/L (±110.5). Initial CK levels do not have predictive ability on mortality or renal dysfunction in contrast to initial creatinine values. Each state of acute kidney injury (AKI) increased mortality compared with those who have not presented this renal dysfunction (P creatinine initial levels are related to progression to acute renal injury and mortality at 30 days. © 2015 Royal Australasian College of Physicians.

  16. Differences in gene expression profiles and signaling pathways in rhabdomyolysis-induced acute kidney injury.

    Science.gov (United States)

    Geng, Xiaodong; Wang, Yuanda; Hong, Quan; Yang, Jurong; Zheng, Wei; Zhang, Gang; Cai, Guangyan; Chen, Xiangmei; Wu, Di

    2015-01-01

    Rhabdomyolysis is a threatening syndrome because it causes the breakdown of skeletal muscle. Muscle destruction leads to the release of myoglobin, intracellular proteins, and electrolytes into the circulation. The aim of this study was to investigate the differences in gene expression profiles and signaling pathways upon rhabdomyolysis-induced acute kidney injury (AKI). In this study, we used glycerol-induced renal injury as a model of rhabdomyolysis-induced AKI. We analyzed data and relevant information from the Gene Expression Omnibus database (No: GSE44925). The gene expression data for three untreated mice were compared to data for five mice with rhabdomyolysis-induced AKI. The expression profiling of the three untreated mice and the five rhabdomyolysis-induced AKI mice was performed using microarray analysis. We examined the levels of Cyp3a13, Rela, Aldh7a1, Jun, CD14. And Cdkn1a using RT-PCR to determine the accuracy of the microarray results. The microarray analysis showed that there were 1050 downregulated and 659 upregulated genes in the rhabdomyolysis-induced AKI mice compared to the control group. The interactions of all differentially expressed genes in the Signal-Net were analyzed. Cyp3a13 and Rela had the most interactions with other genes. The data showed that Rela and Aldh7a1 were the key nodes and had important positions in the Signal-Net. The genes Jun, CD14, and Cdkn1a were also significantly upregulated. The pathway analysis classified the differentially expressed genes into 71 downregulated and 48 upregulated pathways including the PI3K/Akt, MAPK, and NF-κB signaling pathways. The results of this study indicate that the NF-κB, MAPK, PI3K/Akt, and apoptotic pathways are regulated in rhabdomyolysis-induced AKI.

  17. Clinical value of renal injury biomarkers in diagnosis of chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Cheng-lu ZHANG

    2011-12-01

    Full Text Available Objective To investigate the levels of renal injury biomarkers in patients with chronic kidney disease(CKD and evaluate their clinical significances in diagnosis of CKD.Methods A total of 66 subjects(37 patients with CKD and 29 healthy individuals were involved in this study.Serum blood urea nitrogen(SBUN was determined by Glutamate dehydrogenase method;serum creatinine(SCr and urinary creatinine(UCr were detected by sarcosine oxidase method;serum uric acid(SUA was measured by uricase colorimetry;serum cystatin C(Cys C and urinary microalbumin(UmAlbwere analyzed by immunological transmission turbidimetry;urinary protein(U-PROwas measured by Coomassies Brilliant Blue(CBB assay.The UmAlb and U-PRO levels were expressed in units of mg/mmolUCr.Results The results of independent samples t test indicated that significant differences were found in SBUN,SCr,SUA,Cys C,UmAlb and U-PRO(P < 0.05 between patient group and healthy control group.The evaluation of diagnostic effects showed that the areas under the curve at ROC plot for SBUN,SCr,SUA,Cys C,UmAlb and U-PRO were 0.907,0.912,0.742,0.982,0.984 and 0.991,respectively.Conclusions U-PRO,UmAlb and Cys C are ideal biomarkers,SCr and SBUN come next,SUA is the weakest when the above biomarkers are applied to evaluate the renal injury and its severity of the patients with CKD.

  18. [Acute kidney injury after pediatric cardiac surgery: risk factors and outcomes. Proposal for a predictive model].

    Science.gov (United States)

    Cardoso, Bárbara; Laranjo, Sérgio; Gomes, Inês; Freitas, Isabel; Trigo, Conceição; Fragata, Isabel; Fragata, José; Pinto, Fátima

    2016-02-01

    To characterize the epidemiology and risk factors for acute kidney injury (AKI) after pediatric cardiac surgery in our center, to determine its association with poor short-term outcomes, and to develop a logistic regression model that will predict the risk of AKI for the study population. This single-center, retrospective study included consecutive pediatric patients with congenital heart disease who underwent cardiac surgery between January 2010 and December 2012. Exclusion criteria were a history of renal disease, dialysis or renal transplantation. Of the 325 patients included, median age three years (1 day-18 years), AKI occurred in 40 (12.3%) on the first postoperative day. Overall mortality was 13 (4%), nine of whom were in the AKI group. AKI was significantly associated with length of intensive care unit stay, length of mechanical ventilation and in-hospital death (p<0.01). Patients' age and postoperative serum creatinine, blood urea nitrogen and lactate levels were included in the logistic regression model as predictor variables. The model accurately predicted AKI in this population, with a maximum combined sensitivity of 82.1% and specificity of 75.4%. AKI is common and is associated with poor short-term outcomes in this setting. Younger age and higher postoperative serum creatinine, blood urea nitrogen and lactate levels were powerful predictors of renal injury in this population. The proposed model could be a useful tool for risk stratification of these patients. Copyright © 2015 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  19. Unique sex- and age-dependent effects in protective pathways in acute kidney injury.

    Science.gov (United States)

    Boddu, Ravindra; Fan, Chunlan; Rangarajan, Sunil; Sunil, Bhuvana; Bolisetty, Subhashini; Curtis, Lisa M

    2017-09-01

    Sex and age influence susceptibility to acute kidney injury (AKI), with young females exhibiting lowest incidence. In these studies, we investigated mechanisms which may underlie the sex/age-based dissimilarities. Cisplatin (Cp)-induced AKI resulted in morphological evidence of injury in all groups. A minimal rise in plasma creatinine (PCr) was seen in Young Females, whereas in Aged Females, PCr rose precipitously. Relative to Young Males, Aged Males showed significantly, but temporally, comparably elevated PCr. Notably, Aged Females showed significantly greater mortality, whereas Young Females exhibited none. Tissue KIM-1 and plasma NGAL were significantly lower in Young Females than all others. IGFBP7 levels were modestly increased in both Young groups. IGFBP7 levels in Aged Females were significantly elevated at baseline relative to Aged Males, and increased linearly through day 3 , when these levels were comparable in both Aged groups. Plasma cytokine levels similarly showed a pattern of protective effects preferentially in Young Females. Expression of the drug transporter MATE2 did not explain the sex/age distinctions. Heme oxygenase-1 (HO-1) levels (~28-kDa species) showed elevation at day 1 in all groups with highest levels seen in Young Males. Exclusively in Young Females, these levels returned to baseline on day 3 , suggestive of a more efficient recovery. In aggregate, we demonstrate, for the first time, a distinctive pattern of response to AKI in Young Females relative to males which appears to be significantly altered in aging. These distinctions may offer novel targets to exploit therapeutically in both females and males in the treatment of AKI.

  20. Shock Wave Injury to the Kidney in SWL: Review and Perspective

    Science.gov (United States)

    McAteer, James A.; Evan, Andrew P.; Willis, Lynn R.; Connors, Bret A.; Williams, James C.; Pishchalnikov, Yuri A.; Lingeman, James E.

    2007-04-01

    Shock wave lithotripsy (SWL) is a first-line option for treatment for urinary calculi—particularly effective for the removal of uncomplicated stones from the upper urinary tract. The success of lithotripsy is tempered, however, by the occurrence of acute injury that has been reported to progress to long-term complications. SW trauma to the kidney is a vascular lesion characterized by parenchymal and subcapsular bleeding. The acute lesion is dose-dependent, and typically localized to the focal volume of the lithotripter. Cavitation has been implicated in vessel rupture, but SW-shear has the potential to be a primary mechanism for damage as well. Possible chronic adverse effects of SWL may include new-onset hypertension, development of diabetes, and exacerbation of stone disease. If acute trauma could be reduced, it seems likely that serious long-term effects could be minimized, or even eliminated. Reducing the dose of SW's needed for stone breakage is one option. Improved coupling improves stone breakage, and slowing SW rate significantly improves stone-free outcomes. Experiments with animals now show that treatment protocols can be designed to protect against tissue injury. Initiating treatment with low energy SW's dramatically reduces lesion size, and reducing the rate of SW delivery virtually eliminates SW trauma altogether. SWL stands to gain from new advances in technology, as lithotripters become safer and more effective. Perhaps the greatest progress will be made when we have determined the physical mechanisms of SW action both for stone breakage and tissue damage, and have better characterized the biological response to SW's—as this will provide the principles needed to achieve the best combination of safety and efficiency with whatever lithotripter is at hand.

  1. Dynamics of markers of markers of acute kidney injury when using epidural block during resection under warm ischemia

    Directory of Open Access Journals (Sweden)

    O. I. Kit

    2017-01-01

    Full Text Available Objective: to investigate the time course of changes in the early biomarkers of acute kidney injury in patients with clinically localized cancer during partial nephrectomy, as electively indicated, under thermal ischemia with prior epidural block.Materials and methods. To analyze the nephroprotective effect of an epidural block in kidney resection with warm ischemia, markers of acute kidney injury (cystatin C, interleukin 18, NGAL, L-FABP and KIM-1 were studied by ELISA in the blood and urine of 35 patients with local cancer with an epidural block (main group and 37 patients with local cancer without an epidural block (control group before surgery and 40 min after its beginning and on days 1 and 3 of the postoperative period. All patients were divided into 2 groups by the levels of cystatin C in the blood serum: 1000 ng/ml and lower, and over 1000 ng/ml.Results. Epidural block during the perioperative period in kidney resection with warm ischemia for patients with local cancer had an obvious nephroprotective effect allowing maintaining the initial renal functional parameters, in contrast to the standard disease management.

  2. The first description of severe anemia associated with acute kidney injury and adult minimal change disease: a case report

    Directory of Open Access Journals (Sweden)

    Qian Yimei

    2009-01-01

    Full Text Available Abstract Introduction Acute kidney injury in the setting of adult minimal change disease is associated with proteinuria, hypertension and hyperlipidemia but anemia is usually absent. Renal biopsies exhibit foot process effacement as well as tubular interstitial inflammation, acute tubular necrosis or intratubular obstruction. We recently managed a patient with unique clinical and pathological features of minimal change disease, who presented with severe anemia and acute kidney injury, an association not previously reported in the literature. Case presentation A 60-year-old Indian-American woman with a history of hypertension and diabetes mellitus for 10 years presented with progressive oliguria over 2 days. Laboratory data revealed severe hyperkalemia, azotemia, heavy proteinuria and progressively worsening anemia. Urine eosinophils were not seen. Emergent hemodialysis, erythropoietin and blood transfusion were initiated. Serologic tests for hepatitis B, hepatitis C, anti-nuclear antibodies, anti-glomerular basement membrane antibodies and anti-neutrophil cytoplasmic antibodies were negative. Complement levels (C3, C4 and CH50 were normal. Renal biopsy unexpectedly displayed 100% foot process effacement. A 24-hour urine collection detected 6.38 g of protein. Proteinuria and anemia resolved during six weeks of steroid therapy. Renal function recovered completely. No signs of relapse were observed at 8-month follow-up. Conclusion Adult minimal change disease should be considered when a patient presents with proteinuria and severe acute kidney injury even when accompanied by severe anemia. This report adds to a growing body of literature suggesting that in addition to steroid therapy, prompt initiation of erythropoietin therapy may facilitate full recovery of renal function in acute kidney injury.

  3. Successful use of combined high cut-off haemodialysis and bortezomib for acute kidney injury associated with myeloma cast nephropathy.

    LENUS (Irish Health Repository)

    Ward, F

    2012-05-01

    We present the case of a 58-year old female with de novo dialysis-dependent acute kidney injury (AKI) secondary to myeloma cast nephropathy. The patient underwent extended high cut-off haemodialysis (HCO-HD), in conjunction with bortezomib-based chemotherapy, and soon became dialysis independent with normal renal function. To our knowledge, this is the first time this treatment strategy has been employed successfully in an Irish centre.

  4. Acute kidney injury in critically burned patients resuscitated with a protocol that includes low doses of Hydroxyethyl Starch

    OpenAIRE

    Sánchez-Sánchez, M.; Garcia-de-Lorenzo, A.; Cachafeiro, L.; Herrero, E.; Asensio, MJ.; Agrifoglio, A.; Flores, E.; Estebanez, B.; Extremera, P.; Iglesias, C.; Martinez, J.R..

    2016-01-01

    Acute kidney injury (AKI) is an important complication in burn patients. Recently, it has been recommended that hydroxyethyl starch (HES) be avoided in burn patients because it increases the incidence of AKI. Our purpose was to study incidence of AKI in critically ill burn patients resuscitated with Ringer’s solution and supplements of HES. We conducted an observational study of 165 patients admitted to the critical care burn unit (with 30 ± 15% TBSA burned). The main outcome measures were in...

  5. Resolvin D1 Protects Lipopolysaccharide-induced Acute Kidney Injury by Down-regulating Nuclear Factor-kappa B Signal and Inhibiting Apoptosis

    Directory of Open Access Journals (Sweden)

    Yu-Liang Zhao

    2016-01-01

    Conclusion: In LPS-induced AKI, RvD1 could decrease TNF-α level, ameliorate kidney pathological injury, protect kidney function, and improve animal survival by down-regulating NF-κB inflammatory signal as well as inhibiting renal cell apoptosis.

  6. Virtual reality-augmented neurorehabilitation improves motor function and reduces neuropathic pain in patients with incomplete spinal cord injury.

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    Villiger, Michael; Bohli, Dominik; Kiper, Daniel; Pyk, Pawel; Spillmann, Jeremy; Meilick, Bruno; Curt, Armin; Hepp-Reymond, Marie-Claude; Hotz-Boendermaker, Sabina; Eng, Kynan

    2013-10-01

    Neurorehabilitation interventions to improve lower limb function and neuropathic pain have had limited success in people with chronic, incomplete spinal cord injury (iSCI). We hypothesized that intense virtual reality (VR)-augmented training of observed and executed leg movements would improve limb function and neuropathic pain. Patients used a VR system with a first-person view of virtual lower limbs, controlled via movement sensors fitted to the patient's own shoes. Four tasks were used to deliver intensive training of individual muscles (tibialis anterior, quadriceps, leg ad-/abductors). The tasks engaged motivation through feedback of task success. Fourteen chronic iSCI patients were treated over 4 weeks in 16 to 20 sessions of 45 minutes. Outcome measures were 10 Meter Walking Test, Berg Balance Scale, Lower Extremity Motor Score, Spinal Cord Independence Measure, Locomotion and Neuropathic Pain Scale (NPS), obtained at the start and at 4 to 6 weeks before intervention. In addition to positive changes reported by the patients (Patients' Global Impression of Change), measures of walking capacity, balance, and strength revealed improvements in lower limb function. Intensity and unpleasantness of neuropathic pain in half of the affected participants were reduced on the NPS test. Overall findings remained stable 12 to 16 weeks after termination of the training. In a pretest/posttest, uncontrolled design, VR-augmented training was associated with improvements in motor function and neuropathic pain in persons with chronic iSCI, several of which reached the level of a minimal clinically important change. A controlled trial is needed to compare this intervention to active training alone or in combination.

  7. Fas Ligand Has a Greater Impact than TNF-α on Apoptosis and Inflammation in Ischemic Acute Kidney Injury

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    Kengo Furuichi

    2012-02-01

    Full Text Available Background/Aim: Fas ligand (FasL and tumor necrosis factor (TNF-α are major pro-apoptotic molecules and also induce inflammation through cytokine and chemokine production. Although precise intracellular mechanisms of action have been reported for each molecule, the differential impact of these molecules on kidney injury in vivo still requires clarification. Methods: We explored the differential impact of FasL and TNF-α upon apoptosis and inflammation in ischemic acute kidney injury using neutralizing anti-FasL antibodies and TNF-α receptor 1 (TNFR1-deficient mice. Results: TNFR1 deficiency was associated with a lesser anti-inflammatory effect upon leukocyte infiltration and tubular necrosis than treatment with anti-FasL antibody. Furthermore, the number of TUNEL-positive cells was significantly reduced in anti-FasL antibody-treated mice, whereas it was only partially diminished in TNFR1-deficient mice. In vitro studies confirmed these findings. FasL administration induced both apoptosis and cytokine/chemokine production from cultured tubular epithelial cells. However, TNF-α had a limited effect upon tubular epithelial cells. Conclusion: In ischemic acute kidney injury, FasL has a greater impact than TNF-α on the apoptosis and inflammatory reaction through cytokine/chemokine production from tubular epithelial cells.

  8. STUDY OF ACUTE KIDNEY INJURY IN CHILDREN: ITS AETIOLOGY, CLINICAL PROFILE AND OUTCOME

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    Garuda

    2015-03-01

    Full Text Available OBJECTIVES : To determine the incidence , age & sex ratio , analyse the spectrum of Acute Kidney Injury (AKI in its aetiopathology , complications including mortality , prognostic factors and the role of dialysis in the management. METHODS : This prospective observational study was conducted on serial cases of 30 patients a dmitted in Paediatrics department from Feb 2012 - Aug 2014 (30 months. RESULTS : The incidence of AKI was 0.44%. Children in age group of 0 - 4 yrs were affected most , predominantly males. Distribution of AKI according to aetiopathogenesis was Acute Tubular Necrosis (ATN 50% , Haemolytic Uraemic Syndrome (HUS 19.8% , Glomerulonephritis (GN 13.2% , Obstructive uropathy 9.9% and Acute on Chronic renal failure (CRF 6.6%. Dialysis was required in 53.3% of patients. Mortality was 57%. Patients with complications of sepsis , neurological & respiratory problems , hyperkalemia , metabolic acidosis and gastrointestinal bleeding were associated with high mortality. CONCLUSIONS : AKI is a common life threatening condition seen in childhood. Early referral , proper assessment , adequate & timely treatment and prompt institution of dialysis helps in decreasing mortality.

  9. Contrast-induced acute kidney injury: how much contrast is safe?

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    Keaney, John J

    2013-02-14

    Iodinated contrast media (CM) are used in many investigations that a patient may undergo during the course of an in-patient stay. For the vast majority of patients, exposure to CM has no sequelae; however, in a small percentage, it can result in a worsening in renal function termed contrast-induced acute kidney injury (CI-AKI). CI-AKI is one of the leading causes of in-hospital renal dysfunction. It is associated with a significant increase in morbidity and mortality as well as an increased length of hospital stay and costs. Unfortunately, the results of extensive research into pharmacological inventions to prevent CI-AKI remain disappointing. In this article, we briefly outline the pathophysiological mechanisms by which iodinated CM may cause CI-AKI and discuss the evidence for reducing CI-AKI by limiting contrast volumes. In particular, we review the data surrounding the use of contrast volume to glomerular filtration rate ratios, which can be used by clinicians to effectively lower the incidence of CI-AKI in their patients.

  10. Contrast Media Viscosity versus Osmolality in Kidney Injury: Lessons from Animal Studies

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    Seeliger, Erdmann; Lenhard, Diana C.; Persson, Pontus B.

    2014-01-01

    Iodinated contrast media (CM) can induce acute kidney injury (AKI). CM share common iodine-related cytotoxic features but differ considerably with regard to osmolality and viscosity. Meta-analyses of clinical trials generally failed to reveal renal safety differences of modern CM with regard to these physicochemical properties. While most trials' reliance on serum creatinine as outcome measure contributes to this lack of clinical evidence, it largely relies on the nature of prospective clinical trials: effective prophylaxis by ample hydration must be employed. In everyday life, patients are often not well hydrated; here we lack clinical data. However, preclinical studies that directly measured glomerular filtration rate, intrarenal perfusion and oxygenation, and various markers of AKI have shown that the viscosity of CM is of vast importance. In the renal tubules, CM become enriched, as water is reabsorbed, but CM are not. In consequence, tubular fluid viscosity increases exponentially. This hinders glomerular filtration and tubular flow and, thereby, prolongs intrarenal retention of cytotoxic CM. Renal cells become injured, which triggers hypoperfusion and hypoxia, finally leading to AKI. Comparisons between modern CM reveal that moderately elevated osmolality has a renoprotective effect, in particular, in the dehydrated state, because it prevents excessive tubular fluid viscosity. PMID:24707482

  11. Who is at increased risk for acute kidney injury following noncardiac surgery?

    Science.gov (United States)

    Murray, Patrick

    2009-01-01

    Abelha and colleagues evaluated the incidence and determinants of postoperative acute kidney injury (AKI) after major noncardiac surgery in patients with previously normal renal function. In this retrospective study of 1,166 patients with no previous renal insufficiency, who were admitted to a postsurgical intensive care unit (ICU) over a 2-year period, the incidence of AKI was 7.5%. Multivariate analysis identified American Society of Anesthesiologists physical status, Revised Cardiac Risk Index, high-risk surgery and congestive heart disease as preoperative AKI risk factors. AKI was an independent risk factor for hospital mortality (odds ratio = 3.12, 95% confidence interval = 1.41 to 6.93; P = 0.005), and was associated with higher severity of illness scores (Simplified Acute Physiology Score II and Acute Physiology and Chronic Health Evaluation II), longer ICU length of stay, higher ICU mortality, increased hospital mortality and higher mortality at 6-month follow up. Although the study design excluded 121 patients with significant preoperative renal insufficiency by design, the relatively crude serum creatinine cut-offs used certainly permitted inclusion of numerous patients with preoperative renal impairment. Accordingly, the study design failed to quantify the impact of preoperative renal impairment on risk and outcomes of perioperative AKI in noncardiac surgery, and this should be a goal of such studies in the future. Nonetheless, the study is an important addition to the literature in an under-studied population of patients at high risk for AKI.

  12. Early-onset acute kidney injury is a poor prognostic sign for allogeneic SCT recipients.

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    Shingai, N; Morito, T; Najima, Y; Kobayashi, T; Doki, N; Kakihana, K; Ohashi, K; Ando, M

    2015-12-01

    Acute kidney injury (AKI) following stem-cell transplantation (SCT) contributes to a poor prognosis, yet its impact may vary depending on the timing of AKI onset. A prospective cohort study was performed to understand the significance of the onset timing in 103 allogeneic SCT (allo-SCT) recipients. AKI prior to stem-cell engraftment was defined as early AKI and subsequently occurring AKI as late AKI. Propensity score (PS) for early AKI was calculated using a logistic regression model to reduce confounding effects related to differences in clinical background between the early and late AKI groups. The cumulative incidences of early and late AKI were 22.3% and 54.9%, respectively. Non-relapse mortality (NRM) was 39.1% and 7.0%, and overall survival (OS) was 56.5% and 90.9% in early and late AKI at 100 days after AKI, respectively (PSCT was 41.5% and 19.1% in early and late AKI, respectively (P=0.048). Logistic regression analysis adjusted for the PS showed that early AKI was significantly associated with OS (odds ratio (95% confidence interval); 4.63 (1.15-21.4), P=0.031) but with neither NRM (1.25 (0.28-5.33), P=0.766) nor CKD (1.85 (0.41-8.60), P=0.422). In conclusion, early AKI may portend a poor survival for allo-SCT recipients.

  13. Effects of Schizolobium parahyba extract on experimental Bothrops venom-induced acute kidney injury.

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    Monique Silva Martines

    Full Text Available BACKGROUND: Venom-induced acute kidney injury (AKI is a frequent complication of Bothrops snakebite with relevant morbidity and mortality. The aim of this study was to assess the effects of Schizolobium parahyba (SP extract, a natural medicine with presumed anti-Bothrops venom effects, in an experimental model of Bothrops jararaca venom (BV-induced AKI. METHODOLOGY: Groups of 8 to 10 rats received infusions of 0.9% saline (control, C, SP 2 mg/kg, BV 0.25 mg/kg and BV immediately followed by SP (treatment, T in the doses already described. After the respective infusions, animals were assessed for their glomerular filtration rate (GFR, inulin clearance, renal blood flow (RBF, Doppler, blood pressure (BP, intra-arterial transducer, renal vascular resistance (RVR, urinary osmolality (UO, freezing point, urinary neutrophil gelatinase-associated lipocalin (NGAL, enzyme-linked immunosorbent assay [ELISA], lactate dehydrogenase (LDH, kinetic method, hematocrit (Hct, microhematocrit, fibrinogen (Fi, Klauss modified and blinded renal histology (acute tubular necrosis score. PRINCIPAL FINDINGS: BV caused significant decreases in GFR, RBF, UO, HcT and Fi; significant increases in RVR, NGAL and LDH; and acute tubular necrosis. SP did not prevent these changes; instead, it caused a significant decrease in GFR when used alone. CONCLUSION: SP administered simultaneously with BV, in an approximate 10∶1 concentration, did not prevent BV-induced AKI, hemolysis and fibrinogen consumption. SP used alone caused a decrease in GFR.

  14. Ibuprofen-associated acute kidney injury in dehydrated children with acute gastroenteritis.

    Science.gov (United States)

    Balestracci, Alejandro; Ezquer, Mauricio; Elmo, María Eugenia; Molini, Andrea; Thorel, Claudia; Torrents, Milagros; Toledo, Ismael

    2015-10-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) induce acute kidney injury (AKI) in volume-depleted patients; however the prevalence of this complication is likely underestimated. We assessed the impact of ibuprofen exposure on renal function among dehydrated children with acute gastroenteritis (AGE) to further characterize NSAID-associated AKI. Over a 1-year period dehydrated children with AGE (n = 105) were prospectively enrolled and grouped as cases, presenting with AKI (n = 46) or controls, not presenting with AKI (n = 59). AKI was defined by pediatric RIFLE (pRIFLE) criteria. Among the children enrolled in the study, AKI prevalence was 44 %, and 34 (54 %) of the 63 patients who received ibuprofen developed renal impairment. Relative to the controls, children presenting with AKI were younger (median age 0.66 vs. 1.74 years; p dehydration, ibuprofen exposure remained an independent risk factor for AKI (p dehydrated children with AGE. Drug exposure increased the risk for developing AKI by more than twofold, independent of the magnitude of the dehydration.

  15. A new approach to define acute kidney injury in term newborns with hypoxic ischemic encephalopathy.

    Science.gov (United States)

    Gupta, Charu; Massaro, An N; Ray, Patricio E

    2016-07-01

    Current definitions of acute kidney injury (AKI) are not sufficiently sensitive to identify all newborns with AKI during the first week of life. To determine whether the rate of decline of serum creatinine (SCr) during the first week of life can be used to identify newborns with AKI, we reviewed the medical records of 106 term neonates at risk of AKI who were treated with hypothermia for hypoxic ischemic encephalopathy (HIE). Of the newborns enrolled in the study, 69 % showed a normal rate of decline of SCr to ≥50 % and/or reached SCr levels of ≤0.6 mg/dl before the 7th day of life, and therefore had an excellent clinical outcome (control group). Thirteen newborns with HIE (12 %) developed AKI according to an established neonatal definition (AKI-KIDGO group), and an additional 20 newborns (19 %) showed a rate of decline of SCr of newborns in the other two groups required more days of mechanical ventilation and vasopressor drugs and had higher gentamicin levels, more fluid overload, lower urinary epidermal growth factor levels, and a prolonged length of stay. The rate of decline of SCr provides a sensitive approach to identify term newborns with AKI during the first week of life.

  16. Plasmodium falciparum-induced severe malaria with acute kidney injury and jaundice: a case report

    Science.gov (United States)

    Baswin, A.; Siregar, M. L.; Jamil, K. F.

    2018-03-01

    P. falciparum-induced severe malaria with life-threatening complications like acute kidney injury (AKI), jaundice, cerebral malaria, severe anemia, acidosis, and acute respiratory distress syndrome (ARDS). A 31-year-old soldier man who works in Aceh Singkil, Indonesia which is an endemic malaria area presented with a paroxysm of fever, shaking chills and sweats over four days, headache, arthralgia, abdominal pain, pale, jaundice, and oliguria. Urinalysis showed hemoglobinuria. Blood examination showed hemolytic anemia, thrombocytopenia, and hyperbilirubinemia. Falciparum malaria was then confirmed by peripheral blood smear, antimalarial medications were initiated, and hemodialysis was performed for eight times. The patient’s condition and laboratory results were quickly normalized. We report a case of P. falciparum-induced severe malaria with AKI and jaundice. The present case suggests that P. falciparum may induce severe malaria with life-threatening complications, early diagnosis and treatment is important to improve the quality of life of patients. Physicians must be alert for correct diagnosis and proper management of imported tropical malaria when patients have travel history in endemic areas.

  17. The Complex Relationship of Extracorporeal Membrane Oxygenation and Acute Kidney Injury: Causation or Association?

    Science.gov (United States)

    Kilburn, Daniel J; Shekar, Kiran; Fraser, John F

    2016-01-01

    Extracorporeal membrane oxygenation (ECMO) is a modified cardiopulmonary bypass (CPB) circuit capable of providing prolonged cardiorespiratory support. Recent advancement in ECMO technology has resulted in increased utilisation and clinical application. It can be used as a bridge-to-recovery, bridge-to-bridge, bridge-to-transplant, or bridge-to-decision. ECMO can restitute physiology in critically ill patients, which may minimise the risk of progressive multiorgan dysfunction. Alternatively, iatrogenic complications of ECMO clearly contribute to worse outcomes. These factors affect the risk : benefit ratio of ECMO which ultimately influence commencement/timing of ECMO. The complex interplay of pre-ECMO, ECMO, and post-ECMO pathophysiological processes are responsible for the substantial increased incidence of ECMO-associated acute kidney injury (EAKI). The development of EAKI significantly contributes to morbidity and mortality; however, there is a lack of evidence defining a potential benefit or causative link between ECMO and AKI. This area warrants investigation as further research will delineate the mechanisms involved and subsequent strategies to minimise the risk of EAKI. This review summarizes the current literature of ECMO and AKI, considers the possible benefits and risks of ECMO on renal function, outlines the related pathophysiology, highlights relevant investigative tools, and ultimately suggests an approach for future research into this under investigated area of critical care.

  18. The Complex Relationship of Extracorporeal Membrane Oxygenation and Acute Kidney Injury: Causation or Association?

    Directory of Open Access Journals (Sweden)

    Daniel J. Kilburn

    2016-01-01

    Full Text Available Extracorporeal membrane oxygenation (ECMO is a modified cardiopulmonary bypass (CPB circuit capable of providing prolonged cardiorespiratory support. Recent advancement in ECMO technology has resulted in increased utilisation and clinical application. It can be used as a bridge-to-recovery, bridge-to-bridge, bridge-to-transplant, or bridge-to-decision. ECMO can restitute physiology in critically ill patients, which may minimise the risk of progressive multiorgan dysfunction. Alternatively, iatrogenic complications of ECMO clearly contribute to worse outcomes. These factors affect the risk : benefit ratio of ECMO which ultimately influence commencement/timing of ECMO. The complex interplay of pre-ECMO, ECMO, and post-ECMO pathophysiological processes are responsible for the substantial increased incidence of ECMO-associated acute kidney injury (EAKI. The development of EAKI significantly contributes to morbidity and mortality; however, there is a lack of evidence defining a potential benefit or causative link between ECMO and AKI. This area warrants investigation as further research will delineate the mechanisms involved and subsequent strategies to minimise the risk of EAKI. This review summarizes the current literature of ECMO and AKI, considers the possible benefits and risks of ECMO on renal function, outlines the related pathophysiology, highlights relevant investigative tools, and ultimately suggests an approach for future research into this under investigated area of critical care.

  19. Acute kidney injury in preterm infants admitted to a neonatal intensive care unit.

    Science.gov (United States)

    Stojanović, Vesna; Barišić, Nenad; Milanović, Borko; Doronjski, Aleksandra

    2014-11-01

    The factors that contribute to the development of acute kidney injury (AKI) and treatment outcome among prematurely born neonates are not clearly understood. This retrospective study included 150 prematurely born neonates. AKI was defined as an increase of serum creatinine levels ≥0.3 mg/dl compared to basal values. The majority of neonates with AKI (94.8 %) had a body weight 5 on the first day of life, core body temperature hemorrhage, necrotizing enterocolitis, patent ductus arteriosus, as well as a treatment with vancomycin or dopamine were independent risk factors for the development of AKI. After the groups of neonates with and without AKI were adjusted, the calculated risk ratio for a negative outcome of treatment (death) was 2.215 (CI 1.27-3.86) for neonates with AKI. Neonates with AKI had higher serum sodium levels in the third and fourth days of life. AKI is associated with high mortality in preterm neonates. It is very important to identify, as quickly as possible, all infants who are at high risk of developing AKI.

  20. Effect of acute kidney injury on weaning from mechanical ventilation in critically ill patients.

    Science.gov (United States)

    Vieira, José M; Castro, Isac; Curvello-Neto, Américo; Demarzo, Sérgio; Caruso, Pedro; Pastore, Laerte; Imanishe, Marina H; Abdulkader, Regina C R M; Deheinzelin, Daniel

    2007-01-01

    Acute kidney injury (AKI) worsens outcome in various scenarios. We sought to investigate whether the occurrence of AKI has any effect on weaning from mechanical ventilation. Observational, retrospective study in a 23-bed medical/surgical intensive care unit (ICU) in a cancer hospital from January to December 2003. The inclusion criterion was invasive mechanical ventilation for > or =48 hrs. AKI was defined as at least one measurement of serum creatinine of > or =1.5 mg/dL during the ICU stay. Patients were then separated into AKI and non-AKI patients (control group). The criterion for weaning was the combination of positive end-expiratory pressure of or =85% increase in baseline serum creatinine (hazard rate, 2.30; 95% confidence interval, 1.30-4.08), oliguria (hazard rate, 2.51; 95% confidence interval, 1.24-5.08), and the number of antibiotics (hazard rate, 2.64; 95% confidence interval, 1.51-4.63) predicted longer duration of weaning. The length of ICU stay and ICU mortality rate were significantly greater in the AKI patients. After adjusting for Simplified Acute Physiology Score II, oliguria (odds ratio, 30.8; 95% confidence interval, 7.7-123.0) remained as a strong risk factor for mortality. This study shows that renal dysfunction has serious consequences in the duration of mechanical ventilation, weaning from mechanical ventilation, and mortality in critically ill cancer patients.

  1. Metabolic Acidosis and Strong Ion Gap in Critically Ill Patients with Acute Kidney Injury

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    Cai-Mei Zheng

    2014-01-01

    Full Text Available Purpose. To determine the influence of physicochemical parameters on survival in metabolic acidosis (MA and acute kidney injury (AKI patients. Materials and Methods. Seventy-eight MA patients were collected and assigned to AKI or non-AKI group. We analyzed the physiochemical parameters on survival at 24 h, 72 h, 1 week, 1 month, and 3 months after AKI. Results. Mortality rate was higher in the AKI group. AKI group had higher anion gap (AG, strong ion gap (SIG, and apparent strong ion difference (SIDa values than non-AKI group. SIG value was higher in the AKI survivors than nonsurvivors and this value was correlated serum creatinine, phosphate, albumin, and chloride levels. SIG and serum albumin are negatively correlated with Acute Physiology and Chronic Health Evaluation IV scores. AG was associated with mortality at 1 and 3 months post-AKI, whereas SIG value was associated with mortality at 24 h, 72 h, 1 week, 1 month, and 3 months post-AKI. Conclusions. Whether high or low SIG values correlate with mortality in MA patients with AKI depends on its correlation with serum creatinine, chloride, albumin, and phosphate (P levels. AG predicts short-term mortality and SIG value predicts both short- and long-term mortality among MA patients with AKI.

  2. Impact of e-alert systems on the care of patients with acute kidney injury.

    Science.gov (United States)

    Breighner, Crystal M; Kashani, Kianoush B

    2017-09-01

    With the recent advancement in electronic health record systems and meaningful use of information technology incentive programs (i.e., the American Recovery and Reinvestment Act, the Health Information Technology for Economic and Clinical Health Act, and the Centers for Medicare & Medicaid Services), interest in clinical decision support systems has risen. These systems have been used to examine a variety of different syndromes with variable reported effects. In recent years, electronic alerts (e-alerts) have been implemented at various institutions to decrease the morbidity associated with acute kidney injury (AKI). AKI is common, accounting for 1 in 7 hospital admissions, and is associated with increased length of hospital stay and mortality. AKI is often underrecognized, causing delayed intervention. The use of e-alerts may result in earlier recognition and intervention, as well as decreased morbidity and mortality. This must be balanced with the possibility of increased resource utilization that e-alerts may cause. Before widespread implementation, the ethical and legal consequences of not following e-alert recommendations must be established, and the optimal algorithm for AKI e-alert detection must be determined. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Effect of Acetaminophen on the Prevention of Acute Kidney Injury in Patients With Sepsis.

    Science.gov (United States)

    Patanwala, Asad E; Aljuhani, Ohoud; Bakhsh, Hussain; Erstad, Brian L

    2018-01-01

    Acute kidney injury (AKI) commonly occurs in patients with sepsis. Acetaminophen (APAP) has been shown to inhibit lipid peroxidation and, thus, may be renal protective in patients with sepsis. The objective of this study was to determine the effect of APAP on AKI in patients with sepsis. This was a retrospective cohort study conducted at 2 affiliated academic medical centers in the United States. Adult patients who were admitted to the intensive care unit with a diagnosis of severe sepsis were included. Patients were categorized based on whether APAP was received within the first 7 days of hospitalization (APAP or no APAP groups). The primary outcome measure was occurrence or increase in AKI stage from admission. Multivariate logistic regression analyses were used to adjust for potential confounders. There were 238 patients who were included in the study cohort. Of these, 122 received APAP and 116 did not receive APAP. AKI or exacerbation occurred in 16.4% (n = 20) of patients in the APAP group and 19.8% (n = 23) of patients in the no APAP group ( P = 0.505). After adjusting for the most important confounders, there was no significant association between APAP use and AKI (odds ratio = 1.2; 95% CI = 0.6-2.4; P = 0.639). APAP use in critically ill patients with sepsis may not reduce the occurrence or exacerbation of AKI.

  4. Knowledge of acute kidney injury among nurses in two government hospitals in Ondo City, Southwest Nigeria

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    Oluseyi A Adejumo

    2017-01-01

    Full Text Available Adequate knowledge of acute kidney injury (AKI among all health-care providers is essential for early diagnosis and management to reduce the associated burden. This study determined the knowledge of AKI among nurses in two government hospitals in Ondo City, Southwest Nigeria. This cross-sectional descriptive study was carried out in two government hospitals in Ondo City using a self-administered pretested questionnaire that assessed knowledge of AKI and associated factors. A total of 156 respondents participated in the study. Majority were between 20 and 40 years of age and were females. Ninety-nine (63.5% had ≤10 years of nursing experience. A total of 106 (67.5% respondents had received formal lectures on AKI in the past. Only 12 (7.7% respondents had good knowledge of AKI, 98 (62.8% had fair knowledge, and the remaining 46 (29.5% had poor knowledge of AKI. There was a significant association between the knowledge of AKI and having received previous AKI lectures (P = 0.03, but knowledge was not associated with the years of nursing experience (P = 0.37. There was a significant association between having received previous AKI lecture and knowledge of AKI. We, therefore, recommend regular in-service training on AKI for practicing nurses.

  5. Microparticles from kidney-derived mesenchymal stem cells act as carriers of proangiogenic signals and contribute to recovery from acute kidney injury.

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    Hoon Young Choi

    Full Text Available We recently demonstrated the use of in vitro expanded kidney-derived mesenchymal stem cells (KMSC protected peritubular capillary endothelial cells in acute renal ischemia-reperfusion injury. Herein, we isolated and characterized microparticles (MPs from KMSC. We investigated their in vitro biologic effects on human endothelial cells and in vivo renoprotective effects in acute ischemia-reperfusion renal injury. MPs were isolated from the supernatants of KMSC cultured in anoxic conditions in serum-deprived media for 24 hours. KMSC-derived MPs demonstrated the presence of several adhesion molecules normally expressed on KMSC membranes, such as CD29, CD44, CD73, α4, 5, and 6 integrins. Quantitative real time PCR confirmed the presence of 3 splicing variants of VEGF-A (120, 164, 188, bFGF and IGF-1 in isolated MPs. MPs labeled with PKH26 red fluorescence dye were incorporated by cultured human umbilical vein endothelial cells (HUVEC via surface molecules such as CD44, CD29, and α4, 5, and 6 integrins. MP dose dependently improved in vitro HUVEC proliferation and promoted endothelial tube formation on growth factor reduced Matrigel. Moreover, apoptosis of human microvascular endothelial cell was inhibited by MPs. Administration of KMSC-derived MPs into mice with acute renal ischemia was followed by selective engraftment in ischemic kidneys and significant improvement in renal function. This was achieved by improving proliferation, of peritubular capillary endothelial cell and amelioration of peritubular microvascular rarefaction. Our results support the hypothesis that KMSC-derived MPs may act as a source of proangiogenic signals and confer renoprotective effects in ischemic kidneys.

  6. Combining creatinine and volume kinetics identifies missed cases of acute kidney injury following cardiac arrest

    Science.gov (United States)

    2013-01-01

    Introduction Fluid resuscitation in the critically ill often results in a positive fluid balance, potentially diluting the serum creatinine concentration and delaying diagnosis of acute kidney injury (AKI). Methods Dilution during AKI was quantified by combining creatinine and volume kinetics to account for fluid type, and rates of fluid infusion and urine output. The model was refined using simulated patients receiving crystalloids or colloids under four glomerular filtration rate (GFR) change scenarios and then applied to a cohort of critically ill patients following cardiac arrest. Results The creatinine concentration decreased during six hours of fluid infusion at 1 litre-per-hour in simulated patients, irrespective of fluid type or extent of change in GFR (from 0% to 67% reduction). This delayed diagnosis of AKI by 2 to 9 hours. Crystalloids reduced creatinine concentration by 11 to 19% whereas colloids reduced concentration by 36 to 43%. The greatest reduction was at the end of the infusion period. Fluid dilution alone could not explain the rapid reduction of plasma creatinine concentration observed in 39 of 49 patients after cardiac arrest. Additional loss of creatinine production could account for those changes. AKI was suggested in six patients demonstrating little change in creatinine, since a 52 ± 13% reduction in GFR was required after accounting for fluid dilution and reduced creatinine production. Increased injury biomarkers within a few hours of cardiac arrest, including urinary cystatin C and plasma and urinary Neutrophil-Gelatinase-Associated-Lipocalin (biomarker-positive, creatinine-negative patients) also indicated AKI in these patients. Conclusions Creatinine and volume kinetics combined to quantify GFR loss, even in the absence of an increase in creatinine. The model improved disease severity estimation, and demonstrated that diagnostic delays due to dilution are minimally affected by fluid type. Creatinine sampling should be delayed at least

  7. Outcomes of acute kidney injury in children and adults in sub-Saharan Africa: a systematic review.

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    Olowu, Wasiu A; Niang, Abdou; Osafo, Charlotte; Ashuntantang, Gloria; Arogundade, Fatiu A; Porter, John; Naicker, Saraladevi; Luyckx, Valerie A

    2016-04-01

    Access to diagnosis and dialysis for acute kidney injury can be life-saving, but can be prohibitively expensive in low-income settings. The burden of acute kidney injury in sub-Saharan Africa is presumably high but remains unknown. We did a systematic review to assess outcomes of acute kidney injury in sub-Saharan Africa and identify barriers to care. We searched PubMed, African Journals Online, WHO Global Health Library, and Web of Science for articles published between Jan 1, 1990, and Nov 30, 2014. We scored studies, and all were of medium-to-low quality. We made a pragmatic decision to include all studies to best reflect reality, and did a descriptive analysis of extracted data. This study is registered with PROSPERO, number CRD42015015690. We identified 3881 records, of which 41 met inclusion criteria, including 1403 adult patients and 1937 paediatric patients. Acute kidney injury in sub-Saharan Africa is severe, with 1042 (66%) of 1572 children and 178 (70%) 253 of adults needing dialysis in studies reporting dialysis need. Only 666 (64%) of 1042 children (across 11 studies) and 58 (33%) of 178 adults (across four studies) received dialysis when needed. Overall mortality was 34% in children and 32% in adults, but rose to 73% in children and 86% in adults when dialysis was needed but not received. Major barriers to access to care were out-of-pocket costs, erratic hospital resources, late presentation, and female sex. Patients in these studies are those with resources to access care. In view of overall study quality, data interpretation should be cautious, but high mortality and poor access to dialysis are concerning. The global scarcity of resources among patients and health centres highlights the need for a health-system-wide approach to prevention and management of acute kidney injury in sub-Saharan Africa. None. Copyright © 2016 Olowu et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

  8. Atorvastatin attenuates experimental contrast-induced acute kidney injury: a role for TLR4/MyD88 signaling pathway.

    Science.gov (United States)

    Yue, Rongzheng; Zuo, Chuan; Zeng, Jing; Su, Baihai; Tao, Ye; Huang, Songmin; Zeng, Rui

    2017-11-01

    To investigate the protective effect of different atorvastatin doses on contrast-induced acute kidney injury and the related mechanism. Healthy male Sprague-Dawley (SD) rats were randomly divided into the blank control group, experimental control group and different-dose atorvastatin groups. A rat model of contrast-induced acute kidney injury was established. We detected changes in serum creatinine (Scr) and blood urea nitrogen (BUN) before and after model establishment, observed and scored renal tubular injury, analyzed rat renal cell apoptosis, and measure the expression of signal pathway proteins and downstream inflammatory factors. After contrast agent injection, the Scr and BUN levels of the experimental control group were significantly increased, the different doses applied in the atorvastatin group significantly reduced the Scr and BUN levels (p atorvastatin doses have protective effects on contrast-induced acute renal tubular injury in rats, possibly by targeting TLR4, suppressing TLR4 expression, regulating the TLR4/Myd88 signaling pathway, and inhibiting the expression of downstream inflammatory factors.

  9. Voluntary wheel running augments aortic l-arginine transport and endothelial function in rats with chronic kidney disease.

    Science.gov (United States)

    Martens, Christopher R; Kuczmarski, James M; Kim, Jahyun; Guers, John J; Harris, M Brennan; Lennon-Edwards, Shannon; Edwards, David G

    2014-08-15

    Reduced nitric oxide (NO) synthesis contributes to risk for cardiovascular disease in chronic kidney disease (CKD). Vascular uptake of the NO precursor l-arginine (ARG) is attenuated in rodents with CKD, resulting in reduced substrate availability for NO synthesis and impaired vascular function. We tested the effect of 4 wk of voluntary wheel running (RUN) and/or ARG supplementation on endothelium-dependent relaxation (EDR) in rats with CKD. Twelve-week-old male Sprague-Dawley rats underwent ⅚ ablation infarction surgery to induce CKD, or SHAM surgery as a control. Beginning 4 wk following surgery, CKD animals either remained sedentary (SED) or received one of the following interventions: supplemental ARG, RUN, or combined RUN+ARG. Animals were euthanized 8 wk after surgery, and EDR was assessed. EDR was significantly impaired in SED vs. SHAM animals after 8 wk, in response to ACh (10(-9)-10(-5) M) as indicated by a reduced area under the curve (AUC; 44.56 ± 9.01 vs 100 ± 4.58, P RUN and RUN+ARG-treated animals. Maximal relaxation was elevated above SED in RUN+ARG animals only. l-[(3)H]arginine uptake was impaired in both SED and ARG animals and was improved in RUN and RUN+ARG animals. The results suggest that voluntary wheel running is an effective therapy to improve vascular function in CKD and may be more beneficial when combined with l-arginine. Copyright © 2014 the American Physiological Society.

  10. Back-calculating baseline creatinine overestimates prevalence of acute kidney injury with poor sensitivity.

    Science.gov (United States)

    Kork, F; Balzer, F; Krannich, A; Bernardi, M H; Eltzschig, H K; Jankowski, J; Spies, C

    2017-03-01

    Acute kidney injury (AKI) is diagnosed by a 50% increase in creatinine. For patients without a baseline creatinine measurement, guidelines suggest estimating baseline creatinine by back-calculation. The aim of this study was to evaluate different glomerular filtration rate (GFR) equations and different GFR assumptions for back-calculating baseline creatinine as well as the effect on the diagnosis of AKI. The Modification of Diet in Renal Disease, the Chronic Kidney Disease Epidemiology (CKD-EPI) and the Mayo quadratic (MQ) equation were evaluated to estimate baseline creatinine, each under the assumption of either a fixed GFR of 75 mL min -1  1.73 m -2 or an age-adjusted GFR. Estimated baseline creatinine, diagnoses and severity stages of AKI based on estimated baseline creatinine were compared to measured baseline creatinine and corresponding diagnoses and severity stages of AKI. The data of 34 690 surgical patients were analysed. Estimating baseline creatinine overestimated baseline creatinine. Diagnosing AKI based on estimated baseline creatinine had only substantial agreement with AKI diagnoses based on measured baseline creatinine [Cohen's κ ranging from 0.66 (95% CI 0.65-0.68) to 0.77 (95% CI 0.76-0.79)] and overestimated AKI prevalence with fair sensitivity [ranging from 74.3% (95% CI 72.3-76.2) to 90.1% (95% CI 88.6-92.1)]. Staging AKI severity based on estimated baseline creatinine had moderate agreement with AKI severity based on measured baseline creatinine [Cohen's κ ranging from 0.43 (95% CI 0.42-0.44) to 0.53 (95% CI 0.51-0.55)]. Diagnosing AKI and staging AKI severity on the basis of estimated baseline creatinine in surgical patients is not feasible. Patients at risk for post-operative AKI should have a pre-operative creatinine measurement to adequately assess post-operative AKI. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  11. Pre-operative Functional Cardiovascular Reserve Is Associated with Acute Kidney Injury after Intervention.

    Science.gov (United States)

    Saratzis, A; Shakespeare, J; Jones, O; Bown, M J; Mahmood, A; Imray, C H E

    2017-05-01

    Acute kidney injury (AKI) is a common complication after endovascular intervention, associated with poor short and long-term outcomes. However, the mechanisms underlying AKI development remain poorly understood. The impact of pre-existing cardiovascular disease and low cardiovascular reserve (CVR) in AKI is unclear; it remains unknown whether AKI is primarily related to pre-existing comorbidity or to procedural parameters. The association between CVR and AKI after EVAR was therefore assessed. This is a case control study. From a database of 484 patients, 292 undergoing elective endovascular aneurysm repair (EVAR) of an infrarenal abdominal aortic aneurysm (AAA) in two tertiary centres were included. Of these, 73 patients who had developed AKI after EVAR were case matched, based on pre-operative estimated glomerular filtration rate (eGFR; within 5 mL/min/1.73 m 2 ) and age, with patients who had not developed AKI. Cardiopulmonary exercise testing (CPET) was used to assess CVR using the anaerobic threshold (AT). Development of AKI was defined using the Kidney Disease Improving Outcomes (KDIGO) guidance. Associations between CVR (based on AT levels) and AKI development were then analysed. Pre-operative AT levels were significantly different between those who did and did not develop AKI (12.1±2.9 SD vs. 14.8±3.0 mL/min/kg, p < .001). In multivariate analysis, a higher level of AT (per 1 mL/min/kg) was associated with a lower odds ratio (OR) of 0.72 (95% CI, 0.63-0.82, p < .001), relative to AKI development. A pre-operative AT level of < 11 mL/min/kg was associated with post-operative AKI development in adjusted analysis, with an OR of 7.8 (95% CI, 3.75-16.51, p < .001). The area under the curve (receiver operating characteristic) for AT as a predictor of post-operative AKI was 0.81 (standard error, 0.06, 95% CI, 0.69-0.93, p < .001). Poor CVR was strongly associated with the development of AKI. This provides pathophysiological insights into the

  12. Hundred top-cited articles focusing on acute kidney injury: a bibliometric analysis.

    Science.gov (United States)

    Liu, Yuan-Hui; Wang, Sheng-Qi; Xue, Jin-Hua; Liu, Yong; Chen, Ji-Yan; Li, Guo-Feng; He, Peng-Cheng; Tan, Ning

    2016-07-27

    Acute kidney injury (AKI) is a major global health issue, associated with poor short-term and long-term outcomes. Research on AKI is increasing with numerous articles published. However, the quantity and quality of research production in the field of AKI is unclear. To analyse the characteristics of the most cited articles on AKI and to provide information about achievements and developments in AKI, we searched the Science Citation Index Expanded for citations of AKI articles. For the top 100 most frequently cited articles (T100), we evaluated the number of citations, publication time, province of origin, journal, impact factor, topic or subspecialty of the research, and publication type. The T100 articles ranged from a maximum of 1971 citations to a minimum of 215 citations (median 302 citations). T100 articles were published from 1951 to 2011, with most articles published in the 2000s (n=77), especially the 5-year period from 2002 to 2006 (n=51). The publications appeared in 30 journals, predominantly in the general medical journals, led by New England Journal of Medicine (n=17), followed by expert medical journals, led by the Journal of the American Society of Nephrology (n=16) and Kidney International (n=16). The majority (83.7%) of T100 articles were published by teams involving ≥3 authors. T100 articles originated from 15 countries, led by the USA (n=81) followed by Italy (n=9). Among the T100 articles, 69 were clinical research, 25 were basic science, 21 were reviews, 5 were meta-analyses and 3 were clinical guidelines. Most clinical articles (55%) included patients with any cause of AKI, followed by the specific causes of contrast-induced AKI (25%) and cardiac surgery-induced AKI (15%). This study provides a historical perspective on the scientific progress on AKI, and highlights areas of research requiring further investigations and developments. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a

  13. Evaluation of the accuracy of estimated baseline serum creatinine for acute kidney injury diagnosis.

    Science.gov (United States)

    Hatakeyama, Yutaka; Horino, Taro; Nagata, Keitaro; Kataoka, Hiromi; Matsumoto, Tatsuki; Terada, Yoshio; Okuhara, Yoshiyasu

    2018-04-01

    Modern epidemiologic studies of acute kidney injury (AKI) have been facilitated by the increasing availability of electronic medical records. However, pre-morbid reference serum creatinine (SCr) data are often unavailable in such records. Investigators substitute estimated baseline SCr with the eGFR 75 approach, instead of using actually measured baseline SCr. Here, we evaluated the accuracy of estimated baseline SCr for AKI diagnosis in the Japanese population. Inpatients and outpatients aged 18-80 years were retrospectively enrolled. AKI was diagnosed according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria, using SCr levels. The non-AKI and AKI groups were selected using the following criteria: increase 1.5 times greater than baseline SCr ("baseline SCr") or increase 0.3 mg/dL greater than baseline SCr in 48 h ("increase in 48 h"). AKI accuracy defined by the estimated reference SCr, the average SCr value of the non-AKI population (eb-GFR-A approach), or the back-calculated SCr from fixed eGFR = 75 mL/min/1.73 m 2 (eGFR 75 approach, or, eb-GFR-B approach in this study), was evaluated. We analyzed data from 131,358 Japanese patients. The number of patients with reference baseline SCr in the non-AKI and AKI patients were 29,834 and 8952, respectively. For AKI patients diagnosed using "baseline SCr", the AKI diagnostic accuracy rates as defined by eb-GFR-A and eb-GFR-B were 63.5 and 57.7%, respectively, while in AKI diagnosed using "increase in 48 h", the AKI diagnostic accuracy rates as defined by eb-GFR-A and eb-GFR-B were 78.7 and 75.1%, respectively. In non-AKI patients, false-positive rates of AKI misdiagnosed via eb-GFR-A and eb-GFR-B were 7.4 and 6.8%, respectively. AKI diagnosis using the average SCr value of the general population may yield more accurate results than diagnosis using the eGFR 75 approach when the reference SCr is unavailable.

  14. Incidence and risk factors of acute kidney injury among the critically ill neonates

    Directory of Open Access Journals (Sweden)

    Ayman A El-Badawy

    2015-01-01

    Full Text Available Acute kidney injury (AKI is a complex disorder with clinical manifestations ranging from mild dysfunction to complete kidney failure. The published literature on the incidence and outcome of AKI in the critically ill neonatal population is scarce. The aim of this study was to evaluate the types, the associated risk factors and short-term outcome of AKI in the critically ill neonates. A cohort study was conducted including 100 critically ill neonates successively admitted to the Neonatal Intensive Care Unit. The inclusion criteria were a gestational age ≥28 weeks and body weight ≥1 kg. Exclusion criteria included those with multiple congenital anomalies or on drugs altering glomerular filtration rate or AKI developing postoperatively. Neonates were evaluated for the development of AKI [creatinine >1.5 mg/dL and/or blood urea nitrogen (BUN >20 mg/dL] and were assigned as group A (who developed AKI and group B (who did not develop AKI. Forty-one patients developed AKI (group A among whom nine (22% showed oliguric AKI. The most common risk factors among group A patients were sepsis (75.6% and nephrotoxic drug administration (75.6%, followed by shock (39%. There were no statistically significant differences between both groups except for male sex predominance and necrotizing enterocolitis (NEC, which were significantly higher among group A (P <0.05. Use of continuous positive airway pressure (CPAP ventilation was significantly higher in neonates without AKI (13.6% vs 0.0%, P = 0.02. The mortality rate among group A reached 51.2%. Various risk factors including gender, gestational age, birth weight, shock, NEC, sepsis, nephrotoxic drugs, oliguria and mechanical ventilation were studied as regards outcome of group A, and all factors except gender and oliguria proved to be significantly higher in deceased neonates. Male sex and NEC were important risk factors for developing AKI that was predominantly non-oliguric. CPAP ventilation may have a

  15. Using Contingent Reinforcement to Augment Muscle Activation After Perinatal Brachial Plexus Injury: A Pilot Study.

    Science.gov (United States)

    Duff, S V; Sargent, B; Kutch, J J; Berggren, J; Leiby, B E; Fetters, L

    2017-10-20

    Examine the feasibility of increasing muscle activation with electromyographically (EMG)-triggered musical-video as reinforcement for children with perinatal brachial plexus injury (PBPI). Six children with PBPI (9.3 ± 6.3 months; 5 female, 1 male) and 13 typically developing (TD) controls (7.8 ± 3.5 months; 4 female, 9 males) participated. The left arm was affected in 5/6 children with PBPI. We recorded the integral (Vs) of biceps activation with surface EMG during two conditions per arm in one session: (1) 100 second (s) baseline without reinforcement and (2) 300 s reinforcement (musical-video triggered to play with biceps activation above threshold [V]). We examined the relation between the mean integral with reinforcement and hand preference. Mean biceps activation significantly increased from baseline in the affected arm of the group with PBPI by the 2nd (p < .008) and 3rd (p < .0004) 100 s intervals of reinforcement. Six of 6 children with PBPI and 12/13 TD controls increased activation in at least one arm. A lower integral was linked with hand preference for the unaffected right side in the PBPI group. This study supports contingent reinforcement as a feasible method to increase muscle activation. Future work will examine training dose and intensity to increase arm function.

  16. Hypomagnesemia is a risk factor for nonrecovery of renal function and mortality in AIDS patients with acute kidney injury

    Directory of Open Access Journals (Sweden)

    M.S. Biagioni Santos

    2010-03-01

    Full Text Available The objective of the present study was to determine the prevalence of electrolyte disturbances in AIDS patients developing acute kidney injury in the hospital setting, as well as to determine whether such disturbances constitute a risk factor for nephrotoxic and ischemic injury. A prospective, observational cohort study was carried out. Hospitalized AIDS patients were evaluated for age; gender; coinfection with hepatitis; diabetes mellitus; hypertension; time since HIV seroconversion; CD4 count; HIV viral load; proteinuria; serum levels of creatinine, urea, sodium, potassium and magnesium; antiretroviral use; nephrotoxic drug use; sepsis; intensive care unit (ICU admission, and the need for dialysis. Each of these characteristics was correlated with the development of acute kidney injury, with recovery of renal function and with survival. Fifty-four patients developed acute kidney injury: 72% were males, 59% had been HIV-infected for >5 years, 72% had CD4 counts <200 cells/mm³, 87% developed electrolyte disturbances, 33% recovered renal function, and 56% survived. ICU admission, dialysis, sepsis and hypomagnesemia were all significantly associated with nonrecovery of renal function and with mortality. Nonrecovery of renal function was significantly associated with hypomagnesemia, as was mortality in the multivariate analysis. The risks for nonrecovery of renal function and for death were 6.94 and 6.92 times greater, respectively, for patients with hypomagnesemia. In hospitalized AIDS patients, hypomagnesemia is a risk factor for nonrecovery of renal function and for in-hospital mortality. To determine whether hypomagnesemia is a determinant or simply a marker of critical illness, further studies involving magnesium supplementation in AIDS patients are warranted.

  17. Protocatechuic aldehyde attenuates cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammation

    Directory of Open Access Journals (Sweden)

    Li Gao

    2016-12-01

    Full Text Available Cisplatin is a classic chemotherapeutic agent widely used to treat different types of cancers including ovarian, head and neck, testicular and uterine cervical carcinomas. However, cisplatin induces acute kidney injury by directly triggering an excessive inflammatory response, oxidative stress and programmed cell death of renal tubular epithelial cells. All of which lead to higher mortality rates in patients. In this study we examined the protective effect of protocatechuic aldehyde (PA in vitro in cisplatin-treated tubular epithelial cells and in vivo in cisplatin nephropathy. PA is a monomer of Traditional Chinese Medicine isolated from the root of S. miltiorrhiza. Results show that PA prevented cisplatin-induced decline of renal function and histological damage, which was confirmed by attenuation of KIM1 in both mRNA and protein levels. Moreover, PA reduced renal inflammation by suppressing oxidative stress and programmed cell death in response to cisplatin, which was further evidenced by in vitro data. Of note, PA suppressed NAPDH oxidases, including Nox2 and Nox4, in a dosage-dependent manner. Moreover, silencing Nox4, but not Nox2, removed the inhibitory effect of PA on cisplatin-induced renal injury, indicating that Nox4 may play a pivotal role in mediating the protective effect of PA in cisplatin-induced acute kidney injury. Collectively, our data indicate that PA largely blocked cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammation without compromising anti-tumor activity of cisplatin. These findings suggest that PA and its derivatives may serve as potential protective agents for cancer patients with cisplatin treatment.

  18. Hepatic injury induces contrasting response in liver and kidney to chemicals that are metabolically activated: Role of male sex hormone

    International Nuclear Information System (INIS)

    Kim, Young C.; Yim, Hye K.; Jung, Young S.; Park, Jae H.; Kim, Sung Y.

    2007-01-01

    Injury to liver, resulting in loss of its normal physiological/biochemical functions, may adversely affect a secondary organ. We examined the response of the liver and kidney to chemical substances that require metabolic activation for their toxicities in mice with a preceding liver injury. Carbon tetrachloride treatment 24 h prior to a challenging dose of carbon tetrachloride or acetaminophen decreased the resulting hepatotoxicity both in male and female mice as determined by histopathological examination and increases in serum enzyme activities. In contrast, the renal toxicity of the challenging toxicants was elevated markedly in male, but not in female mice. Partial hepatectomy also induced similar changes in the hepatotoxicity and nephrotoxicity of a challenging toxicant, suggesting that the contrasting response of male liver and kidney was associated with the reduction of the hepatic metabolizing capacity. Carbon tetrachloride pretreatment or partial hepatectomy decreased the hepatic xenobiotic-metabolizing enzyme activities in both sexes but elevated the renal p-nitrophenol hydroxylase, p-nitroanisole O-demethylase and aminopyrine N-demethylase activities significantly only in male mice. Increases in Cyp2e1 and Cyp2b expression were also evident in male kidney. Castration of males or testosterone administration to females diminished the sex-related differences in the renal response to an acute liver injury. The results indicate that reduction of the hepatic metabolizing capacity induced by liver injury may render secondary target organs susceptible to chemical substances activated in these organs. This effect may be sex-specific. It is also suggested that an integrated approach should be taken for proper assessment of chemical hazards

  19. Polymyxin-B and vancomycin-associated acute kidney injury in critically ill patients.

    Science.gov (United States)

    Soares, Douglas de Sousa; Reis, André da Fonte; Silva Junior, Geraldo Bezerra da; Leite, Tacyano Tavares; Parente Filho, Sérgio Luiz Arruda; Rocha, Carina Vieira de Oliveira; Daher, Elizabeth De Francesco

    2017-05-01

    This study aims to investigate renal toxicities of Polymyxin B and Vancomycin among critically ill patients and risk factors for acute kidney injury (AKI). This is a cross-sectional study conducted with patients admitted to an intensive care unit (ICU) of a tertiary hospital in Brazil. Patients were divided into two groups: those who used association of Polymyxin B + Vancomycin (Group I) and those who used only Polymyxin B (Group II). Risk factors for AKI were also analyzed. A total of 115 patients were included. Mean age was 59.2 ± 16.1 years, and 52.2% were males. Group I presented higher GFR (117.1 ± 70.5 vs. 91.5 ± 50 ml/min/1.73 m², p = 0.02) as well as lower creatinine (0.9 ± 0.82 vs. 1.0 ± 0.59 mg/dL, p = 0.014) and urea (51.8 ± 23.7 vs. 94.5 ± 4.9 mg/dL, p = 0.006) than group II on admission. Group I also manifested significantly higher incidence of AKI than group II (62.7% vs. 28.5%, p = 0.005), even when stratified according to RIFLE criteria ('Risk' 33.9% vs. 10.7%; 'Injury' 10.2% vs. 8.9%; 'Failure' 18.6% vs. 8.9%; p = 0.03). Accumulated Polymyxin B dose > 10 million IU was an independent predictor for AKI (OR = 2.72, 95% CI = 1.13-6.51, p = 0.024). Although patients who received Polymyxin B plus vancomycin had more favorable clinical profile and higher previous GFR, they presented a higher AKI incidence than those patients who received Polymyxin B alone. Cumulative Polymyxin B dose > 10 million IU was independently associated to AKI.

  20. Sensitivity and Specificity of a Single Emergency Department Measurement of Urinary Neutrophil Gelatinase–Associated Lipocalin for Diagnosing Acute Kidney Injury

    Science.gov (United States)

    Nickolas, Thomas L.; O’Rourke, Matthew J.; Yang, Jun; Sise, Meghan E.; Canetta, Pietro A.; Barasch, Nicholas; Buchen, Charles; Khan, Faris; Mori, Kiyoshi; Giglio, James; Devarajan, Prasad; Barasch, Jonathan

    2010-01-01

    Background A single serum creatinine measurement cannot distinguish acute kidney injury from chronic kidney disease or prerenal azotemia. Objective To test the sensitivity and specificity of a single measurement of urinary neutrophil gelatinase–associated lipocalin (NGAL) and other urinary proteins to detect acute kidney injury in a spectrum of patients. Design Prospective cohort study. Setting Emergency department of Columbia University Medical Center, New York, New York. Participants 635 patients admitted to the hospital with acute kidney injury, prerenal azotemia, chronic kidney disease, or normal kidney function. Measurements Diagnosis of acute kidney injury was based on the RIFLE (risk, injury, failure, loss, and end-stage) criteria and assigned by researchers who were blinded to experimental measurements. Urinary NGAL was measured by immunoblot, N-acetyl-β-D-glucosaminidase (NAG) by enzyme measurement, α1-microglobulin and α1-acid glycoprotein by immunonephelometry, and serum creatinine by Jaffe kinetic reaction. Experimental measurements were not available to treating physicians. Results Patients with acute kidney injury had a significantly elevated mean urinary NGAL level compared with the other kidney function groups (416 μg/g creatinine [SD, 387]; P = 0.001). At a cutoff value of 130 μg/g creatinine, sensitivity and specificity of NGAL for detecting acute injury were 0.900 (95% CI, 0.73 to 0.98) and 0.995 (CI, 0.990 to 1.00), respectively, and positive and negative likelihood ratios were 181.5 (CI, 58.33 to 564.71) and 0.10 (CI, 0.03 to 0.29); these values were superior to those for NAG, α1-microglobulin, α1-acid glycoprotein, fractional excretion of sodium, and serum creatinine. In multiple logistic regression, urinary NGAL level was highly predictive of clinical outcomes, including nephrology consultation, dialysis, and admission to the intensive care unit (odds ratio, 24.71 [CI, 7.69 to 79.42]). Limitations All patients came from a single

  1. Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury.

    Science.gov (United States)

    Nickolas, Thomas L; O'Rourke, Matthew J; Yang, Jun; Sise, Meghan E; Canetta, Pietro A; Barasch, Nicholas; Buchen, Charles; Khan, Faris; Mori, Kiyoshi; Giglio, James; Devarajan, Prasad; Barasch, Jonathan

    2008-06-03

    A single serum creatinine measurement cannot distinguish acute kidney injury from chronic kidney disease or prerenal azotemia. To test the sensitivity and specificity of a single measurement of urinary neutrophil gelatinase-associated lipocalin (NGAL) and other urinary proteins to detect acute kidney injury in a spectrum of patients. Prospective cohort study. Emergency department of Columbia University Medical Center, New York, New York. 635 patients admitted to the hospital with acute kidney injury, prerenal azotemia, chronic kidney disease, or normal kidney function. Diagnosis of acute kidney injury was based on the RIFLE (risk, injury, failure, loss, and end-stage) criteria and assigned by researchers who were blinded to experimental measurements. Urinary NGAL was measured by immunoblot, N-acetyl-beta-d-glucosaminidase (NAG) by enzyme measurement, alpha1-microglobulin and alpha(1)-acid glycoprotein by immunonephelometry, and serum creatinine by Jaffe kinetic reaction. Experimental measurements were not available to treating physicians. Patients with acute kidney injury had a significantly elevated mean urinary NGAL level compared with the other kidney function groups (416 microg/g creatinine [SD, 387]; P = 0.001). At a cutoff value of 130 microg/g creatinine, sensitivity and specificity of NGAL for detecting acute injury were 0.900 (95% CI, 0.73 to 0.98) and 0.995 (CI, 0.990 to 1.00), respectively, and positive and negative likelihood ratios were 181.5 (CI, 58.33 to 564.71) and 0.10 (CI, 0.03 to 0.29); these values were superior to those for NAG, alpha1-microglobulin, alpha1-acid glycoprotein, fractional excretion of sodium, and serum creatinine. In multiple logistic regression, urinary NGAL level was highly predictive of clinical outcomes, including nephrology consultation, dialysis, and admission to the intensive care unit (odds ratio, 24.71 [CI, 7.69 to 79.42]). All patients came from a single center. Few kidney biopsies were performed. A single measurement

  2. Acute kidney injury in cats and dogs: A proportional meta-analysis of case series studies

    Science.gov (United States)

    Legatti, Sabrina Almeida Moreira; Legatti, Emerson; Botan, Andresa Graciutti; Camargo, Samira Esteves Afonso; Agarwal, Arnav; Barretti, Pasqual; Paes, Antônio Carlos

    2018-01-01

    Introduction Risk of mortality in the setting of acute kidney injury (AKI) in cats and dogs remains unclear. Objectives To evaluate the incidence of mortality in cats and dogs with AKI based on etiology (i.e. infectious versus non-infectious; receiving dialysis versus conservative treatment). Materials and methods Ovid Medline, EMBASE, and LILACS were searched up to July 2016. Articles were deemed eligible if they were case series studies evaluating the incidence of all-cause mortality in cats and dogs with AKI, regardless of etiology or the nature of treatment. Results Eighteen case series involving 1,201animalsproved eligible. The pooled proportions for overall mortality were: cats53.1% [95% CI 0.475, 0.586; I2 = 11,9%, p = 0.3352]; dogs 45.0% [95% CI 0.33, 0.58; I2 = 91.5%, P dogs, 19.2% [95% CI 0.134, 0.258; I2 = 37.7%, P = 0.0982]; AKI due non-infectious etiology for cats and dogs, 59.9% [95% CI 0.532, 0.663; I2 = 51.0%, P = 0.0211]. Conclusion Our findings suggest higher rates of overall mortality in cats and dogs with AKI due to non-infectious etiologies relative to infectious etiologies, and showed non-significant differences in terms of higher rates associated with dialysis compared to conservative management. Further investigations regarding optimal time to initiate dialysis and the development of clinical models to prognosticate the course of disease and guide optimal treatment initiation for less severe cases of AKI in cats and dogs is warranted. PMID:29370180

  3. Allopurinol attenuates rhabdomyolysis-associated acute kidney injury: Renal and muscular protection.

    Science.gov (United States)

    Gois, Pedro H F; Canale, Daniele; Volpini, Rildo A; Ferreira, Daniela; Veras, Mariana M; Andrade-Oliveira, Vinicius; Câmara, Niels O S; Shimizu, Maria H M; Seguro, Antonio C

    2016-12-01

    Acute kidney injury (AKI) is the most severe complication of rhabdomyolysis. Allopurinol (Allo), a xanthine oxidase inhibitor, has been in the spotlight in the last decade due to new therapeutic applications related to its potent antioxidant effect. The aim of this study was to evaluate the efficacy of Allo in the prevention and treatment of rhabdomyolysis-associated AKI. Male Wistar rats were divided into five groups: saline control group; prophylactic Allo (300mg/L of drinking water, 7 days); glycerol (50%, 5ml/kg, IM); prophylactic Allo + glycerol; and therapeutic Allo (50mg/Kg, IV, 30min after glycerol injection) + glycerol. Glycerol-injected rats showed markedly reduced glomerular filtration rate associated with renal vasoconstriction, renal tubular damage, increased oxidative stress, apoptosis and inflammation. Allo ameliorated all these alterations. We found 8-isoprostane-PGF 2a (F2-IsoP) as a main factor involved in the oxidative stress-mediated renal vasoconstriction following rhabdomyolysis. Allo reduced F2-IsoP renal expression and restored renal blood flow. Allo also reduced oxidative stress in the damaged muscle, attenuated muscle lesion/inflammation and accelerated muscular recovery. Moreover, we showed new insights into the pathogenesis of rhabdomyolysis-associated AKI, whereas Allo treatment reduced renal inflammation by decreasing renal tissue uric acid levels and consequently inhibiting the inflammasome cascade. Allo treatment attenuates renal dysfunction in a model of rhabdomyolysis-associated AKI by reducing oxidative stress (systemic, renal and muscular), apoptosis and inflammation. This may represent a new therapeutic approach for rhabdomyolysis-associated AKI - a new use for an old and widely available medication. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Urinary metabonomics elucidate the therapeutic mechanism of Orthosiphon stamineus in mouse crystal-induced kidney injury.

    Science.gov (United States)

    Gao, Songyan; Chen, Wei; Peng, Zhongjiang; Li, Na; Su, Li; Lv, Diya; Li, Ling; Lin, Qishan; Dong, Xin; Guo, Zhiyong; Lou, Ziyang

    2015-05-26

    Orthosiphon stamineus (OS), a traditional Chinese herb, is often used for promoting urination and treating nephrolithiasis. Urolithiasis is a major worldwide public health burden due to its high incidence of recurrence and damage to renal function. However, the etiology for urolithiasis is not well understood. Metabonomics, the systematic study of small molecule metabolites present in biological samples, has become a valid and powerful tool for understanding disease phenotypes. In this study, a urinary metabolic profiling analysis was performed in a mouse model of renal calcium oxalate crystal deposition to identify potential biomarkers for crystal-induced renal damage and the anti-crystal mechanism of OS. Thirty six mice were randomly divided into six groups including Saline, Crystal, Cystone and OS at dosages of 0.5g/kg, 1g/kg, and 2g/kg. A metabonomics approach using ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) was developed to perform the urinary metabolic profiling analysis. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were utilized to identify differences between the metabolic profiles of mice in the saline control group and crystal group. Using partial least squares-discriminant analysis, 30 metabolites were identified as potential biomarkers of crystal-induced renal damage. Most of them were primarily involved in amino acid metabolism, taurine and hypotaurine metabolism, purine metabolism, and the citrate cycle (TCA). After the treatment with OS, the levels of 20 biomarkers had returned to the levels of the control samples. Our results suggest that OS has a protective effect for mice with crystal-induced kidney injury via the regulation of multiple metabolic pathways primarily involving amino acid, energy and choline metabolism. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Outcome and quality of life of patients with acute kidney injury after major surgery.

    Science.gov (United States)

    Abelha, F J; Botelho, M; Fernandes, V; Barros, H

    2009-01-01

    In postoperative critically-ill patients who develop Acute Kidney Injury (AKI) it is important to focus on survival and quality of life beyond hospital discharge. The aim of the study was to evaluate outcome and quality of life in patients that develop AKI after major surgery. This retrospective study was carried out in a Post-Anaesthesia Care Unit with five intensive care beds during 2 years. Patients were followed for the development of AKI. Preoperative characteristics, intra-operative management and outcome were evaluated. Six months after discharge, these patients were contacted to complete a Short Form-36 questionnaire (SF-36) and to have their dependency in ADL evaluated. Chi-square or Fischer's exact test were used to compare proportions between groups. A "t test" and a paired "t test" for independent groups was used for comparisons. Of 1584 patients admitted to the PACU, 1200 patients met the inclusion criteria. One hundred-fourteen patients (9.6%) met AKI criteria. Patients with AKI were more severely ill, stayed longer at the PACU. Among 71 hospital survivors at 6 months follow-up, 50 completed the questionnaires. Fifty-two percent of patients reported that their general level of health was better on the day they answered the questionnaire than 12 months earlier. Patients that met AKI criteria after surgery had worse SF-36 scores for physical function, role physical and role emotional domains. Six months after PACU discharge, patients that met AKI criteria were more dependent in I-ADL but not in P-ADL. Patients that develop AKI improved self-perception of quality of life despite having high rate of dependency in ADL tasks. For physical function and role physical domains they had worse scores than PACU patients that did not develop AKI.

  6. Acute Kidney Injury Facilitates Hypocalcemia by Exacerbating the Hyperphosphatemic Effect of Muscle Damage in Rhabdomyolysis.

    Science.gov (United States)

    Higaki, Masato; Tanemoto, Masayuki; Shiraishi, Takeshi; Taniguchi, Kei; Fujigaki, Yoshihide; Uchida, Shunya

    2015-01-01

    Hypocalcemia is an important complication of rhabdomyolysis for which several pathogenic factors, including acute kidney injury (AKI), have been proposed. To gain insight regarding the hypocalcemic roles of AKI in rhabdomyolysis, we retrospectively examined patients with rhabdomyolysis. Of 28,387 patients admitted to the Department of Internal Medicine, 51 patients met the inclusion criteria for the study. Serum calcium was analyzed based on laboratory data including indicators of AKI, serum creatine kinase (CK) and serum inorganic phosphate (iP). Twenty-two patients (43%) had hypocalcemia. Compared with patients without hypocalcemia, they had a higher prevalence of AKI (82 vs. 55%; p = 0.046), higher levels of peak CK (39,100 ± 50,600 vs. 9,800 ± 11,900 IU/l; p = 0.003) and higher levels of peak iP (1.77 ± 1.10 vs. 1.10 ± 0.35 mmol/l; p = 0.007). Indicators of AKI were correlated with peak CK and peak iP and were not significant variables in the regression analysis for hypocalcemia. Peak CK and peak iP were not correlated with each other. Impaired phosphate use by muscle contributed to the increased iP. These findings indicate that muscle damage is the primary hypocalcemic factor in rhabdomyolysis. AKI facilitated hypocalcemia by exacerbating the hyperphosphatemic effects of muscle damage. Aggressive hydration, which could increase oxygen supply and subsequently repair phosphate use in muscle, might reduce the incidence of hypocalcemia in rhabdomyolysis. © 2015 S. Karger AG, Basel.

  7. Leptospirosis-associated acute kidney injury: penicillin at the late stage is still controversial.

    Science.gov (United States)

    Daher, E F; Silva, G B; de Abreu, K L S; Mota, R M S; Batista, D V; Rocha, N A; Araújo, S M H A; Libório, A B

    2012-08-01

    Some antimicrobial agents are active in vitro against Leptospiras. The use of penicillins at the late stage of leptospirosis is still controversial. We aimed to evaluate the use of penicillin in patients with leptospirosis-associated acute kidney injury (AKI). A retrospective study was conducted of patients with leptospirosis admitted to two hospitals in Fortaleza city, Brazil, between 1985 and 2008. AKI was defined according to the RIFLE and AKIN classifications. Patients were divided in two groups according to whether they were treated with a penicillin or not. Two hundred and eighty-seven patients were included, with an average age of 36·8±15·6 years and mostly male (80·8%). One hundred and twelve patients (39%) received a penicillin. Patients treated with a penicillin were younger (32±14 years vs. 39±16 years, P=0·0002) and had a shorter hospital stay (8·4±5·0 vs. 11±7·7 days, Ppenicillin group (111±21 vs. 119±22 mmHg, P=0·04). AKI, need of dialysis and renal recovery at the time of hospital discharge were more frequent in patients who did not use a penicillin (Ppenicillin, remains controversial. The main benefit of using penicillin in the present study was a reduction in the length of hospital stay and fewer complications, such as AKI, but its use was not associated with a decrease in mortality. On balance of risks and benefits, we recommend the use of penicillin in late-stage leptospirosis. © 2011 Blackwell Publishing Ltd.

  8. Hypoalbuminemia and acute kidney injury: a meta-analysis of observational clinical studies.

    Science.gov (United States)