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Sample records for augment kidney injury

  1. Injury - kidney and ureter

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    Kidney damage; Toxic injury of the kidney; Kidney injury; Traumatic injury of the kidney; Fractured kidney; Inflammatory injury of the kidney; Bruised kidney; Ureteral injury; Pre-renal failure - injury, ...

  2. [Acute kidney injury

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    Hageman, D.; Kooman, J.P.; Lance, M.D.; Heurn, L.W. van; 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. Acute kidney injury during pregnancy.

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    Van Hook, James W

    2014-12-01

    Acute kidney injury complicates the care of a relatively small number of pregnant and postpartum women. Several pregnancy-related disorders such as preeclampsia and thrombotic microangiopathies may produce acute kidney injury. Prerenal azotemia is another common cause of acute kidney injury in pregnancy. This manuscript will review pregnancy-associated acute kidney injury from a renal functional perspective. Pathophysiology of acute kidney injury will be reviewed. Specific conditions causing acute kidney injury and treatments will be compared.

  4. [Acute Kidney Injury].

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    Brix, Silke; Stahl, Rolf

    2017-02-01

    Acute kidney injury (AKI) is an important part of renal diseases and a common clinical problem. AKI is an acute decline in renal function. Due to a lack of therapeutic options, prevention and optimal management of patients with AKI are the most important strategies. Although seldom the sole cause of patients' death, AKI is associated with a significant increase in mortality. Our objective is to draw the attention towards the prevention of AKI of non-renal causes.

  5. [Ascites and acute kidney injury].

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    Piano, Salvatore; Tonon, Marta; Angeli, Paolo

    2016-07-01

    Ascites is the most common complication of cirrhosis. Ascites develops as a consequence of an abnormal splanchnic vasodilation with reduction of effecting circulating volume and activation of endogenous vasoconstrictors system causing salt and water retention. Patients with ascites have a high risk to develop further complications of cirrhosis such as hyponatremia, spontaneous bacterial peritonitis and acute kidney injury resulting in a poor survival. In recent years, new studies helped a better understanding of the pathophysiology of ascites and acute kidney injury in cirrhosis. Furthermore, new diagnostic criteria have been proposed for acute kidney injury and hepatorenal syndrome and a new algorithm for their management has been recommended with the aim of an early diagnosis and treatment. Herein we will review the current knowledge on the pathophysiology, diagnosis and treatment of ascites and acute kidney injury in patients with cirrhosis and we will identify the unmet needs that should be clarified in the next years.

  6. Sepsis and Acute Kidney Injury.

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    Bilgili, Beliz; Haliloğlu, Murat; Cinel, İsmail

    2014-12-01

    Acute kindney injury (AKI) 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. In intensive care unit sepsis and septic shock are leading causes of AKI. Sepsis-induced AKI literally acts as a biologic indicator of clinical deterioration. AKI triggers variety of immune, inflammatory, metabolic and humoral patways; ultimately leading distant organ dysfunction and increases morbidity and mortality. Serial mesurements of creatinine and urine volume do not make it possible to diagnose AKI at early stages. Serum creatinine influenced by age, weight, hydration status and become apparent only when the kidneys have lost 50% of their function. For that reason we need new markers, and many biomarkers in the diagnosis of early AKI activity is assessed. Historically "Risk-Injury-Failure-Loss-Endstage" (RIFLE), "Acute Kidney Injury Netwok" (AKIN) and "The Kidney Disease/ Improving Global Outcomes" (KDIGO) classification systems are used for diagnosing easily in clinical practice and research and grading disease. Classifications including diagnostic criteria are formed for the identification of AKI. Neutrophil gelatinase associated lipocalin (NGAL), cystatin-C (Cys-C), kidney injury molecule-1 (KIM-1) and also "cell cycle arrest" molecules has been concerned for clinical use. In this review the pathophysiology of AKI, with the relationship of sepsis and the importance of early diagnosis of AKI is evaluated.

  7. Acute kidney injury in children

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    Peco-Antić Amira

    2014-01-01

    Full Text Available Acute kidney injury (AKI is a clinical condition considered to be the consequence of a sudden decrease (>25% or discontinuation of renal function. The term AKI is used instead of the previous term acute renal failure, because it has been demonstrated that even minor renal lesions may cause far-reaching consequences on human health. Contemporary classifications of AKI (RIFLE and AKIN are based on the change of serum creatinine and urinary output. In the developed countries, AKI is most often caused by renal ischemia, nephrotoxins and sepsis, rather than a (primary diffuse renal disease, such as glomerulonephritis, interstitial nephritis, renovascular disorder and thrombotic microangiopathy. The main risk factors for hospital AKI are mechanical ventilation, use of vasoactive drugs, stem cell transplantation and diuretic-resistant hypervolemia. Prerenal and parenchymal AKI (previously known as acute tubular necrosis jointly account for 2/3 of all AKI causes. Diuresis and serum creatinine concentration are not early diagnostic markers of AKI. Potential early biomarkers of AKI are neutrophil gelatinase-associated lipocalin (NGAL, cystatin C, kidney injury molecule-1 (KIM-1, interleukins 6, 8 and 18, and liver-type fatty acid-binding protein (L-FABP. Early detection of kidney impairment, before the increase of serum creatinine, is important for timely initiated therapy and recovery. The goal of AKI treatment is to normalize the fluid and electrolyte status, as well as the correction of acidosis and blood pressure. Since a severe fluid overload resistant to diuretics and inotropic agents is associated with a poor outcome, the initiation of dialysis should not be delayed. The mortality rate of AKI is highest in critically ill children with multiple organ failure and hemodynamically unstable patients.

  8. New biomarkers of acute kidney injury

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    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

  9. Spectroscopic Monitoring of Kidney Tissue Ischemic Injury

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    Demos, S G; Fitzgerald, J T; Michalopoulou, A P; Troppmann, C

    2004-03-11

    Noninvasive evaluation of tissue viability of donor kidneys used for transplantation is an issue that current technology is not able to address. In this work, we explore optical spectroscopy for its potential to assess the degree of ischemic damage in kidney tissue. We hypothesized that ischemic damage to kidney tissue will give rise to changes in its optical properties which in turn may be used to asses the degree of tissue injury. The experimental results demonstrate that the autofluorescence intensity of the injured kidney is decreasing as a function of time exposed to ischemic injury. Changes were also observed in the NIR light scattering intensities most probably arising from changes due to injury and death of the tissue.

  10. Contrast-associated Acute Kidney Injury.

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    Weisbord, Steven D; Palevsky, Paul M

    2015-10-01

    Contrast-associated acute kidney injury (CAAKI) is a common iatrogenic condition. The principal risk factors for CAAKI are underlying renal impairment; diabetes in the setting of kidney disease; and intravascular volume depletion, effective or absolute. CAAKI is associated with serious adverse short-term and long-term outcomes, including mortality and more rapidly progressive chronic kidney disease, although the causal nature of these associations remains unproved. Patients with chronic kidney disease and other risk factors for CAAKI who present with acute coronary syndrome should undergo indicated angiographic procedures.

  11. Erythropoietin (EPO) in acute kidney injury

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    Moore, Elizabeth; Bellomo, Rinaldo

    2011-01-01

    Erythropoietin (EPO) is a 30.4 kDa glycoprotein produced by the kidney, and is mostly well-known for its physiological function in regulating red blood cell production in the bone marrow. Accumulating evidence, however, suggests that EPO has additional organ protective effects, which may be useful in the prevention or treatment of acute kidney injury. These protective mechanisms are multifactorial in nature and include inhibition of apoptotic cell death, stimulation of cellular regeneration, ...

  12. [Pregnancy-related acute kidney injury].

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    Filipowicz, Ewa; Staszków, Monika

    Acute kidney injury (AKI) in obstetrics may be caused by the same disorders that are observed in the general population or may be specific for a pregnancy such as: preeclampsia, HELLP syndrome or acute fatty liver of pregnancy. The renal changes may be only temporary, and resolve within a few weeks postpartum, or may become irreversible leading to a progression of chronic kidney disease (CKD). In the article the most important pregnancy related syndromes associated with AKI have been shortly reviewed.

  13. Transplanting Kidneys from Deceased Donors With Severe Acute Kidney Injury.

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    Heilman, R L; Smith, M L; Kurian, S M; Huskey, J; Batra, R K; Chakkera, H A; Katariya, N N; Khamash, H; Moss, A; Salomon, D R; Reddy, K S

    2015-08-01

    Our aim was to determine outcomes with transplanting kidneys from deceased donors with acute kidney injury, defined as a donor with terminal serum creatinine ≥2.0 mg/dL, or a donor requiring acute renal replacement therapy. We included all patients who received deceased donor kidney transplant from June 2004 to October 2013. There were 162 AKI donor transplant recipients (21% of deceased donor transplants): 139 in the standard criteria donor (SCD) and 23 in the expanded criteria donor (ECD) cohort. 71% of the AKI donors had stage 3 (severe AKI), based on acute kidney injury network (AKIN) staging. Protocol biopsies were done at 1, 4, and 12 months posttransplant. One and four month formalin-fixed paraffin embedded (FFPE) biopsies from 48 patients (24 AKI donors, 24 non-AKI) underwent global gene expression profiling using DNA microarrays (96 arrays). DGF was more common in the AKI group but eGFR, graft survival at 1 year and proportion with IF/TA>2 at 1 year were similar for the two groups. At 1 month, there were 898 differentially expressed genes in the AKI group (p-value kidneys from deceased donors with AKI is safe and has excellent outcomes.

  14. Kidney injuries related to ipilimumab.

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    Izzedine, Hassane; Gueutin, Victor; Gharbi, Chems; Mateus, Christine; Robert, Caroline; Routier, Emilie; Thomas, Marina; Baumelou, Alain; Rouvier, Philippe

    2014-08-01

    Monoclonal antibodies directed against the immune checkpoint protein cytotoxic T-lymphocyte antigen-4 (CTLA-4; CD152) have been investigated in metastatic melanoma and other cancers and have shown promising results. Inhibition of CTLA-4 characteristically induces well-known side effects called "immune-related adverse events" (irAEs). IrAEs mainly include colitis, dermatitis, hepatitis, endocrinopathies; uveitis, iridocyclitis, neuropathies, and inflammatory myopathy have occasionally been reported. Kidney involvement is rare. We report 2 cases of acute granulomatous interstitial nephritis and present, based on literature review, renal disorders related to Ipilimumab therapy. Autoimmune symptoms have to be carefully checked for patients treated with CTLA-4 inhibitors. In order to reduce the risk of sequelae, early recognition of irAEs and treatment initiation are crucial.

  15. Erythropoietin (EPO) in acute kidney injury.

    Science.gov (United States)

    Moore, Elizabeth; Bellomo, Rinaldo

    2011-03-21

    Erythropoietin (EPO) is a 30.4 kDa glycoprotein produced by the kidney, and is mostly well-known for its physiological function in regulating red blood cell production in the bone marrow. Accumulating evidence, however, suggests that EPO has additional organ protective effects, which may be useful in the prevention or treatment of acute kidney injury. These protective mechanisms are multifactorial in nature and include inhibition of apoptotic cell death, stimulation of cellular regeneration, inhibition of deleterious pathways, and promotion of recovery.In this article, we review the physiology of EPO, assess previous work that supports the role of EPO as a general tissue protective agent, and explain the mechanisms by which it may achieve this tissue protective effect. We then focus on experimental and clinical data that suggest that EPO has a kidney protective effect.

  16. [Perioperative acute kidney injury and failure].

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    Chhor, Vibol; Journois, Didier

    2014-04-01

    Perioperative period is very likely to lead to acute renal failure because of anesthesia (general or perimedullary) and/or surgery which can cause acute kidney injury. Characterization of acute renal failure is based on serum creatinine level which is imprecise during and following surgery. Studies are based on various definitions of acute renal failure with different thresholds which skewed their comparisons. The RIFLE classification (risk, injury, failure, loss, end stage kidney disease) allows clinicians to distinguish in a similar manner between different stages of acute kidney injury rather than using a unique definition of acute renal failure. Acute renal failure during the perioperative period can mainly be explained by iatrogenic, hemodynamic or surgical causes and can result in an increased morbi-mortality. Prevention of this complication requires hemodynamic optimization (venous return, cardiac output, vascular resistance), discontinuation of nephrotoxic drugs but also knowledge of the different steps of the surgery to avoid further degradation of renal perfusion. Diuretics do not prevent acute renal failure and may even push it forward especially during the perioperative period when venous retourn is already reduced. Edema or weight gain following surgery are not correlated with the vascular compartment volume, much less with renal perfusion. Treatment of perioperative acute renal failure is similar to other acute renal failure. Renal replacement therapy must be mastered to prevent any additional risk of hemodynamic instability or hydro-electrolytic imbalance.

  17. Intestinal microbiota-kidney cross talk in acute kidney injury and chronic kidney disease.

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    Noel, Sanjeev; Martina-Lingua, Maria N; Bandapalle, Samatha; Pluznick, Jennifer; Hamad, Abdel Rahim A; Peterson, Daniel A; Rabb, Hamid

    2014-01-01

    The pathophysiology of acute kidney injury (AKI) involves multiple and overlapping immunological, biochemical, and hemodynamic mechanisms that modulate the effects of both the initial insult and the subsequent repair. Limited but recent experimental data have revealed that the intestinal microbiota significantly affects outcomes in AKI. Additional evidence shows significant changes in the intestinal microbiota in chronic kidney disease patients and in experimental AKI. In this minireview, we discuss the current status of the effect of intestinal microbiota on kidney diseases, the immunomodulatory effects of intestinal microbiota, and the potential mechanisms by which microbiota can modify kidney diseases and vice versa. We also propose future studies to clarify the role of intestinal microbiota in kidney diseases and to explore how the modification of gut microbiota may be a potential therapeutic tool.

  18. Acute kidney injury: A rare cause

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    Satish Mendonca

    2015-01-01

    Full Text Available We present a young lady who consumed hair dye, which contained paraphenylene diamine (PPD, as a means of deliberate self-harm. This resulted in severe angio-neurotic edema for which she had to be ventilated, and thereafter developed rhabdomyolysis leading to acute kidney injury (AKI. The unusual aspect was that the patient continued to have flaccid quadriparesis and inability to regain kidney function. Renal biopsy performed 10 weeks after the dye consumption revealed severe acute tubular necrosis with myoglobin pigment casts. This suggests that PPD has a long-term effect leading to ongoing myoglobinuria, causing flaccid paralysis to persist and preventing the recovery of AKI. In such instances, timely treatment to prevent AKI in the form alkalinization of urine should be initiated promptly. Secondly, because PPD is a nondialyzable toxin, and its long-term effect necessitates its speedy removal, hemoperfusion might be helpful and is worth considering

  19. Acute kidney injury in the pediatric population.

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    Garisto, Cristiana; Favia, Isabella; Ricci, Zaccaria; Averardi, Marco; Picardo, Sergio; Cruz, Dinna N

    2010-01-01

    The care of acute kidney injury (AKI) in critically ill children shares several features with adult AKI with some critical distinctions: in both settings, however, the exact identification of renal dysfunction, in-depth knowledge of disparate risk factors and patient-specific management are the primary targets in order to provide optimal care. This article will specifically review recent work published on pediatric AKI about definition and epidemiology, the possible etiologies in specific conditions, and the newest laboratory investigations necessary to diagnose AKI severity. A short description of pediatric renal replacement therapies and their potential application to extracorporeal membrane oxygenation will also be described.

  20. Mechanism of Platinum Derivatives Induced Kidney Injury

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    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.

  1. Kidney injury and heme oxygenase-1

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    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.   

  2. Acute Kidney Injury – An Update

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    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.

  3. Slit2-Robo signaling in inflammation and kidney injury.

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    Chaturvedi, Swasti; Robinson, Lisa A

    2015-04-01

    Acute kidney injury is an increasingly common global health problem and is associated with severe morbidity and mortality. In addition to facing high mortality rates, the survivors of acute kidney injury are at increased risk of developing chronic kidney disease and end-stage renal disease. Renal ischemia-reperfusion injury (IRI) is the most common cause of acute kidney injury, and results from impaired delivery of oxygen and nutrients to the kidney. Massive leukocyte influx into the post-ischemic kidney is one of the hallmarks of IRI. The recruited leukocytes exacerbate tissue damage and, if uncontrolled, initiate the progressive changes that lead to renal fibrosis and chronic kidney disease. Early on, recruitment and activation of platelets promotes microthrombosis in the injured kidney, further exacerbating kidney damage. The diversity, complexity, and multiplicity of pathways involved in leukocyte recruitment and platelet activation make it extremely challenging to control these processes, and past efforts have met with limited success in human trials. A generalized strategy to inhibit infiltration of inflammatory leukocytes and platelets, thereby reducing inflammation and injury, may prove to be more beneficial. In this review, we summarize recent findings demonstrating that the neuronal guidance cues, Slit and Roundabout (Robo), prevent the migration of multiple leukocyte subsets towards diverse inflammatory chemoattractants, and have potent anti-platelet functions in vitro and in vivo. These properties uniquely position Slit2 as a novel therapeutic that could be used to prevent acute kidney injury associated with IRI.

  4. Laboratory test surveillance following acute kidney injury.

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    Michael E Matheny

    Full Text Available BACKGROUND: Patients with hospitalized acute kidney injury (AKI are at increased risk for accelerated loss of kidney function, morbidity, and mortality. We sought to inform efforts at improving post-AKI outcomes by describing the receipt of renal-specific laboratory test surveillance among a large high-risk cohort. METHODS: We acquired clinical data from the Electronic health record (EHR of 5 Veterans Affairs (VA hospitals to identify patients hospitalized with AKI from January 1st, 2002 to December 31st, 2009, and followed these patients for 1 year or until death, enrollment in palliative care, or improvement in renal function to estimated GFR (eGFR ≥ 60 L/min/1.73 m(2. Using demographic data, administrative codes, and laboratory test data, we evaluated the receipt and timing of outpatient testing for serum concentrations of creatinine and any as well as quantitative proteinuria recommended for CKD risk stratification. Additionally, we reported the rate of phosphorus and parathyroid hormone (PTH monitoring recommended for chronic kidney disease (CKD patients. RESULTS: A total of 10,955 patients admitted with AKI were discharged with an eGFR<60 mL/min/1.73 m2. During outpatient follow-up at 90 and 365 days, respectively, creatinine was measured on 69% and 85% of patients, quantitative proteinuria was measured on 6% and 12% of patients, PTH or phosphorus was measured on 10% and 15% of patients. CONCLUSIONS: Measurement of creatinine was common among all patients following AKI. However, patients with AKI were infrequently monitored with assessments of quantitative proteinuria or mineral metabolism disorder, even for patients with baseline kidney disease.

  5. Suramin protects from cisplatin-induced acute kidney injury.

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    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; Siskind, Leah J

    2016-02-01

    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.

  6. Acute kidney injury in asphyxiated neonates

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    Roy Amardiyanto

    2013-07-01

    Full Text Available Background Asphyxia neonatorum may result in multiorgan dysfunction including renal involvement. There is no consensus on the determination of acute kidney injury (AKI in neonates making establishment of the diagnosis and its management becomes difficult. The Acute Kidney Injury Network (AKIN recommends AKI criteria based on increased serum creatinine level and reduced urine output. Objectives To identify the prevalence of AKI in asphyxiated neonates using the AKIN criteria, to compare the difference of AKI stages, and the glomerular filtration rates (GFR between moderate and severe asphyxia. Methods This was a cross-sectional analytical study conducted between July 2012 and January 2013. Subjects were all asphyxiated neonates (Apgar score 35 weeks delivered and hospitalized in Cipto Mangunkusumo Hospital and Koja District Hospital, Jakarta, Indonesia. Glomerular filtration rate was calculated using the components of urine creatinine, serum creatinine, and urine output; while AKI stages were determined according to AKIN criteria. Urinary output was measured via urethral catheterization. Results Of 94 subjects, there were 70 neonates with moderate and 24 neonates with severe asphyxia, with the prevalence of AKI was 63%. Twenty one out of 24 neonates with severe asphyxia experienced AKI, while neonates with moderate asphyxia who experienced AKI was 38 out of 70 subjects (54%. Two third of neonates with severe asphyxia who experienced AKI had stage 3 of AKI. More severe AKI stages and lower median GFR were found in neonates with severe compared to moderate asphyxia (P<0.001. Conclusion The prevalence of AKI in neonatal asphyxia is high (63%. The more severe degree of neonatal asphyxia, the more severe AKI stage and the lower median GFR. [Paediatr Indones. 2013;53:232-8.].

  7. Acute kidney injury in the pregnant patient.

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    Nwoko, Rosemary; Plecas, Darko; Garovic, Vesna D

    2012-12-01

    Acute kidney injury (AKI) is costly and is associated with increased mortality and morbidity. An understanding of the renal physiologic changes that occur during pregnancy is essential for proper evaluation, diagnosis, and management of AKI. As in the general population, AKI can occur from prerenal, intrinsic, and post-renal causes. Major causes of pre-renal azotemia include hyperemesis gravidarum and uterine hemorrhage in the setting of placental abruption. Intrinsic etiologies include infections from acute pyelonephritis and septic abortion, bilateral cortical necrosis, and acute tubular necrosis. Particular attention should be paid to specific conditions that lead to AKI during the second and third trimesters, such as preeclampsia, HELLP syndrome, acute fatty liver of pregnancy, and TTP-HUS. For each of these disorders, delivery of the fetus is the recommended therapeutic option, with additional therapies indicated for each specific disease entity. An understanding of the various etiologies of AKI in the pregnant patient is key to the appropriate clinical management, prevention of adverse maternal outcomes, and safe delivery of the fetus. In pregnant women with pre-existing kidney disease, the degree of renal dysfunction is the major determining factor of pregnancy outcomes, which may further be complicated by a prior history of hypertension.

  8. Malarial acute kidney injury: Prognostic markers

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    Ruhi Khan

    2013-01-01

    Full Text Available Background: Malaria has protean clinical manifestations and acute kidney injury (AKI is one of its serious and life threatening complications. This study was carried out to describe the clinical characteristics, and factors associated with adverse outcomes, in patients with malarial AKI. Materials and Methods: Data of 100 patients with AKI and smear positive malaria was retrospectively analyzed to evaluate the incidence, clinical profile, outcome and predictors of mortality among all cases presented to us at the Nephrology unit of Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh between November 2010 to October 2011. Results were expressed as mean, standard deviation (SD and range. Results: One hundred (22.1% (68 males, 32 females cases of malaria induced AKI, amongst 452 total cases of AKI, were evaluated. The mean age (± SD was 30 ± 11.23 years. Male to female ratio was 3.3:1. Plasmodium falciparum was reported in 76%, P. vivax in 11%, and both in 13% patients. The mean serum creatinine was 8.7 ± 3.7 mg%, and oligo/anuria was present in 84% of the patients. 78% of the patients required hemodialysis. 67% of the patients recovered completely, 12% did not show full recovery, and 6% developed chronic kidney failure. Mortality occurred in 15% of the patients. Conclusion : Malarial AKI most commonly occurs in patients infected by Plasmodium Falciparum. Falciparum malaria associated with AKI is a life threatening condition. Prolonged disease duration, low hemoglobin, oligo/anuria on admission, hyperbilirubinemia, cerebral malaria, disseminated intravascular coagulation, and high serum creatinine were the main predictors of mortality in our study.

  9. Acute kidney injury in dengue virus infection

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    Khalil, Muhammad A.M.; Sarwar, Sarfaraz; Chaudry, Muhammad A.; Maqbool, Baila; Khalil, Zarghoona; Tan, Jackson; Yaqub, Sonia; Hussain, Syed A.

    2012-01-01

    Background Dengue is a growing public health problem in Pakistan and acute kidney injury (AKI) is one of the least studied complications of dengue virus infection (DVI). The aim of this study was to determine the frequency, severity and predictors of AKI in patients with DVI and to study the impact of AKI on the length of hospital stay and mortality. Methods We retrospectively reviewed medical records of patients aged ≥14 years hospitalized with a primary diagnosis of DVI at Aga Khan University Hospital Karachi between January 2008 and December 2010. Binary logistic regression models were constructed to identify factors associated with the development of AKI and to study the impact of AKI on hospital stays of more than 3 days. Results Out of 532 patients, AKI was present in 13.3% (71/532). Approximately two-thirds (64.8%) of these patients had mild AKI and a third (35.2%) had moderate to severe AKI. Independent predictors for AKI were male gender [odds ratio (OD) 4.43; 95% CI 1.92–10.23], presence of dengue hemorrhagic and dengue shock syndrome (DSS, OD 2.14; 95% CI 1.06–4.32), neurological involvement (OD 12.08; 95% CI 2.82–51.77) and prolonged activated partial thromboplastin time (aPTT, OD 1.81; 95% CI 1.003–3.26). AKI was associated with a length of stay ≥3 days when compared with those who did not have AKI (OD 2.98; 95% CI 1.66–5.34). Eight patients (11.3%) with AKI died whereas there were no mortalities in patients without AKI (P < 0.001). Only 5 patients (7%) had persistent kidney dysfunction at discharge. Conclusions AKI in DVI is associated with neurological involvement, prolongation of aPTT, greater length of hospital stay and increased mortality. PMID:26019813

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

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

    2017-02-01

    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 large UK cohort. A retrospective analysis of the UK Transplant Registry evaluated deceased donors between 2003 and 2013. Donors were classified as no AKI, or AKI stage 1-3 according to Acute Kidney Injury Network (AKIN) criteria. Relationship of AKI with delayed graft function/primary nonfunction (DGF/PNF), estimated glomerular filtration rate (eGFR), and graft-survival at 90 days and 1 year was analyzed. There were 11 219 kidneys (1869 [17%] with AKI) included. Graft failure at 1 year is greater for donors with AKI than for those without (graft survival 89% vs. 91%, p = 0.02; odds ratio (OR) 1.20 [95% confidence interval (CI): 1.03-1.41]). DGF rates increase with donor AKI stage (p kidneys (9% vs. 4%, p = 0.04) Analysis of association between AKI and recipient eGFR suggests a risk of inferior eGFR with AKI versus no AKI (p kidneys from donors with AKI. We conclude that AKI stage 1 or 2 kidneys should be used; however, caution is advised for AKI stage 3 donors.

  11. Acute kidney injury in pregnancy: a clinical challenge

    OpenAIRE

    Machado, S.; Figueiredo, N.; Borges, A.; Pais, MS; Freitas, L; Moura, P.; Campos, M.

    2012-01-01

    The incidence of acute kidney injury in pregnancy declined significantly over the second half of the 20th century; however, it is still associated with major maternal and perinatal morbidity and mortality. A set of systemic and renal physiological adaptive mechanisms occur during a normal gestation that will constrain several changes in laboratory parameters of renal function, electrolytes, fluid and acid-base balances. The diagnosis of acute kidney injury in pregnancy is based on the serum c...

  12. 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.

  13. Pregnancy related acute kidney injury: nondialytic management

    Directory of Open Access Journals (Sweden)

    Kaliki Hymavathi Reddy

    2015-04-01

    Full Text Available Acute Kidney Injury (AKI is associated with increased mortality and morbidity unless timely diagnosed and promptly managed. An understanding of the renal physiologic changes that occur during pregnancy is essential for Proper evaluation, diagnosis, and management of Pregnancy Related AKI (PRAKI. In the general population, AKI can occur from prerenal, intrinsic/renal, and post-renal causes. Major causes of pre-renal azotemia include hyperemesis gravidarum and uterine hemorrhage in the setting of placental abruption. Intrinsic etiologies include infections from acute pyelonephritis and septic abortion, bilateral cortical necrosis, and acute tubular necrosis. Particular attention should be paid to specific conditions that lead to AKI during the second and third trimesters, such as preeclampsia, HELLP syndrome, acute fatty liver of pregnancy, and TTP-HUS. An understanding of the various etiologies of AKI in the pregnant patient is key to the appropriate clinical management and prevention of adverse maternal/fetal outcomes. Sometimes PRAKI may require intensive management and even dialysis adding additional economical burden to the patient. We here, with report an interesting case of PRAKI diagnosed and managed in time by simple medical measures thus delivering an effective treatment at a much lesser cost. [Int J Reprod Contracept Obstet Gynecol 2015; 4(2.000: 486-489

  14. Acute Kidney Injury:Global Health Alert

    Institute of Scientific and Technical Information of China (English)

    Philip Kam TaoLi; Emmanuel A Burdmann; Ravindra L Mehta

    2013-01-01

    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.

  15. Endothelial pentraxin 3 contributes to murine ischemic acute kidney injury

    Science.gov (United States)

    Chen, Jianlin; Matzuk, Martin M.; Zhou, Xin J.; Lu, Christopher Y.

    2012-01-01

    Toll-like receptor 4 (TLR4), a receptor forDamage Associated Molecular Pattern Molecules and also the lipopolysaccharide receptor, is required for early endothelial activation leading to maximal inflammation and injury during murine ischemic acute kidney injury. DNA microarray analysis of ischemic kidneys from TLR4-sufficient and deficient mice showed that pentraxin 3 (PTX3) was upregulated only on the former while transgenic knockout of PTX3 ameliorated acute kidney injury. PTX3 was expressed predominantly on peritubular endothelia of the outer medulla of the kidney in control mice. Acute kidney injury increased PTX3 protein in the kidney and the plasma where it may be a biomarker of the injury. Stimulation by hydrogen peroxide, or the TLR4 ligands recombinant human High-Mobility Group protein B1 or lipopolysaccharide, induced PTX3 expression in the Mile Sven 1 endothelial cell line and in primary renal endothelial cells suggesting that endothelial PTX3 was induced by pathways involving TLR4 and reactive oxygen species. This increase was inhibited by conditional endothelial knockout of Myeloid differentiation primary response gene 88, a mediator of a TLR4 intracellular signaling pathway. Compared to wild type mice, PTX3 knockout mice had decreased endothelial expression of cell adhesion molecules at 4 hours of reperfusion possibly contributing to a decreased early maladaptive inflammation in the kidneys of knockout mice. At 24 hours of reperfusion, PTX3 knockout increased expression of endothelial adhesion molecules when regulatory and reparative leukocytes enter the kidney. Thus, endothelial PTX3 plays a pivotal role in the pathogenesis of ischemic acute kidney injury. PMID:22895517

  16. Acute kidney injury and bilateral symmetrical enlargement of the kidneys as first presentation of B-cell lymphoblastic lymphoma.

    Science.gov (United States)

    Shi, Su-fang; Zhou, Fu-de; Zou, Wan-zhong; Wang, Hai-yan

    2012-12-01

    Lymphoblastic lymphoma is an uncommon subtype of lymphoid neoplasm in adults. Acute kidney injury at initial presentation due to lymphoblastic lymphoma infiltration of the kidneys has rarely been described. We report a 19-year-old woman who presented with acute kidney injury due to massive lymphomatous infiltration of the kidneys. The diagnosis of B-cell lymphoblastic lymphoma was established by immunohistochemical study of the biopsied kidney. The patient had an excellent response to the VDCLP protocol (vincristine, daunomycin, cyclophosphamide, asparaginase, and dexamethasone) with sustained remission. We recommend that lymphomatous infiltration be considered in patients presenting with unexplained acute kidney injury and enlarged kidneys.

  17. Kidney injury molecule-1: A urinary biomarker for contrast-induced acute kidney injury

    Directory of Open Access Journals (Sweden)

    M Vijayasimha

    2014-01-01

    Full Text Available Background: Urinary kidney injury molecule 1 (KIM-1 is an early biomarker for renal damage. A few studies have been published analyzing the potential use of urinary KIM-1 as a biomarker for acute kidney injury (AKI. However, no study has been done related to AKI associated with contrast administration. Aim: To search for new markers to identify AKI associated with contrast administration earlier than serum creatinine. Materials and Methods: We studied 100 consecutive patients with normal serum creatinine undergoing angiographic procedure. We assessed urine KIM-1, at 4, 8, and 24 hours after the angiographic procedure. Serum creatinine was measured at basal, 24, and 48 hours after the procedure. Results: There was a significant rise in urinary KIM-1 levels at 24 hours after the angiographic procedure. The presence of contrast induced nephropathy associated with AKI was 12%. Conclusion: The present study highlighted the importance of urinary KIM-1 in detecting AKI associated with contrast administration earlier than Serum creatinine.

  18. Biomarkers in acute kidney injury: Evidence or paradigm?

    Science.gov (United States)

    Lombi, Fernando; Muryan, Alexis; Canzonieri, Romina; Trimarchi, Hernán

    2016-01-01

    Acute kidney injury in the critically ill represents an independent risk factor of morbidity and mortality in the short and long terms, with significant economic impacts in terms of public health costs. Currently its diagnosis is still based on the presence of oliguria and/or a gradual increase in serum creatinine, which make the diagnosis a delayed event and to detriment of the so-called 'therapeutic window'. The appearance of new biomarkers of acute kidney injury could potentially improve this situation, contributing to the detection of 'subclinical acute kidney injury', which could allow the precocious employment of multiple treatment strategies in order to preserve kidney function. However these new biomarkers display sensitive features that may threaten their full capacity of action, which focus specifically on their additional contribution in the early approach of the situation, given the lack of specific validated treatments for acute kidney injury. This review aims to analyze the strengths and weaknesses of these new tools in the early management of acute kidney injury.

  19. Environmental injury to the kidney: Interstitial nephritis

    Directory of Open Access Journals (Sweden)

    James C. Chan

    2014-10-01

    Full Text Available The First Emperor of China (Qin Shi Huang: 259–210 BCE would have been interested in interstitial nephritis. He might conceivably be fascinated to know that consumption of mercury elixir, instead of giving him immortality, might have shortened his life by giving him interstitial nephritis. In the Balkan region of Eastern Europe, clustering of a peculiar interstitial nephritis is prevalent. One environmental risk contributing to Balkan endemic nephritis is aristolochic acid contamination of cooking flour, drinking water, and herbal medicine. In addition, the popular use of nonprescription Chinese weight reduction herbs and public unawareness of the consequential aristolochic acid nephropathy has become a worldwide problem. Finally, the mighty Romans of antiquity lost their empire, arguably due to lead in their wine containers, lead water pipes, and lead cooking utensils. In modern times, lead paint has become universally banned, which has resulted in a reduction of lead-induced interstitial nephritis. In recent decades, bisphenol A (BPA has been identified as a new environmental risk. BPA is in the plastic coating of food and beverage containers to prevent corrosion. BPA is so ubiquitous that urinary BPA and proteinuria are present in a high percentage of the population. BPA-induced kidney injury and other health concerns have led certain countries to ban BPA. Now, BPA-free containers are being introduced with great fanfare by manufacturers, but safety issues on all plastic products remain. It begs the question whether “plastics” of today take the place of “lead” in ancient Rome. This is a challenging question without an answer at this point.

  20. Inflammatory Mechanisms of Organ Crosstalk during Ischemic Acute Kidney Injury

    Directory of Open Access Journals (Sweden)

    Laura E. White

    2012-01-01

    Full Text Available Acute kidney injury (AKI is a common complication during inpatient hospitalization, and clinical outcomes remain poor despite advancements in renal replacement therapy. AKI in the setting of multiple organ failure (MOF remains a formidable challenge to clinicians and incurs an unacceptably high mortality rate. Kidney ischemia-reperfusion injury (IRI incites a proinflammatory cascade and releases cellular and soluble mediators with systemic implications for remote organ injury. Evidence from preclinical models cites mechanisms of organ crosstalk during ischemic AKI including the expression of cellular adhesion molecules, lymphocyte trafficking, release of proinflammatory cytokines and chemokines, and modification of the host innate and adaptive immune response systems. In this paper, the influence of kidney IRI on systemic inflammation and distant organ injury will be examined. Recent experimental data and evolving concepts of organ crosstalk during ischemic AKI will also be discussed in detail.

  1. Renoprotective mechanisms of morin in cisplatin-induced kidney injury.

    Science.gov (United States)

    Wei, Zhengkai; He, Xuexiu; Kou, Jinhua; Wang, Jingjing; Chen, Libin; Yao, Minjun; Zhou, Ershun; Fu, Yunhe; Guo, Changming; Yang, Zhengtao

    2015-09-01

    In this study, we investigated the renoprotective effects of morin on cisplatin-induced kidney injury in mice. Serum creatinine and blood urea nitrogen (BUN) levels, glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD) activities were determined according to the corresponding kits. The mRNA levels of TNF-α and IL-1β in kidney tissues were measured by quantitative real-time PCR (qRT-PCR). The activities of cytochrome P450 2E1 (CYP2E1), nuclear factor kappa B (NF-κB) p65, P38 mitogen-activated protein kinase (MAPK), Bax, p53 and cleaved caspase 3 were evaluated by western blotting. The results showed that the model of cisplatin-induced kidney injury was successfully replicated, and morin significantly attenuated histopathological changes and decreased the levels of TNF-α and IL-1β in the kidneys. In addition, morin attenuated the activation of CYP2E1, phospho-NF-κB p65, phospho-P38 MAPK, Bax, phospho-p53 and cleaved caspase 3 in CP-induced kidney injury. In conclusion, these results indicated that the renoprotective mechanisms of morin may be attributed to the suppression of oxidative stress, inflammation and apoptosis in CP-induced kidney injury.

  2. Acute kidney injury in pregnancy: a clinical challenge.

    Science.gov (United States)

    Machado, Susana; Figueiredo, Nuno; Borges, Andreia; São José Pais, Maria; Freitas, Luís; Moura, Paulo; Campos, Mário

    2012-01-01

    The incidence of acute kidney injury in pregnancy declined significantly over the second half of the 20th century; however, it is still associated with major maternal and perinatal morbidity and mortality. A set of systemic and renal physiological adaptive mechanisms occur during a normal gestation that will constrain several changes in laboratory parameters of renal function, electrolytes, fluid and acid-base balances. The diagnosis of acute kidney injury in pregnancy is based on the serum creatinine increase. The usual formulas for estimating glomerular filtration rate are not validated in this population. During the first trimester of gestation, acute kidney injury develops most often due to hyperemesis gravidarum or septic abortion. In the third trimester, the differential diagnosis is more challenging for the obstetrician and the nephrologist and comprises some pathologies that are reviewed in this article: preeclampsia/HELLP syndrome, acute fatty liver of pregnancy and thrombotic microangiopathies.

  3. 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...

  4. 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.

  5. An analysis of clinical characteristics of septic acute kidney injury by using criteria of Kidney Disease:Improving Global Outcomes

    Institute of Scientific and Technical Information of China (English)

    臧芝栋

    2013-01-01

    Objective To evaluate the value of kidney Disease:Improving Global Outcomes(KDIGO) criteria in investigating clinical feature and prognosis of acute kidney injury(AKI) patients with sepsis in ICU.Methods

  6. Acute Kidney Injury: Tubular Markers and Risk for Chronic Kidney Disease and End-Stage Kidney Failure.

    Science.gov (United States)

    Tan, Hon Liang; Yap, John Q; Qian, Qi

    2016-01-01

    Acute kidney injury (AKI) is a common clinical syndrome directly related to patient short-term and long-term morbidity and mortality. Over the last decade, the occurrence rate of AKI has been increasing, and there has also been a growing epidemic of chronic kidney diseases (CKD) and end-stage kidney disease (ESRD) linked to severe and repeated episodes of AKIs. The detection and management of AKI are currently far from satisfactory. A large proportion of AKI patients, especially those with preexisting CKD, are at an increased risk of non-resolving AKI and progressing to CKD and ESRD. Proposed pathological processes that contribute to the transition of AKI to CKD and ESRD include severity and frequency of kidney injury, alterations of tubular cell phenotype with cells predominantly in the G2/M phase, interstitial fibrosis and microvascular rarification related to loss of endothelial-pericyte interactions and pericyte dedifferentiation. Innate immune responses, especially dendritic cell responses related to inadequate adenosine receptor (2a)-mediated signals, autophagic insufficiency and renin-angiotensin system activation have also been implicated in the progression of AKI and transitions from AKI to CKD and ESRD. Although promising advances have been made in understanding the pathophysiology of AKI and AKI consequences, much more work needs to be done in developing biomarkers for detecting early kidney injury, prognosticating kidney disease progression and developing strategies to effectively treat AKI and to minimize AKI progression to CKD and ESRD.

  7. Kidney injury associated with telavancin dosing regimen in an animal model.

    Science.gov (United States)

    Tam, Vincent H; Ledesma, Kimberly R; Bowers, Dana R; Zhou, Jian; Truong, Luan D

    2015-05-01

    The elevation of serum creatinine levels is a concern with telavancin therapy. We examined the onset of kidney injury associated with telavancin in an animal model. Urine samples were collected at baseline and daily to determine the concentrations of kidney injury molecule 1 (KIM-1), a marker for early kidney injury. When a clinically relevant exposure of telavancin was given daily to rats, some differences in kidney injury were attributed to the dosing regimen. Further investigations of alternative telavancin dosing regimens are warranted.

  8. Complement activation and kidney injury molecule-1-associated proximal tubule injury in severe preeclampsia.

    Science.gov (United States)

    Burwick, Richard M; Easter, Sarah Rae; Dawood, Hassan Y; Yamamoto, Hidemi S; Fichorova, Raina N; Feinberg, Bruce B

    2014-10-01

    Kidney injury with proteinuria is a characteristic feature of preeclampsia, yet the nature of injury in specific regions of the nephron is incompletely understood. Our study aimed to use existing urinary biomarkers to describe the pattern of kidney injury and proteinuria in pregnancies affected by severe preeclampsia. We performed a case-control study of pregnant women from Brigham and Women's Hospital from 2012 to 2013. We matched cases of severe preeclampsia (n=25) 1:1 by parity and gestational age to 2 control groups with and without chronic hypertension. Urinary levels of kidney injury molecule-1 and complement components (C3a, C5a, and C5b-9) were measured by enzyme-linked immunosorbent assay, and other markers (albumin, β2 microglobulin, cystatin C, epithelial growth factor, neutrophil gelatinase-associated lipocalin, osteopontin, and uromodulin) were measured simultaneously with a multiplex electrochemiluminescence assay. Median values between groups were compared with the Wilcoxon signed-rank test and correlations with Spearman correlation coefficient. Analysis of urinary markers revealed higher excretion of albumin and kidney injury molecule-1 and lower excretion of neutrophil gelatinase-associated lipocalin and epithelial growth factor in severe preeclampsia compared with chronic hypertension and healthy controls. Among subjects with severe preeclampsia, urinary excretion of complement activation products correlated most closely with kidney injury molecule-1, a specific marker of proximal tubule injury (C5a: r=0.60; P=0.001; and C5b-9: r=0.75; Pkidney injury in severe preeclampsia that is characterized by glomerular impairment and complement-mediated inflammation and injury, possibly localized to the proximal tubule in association with kidney injury molecule-1.

  9. Preliminary Experience of Integrative Medicine in Acute Kidney Injury

    Institute of Scientific and Technical Information of China (English)

    RAO Xiang-rong

    2010-01-01

    @@ Acute kidney injury (AKI), a concept that replaces the traditional concept known as acute renal failure (ARF),has been adopted by more and more nephrologists and intensive-care specialists in recent years. The definition and diagnostic criteria of AKI are quite different from thoseof ARF(1).

  10. Acute kidney injury in imported Plasmodium falciparum malaria

    NARCIS (Netherlands)

    L.C. Koopmans, L.C. (Liese); M.E. van Wolfswinkel (Marlies); D.A. Hesselink (Dennis); E.J. Hoorn (Ewout); R. Koelewijn (Rob); J.J. van Hellemond (Jaap); P.J. van Genderen (P.)

    2015-01-01

    textabstractBackground: Acute kidney injury (AKI) is a known complication of malaria, and is reported to occur in up to 40 % of adult patients with a severe Plasmodium falciparum infection in endemic regions. To gain insight in the incidence and risk factors of AKI in imported P. falciparum malaria,

  11. Clinical analysis on 624 elderly patients with acute kidney injury

    Institute of Scientific and Technical Information of China (English)

    邹琴

    2012-01-01

    Objective To investigate the pathogens, clinical characteristic and therapeutic method of acute kidney injury(AKI).Methods The morbidity,composition of pathogeny,staging and prognosis of 624 cases with AKI recruited by our department from January 1999 to December 2009.

  12. 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

    2006-01-01

    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 dete

  13. Pathophysiology of Cisplatin-Induced Acute Kidney Injury

    Directory of Open Access Journals (Sweden)

    Abdullah Ozkok

    2014-01-01

    Full Text Available Cisplatin and other platinum derivatives are the most widely used chemotherapeutic agents to treat solid tumors including ovarian, head and neck, and testicular germ cell tumors. A known complication of cisplatin administration is acute kidney injury (AKI. The nephrotoxic effect of cisplatin is cumulative and dose-dependent and often necessitates dose reduction or withdrawal. Recurrent episodes of AKI may result in chronic kidney disease. The pathophysiology of cisplatin-induced AKI involves proximal tubular injury, oxidative stress, inflammation, and vascular injury in the kidney. There is predominantly acute tubular necrosis and also apoptosis in the proximal tubules. There is activation of multiple proinflammatory cytokines and infiltration of inflammatory cells in the kidney. Inhibition of the proinflammatory cytokines TNF-α or IL-33 or depletion of CD4+ T cells or mast cells protects against cisplatin-induced AKI. Cisplatin also causes endothelial cell injury. An understanding of the pathogenesis of cisplatin-induced AKI is important for the development of adjunctive therapies to prevent AKI, to lessen the need for dose decrease or drug withdrawal, and to lessen patient morbidity and mortality.

  14. Acute kidney injury: changing lexicography, definitions, and epidemiology.

    Science.gov (United States)

    Himmelfarb, J; Ikizler, T A

    2007-05-01

    In recent years, there have been numerous advances in understanding the molecular determinants of functional kidney injury after ischemic and/or toxic exposure. However, translation of successful novel therapies designed to attenuate kidney functional injury from animal models to the clinical sphere has had modest results. This lack of translatability is at least in part due to lack of sufficient standardization in definitions and classification of cases of acute kidney injury (AKI), an incomplete understanding of the natural history of human AKI, and a limited understanding of how kidney injury interacts with other organ system failure in the context of systemic metabolic abnormalities. A concerted effort is now being made by nephrologists and intensivists to arrive at standardized terminology and classification of AKI. There have also been dramatic advances in our understanding of the epidemiology and natural history of AKI, particularly in the hospital and intensive care unit setting. Promising strategies are now being developed which may ultimately lead to improved outcomes for patients at risk for or who have developed AKI, which should be readily testable in the coming decade.

  15. Acute Kidney Injury Induced by Herbal Products: A Case Report

    Directory of Open Access Journals (Sweden)

    Erhan TATAR

    2014-09-01

    Full Text Available Recently, consumption of herbal products has become widespread both in Turkey and worldwide. However, the safety of these products is substantially controversial. We here present a case of acute kidney injury in a patient with excessive use of herbal products for cardio-protective purposes.

  16. Urinary Kidney Injury Molecule-1 (KIM-1 in Early Diagnosis of Acute Kidney Injury in Pediatric Critically Ill

    Directory of Open Access Journals (Sweden)

    Irma Lestari Paramastuty

    2016-04-01

    Full Text Available Acute kidney injury (AKI often associated with a high hospital morbi-mortality rate in the intensive care unit patients. Kidney injury molecule-1 (KIM-1, has many characteristics of ideal biomarker for kidney injury. The aim of this study was to compared the temporal pattern of elevation urinary KIM-1 level following critically ill children with SCr as standart biomarker of AKI. Prospective analytic observational study was conducted during October to March 2014 in the Saiful Anwar General Hospital and Physiology Laboratory Brawijaya University. There were 13 critically ill as subjects. SCr and KIM-1 levels from all subjects were measured three times ( at admission, after 1st and 6th hour. Subjects were devided into AKI - non-AKI groups by SCr level and survivor - non survivor group at the and of the observations. Results showed that there were significantly increased levels of KIM-1 in the AKI and non-AKI and survivor-non survivor group at time point. However, we found that delta KIM-1 at time point increased significant in non AKI group and survivor group. KIM-1 at admission can diagnosed AKI in critically ill children. We conclude that urinary KIM-1 is a sensitive non-invasive biomarker to diagnosed acute kidney injury in critically ill children. Increase level of KIM-1 by time shows protective and good outcome in critically ill children.

  17. Seatbelt injury resulting in functional loss of a transplanted kidney.

    Science.gov (United States)

    McHugh, Patrick P; Clifford, Timothy M; Johnston, Thomas D; Banerjee, Ambar S; Gedaly, Roberto; Jeon, Hoonbae; Ranjan, Dinesh

    2008-09-01

    The transplanted kidney, lying heterotopically in the iliac fossa, is especially vulnerable to damage from blunt trauma, particularly compression by vehicle seatbelt. We present a case wherein a functioning renal allograft lying in the right iliac fossa was severely injured by seatbelt compression, resulting in significant functional compromise and eventual loss. The patient later underwent successful retransplantation with a second living donor kidney. Management of injured renal transplant recipients requires appreciation of mechanisms likely to cause damage to the graft, as well as familiarity with available treatment options, both surgical and nonsurgical. As functional life spans of renal allografts improve, this type of injury will most likely be encountered with increasing frequency.

  18. Association between the levels of urine kidney injury molecule-1 and the progression of acute kidney injury in the elderly

    Science.gov (United States)

    Wang, Chunlin; Che, Xiajing; Shao, Xinghua; Xu, Yao; Ni, Zhaohui; Mou, Shan

    2017-01-01

    Background The factors influencing the prognosis of acute kidney injury (AKI) were analyzed in a group of elderly AKI patients to determine the markers of early prognosis. Methods A total of 258 patients were screened, and 201 patients were enrolled in the study. Eventually, 184 AKI patients were included in the study, including 79 elderly AKI patients (≥60 years old). During one year of follow-up, renal function changes were observed, and the risk factors that influenced the prognosis of AKI were analyzed. Results When AKI occurred, the urine kidney injury molecule-1 (uKIM-1) level was significantly higher in the progressive deterioration of renal function group than in the renal function stable group. The ROC curve analysis revealed that the area under the curve for poor progressive deterioration of renal function as predicted by the uKIM-1 level was 0.681. At a cutoff point of 2.46 ng/mg, the sensitivity was 71.9% and the specificity was 70.0%. In elderly AKI patients, uKIM-1 levels exceeding 2.46 ng/mg were positively associated with poor kidney prognosis. Conclusions Elderly AKI patients are at risk of developing progressive deterioration of renal function. In elderly AKI patients, the high uKIM-1 level may predict the prognosis of kidney function and may be used as an early screening indicator of poor kidney prognosis. PMID:28187124

  19. 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.

  20. [Uncaria tomentosa and acute ischemic kidney injury in rats].

    Science.gov (United States)

    de Fátima Fernandes Vattimo, Maria; da Silva, Natalia Oliveira

    2011-03-01

    The objective of this study was to evaluate the renoprotective effects of Uncaria Tomentosa (cat's claw) on ischemic acute kidney injury induced by renal clamping in rats. The hypoxia and hypoperfusion increase the production of reactive species already present in the inflammatory process. Results showed that the renal function evaluated by creatinine clearance, the urinary excretion of peroxides and malondealdehyde indexes demonstrated that UT induced renoprotection, probably related to its antioxidant activities.

  1. Relation between acute kidney injury and pregnancy-related factors

    OpenAIRE

    Monchai Siribamrungwong; Pawadee Chinudomwong

    2016-01-01

    Acute kidney injury (AKI) is a serious problem during pregnancy. Once occurred, it brings about devastating maternal and fetal outcomes. Among developed nations, the trend of pregnancy-related AKI (PRAKI) is on a decline due to the advances in obstetrics care and the legality of abortion. On the contrary, this situation remains one of the major health problems in the developing countries. Though some improvements have been observed, PRAKI still causes high maternal morbidity and mortality, le...

  2. Acute kidney injury in sepsis: transient or intrinsic?

    Science.gov (United States)

    Jörres, Achim

    2013-11-20

    The negative prediction of intrinsic versus transient acute kidney injury (AKI) in septic patients may be facilitated by combined assessment of fractional excretion of sodium and urea. If both excretions are high this would signal the presence of transient AKI and suggest that successful restoration of diuresis by conservative therapy is likely, thus supporting a wait-and-watch approach regarding the initiation of acute renal replacement therapy.

  3. Lithium-induced minimal change disease and acute kidney injury

    OpenAIRE

    Parul Tandon; Natalie Wong; Zaltzman, Jeffrey S.

    2015-01-01

    Context: Lithium carbonate is a psychiatric medication commonly used in the treatment of bipolar disorder. It has been implicated in inducing nephrogenic diabetes inspidus, chronic tubulointerstitial nephropathy, and acute tubular necrosis. We describe a case of lithium-induced minimal change disease (MCD) and acute kidney injury (AKI). Case Report: A 32-year-old female with a medical history of bipolar disorder treated with chronic lithium therapy presented with anasarca, fatigue, and tremor...

  4. 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.

  5. Losartan reduces ensuing chronic kidney disease and mortality after acute kidney injury

    Science.gov (United States)

    Cheng, Shun-Yang; Chou, Yu-Hsiang; Liao, Fang-Ling; Lin, Chi-Chun; Chang, Fan-Chi; Liu, Chia-Hao; Huang, Tao-Min; Lai, Chun-Fu; Lin, Yu-Feng; Wu, Vin-Cent; Chu, Tzong-Shinn; Wu, Ming-Shiou; Lin, Shuei-Liong

    2016-01-01

    Acute kidney injury (AKI) is an important risk factor for incident chronic kidney disease (CKD). Clinical studies disclose that ensuing CKD progresses after functional recovery from AKI, but the underlying mechanisms remain illusive. Using a murine model representing AKI-CKD continuum, we show angiotensin II type 1a (AT1a) receptor signaling as one of the underlying mechanisms. Male adult CD-1 mice presented severe AKI with 20% mortality within 2 weeks after right nephrectomy and left renal ischemia-reperfusion injury. Despite functional recovery, focal tubular atrophy, interstitial cell infiltration and fibrosis, upregulation of genes encoding angiotensinogen and AT1a receptor were shown in kidneys 4 weeks after AKI. Thereafter mice manifested increase of blood pressure, albuminuria and azotemia progressively. Drinking water with or without losartan or hydralazine was administered to mice from 4 weeks after AKI. Increase of mortality, blood pressure, albuminuria, azotemia and kidney fibrosis was noted in mice with vehicle administration during the 5-month experimental period. On the contrary, these parameters in mice with losartan administration were reduced to the levels shown in control group. Hydralazine did not provide similar beneficial effect though blood pressure was controlled. These findings demonstrate that losartan can reduce ensuing CKD and mortality after functional recovery from AKI. PMID:27677327

  6. Pharmacological Strategies to Prevent Contrast-Induced Acute Kidney Injury

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    Pattharawin Pattharanitima

    2014-01-01

    Full Text Available Contrast-induced acute kidney injury (CI-AKI is the most common iatrogenic cause of acute kidney injury after intravenous contrast media administration. In general, the incidence of CI-AKI is low in patients with normal renal function. However, the rate is remarkably elevated in patients with preexisting chronic kidney disease, diabetes mellitus, old age, high volume of contrast agent, congestive heart failure, hypotension, anemia, use of nephrotoxic drug, and volume depletion. Consequently, CI-AKI particularly in high risk patients contributes to extended hospitalizations and increases long-term morbidity and mortality. The pathogenesis of CI-AKI involves at least three mechanisms; contrast agents induce renal vasoconstriction, increase of oxygen free radicals through oxidative stress, and direct tubular toxicity. Several strategies to prevent CI-AKI have been evaluated in experimental studies and clinical trials. At present, intravascular volume expansion with either isotonic saline or sodium bicarbonate solutions has provided more consistent positive results and was recommended in the prevention of CI-AKI. However, the proportion of patients with risk still develops CI-AKI. This review critically evaluated the current evidence for pharmacological strategies to prevent CI-AKI in patients with a risk of developing CI-AKI.

  7. Acute kidney injury in pregnancy-current status.

    Science.gov (United States)

    Acharya, Anjali; Santos, Jolina; Linde, Brian; Anis, Kisra

    2013-05-01

    Pregnancy-related acute kidney injury (PR-AKI) causes significant maternal and fetal morbidity and mortality. Management of PR-AKI warrants a thorough understanding of the physiologic adaptations in the kidney and the urinary tract. Categorization of etiologies of PR-AKI is similar to that of acute kidney injury (AKI) in the nonpregnant population. The causes differ between developed and developing countries, with thrombotic microangiopathies (TMAs) being common in the former and septic abortion and puerperal sepsis in the latter. The incidence of PR-AKI is reported to be on a decline, but there is no consensus on the exact definition of the condition. The physiologic changes in pregnancy make diagnosis of PR-AKI difficult. Newer biomarkers are being studied extensively but are not yet available for clinical use. Early and accurate diagnosis is necessary to improve maternal and fetal outcomes. Timely identification of "at-risk" individuals and treatment of underlying conditions such as sepsis, preeclampsia, and TMAs remain the cornerstone of management. Questions regarding renal replacement therapy such as modality, optimal prescription, and timing of initiation in PR-AKI remain unclear. There is a need to systematically explore these variables to improve care of women with PR-AKI.

  8. Acute kidney injury in acute on chronic liver failure.

    Science.gov (United States)

    Maiwall, Rakhi; Sarin, S K; Moreau, Richard

    2016-03-01

    Acute on chronic liver failure (ACLF) is a distinct clinical entity; however, there is still debate in the way it is defined in the East as compared to the West, especially with respect to incorporation of kidney dysfunction or failure in the definition of ACLF. Kidney dysfunction is defined as serum creatinine between 1.5 and 1.9 mg/dl and kidney failure as serum creatinine of more than 2 mg/dl or requirement of renal replacement therapy according to the EASL-CLIF Consortium. Kidney dysfunction or failure is universally present in patients with ACLF according to the definition by the EASL-CLIF Consortium while on the contrary the APASL definition of ACLF does not incorporate kidney dysfunction or failure in its definition. Recently, both the diagnosis and management of renal failure in patients with cirrhosis has changed with the advent of the acute kidney injury (AKI) criteria defined as an abrupt decline in renal functions, characterized by an absolute increase in serum creatinine of 0.3 mg/dl within 48 h or an increase of more than 50 % from baseline, which is known or presumed to have occurred in the previous 7 days. Further, recent studies in patients with cirrhosis have shown the utility of biomarkers for the diagnosis of AKI. The present review covers the pathogenetic mechanisms, diagnosis, prognosis as well as management of AKI in patients with ACLF from both a Western as well as an Eastern perspective. The review identifies an unmet need to diagnose AKI and prevent this ominous complication in patients with ACLF.

  9. Diagnostic utility of kidney biopsy in patients with sarcoidosis and acute kidney injury

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    Nadasdy T

    2011-09-01

    Full Text Available Ravish Shah1, Ganesh Shidham1, Anil Agarwal1, Alia Albawardi2, Tibor Nadasdy21Division of Nephrology, 2Division of Renal Pathology, The Ohio State University, Columbus, Ohio, USABackground: Sarcoidosis is an idiopathic multisystem disease characterized by noncaseating granulomatous inflammation. Renal biopsy is often performed to evaluate the patient with sarcoidosis and acute kidney injury (AKI. Diagnosis rests on the demonstration of noncaseating granulomas and exclusion of other causes of granulomatous inflammation. This paper reports a patient with pulmonary sarcoidosis and AKI whose renal function improved after prednisone therapy despite the absence of kidney biopsy findings characteristic of sarcoidosis.Case report: A 63-year-old Caucasian male with history of hypertension was treated for pulmonary sarcoidosis with a 6-month course of prednisone. His creatinine was 1.6 mg/dL during the course. Two months after finishing treatment, he presented with creatinine of 4 mg/dL. A kidney biopsy was performed, which showed nonspecific changes without evidence of granuloma or active interstitial inflammation. He was empirically started on prednisone for presumed renal sarcoidosis, even with a nondiagnostic kidney biopsy finding. Within a month of treatment, his serum creatinine improved to 2 mg/dL, though not to baseline. He continues to be stable on low-dose prednisone. With this case as a background, we aimed to determine the incidence of inconclusive kidney biopsies in patients with sarcoidosis presenting with AKI and to identify the various histological findings seen in this group of patients.Methods: In this retrospective study, all patients who had native renal biopsies read at The Ohio State University over the period of 6 years were identified. Those patients with a diagnosis of sarcoidosis, presenting with AKI, were included for further review.Results: Out of 21 kidney biopsies done in patients with sarcoidosis over a period of 6 years

  10. Outpatient nephrology referral rates after acute kidney injury.

    Science.gov (United States)

    Siew, Edward D; Peterson, Josh F; Eden, Svetlana K; Hung, Adriana M; Speroff, Theodore; Ikizler, T Alp; Matheny, Michael E

    2012-02-01

    AKI associates with an increased risk for the development and progression of CKD and mortality. Processes of care after an episode of AKI are not well described. Here, we examined the likelihood of nephrology referral among survivors of AKI at risk for subsequent decline in kidney function in a US Department of Veterans Affairs database. We identified 3929 survivors of AKI hospitalized between January 2003 and December 2008 who had an estimated GFR (eGFR) <60 ml/min per 1.73 m(2) 30 days after peak injury. We analyzed time to referral considering improvement in kidney function (eGFR ≥60 ml/min per 1.73 m(2)), dialysis initiation, and death as competing risks over a 12-month surveillance period. Median age was 73 years (interquartile range, 62-79 years) and the prevalence of preadmission kidney dysfunction (baseline eGFR <60 ml/min per 1.73 m(2)) was 60%. Overall mortality during the surveillance period was 22%. The cumulative incidence of nephrology referral before dying, initiating dialysis, or experiencing an improvement in kidney function was 8.5% (95% confidence interval, 7.6-9.4). Severity of AKI did not affect referral rates. These data demonstrate that a minority of at-risk survivors are referred for nephrology care after an episode of AKI. Determining how to best identify survivors of AKI who are at highest risk for complications and progression of CKD could facilitate early nephrology-based interventions.

  11. [Metformin-associated lactic acidosis and acute kidney injury].

    Science.gov (United States)

    Greco, Paolo; Regolisti, Giuseppe; Antoniotti, Riccardo; Maccari, Caterina; Parenti, Elisabetta; Corrado, Silvia; Fiaccadori, Enrico

    2016-01-01

    Metformin is recommended as the treatment of choice in patients with type 2 diabetes mellitus because of its efficacy, general tolerability and low cost. Recent guidelines have extended the use of metformin to patients with Chronic Kidney Disease (CKD) up to stage III. However, in the recent literature, cases of MALA (metformin-associated lactic acidosis) are increasingly reported. MALA is the most dangerous side effect of the drug, with an incidence rate of 2-9 cases per 100000 person-years of exposure. We report on two patients with accidental metformin overdose, severe lactic acidosis and acute kidney injury. In both cases, the usual dose of metformin was inappropriate with respect to the level of kidney dysfunction (CKD stage III). As both patients met the criteria for renal replacement therapy in metformin poisoning, they were treated effectively with sustained low-efficiency dialysis until normalization of serum lactate and bicarbonate values. Clinical status and kidney function improved and both patients could be discharged from the hospital.

  12. 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.

  13. Epoxyeicosatrienoic acid analog attenuates angiotensin II hypertension and kidney injury.

    Science.gov (United States)

    Khan, Abdul Hye; Falck, John R; Manthati, Vijaya L; Campbell, William B; Imig, John D

    2014-01-01

    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 (10 mg/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.

  14. 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

  15. Does Dexpantenol Protect the Kidney from Ischemia-Reperfusion Injury?

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    Sezen ÖZKISACIK

    2011-05-01

    Full Text Available OBJECTIVES: Tissue injury occurs following reperfusion after creation of ischemia. Plenty of chemical agents have been shown to protect from such an injury. We planned to evaluate the protective effect of dexpanthenol (dxp in ischemia-reperfusion injury. MATERIAL and METHODS: 24 adult rats were used and divided into 3 groups. A right nephrectomy was performed through a median laparotomy incision in all groups. Additionally, in group 1 (sham group, left nephrectomy was made 6 hours later without creation of ischemia. In group 2 (Saline group, the left kidney was left ischemic for 1 hour and reperfusion was established for 6 hours. Saline was administered intraperitoneally thirty minutes before creation of ischemia and just before reperfusion. In group 3 (Dexpanthenol group, the left kidney was left ischemic for 1 hour and reperfusion was established for 6 hours. Dxp (500 mg/kg was administered intraperitoneally thirty minutes before creation of ischemia and just before reperfusion. A left nephrectomy was performed at the end of the 6 hours of reperfusion. Nephrectomy specimens were histopathologically analysed for congestion, inflammation and necrosis. Tissue NO, glutathione reductase, catalase and MDA levels were measured. RESULTS: There was no significant differences between the groups histopathologically or biochemically. CONCLUSION: Dexpanthenol is the biologically active form of pantothenic acid and has an antioxidant effect. Our study was not in correlation with the literature regarding a protective effect of dxp on various organs via its antioxidant effect.

  16. DNA damage response in nephrotoxic and ischemic kidney injury.

    Science.gov (United States)

    Yan, Mingjuan; Tang, Chengyuan; Ma, Zhengwei; Huang, Shuang; Dong, Zheng

    2016-10-27

    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.

  17. When to correct coagulopathy in acute kidney injury?

    Science.gov (United States)

    Kaur, Manpreet; Gupta, Babita; D’souza, Nita; Shende, Seema

    2012-01-01

    Incidence of acute kidney injury (AKI) in adult trauma patients is 18% with 70% requiring renal replacement therapy. It is a challenge to treat AKI with coagulopathy since there are no defined transfusion triggers for these patients. We report a case wherein a polytrauma patient developed AKI for which he/she was dialysed and subsequently had an intracerebral bleed. There is a need to develop guidelines to transfusion triggers in AKI patients keeping vigilance on fluid overload, hyperkalemia and uraemia-induced platelet dysfunction. PMID:25885629

  18. Nutritional parameters are associated with mortality in acute kidney injury

    Directory of Open Access Journals (Sweden)

    Marina Nogueira Berbel

    2014-07-01

    Full Text Available OBJECTIVE:The objective of this study was to perform a nutritional assessment of acute kidney injury patients and to identify the relationship between nutritional markers and outcomes.METHOD:This was a prospective and observational study. Patients who were hospitalized at the Hospital of Botucatu School of Medicine were evaluated between January 2009 and December 2011. We evaluated a total of 133 patients with a clinical diagnosis of acute kidney injury and a clinical presentation suggestive of acute tubular necrosis. We explored the associations between clinical, laboratory and nutritional markers and in-hospital mortality. Multivariable logistic regression was used to adjust for confounding and selection bias.RESULTS:Non-survivor patients were older (67±14 vs. 59±16 years and exhibited a higher prevalence of sepsis (57.1 vs. 21.4% and higher Acute Tubular Necrosis-Individual Severity Scores (0.60±0.22 vs. 0.41±0.21 than did survivor patients. Based on the multivariable analysis, laboratorial parameters such as blood urea nitrogen and C-reactive protein were associated with a higher risk of death (OR: 1.013, p= 0.0052; OR: 1.050, p= 0.01, respectively, and nutritional parameters such as low calorie intake, higher levels of edema, lower resistance based on bioelectrical impedance analysis and a more negative nitrogen balance were significantly associated with a higher risk of death (OR: 0.950, p= 0.01; OR: 1.138, p= 0.03; OR: 0.995, p= 0.03; OR: 0.934, p= 0.04, respectively.CONCLUSIONS:In acute kidney injury patients, a nutritional assessment seems to identify nutritional markers that are associated with outcome. In this study, a low caloric intake, higher C-reactive protein levels, the presence of edema, a lower resistance measured during a bioelectrical impedance analysis and a lower nitrogen balance were significantly associated with risk of death in acute kidney injury patients.

  19. Management of Acute Kidney Injury in Pregnancy for the Obstetrician.

    Science.gov (United States)

    Acharya, Anjali

    2016-12-01

    Acute kidney injury (AKI) is a complex disorder that occurs in several clinical settings. During pregnancy, there are additional unique conditions that contribute to AKI. The clinical manifestations of AKI during pregnancy range from a minimal elevation in serum creatinine to renal failure requiring renal replacement therapy, similar to AKI in the general population. Recent epidemiologic studies in the general population show an increase in mortality associated with AKI, particularly when dialysis is required. The incidence of AKI in pregnancy remains a cause of significant morbidity and mortality.

  20. Epidemiology of Acute Kidney Injury in Critically Ill Children and Young Adults.

    Science.gov (United States)

    Kaddourah, Ahmad; Basu, Rajit K; Bagshaw, Sean M; Goldstein, Stuart L

    2017-01-05

    Background The epidemiologic characteristics of children and young adults with acute kidney injury have been described in single-center and retrospective studies. We conducted a multinational, prospective study involving patients admitted to pediatric intensive care units to define the incremental risk of death and complications associated with severe acute kidney injury. Methods We used the Kidney Disease: Improving Global Outcomes criteria to define acute kidney injury. Severe acute kidney injury was defined as stage 2 or 3 acute kidney injury (plasma creatinine level ≥2 times the baseline level or urine output <0.5 ml per kilogram of body weight per hour for ≥12 hours) and was assessed for the first 7 days of intensive care. All patients 3 months to 25 years of age who were admitted to 1 of 32 participating units were screened during 3 consecutive months. The primary outcome was 28-day mortality. Results A total of 4683 patients were evaluated; acute kidney injury developed in 1261 patients (26.9%; 95% confidence interval [CI], 25.6 to 28.2), and severe acute kidney injury developed in 543 patients (11.6%; 95% CI, 10.7 to 12.5). Severe acute kidney injury conferred an increased risk of death by day 28 after adjustment for 16 covariates (adjusted odds ratio, 1.77; 95% CI, 1.17 to 2.68); death occurred in 60 of the 543 patients (11.0%) with severe acute kidney injury versus 105 of the 4140 patients (2.5%) without severe acute kidney injury (P<0.001). Severe acute kidney injury was associated with increased use of mechanical ventilation and renal-replacement therapy. A stepwise increase in 28-day mortality was associated with worsening severity of acute kidney injury (P<0.001 by log-rank test). Assessment of acute kidney injury according to the plasma creatinine level alone failed to identify acute kidney injury in 67.2% of the patients with low urine output. Conclusions Acute kidney injury is common and is associated with poor outcomes, including increased

  1. Endothelial glycocalyx damage is associated with leptospirosis acute kidney injury.

    Science.gov (United States)

    Libório, Alexandre Braga; Braz, Marcelo Boecker Munoz; Seguro, Antonio Carlos; Meneses, Gdayllon C; Neves, Fernanda Macedo de Oliveira; Pedrosa, Danielle Carvalho; Cavalcanti, Luciano Pamplona de Góes; Martins, Alice Maria Costa; Daher, Elizabeth de Francesco

    2015-03-01

    Leptospirosis is a common disease in tropical countries, and the kidney is one of the main target organs. Membrane proteins of Leptospira are capable of causing endothelial damage in vitro, but there have been no studies in humans evaluating endothelial glycocalyx damage and its correlation with acute kidney injury (AKI). We performed a cohort study in an outbreak of leptospirosis among military personnel. AKI was diagnosed in 14 of 46 (30.4%) patients. Leptospirosis was associated with higher levels of intercellular adhesion molecule-1 (ICAM-1; 483.1 ± 31.7 versus 234.9 ± 24.4 mg/L, P leptospirosis-associated AKI had increased level of syndecan-1 (112.1 ± 45.4 versus 41.5 ± 11.7 ng/mL, P = 0.021) and ICAM-1 (576.9 ± 70.4 versus 434.9 ± 35.3, P = 0.034) compared with leptospirosis patients with no AKI. Association was verified between syndecan-1 and ICAM-1 with serum creatinine elevation and neutrophil gelatinase-associated lipocalin (NGAL) levels. This association remained even after multivariate analysis including other AKI-associated characteristics. Endothelial injury biomarkers are associated with leptospirosis-associated renal damage.

  2. 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.

  3. TNF Superfamily: A Growing Saga of Kidney Injury Modulators

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    Maria D. Sanchez-Niño

    2010-01-01

    Full Text Available Members of the TNF superfamily participate in kidney disease. Tumor necrosis factor (TNF and Fas ligand regulate renal cell survival and inflammation, and therapeutic targeting improves the outcome of experimental renal injury. TNF-related apoptosis-inducing ligand (TRAIL and its potential decoy receptor osteoprotegerin are the two most upregulated death-related genes in human diabetic nephropathy. TRAIL activates NF-kappaB in tubular cells and promotes apoptosis in tubular cells and podocytes, especially in a high-glucose environment. By contrast, osteoprotegerin plays a protective role against TRAIL-induced apoptosis. Another family member, TNF-like weak inducer of apoptosis (TWEAK induces inflammation and tubular cell death or proliferation, depending on the microenvironment. While TNF only activates canonical NF-kappaB signaling, TWEAK promotes both canonical and noncanonical NF-kappaB activation in tubular cells, regulating different inflammatory responses. TWEAK promotes the secretion of MCP-1 and RANTES through NF-kappaB RelA-containing complexes and upregulates CCl21 and CCL19 expression through NF-kappaB inducing kinase (NIK- dependent RelB/NF-kappaB2 complexes. In vivo TWEAK promotes postnephrectomy compensatory renal cell proliferation in a noninflammatory milieu. However, in the inflammatory milieu of acute kidney injury, TWEAK promotes tubular cell death and inflammation. Therapeutic targeting of TNF superfamily cytokines, including multipronged approaches targeting several cytokines should be further explored.

  4. 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

  5. Multiphoton imaging for assessing renal disposition in acute kidney injury

    Science.gov (United States)

    Liu, Xin; Liang, Xiaowen; Wang, Haolu; Roberts, Darren M.; Roberts, Michael S.

    2016-11-01

    Estimation of renal function and drug renal disposition in acute kidney injury (AKI), is important for appropriate dosing of drugs and adjustment of therapeutic strategies, but is challenging due to fluctuations in kidney function. Multiphoton microscopy has been shown to be a useful tool in studying drug disposition in liver and can reflect dynamic changes of liver function. We extend this imaging technique to investigate glomerular filtration rate (GFR) and tubular transporter functional change in various animal models of AKI, which mimic a broad range of causes of AKI such as hypoxia (renal ischemia- reperfusion), therapeutic drugs (e.g. cisplatin), rhabdomyolysis (e.g. glycerol-induced) and sepsis (e.g. LPSinduced). The MPM images revealed acute injury of tubular cells as indicated by reduced autofluorescence and cellular vacuolation in AKI groups compared to control group. In control animal, systemically injected FITC-labelled inulin was rapidly cleared from glomerulus, while the clearance of FITC-inulin was significantly delayed in most of animals in AKI group, which may reflect the reduced GFR in AKI. Following intravenous injection, rhodamine 123, a fluorescent substrate of p-glycoprotein (one of tubular transporter), was excreted into urine in proximal tubule via p-glycoprotein; in response to AKI, rhodamine 123 was retained in tubular cells as revealed by slower decay of fluorescence intensity, indicating P-gp transporter dysfunction in AKI. Thus, real-time changes in GFR and transporter function can be imaged in rodent kidney with AKI using multiphoton excitation of exogenously injected fluorescent markers.

  6. Energy and Oxygen Metabolism Disorder During Septic Acute Kidney Injury

    Directory of Open Access Journals (Sweden)

    Rong-li Yang

    2014-08-01

    Full Text Available Background/Aims: Acute kidney injury (AKI during septic shock, which is one of the most common clinical syndromes in the intensive care unit (ICU, has a high mortality rate and poor prognosis, partly because of a poor understanding of the pathogenesis of renal dysfunction during septic shock. Although ischemic injury of the kidney has been reported to result from adenosine triphosphate (ATP depletion, increasing evidence has demonstrated that AKI occurs in the absence of renal hypoperfusion and even occurs during normal or increased renal blood flow (RBF; nevertheless, whether energy metabolism disorder is involved in septic AKI and whether it changes according to renal hemodynamics have not been established. Moreover, tubular cell apoptosis, which is closely related to ATP depletion, rather than necrosis, has been shown to be the major form of cell injury during AKI. Methods: We used canine endotoxin shock models to investigate the hemodynamics, renal energy metabolism, renal oxygen metabolism, and pathological changes during septic AKI and to explore the underlying mechanisms of septic AKI. Results: The present results revealed that the nicotinamide adenine dinucleotide (NAD+ pool and the ATP/adenosine diphosphate (ADP ratio were significantly decreased during the early phase of septic AKI, which is accompanied by a decreased renal oxygen extraction ratio (O2ER% and decreased renal oxygen consumption (VO2. Furthermore, significant apoptosis was observed following renal dysfunction. RBF and renal oxygen delivery were not significantly altered. Conclusion: These results suggest that imbalanced energy metabolism, rather than tubular cell apoptosis, may be the initiator of renal dysfunction during septic shock.

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

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

    2017-03-07

    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.

  8. 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.

  9. Acute kidney injury in pregnancy: the thrombotic microangiopathies.

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    Ganesan, Chitra; Maynard, Sharon E

    2011-01-01

    Acute kidney injury (AKI) is a rare but serious complication of pregnancy. Although prerenal and ischemic causes of AKI are most common, renal insufficiency can complicate several other pregnancy-specific conditions. In particular, severe preeclampsia/HELLP syndrome, acute fatty liver of pregnancy (AFLP) and thrombotic thrombocytopenic purpura (TTP) are all frequently complicated by AKI, and share several clinical features which pose diagnostic challenges to the clinician. In this article, we discuss the clinical and laboratory features, pathophysiology and treatment of these 3 conditions, with particular attention to renal manifestations. It is imperative to distinguish these conditions to make appropriate therapeutic decisions which can be lifesaving for the mother and fetus. Typically AFLP and HELLP improve after delivery of the fetus, whereas plasma exchange is the first-line treatment for TTP.

  10. Acute kidney injury in acute liver failure: a review.

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    Moore, Joanna K; Love, Eleanor; Craig, Darren G; Hayes, Peter C; Simpson, Kenneth J

    2013-11-01

    Acute liver failure is a rare and often devastating condition consequent on massive liver cell necrosis that frequently affects young, previously healthy individuals resulting in altered cognitive function, coagulopathy and peripheral vasodilation. These patients frequently develop concurrent acute kidney injury (AKI). This abrupt and sustained decline in renal function, through a number of pathogenic mechanisms such as renal hypoperfusion, direct drug-induced nephrotoxicity or sepsis/systemic inflammatory response contributes to increased morbidity and is strongly associated with a worse prognosis. Improved understanding of the pathophysiology AKI in the context of acute liver failure may be beneficial in a number of areas; the development of new and sensitive biomarkers of renal dysfunction, refining prognosis and organ allocation, and ultimately leading to the development of novel treatment strategies, these issues are discussed in more detail in this expert review.

  11. 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.

  12. An Unusual Complication of Foam Sclerotherapy: Acute Kidney Injury

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    Müge EREK

    2014-09-01

    Full Text Available Sclerotherapy, in which an irritant solution is administered, is a method used to treat venous failure that results in complete venous destruction due to endothelial reaction and fibrosis. In recent years, foam sclerotherapy, in which a sclerosing agent (aethyl sclerole and air are mixed until they turn into foam and the resultant mixture is injected into noticeable veins directly and into other veins under ultrasonography in doses depending on the diameters of the varices, has been introduced. The drugs or gases used in foam sclerotherapy can cause local or systemic complications. Foam affects vessel endothelial cells and causes severe spasm in the vessel. It has been reported that endothelin-1 levels are high after foam sclerotherapy compared to the initial levels and that neurological complications vary with the endothelin levels. In this report, we present a case of acute kidney injury due to acute tubular necrosis probably caused by endothelin release following foam sclerotherapy.

  13. Acute kidney injury requiring hemodialysis in the tropics.

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    Okunola, Oluyomi O; Ayodele, Olugbenga E; Adekanle, Adebode D

    2012-11-01

    The morbidity and mortality from acute kidney injury (AKI) have remained relatively high over the last six decades. The triad of infections, nephrotoxins and obstetric complications are still major causes of acute kidney injury in the tropics. This retrospective study is a five-year audit of acute renal failure (ARF) (or stage 3 AKI) in patients requiring hemodialysis at the renal unit of the Department of Medicine of the Ladoke Akintola University of Technology (LAUTECH) Teaching Hospital, Osogbo, Nigeria. A total of 80 patients with AKI were treated over a five-year period at our center, of which 45 (56.2%) were in ARF, i.e. stage 3 AKI requiring hemodialysis. There were 24 males and 21 females. The most common cause of ARF among the patients was sepsis syndrome 16 (35.5%), while pregnancy-related cases accounted for 15 (33.3%) and nephrotoxins for 6 (13.3%). Five (33%) of the 15 pregnancy-related patients survived, and all were cases of septic abortion. Of the other 10 patients that did not survive, three (30%) had post-partum hemorrhage and seven (70%) post-partum eclampsia. In all, the mortality rate among our AKI presenting for hemodialysis at our center over a given year period was 28.8%. Majority of these were eclampsia related. The causes of ARF still remain the same in the tropics, eclampsia portends poor prognosis. Concerted efforts should be made at limiting this trend by active preventive services and early recognition of high-risk obstetrics cases.

  14. Acute kidney injury requiring hemodialysis in the tropics

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    Oluyomi O Okunola

    2012-01-01

    Full Text Available The morbidity and mortality from acute kidney injury (AKI have remained relatively high over the last six decades. The triad of infections, nephrotoxins and obstetric complications are still major causes of acute kidney injury in the tropics. This retrospective study is a five-year audit of acute renal failure (ARF (or stage 3 AKI in patients requiring hemodialysis at the renal unit of the Department of Medicine of the Ladoke Akintola University of Technology (LAUTECH Teaching Hospital, Osogbo, Nigeria. A total of 80 patients with AKI were treated over a five-year period at our center, of which 45 (56.2% were in ARF, i.e. stage 3 AKI requiring hemodialysis. There were 24 males and 21 females. The most common cause of ARF among the patients was sepsis syndrome 16 (35.5%, while pregnancy-related cases accounted for 15 (33.3% and nephrotoxins for 6 (13.3%. Five (33% of the 15 pregnancy-related patients survived, and all were cases of septic abortion. Of the other 10 patients that did not survive, three (30% had post-partum hemorrhage and seven (70% post-partum eclampsia. In all, the mortality rate among our AKI presenting for hemodialysis at our center over a given year period was 28.8%. Majority of these were eclampsia related. The causes of ARF still remain the same in the tropics, eclampsia portends poor prognosis. Concerted efforts should be made at limiting this trend by active preventive services and early recognition of high-risk obstetrics cases.

  15. Special nutrition challenges: current approach to acute kidney injury.

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    McCarthy, Mary S; Phipps, Shauna C

    2014-02-01

    Acute kidney injury (AKI), previously known as acute renal failure, is defined as a sudden decline in glomerular filtration rate with accumulation of metabolic waste products, toxins, and drugs, as well as alteration in the intrinsic functions of the kidney. Reports of mortality are as high as 80%, with numerous contributing causes including infection, cardiorespiratory complications, and cardiovascular disease. Concurrent with the high prevalence of critical illness in this population is the protein energy wasting (PEW), seen in up to 42% of patients upon intensive care unit admission. The pathophysiologic derangements of critical illness, the low energy and protein stores, and uremic complications require early nutrition intervention to attenuate the inflammatory response and oxidative stress, improve endothelial function, stabilize blood sugar, and preserve lean body mass. This article addresses the unique challenges of nutrition support for the patient with AKI in the setting of critical illness and renal replacement therapy. Evidence-based recommendations are provided to meet the macronutrient and micronutrient requirements of this heterogeneous and complex patient population.

  16. Acute kidney injury in patients with pulmonary embolism

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    Chang, Chih-Hsiang; Fu, Chung-Ming; Fan, Pei-Chun; Chen, Shao-Wei; Chang, Su-Wei; Mao, Chun-Tai; Tian, Ya-Chung; Chen, Yung-Chang; Chu, Pao-Hsien; Chen, Tien-Hsing

    2017-01-01

    Abstract Acute kidney injury (AKI) is overlooked in patients with pulmonary embolism (PE). Risk factors for and long-term outcomes of this complication remain unknown. This study evaluated the predictors and prognosis of AKI in patients with PE. This retrospective cohort study used Taiwan's National Health Insurance Research Database. We enrolled a total of 7588 patients who were admitted to a hospital for PE from January1997 to December 2011 and administered anticoagulation or thrombolytic agents. All demographic data, risk factors, and outcomes were analyzed. AKI was diagnosed in 372 (4.9%) patients. Multivariate logistic regression analysis revealed pre-existing chronic kidney disease, hypertension, diabetes mellitus, massive PE, anemia, and sepsis as independent risk factors for AKI. In the long-term follow-up, the survival rate was similar in the AKI and non-AKI groups. Careful risk factor screening and intensive intervention in patients with AKI might yield outcomes similar to those in patients without AKI. PMID:28248851

  17. Lithium-induced minimal change disease and acute kidney injury

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    Parul Tandon

    2015-01-01

    Full Text Available Context: Lithium carbonate is a psychiatric medication commonly used in the treatment of bipolar disorder. It has been implicated in inducing nephrogenic diabetes inspidus, chronic tubulointerstitial nephropathy, and acute tubular necrosis. We describe a case of lithium-induced minimal change disease (MCD and acute kidney injury (AKI. Case Report: A 32-year-old female with a medical history of bipolar disorder treated with chronic lithium therapy presented with anasarca, fatigue, and tremors. Work-up revealed supra-therapeutic lithium levels, hypoalbuminemia, and significant proteinuria. The patient was treated conservatively with fluids and discontinuation of lithium therapy. Subsequently, she developed significant AKI and persistent proteinuria. She underwent a renal biopsy that demonstrated effacement of podocyte foot processes consistent with lithium-induced MCD. This was treated with corticosteroids, which decreased the proteinuria and resolved all the patient′s symptoms. Conclusion: Lithium-induced MCD is a rare disease that affects patients of all ages. It is often associated with therapeutic lithium and is typically resolved with discontinuation of lithium. In some cases, concurrent AKI may result due to vascular obstruction from hyperalbuminuria and associated renal interstitial edema. Corticosteroids may be needed to reduce the proteinuria and prevent progression to chronic kidney disease. As such, patients on lithium therapy may benefit from monitoring of glomerular function via urinalysis to prevent the onset of nephrotic syndrome.

  18. 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.

  19. CXCR2 knockout mice are protected against DSS-colitis-induced acute kidney injury and inflammation.

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    Ranganathan, Punithavathi; Jayakumar, Calpurnia; Manicassamy, Santhakumar; Ramesh, Ganesan

    2013-11-15

    Organ cross talk exists in many diseases of the human and animal models of human diseases. A recent study demonstrated that inflammatory mediators can cause acute kidney injury and neutrophil infiltration in a mouse model of dextran sodium sulfate (DSS)-colitis. However, the chemokines and their receptors that may mediate distant organ effects in colitis are unknown. We hypothesized that keratinocyte chemoattractant (KC)/IL-8 receptor chemokine (C-X-C motif) ligand 2 (CXCL2) mediates DSS-colitis-induced acute kidney injury. Consistent with our hypothesis, wild-type (WT) mice developed severe colitis with DSS treatment, which was associated with inflammatory cytokine and chemokine expression and neutrophil infiltration in the colon. DSS-colitis in WT was accompanied by acute kidney injury and enhanced expression of inflammatory cytokines in the kidney. However, CXCR2 knockout mice were protected against DSS-colitis as well as acute kidney injury. Moreover, the expression of cytokines and chemokines and neutrophil infiltration was blunted in CXCR2 knockout mice in the colon and kidney. Administration of recombinant KC exacerbated DSS-colitis-induced acute kidney injury. Our results suggest that KC/IL-8 and its receptor CXCR2 are critical and major mediators of organ cross talk in DSS colitis and neutralization of CXCR2 will help to reduce the incidence of acute kidney injury due to ulcerative colitis and Crohn's disease in humans.

  20. Protection of the Transplant Kidney from Preservation Injury by Inhibition of Matrix Metalloproteinases.

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    Michael A J Moser

    Full Text Available Matrix metalloproteinases (MMPs, particularly MMP-2 and MMP-9, play an important role in ischemic injury to the heart, yet it is not known if these MMPs are involved in the injury that occurs to the transplant kidney. We therefore studied the pharmacologic protection of transplant kidneys during machine cold perfusion.Human kidney perfusates were analyzed for the presence of injury markers such as cytochrome c oxidase, lactate dehydrogenase, and neutrophil-gelatinase associated lipocalin (NGAL, and MMP-2 and MMP-9 were measured. The effects of MMP inhibitors MMP-2 siRNA and doxycycline were studied in an animal model of donation after circulatory determination of death (DCDD.Markers of injury were present in all analyzed perfusates, with higher levels seen in perfusates from human kidneys donated after controlled DCDD compared to brain death and in perfusate from kidneys with delayed graft function. When rat kidneys were perfused at 4°C for 22 hours with the addition of MMP inhibitors, this resulted in markedly reduced levels of MMP-2, MMP-9 and analyzed injury markers.Based on our study, MMPs are involved in preservation injury and the supplementation of preservation solution with MMP inhibitors is a potential novel strategy in protecting the transplant kidney from preservation injury.

  1. Acute kidney injury in children: Enhancing diagnosis with novel biomarkers

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    Samuel Nkachukwu Uwaezuoke

    2016-07-01

    Full Text Available This narrative review aims to appraise the sensitivity and specificity of novel biomarkers in identifying acute kidney injury (AKI in children. Serum creatinine represents a poor traditional biomarker for AKI due to some limitations. Although alternative reliable biomarkers that would better identify individuals at high risk for developing AKI, identify AKI early enough, monitor its progression and patients' recovery, as well as identify those patients at higher risk for poor outcomes are not yet available in renal care, the search-light has recently been focused on various novel biomarkers, some of which could provide this information in time ahead. Several studies have established their predictive value. However, none of them could solely fulfill all the criteria of the ideal biomarker. Therefore, to increase their sensitivity and specificity and enhance the diagnosis of AKI, constellations of different biomarkers with specific features are probably required. In future, the diagnostic evaluation of AKI in intensive care units will have to undergo a paradigm shift from serum creatinine as the traditional biomarker to tissue-specific injury biomarkers. A panel of these novel biomarkers employed at the bedside setting will ultimately revolutionize the diagnosis and prognostication of AKI in children.

  2. An unusual cause of acute kidney injury due to oxalate nephropathy in systemic scleroderma.

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    Mascio, Heather M; Joya, Christie A; Plasse, Richard A; Baker, Thomas P; Flessner, Michael F; Nee, Robert

    2015-08-01

    Oxalate nephropathy is an uncommon cause of acute kidney injury. Far rarer is its association with scleroderma, with only one other published case report in the literature. We report a case of a 75-year-old African-American female with a history of systemic scleroderma manifested by chronic pseudo-obstruction and small intestinal bacterial overgrowth (SIBO) treated with rifaximin, who presented with acute kidney injury with normal blood pressure. A renal biopsy demonstrated extensive acute tubular injury with numerous intratubular birefringent crystals, consistent with oxalate nephropathy. We hypothesize that her recent treatment with rifaximin for SIBO and decreased intestinal transit time in pseudo-obstruction may have significantly increased intestinal oxalate absorption, leading to acute kidney injury. Oxalate nephropathy should be considered in the differential diagnosis of acute kidney injury in scleroderma with normotension, and subsequent evaluation should be focused on bowel function to include alterations in gut flora due to antibiotic administration.

  3. Baseline donor chronic renal injury confers the same transplant survival disadvantage for DCD and DBD kidneys.

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    Kosmoliaptsis, V; Salji, M; Bardsley, V; Chen, Y; Thiru, S; Griffiths, M H; Copley, H C; Saeb-Parsy, K; Bradley, J A; Torpey, N; Pettigrew, G J

    2015-03-01

    Histological assessment of baseline chronic kidney injury may discriminate kidneys that are suitable for transplantation, but has not been validated for appraisal of donation after circulatory death (DCD) kidneys. 'Time-zero' biopsies for 371 consecutive, solitary, deceased-donor kidneys transplanted at our center between 2006 and 2010 (65.5% DCD, 34.5% donation after brain death [DBD]) were reviewed and baseline chronic degenerative injury scored using Remuzzi's classification. High scores correlated with donor age and extended criteria donors (42% of donors), but the spectrum of scores was similar for DCD and DBD kidneys. Transplant outcomes for kidneys scoring from 0 to 4 were comparable (1 and 3 year graft survival 95% and 92%), but were much poorer for kidneys scoring ≥5, with 1 year graft survival only 73%, and 12.5% suffering primary nonfunction. Critically, high Remuzzi scores conferred the same survival disadvantage for DCD and DBD kidneys. On multi-variable regression analysis, time-zero biopsy score was the only independent predictor for graft survival, whereas one-year graft estimated glomerular filtration rate (eGFR) correlated with donor age and biopsy score. In conclusion, the relationship between severity of chronic kidney injury and transplant outcome is similar for DCD and DBD kidneys. Kidneys with Remuzzi scores of ≤4 can be implanted singly with acceptable results.

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

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    Grunz-Borgmann, Elizabeth A.; Nichols, LaNita A.; Wang, Xinhui; Parrish, Alan R.

    2017-01-01

    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. PMID:28208580

  5. Acute kidney injury and chronic kidney disease: an integrated clinical syndrome.

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    Chawla, Lakhmir S; Kimmel, Paul L

    2012-09-01

    The previous conventional wisdom that survivors of acute kidney injury (AKI) tend to do well and fully recover renal function appears to be flawed. AKI can cause end-stage renal disease (ESRD) directly, and increase the risk of developing incident chronic kidney disease (CKD) and worsening of underlying CKD. In addition, severity, duration, and frequency of AKI appear to be important predictors of poor patient outcomes. CKD is an important risk factor for the development and ascertainment of AKI. Experimental data support the clinical observations and the bidirectional nature of the relationships between AKI and CKD. Reductions in renal mass and nephron number, vascular insufficiency, cell cycle disruption, and maladaptive repair mechanisms appear to be important modulators of progression in patients with and without coexistent CKD. Distinction between AKI and CKD may be artificial. Consideration should be given to the integrated clinical syndrome of diminished GFR, with acute and chronic stages, where spectrum of disease state and outcome is determined by host factors, including the balance of adaptive and maladaptive repair mechanisms over time. Physicians must provide long-term follow-up to patients with first episodes of AKI, even if they presented with normal renal function.

  6. Herbal Medicines for Acute Kidney Injury: Evidence, Gaps and Frontiers

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    Valérian Bunel

    2015-07-01

    Full Text Available Acute kidney injury (AKI is a major health threat worldwide. The literature on herbal intervention in AKI was searched from English and Chinese databases and reports were critically analyzed in terms of preventing AKI, promoting repair and regeneration, enhancing extrarenal clearance of uremic toxins, and preventing progression to chronic kidney disease (CKD. Altogether, 16 herbal formulae and a few extracts derived from individual herbs were reported to prevent or mitigate AKI in animal models induced by renal ischemia/reperfusion, cisplastin, gentamicin, glycerol, adenine, sepsis or physical exhaustion. Four formulae and six individual herbs were reported to accelerate recovery and/or to prevent CKD in established AKI animal models. Intrarectal herbal medicines, with or without simultaneous oral administration, were reported in six clinical trials and in an animal model to increase extrarenal clearance of uremic toxins. Additional 13 clinical trials reported oral or intravenous herbal interventions in AKI of different etiologies. Despite recurring problems, notably poor compliance with good practice guidelines for clinical trials and for authentication, naming and quality control of herbal materials, accumulating experimental data on the preventive effects of herbal medicines in AKI look encouraging and urge for better, definitive trials to guide clinical practice. Herbal enemas promoting extrarenal clearance of uremic toxins seem cost-effective, but better clinical evidence is certainly needed before any affirmative recommendation be made for AKI patients without access to dialysis. New frontiers, however, lie in those herbal remedies that promote repair/regeneration and prevent chronicity after AKI. Recent experimental data suggest that this may be possible.

  7. Acute kidney injury following spinal instrumentation surgery in children

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    Jöbsis, Jasper J; Alabbas, Abdullah; Milner, Ruth; Reilly, Christopher; Mulpuri, Kishore; Mammen, Cherry

    2017-01-01

    AIM To determine acute kidney in jury (AKI) incidence and potential risk factors of AKI in children undergoing spinal instrumentation surgery. METHODS AKI incidence in children undergoing spinal instrumentation surgery at British Columbia Children’s Hospital between January 2006 and December 2008 was determined by the Acute Kidney Injury Networ classification using serum creatinine and urine output criteria. During this specific time period, all patients following spinal surgery were monitored in the pediatric intensive care unit and had an indwelling Foley catheter permitting hourly urine output recording. Cases of AKI were identified from our database. From the remaining cohort, we selected group-matched controls that did not satisfy criteria for AKI. The controls were matched for sex, age and underlying diagnosis (idiopathic vs non-idiopathic scoliosis). RESULTS Thirty five of 208 patients met criteria for AKI with an incidence of 17% (95%CI: 12%-23%). Of all children who developed AKI, 17 (49%) developed mild AKI (AKI Stage 1), 17 (49%) developed moderate AKI (Stage 2) and 1 patient (3%) met criteria for severe AKI (Stage 3). An inverse relationship was observed with AKI incidence and the amount of fluids received intra-operatively. An inverse relationship was observed with AKI incidence and the amount of fluids received intra-operatively classified by fluid tertiles: 70% incidence in those that received the least amount of fluids vs 29% that received the most fluids (> 7.9, P = 0.02). Patients who developed AKI were more frequently exposed to nephrotoxins (non steroidal anti inflammatory drugs or aminoglycosides) than control patients during their peri-operative course (60% vs 22%, P < 0.001). CONCLUSION We observed a high incidence of AKI following spinal instrumentation surgery in children that is potentially related to the frequent use of nephrotoxins and the amount of fluid administered peri-operatively. PMID:28316941

  8. Eriodictyol attenuates cisplatin-induced kidney injury by inhibiting oxidative stress and inflammation.

    Science.gov (United States)

    Li, Cheng-zhen; Jin, Hai-hong; Sun, Hong-xin; Zhang, Zhong-zhe; Zheng, Jia-xin; Li, Shu-hua; Han, Seong-ho

    2016-02-05

    Eriodictyol, a flavonoid present in citrus fruits, has been reported to have antioxidant and anti-inflammatory effects. In this study, the protective effects of eriodictyol on cisplatin (CP)-induced kidney injury were detected. CP-induced kidney injury model was established by administration of CP (20mg/kg). The results showed that treatment of eriodictyol inhibited the production of blood urea nitrogen (BUN), creatinine, MDA, TBARS, reactive oxygen species (ROS), as well as the production of TNF-α, and IL-1β in kidney tissues induced by CP. Eriodictyol also up-regulated the activities of SOD, CAT, and GSH-PX decreased by CP. Furthermore, eriodictyol was found to up-regulate the expression of Nrf2/HO-1 and inhibited CP-induced NF-κB activation in kidney tissues. In conclusion, eriodictyol protected against CP-induced kidney injury through activating Nrf2 and inhibiting NF-κB activation.

  9. Kidney Injury Molecule-1 Protects against Gα12 Activation and Tissue Damage in Renal Ischemia-Reperfusion Injury

    Science.gov (United States)

    Ismail, Ola Z.; Zhang, Xizhong; Wei, Junjun; Haig, Aaron; Denker, Bradley M.; Suri, Rita S.; Sener, Alp; Gunaratnam, Lakshman

    2016-01-01

    Ischemic acute kidney injury is a serious untreatable condition. Activation of the G protein α12 (Gα12) subunit by reactive oxygen species is a major cause of tissue damage during renal ischemia-reperfusion injury. Kidney injury molecule-1 (KIM-1) is a transmembrane glycoprotein that is highly up-regulated during acute kidney injury, but the physiologic significance of this up-regulation is unclear. Here, we report for the first time that Kim-1 inhibits Gα12 activation and protects mice against renal ischemia-reperfusion injury. We reveal that Kim-1 physically interacts with and inhibits cellular Gα12 activation after inflammatory stimuli, including reactive oxygen species, by blocking GTP binding to Gα12. Compared with Kim-1+/+ mice, Kim-1−/− mice exhibited greater Gα12 and downstream Src activation both in primary tubular epithelial cells after in vitro stimulation with H2O2 and in whole kidneys after unilateral renal artery clamping. Finally, we show that Kim-1–deficient mice had more severe kidney dysfunction and tissue damage after bilateral renal artery clamping, compared with wild-type mice. Our results suggest that KIM-1 is an endogenous protective mechanism against renal ischemia-reperfusion injury through inhibition of Gα12. PMID:25759266

  10. 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.

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

    NARCIS (Netherlands)

    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. Challenges of treating a 466-kilogram man with acute kidney injury.

    Science.gov (United States)

    Friedman, Allon N; Decker, Brian; Seele, Louis; Hellman, Richard N

    2008-07-01

    Caring for super obese patients (body mass index > 50 kg/m(2)) presents a number of complex and unique clinical challenges, particularly when acute kidney injury is present. We describe our experience treating the heaviest individual with acute kidney injury requiring renal replacement therapy reported to date. A 24-year-old black man was admitted to our hospital with fever, vomiting, progressive weakness, shortness of breath, and hemoptysis. Admission weight was 1,024 lbs (466 kg), height was 6 ft 4 in (1.9 m), and body mass index was 125 kg/m(2). During hospitalization, the patient experienced oligoanuric acute kidney injury and required initiation of continuous and subsequently intermittent renal replacement therapy. This clinical scenario identifies the many challenges involved in caring for super obese patients with acute kidney injury and may be a harbinger of what awaits the nephrology community in the obesity pandemic era.

  13. An unusual case of reversible acute kidney injury due to chlorine dioxide poisoning.

    Science.gov (United States)

    Bathina, Gangadhar; Yadla, Manjusha; Burri, Srikanth; Enganti, Rama; Prasad Ch, Rajendra; Deshpande, Pradeep; Ch, Ramesh; Prayaga, Aruna; Uppin, Megha

    2013-09-01

    Chlorine dioxide is a commonly used water disinfectant. Toxicity of chlorine dioxide and its metabolites is rare. In experimental studies, it was shown that acute and chronic toxicity were associated with insignificant hematological changes. Acute kidney injury due to chlorine dioxide was not reported. Two cases of renal toxicity due to its metabolites, chlorate and chlorite were reported. Herein, we report a case of chlorine dioxide poisoning presenting with acute kidney injury.

  14. Acute ischemic injury to the renal microvasculature in human kidney transplantation.

    NARCIS (Netherlands)

    Snoeijs, M.G.; Vink, H.; Voesten, N.; Christiaans, M.H.; Daemen, J.W.; Peppelenbosch, A.G.; Tordoir, J.H.; Peutz-Kootstra, C.J.; Buurman, W.A.; Schurink, G.W.; Heurn, L.W.E. van

    2010-01-01

    Increased understanding of the pathophysiology of ischemic acute kidney injury in renal transplantation may lead to novel therapies that improve early graft function. Therefore, we studied the renal microcirculation in ischemically injured kidneys from donors after cardiac death (DCD) and in living

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Sepsis-induced acute kidney injury in patients with cirrhosis.

    Science.gov (United States)

    Angeli, Paolo; Tonon, Marta; Pilutti, Chiara; Morando, Filippo; Piano, Salvatore

    2016-01-01

    Acute kidney injury (AKI) is a common and life-threatening complication in patients with cirrhosis. Recently, new criteria for the diagnosis of AKI have been proposed in patients with cirrhosis by the International Club of Ascites. Almost all types of bacterial infections can induce AKI in patients with cirrhosis representing its most common precipitating event. The bacterial infection-induced AKI usually meets the diagnostic criteria of hepatorenal syndrome (HRS). Well in keeping with the "splanchnic arterial vasodilation hypothesis", it has been stated that HRS develops as a consequence of a severe reduction of effective circulating volume related to splanchnic arterial vasodilation and to an inadequate cardiac output. Nevertheless, the role of bacterial infections in precipitating organ failures, including renal failure, is enhanced when their course is characterized by the development of a systemic inflammatory response syndrome (SIRS), thus, when sepsis occurs. Sepsis has been shown to be capable to induce "per se" AKI in animals as well as in patients conditioning also the features of renal damage. This observation suggests that when precipitated by sepsis, the pathogenesis and the clinical course of AKI also in patients with cirrhosis may differentiate to a certain extent from AKI with another or no precipitating factor. The purpose of this review is to describe the features of AKI precipitated by bacterial infections and to highlight whether infection and/or the development of SIRS may influence its clinical course, and, in particular, the response to treatment.

  17. Relation between acute kidney injury and pregnancy-related factors

    Institute of Scientific and Technical Information of China (English)

    Monchai Siribamrungwong; Pawadee Chinudomwong

    2016-01-01

    Acute kidney injury (AKI) is a serious problem during pregnancy. Once occurred, it brings about devastating maternal and fetal outcomes. Among developed nations, the trend of pregnancy-related AKI (PRAKI) is on a decline due to the advances in obstetrics care and the legality of abortion. On the contrary, this situation remains one of the major health problems in the developing countries. Though some improvements have been observed, PRAKI still causes high maternal morbidity and mortality, leading to fetal losses. This article aims to review current studies with regards to obstetrics related AKI. Most of the studies in this review were carried out in observational, both prospective and retrospective, studies. Results demonstrated a variety of major PRAKI causes such as hypertensive disorders in pregnancy, obstetric hemorrhage, sepsis, thrombotic micro-angiopathy and acute fatty liver in pregnancy. Aside from awareness of the etiologies of PRAKI, understanding the physiological renal adaptation during pregnancy is crucial for early detection, diagnosis, and proper management to prevent the obstetric complications.

  18. Relation between acute kidney injury and pregnancy-related factors

    Directory of Open Access Journals (Sweden)

    Monchai Siribamrungwong

    2016-01-01

    Full Text Available Acute kidney injury (AKI is a serious problem during pregnancy. Once occurred, it brings about devastating maternal and fetal outcomes. Among developed nations, the trend of pregnancy-related AKI (PRAKI is on a decline due to the advances in obstetrics care and the legality of abortion. On the contrary, this situation remains one of the major health problems in the developing countries. Though some improvements have been observed, PRAKI still causes high maternal morbidity and mortality, leading to fetal losses. This article aims to review current studies with regards to obstetrics related AKI. Most of the studies in this review were carried out in observational, both prospective and retrospective, studies. Results demonstrated a variety of major PRAKI causes such as hypertensive disorders in pregnancy, obstetric hemorrhage, sepsis, thrombotic microangiopathy and acute fatty liver in pregnancy. Aside from awareness of the etiologies of PRAKI, understanding the physiological renal adaptation during pregnancy is crucial for early detection, diagnosis, and proper management to prevent the obstetric complications.

  19. Hyperglycemia and Acute Kidney Injury During the Perioperative Period.

    Science.gov (United States)

    Mendez, Carlos E; Der Mesropian, Paul J; Mathew, Roy O; Slawski, Barbara

    2016-01-01

    Hyperglycemia and acute kidney injury (AKI) are frequently observed during the perioperative period. Substantial evidence indicates that hyperglycemia increases the prevalence of AKI as a surgical complication. Patients who develop hyperglycemia and AKI during the perioperative period are at significantly elevated risk for poor outcomes such as major adverse cardiac events and all-cause mortality. Early observational and interventional trials demonstrated that the use of intensive insulin therapy to achieve strict glycemic control resulted in remarkable reductions of AKI in surgical populations. However, more recent interventional trials and meta-analyses have produced contradictory evidence questioning the renal benefits of strict glycemic control. Although the exact mechanisms through which hyperglycemia increases the risk of AKI have not been elucidated, multiple pathophysiologic pathways have been proposed. Hypoglycemia and glycemic variability may also play a significant role in the development of AKI. In this literature review, the complex relationship between hyperglycemia and AKI as well as its impact on clinical outcomes during the perioperative period is explored.

  20. Pediatric acute kidney injury: Appraisal of predictors and prognostic indicators

    Directory of Open Access Journals (Sweden)

    Samuel Nkachukwu Uwaezuoke

    2017-01-01

    Full Text Available Acute kidney injury (AKI is a major contributor to childhood morbidity and mortality worldwide. In spite of the advances in renal replacement therapy, there has been a minimal reduction in AKI-related morbidity and mortality. Identifying the prognostic indicators and the risk factors that predict disease onset and progression, and instituting appropriate measures will lead to better survival outcomes. This narrative review seeks to appraise the predictors and prognostic indicators of pediatric AKI. Several biomarkers clearly stand out as predictors and prognostic indicators of the acute disease. Some of them are urine angiotensinogen, fibroblast growth factor-23, cystacin C, neutrophil gelatinase-associated lipocalin, tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7. Combining few of these biomarkers with clinical prediction models has improved their predictive and prognostic utility for AKI. Hemodynamic parameters such as indexed systemic oxygen delivery and mean arterial blood pressure have been proved to be reliable in predicting the occurrence and progression of the disease and its outcomes. Miscellaneous predictors and prognostic indicators like AKI definition criteria, presence of co-morbidities, and health-related quality of life assessment have also been documented from evidence-based studies. An understanding and application of these indices will obviously help to reduce AKI mortality in children.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Metabonomics of acute kidney injury in children after cardiac surgery.

    Science.gov (United States)

    Beger, Richard D; Holland, Ricky D; Sun, Jinchun; Schnackenberg, Laura K; Moore, Page C; Dent, Catherine L; Devarajan, Prasad; Portilla, Didier

    2008-06-01

    Acute kidney injury (AKI) is a major complication in children who undergo cardiopulmonary bypass surgery. We performed metabonomic analyses of urine samples obtained from 40 children that underwent cardiac surgery for correction of congenital cardiac defects. Serial urine samples were obtained from each patient prior to surgery and at 4 h and 12 h after surgery. AKI, defined as a 50% or greater rise in baseline level of serum creatinine, was noted in 21 children at 48-72 h after cardiac surgery. The principal component analysis of liquid chromatography/mass spectrometry (LC/MS) negative ionization data of the urine samples obtained 4 h and 12 h after surgery from patients who develop AKI clustered away from patients who did not develop AKI. The LC/MS peak with mass-to-charge ratio (m/z) 261.01 and retention time (tR) 4.92 min was further analyzed by tandem mass spectrometry (MS/MS) and identified as homovanillic acid sulfate (HVA-SO4), a dopamine metabolite. By MS single-reaction monitoring, the sensitivity was 0.90 and specificity was 0.95 for a cut-off value of 24 ng/microl for HVA-SO4 at 12 h after surgery. We concluded that urinary HVA-SO4 represents a novel, sensitive, and predictive early biomarker of AKI after pediatric cardiac surgery.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Increased incidence of acute kidney injury with aprotinin use during cardiac surgery detected with urinary NGAL

    DEFF Research Database (Denmark)

    Wagener, G.; Gubitosa, G.; Wang, S.;

    2008-01-01

    BACKGROUND: Use of aprotinin has been associated with acute kidney injury after cardiac surgery. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel, very sensitive marker for renal injury. Urinary NGAL may be able to detect renal injury caused by aprotinin. This study determined...... if the use of aprotinin is associated with an increased incidence of acute kidney injury and increased levels of urinary NGAL. METHODS: In this prospective, observational study 369 patients undergoing cardiac surgery were enrolled. 205 patients received aprotinin and 164 received epsilon amino-caproic acid...... intraoperatively. Urinary NGAL was measured before and immediately after cardiac surgery and 3, 18 and 24 h later. The association of aprotinin use with the incidence of acute kidney injury (increase of serum creatinine >0.5 mg/dl) and NGAL levels was determined using logistic and linear regression models. RESULTS...

  5. Protective effect of pioglitazone on kidney injury in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Xiao-Hui Peng; Pei-Yu Liang; Shan-Ji Ou; Xiong-Bing Zu

    2014-01-01

    Objective:To investigate the protective effect of pioglitazone on kidney injury in diabetic rat model and its mechanisms.Methods:Forty healthySpragueDawley rats were selected and randomly divided into five groups, with8 rats in each group.GroupA served as control group and were administered with sterile citrate buffer(i.p.) as placebo.GroupsB,C,D andE rats were injected(i.p.) with streptozotocin to induce typeⅠdiabetes.Diabetic rats inGroupB were intragastrically administered with sterile saline solution alone.GroupsC,D andE rats were intragastrically given pioglitazone hydrochloride suspension at doses of10,20,30 mg/kg per day, respectively.After eight weeks of treatment, all rats were anesthetized and blood was withdrawn from the abdominal aortic for detection of hemoglobinA1c, serum creatinine(SCr) and blood urea nitrogen(BUN) levels.Rats were then sacrificed and the left kidney was excised for calculation of kidney hypertrophy index(KHI), observation of renal pathological changes using light microscope and electron microscope.Mean glomerular cross-sectional areas(MGA), mean glomerular volume (MGV), glomerular basement membrane thickness and foot process fusion ratio were calculated. RT-PCR was employed for detection of podocalyxin(PCX) protein expression.Results:Results showed that levels of hemoglobinA1c,BUN,SCr inGroupsB,C,D andE rats were significantly higher than those inGroupA(P<0.05), whileBUN andSCr levels in rats ofGroupsC,D andE were significantly lower than those inGroupB(P<0.05).KHI,MGA andMGV levels were significantly higher inGroupsB,C,D andE rats than those inGroupA(P<0.05);KHI andMGA levels inGroup B rats were significantly higher than those inGroupsC,D andE(P<0.05) andMGV inGroups D andE was significantly lower than that inGroupsB andC(P<0.05).Histology study showed normal glomerulus structure, morphology, volume, endothelial cells and mesangial cells as well as clear glomerular capillary inGroupA rats.Renal mesangial matrix proliferation and

  6. Congestive kidney failure in cardiac surgery: the relationship between central venous pressure and acute kidney injury.

    Science.gov (United States)

    Gambardella, Ivancarmine; Gaudino, Mario; Ronco, Claudio; Lau, Christopher; Ivascu, Natalia; Girardi, Leonard N

    2016-11-01

    Acute kidney injury (AKI) in cardiac surgery has traditionally been linked to reduced arterial perfusion. There is ongoing evidence that central venous pressure (CVP) has a pivotal role in precipitating acute renal dysfunction in cardiac medical and surgical settings. We can regard this AKI driven by systemic venous hypertension as 'kidney congestive failure'. In the cardiac surgery population as a whole, when the CVP value reaches the threshold of 14 mmHg in postoperative period, the risk of AKI increases 2-fold with an odds ratio (OR) of 1.99, 95% confidence interval (95% CI) of 1.16-3.40. In cardiac surgery subsets where venous hypertension is a hallmark feature, the incidence of AKI is higher (tricuspid disease 30%, carcinoid valve disease 22%). Even in the non-chronically congested coronary artery bypass population, CVP measured 6 h postoperatively showed significant association to renal failure: risk-adjusted OR for AKI was 5.5 (95% CI 1.93-15.5; P = 0.001) with every 5 mmHg rise in CVP for patients with CVP <9 mmHg; for CVP increments of 5 mmHg above the threshold of 9 mmHg, the risk-adjusted OR for AKI was 1.3 (95% CI 1.01-1.65; P = 0.045). This and other clinical evidence are discussed along with the underlying pathophysiological mechanisms, involving the supremacy of volume receptors in regulating the autonomic output in hypervolaemia, and the regional effect of venous congestion on the nephron. The effect of CVP on renal function was found to be modulated by ventricular function class, aetiology and acuity of venous congestion. Evidence suggests that acute increases of CVP should be actively treated to avoid a deterioration of the renal function, particularly in patients with poor ventricular fraction. Besides, the practice of treating right heart failure with fluid loading should be avoided in favour of other ways to optimize haemodynamics in this setting, because of the detrimental effects on the kidney function.

  7. Mitochondria-Targeted Antioxidants: Future Perspectives in Kidney Ischemia Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Aleksandra Kezic

    2016-01-01

    Full Text Available Kidney ischemia/reperfusion injury emerges in various clinical settings as a great problem complicating the course and outcome. Ischemia/reperfusion injury is still an unsolved puzzle with a great diversity of investigational approaches, putting the focus on oxidative stress and mitochondria. Mitochondria are both sources and targets of ROS. They participate in initiation and progression of kidney ischemia/reperfusion injury linking oxidative stress, inflammation, and cell death. The dependence of kidney proximal tubule cells on oxidative mitochondrial metabolism makes them particularly prone to harmful effects of mitochondrial damage. The administration of antioxidants has been used as a way to prevent and treat kidney ischemia/reperfusion injury for a long time. Recently a new method based on mitochondria-targeted antioxidants has become the focus of interest. Here we review the current status of results achieved in numerous studies investigating these novel compounds in ischemia/reperfusion injury which specifically target mitochondria such as MitoQ, Szeto-Schiller (SS peptides (Bendavia, SkQ1 and SkQR1, and superoxide dismutase mimics. Based on the favorable results obtained in the studies that have examined myocardial ischemia/reperfusion injury, ongoing clinical trials investigate the efficacy of some novel therapeutics in preventing myocardial infarct. This also implies future strategies in preventing kidney ischemia/reperfusion injury.

  8. Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model.

    Science.gov (United States)

    Wang, Xuexiang; Johnson, Ashley C; Williams, Jan M; White, Tiffani; Chade, Alejandro R; Zhang, Jie; Liu, Ruisheng; Roman, Richard J; Lee, Jonathan W; Kyle, Patrick B; Solberg-Woods, Leah; Garrett, Michael R

    2015-07-01

    Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%-75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney.

  9. Analyses of acute kidney injury biomarkers by ultra-high performance liquid chromatography with mass spectrometry.

    Science.gov (United States)

    Al Za'abi, Mohammed; Ali, Badreldin H; ALOthman, Zeid A; Ali, Imran

    2016-01-01

    The newly developed acute kidney injury biomarkers are very important for the early and timely detection of kidney diseases. This review contains details of the analyses of several acute kidney injury biomarkers using ultra-high performance liquid chromatography-mass spectrometry in urine and plasma samples. In this review we attempt to discuss some aspects of the types of the biomarkers, patents, sample preparation, and the analyses. Besides, efforts were also made to discuss the possible uses of superficially porous (core-shell) columns in traditional and inexpensive high-performance liquid chromatography instruments. Additionally, the challenges and the future prospects are also highlighted. The present review will be useful for the academicians, scientists, and clinicians for the early detection of acute kidney injury biomarkers.

  10. Assessment of Plasma and NGAL for the Early Prediction of Acute Kidney Injury After Cardiac Surgery in Adults Study

    Science.gov (United States)

    2016-04-11

    Acute Kidney Injury (AKI); Chronic Kidney Disease (CKD); End Stage Renal Disease (ESRD); Estimated Glomerular Filtration Rate (eGFR); Neutrophil Gelatinase-associated Lipocalin (NGAL); Serum Creatinine (SCr); Urine Creatinine (UCr); Urine Albumin (UAlb)

  11. Acute kidney injury in stable COPD and at exacerbation

    Directory of Open Access Journals (Sweden)

    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

  12. Plant recombinant erythropoietin attenuates inflammatory kidney cell injury.

    Science.gov (United States)

    Conley, Andrew J; Mohib, Kanishka; Jevnikar, Anthony M; Brandle, Jim E

    2009-02-01

    Human erythropoietin (EPO) is a pleiotropic cytokine with remarkable tissue-protective activities in addition to its well-established role in red blood cell production. Unfortunately, conventional mammalian cell cultures are unlikely to meet the anticipated market demands for recombinant EPO because of limited capacity and high production costs. Plant expression systems may address these limitations to enable practical, cost-effective delivery of EPO in tissue injury prevention therapeutics. In this study, we produced human EPO in tobacco and demonstrated that plant-derived EPO had tissue-protective activity. Our results indicated that targeting to the endoplasmic reticulum (ER) provided the highest accumulation levels of EPO, with a yield approaching 0.05% of total soluble protein in tobacco leaves. The codon optimization of the human EPO gene for plant expression had no clear advantage; furthermore, the human EPO signal peptide performed better than a tobacco signal peptide. In addition, we found that glycosylation was essential for the stability of plant recombinant EPO, whereas the presence of an elastin-like polypeptide fusion had a limited positive impact on the level of EPO accumulation. Confocal microscopy showed that apoplast and ER-targeted EPO were correctly localized, and N-glycan analysis demonstrated that complex plant glycans existed on apoplast-targeted EPO, but not on ER-targeted EPO. Importantly, plant-derived EPO had enhanced receptor-binding affinity and was able to protect kidney epithelial cells from cytokine-induced death in vitro. These findings demonstrate that tobacco plants may be an attractive alternative for the production of large amounts of biologically active EPO.

  13. Establishing the flow cytometric assessment of myeloid cells in kidney ischemia/reperfusion injury.

    Science.gov (United States)

    Williams, Timothy M; Wise, Andrea F; Alikhan, Maliha A; Layton, Daniel S; Ricardo, Sharon D

    2014-03-01

    Polychromatic flow cytometry is a powerful tool for assessing populations of cells in the kidney through times of homeostasis, disease and tissue remodeling. In particular, macrophages have been identified as having central roles in these three settings. However, because of the plasticity of myeloid cells it has been difficult to define a specific immunophenotype for these cells in the kidney. This study developed a gating strategy for identifying and assessing monocyte and macrophage subpopulations, along with neutrophils and epithelial cells in the healthy kidney and following ischemia/reperfusion (IR) injury in mice, using antibodies against CD45, CD11b, CD11c, Ly6C, Ly6G, F4/80, CSF-1R (CD115), MHC class II, mannose receptor (MR or CD206), an alternatively activated macrophage marker, and the epithelial cell adhesion marker (EpCAM or CD326). Backgating analysis and assessment of autofluorescence was used to extend the knowledge of various cell types and the changes that occur in the kidney at various time-points post-IR injury. In addition, the impact of enzymatic digestion of kidneys on cell surface markers and cell viability was assessed. Comparisons of kidney myeloid populations were also made with those in the spleen. These results provide a useful reference for future analyses of therapies aimed at modulating inflammation and enhancing endogenous remodeling following kidney injury.

  14. Microchimeric fetal cells are recruited to maternal kidney following injury and activate collagen type I transcription.

    Science.gov (United States)

    Bou-Gharios, George; Amin, Farhana; Hill, Peter; Nakamura, Hiroyuki; Maxwell, Patrick; Fisk, Nicholas M

    2011-01-01

    Fetal cells enter the maternal circulation from the early first trimester of pregnancy, where they persist in tissue decades later. We investigated in mice whether fetal microchimeric cells (FMCs) can be detected in maternal kidney, and whether they play a role in kidney homeostasis. FMCs were identified in vivo in two models: one an adaptive model following unilateral nephrectomy, the other an injury via unilateral renal ischaemia reperfusion. Both models were carried out in mothers that had been mated with transgenic mice expressing luciferase transgene under the control of collagen type I, and had given birth to either 1 or 3 litters. FMCs were detected by Y-probe fluorescent in situ hybridization (FISH) and bioluminescence, and the cell number quantified by real-time polymerase chain reaction. In the adaptive model, the remaining kidney showed more cells by all 3 parameters compared with the nephrectomized kidney, while ischaemia reperfusion resulted in higher levels of FMC participation in injured compared to contralateral kidneys. Bioluminescence showed that FMCs switch on collagen type I transcription implicating mesenchymal lineage cells. After injury, Y-probe in situ hydridization was found mainly in the tubular epithelial network. Finally, we compared FMCs with bone marrow cells and found similar dynamics but altered distribution within the kidney. We conclude that FMCs (1) are long-term sequelae of pregnancy and (2) are recruited to the kidney as a result of injury or adaptation, where they activate the transcriptional machinery of matrix proteins.

  15. 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.

  16. BMP-7 Signaling and its Critical Roles in Kidney Development, the Responses to Renal Injury, and Chronic Kidney Disease.

    Science.gov (United States)

    Manson, Scott R; Austin, Paul F; Guo, Qiusha; Moore, Katelynn H

    2015-01-01

    Chronic kidney disease (CKD) is a significant health problem that most commonly results from congenital abnormalities in children and chronic renal injury in adults. The therapeutic potential of BMP-7 was first recognized nearly two decades ago with studies demonstrating its requirement for kidney development and ability to inhibit the pathogenesis of renal injury in models of CKD. Since this time, our understanding of CKD has advanced considerably and treatment strategies have evolved with the identification of many additional signaling pathways, cell types, and pathologic processes that contribute to disease progression. The purpose of this review is to revisit the seminal studies that initially established the importance of BMP-7, highlight recent advances in BMP-7 research, and then integrate this knowledge with current research paradigms. We will provide an overview of the evolutionarily conserved roles of BMP proteins and the features that allow BMP signaling pathways to function as critical signaling nodes for controlling biological processes, including those related to CKD. We will discuss the multifaceted functions of BMP-7 during kidney development and the potential for alterations in BMP-7 signaling to result in congenital abnormalities and pediatric kidney disease. We will summarize the renal protective effects of recombinant BMP-7 in experimental models of CKD and then propose a model to describe the potential physiological role of endogenous BMP-7 in the innate repair mechanisms of the kidneys that respond to renal injury. Finally, we will highlight emerging clinical approaches for applying our knowledge of BMP-7 toward improving the treatment of patients with CKD.

  17. Proteome analysis of acute kidney injury - Discovery of new predominantly renal candidates for biomarker of kidney disease.

    Science.gov (United States)

    Malagrino, Pamella Araujo; Venturini, Gabriela; Yogi, Patrícia Schneider; Dariolli, Rafael; Padilha, Kallyandra; Kiers, Bianca; Gois, Tamiris Carneiro; Cardozo, Karina Helena Morais; Carvalho, Valdemir Melechco; Salgueiro, Jéssica Silva; Girardi, Adriana Castello Costa; Titan, Silvia Maria de Oliveira; Krieger, José Eduardo; Pereira, Alexandre Costa

    2017-01-16

    The main bottleneck in studies aiming to identify novel biomarkers in acute kidney injury (AKI) has been the identification of markers that are organ and process specific. Here, we have used different tissues from a controlled porcine renal ischemia/reperfusion (I/R) model to identify new, predominantly renal biomarker candidates for kidney disease. Urine and serum samples were analyzed in pre-ischemia, ischemia (60min) and 4, 11 and 16h post-reperfusion, and renal cortex samples after 24h of reperfusion. Peptides were analyzed on the Q-Exactive™. In renal cortex proteome, we observed an increase in the synthesis of proteins in the ischemic kidney compared to the contralateral, highlighted by transcription factors and epithelial adherens junction proteins. Intersecting the set of proteins up- or down-regulated in the ischemic tissue with both serum and urine proteomes, we identified 6 proteins in the serum that may provide a set of targets for kidney injury. Additionally, we identified 49, being 4 predominantly renal, proteins in urine. As prove of concept, we validated one of the identified biomarkers, dipeptidyl peptidase IV, in a set of patients with diabetic nephropathy. In conclusion, we identified 55 systemic proteins, some of them predominantly renal, candidates for biomarkers of renal disease.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kwak, W. J.; Kim, J. W.; Park, K. M.; Lee, S. W.; Ahn, B. C.; Lee, J. T.; Yoo, J. S. [Kyungpook National University School of Medicine, Daegu (Korea, Republic of)

    2007-07-01

    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. {sup 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, {sup 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 {sup 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, {sup 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 {sup 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 {sup 99m}Tc-DMSA uptake of injured kidney kept decreasing up to 3 w while normal kidney showed increased {sup 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 {sup 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.

  19. Injury to a transplanted kidney during caesarean section: a case report.

    Science.gov (United States)

    Shrestha, Badri Man; Throssell, David; McKane, William; Raftery, Andrew Thomas

    2007-06-01

    As fertility is restored after renal transplant, more female recipients of a renal transplant successfully complete pregnancies that are safe for the mother, the fetus, and the renal allograft. Although the transplanted kidney lies in one of the iliac fossae, normal vaginal delivery is not impeded by this positioning. Caesarean section is indicated in many scenarios, primarily for obstetric reasons, particularly when the transplanted kidney lies in a position where it could be injured. Here, we report our experiences managing a rare instance of injury to a transplanted kidney during caesarean section and discuss the relevant aspects of its management. To our knowledge, this is the first report in the English literature of an injury to a transplanted kidney during caesarean section.

  20. Lung T lymphocyte trafficking and activation during ischemic acute kidney injury.

    Science.gov (United States)

    Lie, Mihaela L; White, Laura E; Santora, Rachel J; Park, Jong M; Rabb, Hamid; Hassoun, Heitham T

    2012-09-15

    Despite advances in renal replacement therapy, the mortality rate for acute kidney injury (AKI) remains unacceptably high, likely owing to extrarenal organ dysfunction. Kidney ischemia-reperfusion injury (IRI) activates cellular and soluble mediators that facilitate organ crosstalk and induce caspase-dependent lung apoptosis and injury through a TNFR1-dependent pathway. Given that T lymphocytes mediate local IRI in the kidney and are known to drive TNFR1-mediated apoptosis, we hypothesized that T lymphocytes activated during kidney IRI would traffic to the lung and mediate pulmonary apoptosis during AKI. In an established murine model of kidney IRI, we identified trafficking of CD3+ T lymphocytes to the lung during kidney IRI by flow cytometry and immunohistochemistry. T lymphocytes were primarily of the CD3+CD8+ phenotype; however, both CD3+CD4+ and CD3+CD8+ T lymphocytes expressed CD69 and CD25 activation markers during ischemic AKI. The activated lung T lymphocytes did not demonstrate an increased expression of intracellular TNF-α or surface TNFR1. Kidney IRI induced pulmonary apoptosis measured by caspase-3 activation in wild-type controls, but not in T cell-deficient (T(nu/nu)) mice. Adoptive transfer of murine wild-type T lymphocytes into T(nu/nu) mice restored the injury phenotype with increased cellular apoptosis and lung microvascular barrier dysfunction, suggesting that ischemic AKI-induced pulmonary apoptosis is T cell dependent. Kidney-lung crosstalk during AKI represents a complex biological process, and although T lymphocytes appear to serve a prominent role in the interorgan effects of AKI, further experiments are necessary to elucidate the specific role of activated T cells in modulating pulmonary apoptosis.

  1. Severe metabolic alkalosis and recurrent acute on chronic kidney injury in a patient with Crohn's disease

    OpenAIRE

    Schmid Axel; Küttner Axel; Amann Kerstin U; Opgenoorth Mirian; Schnellhardt Susanne; Jacobi Johannes; Eckardt Kai-Uwe; Hilgers Karl F

    2010-01-01

    Abstract Background Diarrhea is common in patients with Crohn's disease and may be accompanied by acid base disorders, most commonly metabolic acidosis due to intestinal loss of bicarbonate. Case Presentation Here, we present a case of severe metabolic alkalosis in a young patient suffering from M. Crohn. The patient had undergone multiple resections of the intestine and suffered from chronic kidney disease. He was now referred to our clinic for recurrent acute kidney injury, the nature of wh...

  2. Myeloperoxidase formation of PAF receptor ligands induces PAF receptor-dependent kidney injury during ethanol consumption.

    Science.gov (United States)

    Latchoumycandane, Calivarathan; Nagy, Laura E; McIntyre, Thomas M

    2015-09-01

    Cytochrome P450 2E1 (CYP2E1) induction and oxidative metabolism of ethanol in hepatocytes inflame and damage liver. Chronic ethanol ingestion also induces kidney dysfunction, which is associated with mortality from alcoholic hepatitis. Whether the kidney is directly affected by ethanol or is secondary to liver damage is not established. We found that CYP2E1 was induced in kidney tubules of mice chronically ingesting a modified Lieber-deCarli liquid ethanol diet. Phospholipids of kidney tubules were oxidized and fragmented in ethanol-fed mice with accumulation of azelaoyl phosphatidylcholine (Az-PC), a nonbiosynthetic product formed only by oxidative truncation of polyunsaturated phosphatidylcholine. Az-PC stimulates the inflammatory PAF receptor (PTAFR) abundantly expressed by neutrophils and kidney tubules, and inflammatory cells and myeloperoxidase-containing neutrophils accumulated in the kidneys of ethanol-fed mice after significant hysteresis. Decreased kidney filtration and induction of the acute kidney injury biomarker KIM-1 in tubules temporally correlated with leukocyte infiltration. Genetic ablation of PTAFR reduced accumulation of PTAFR ligands and reduced leukocyte infiltration into kidneys. Loss of this receptor in PTAFR(-/-) mice also suppressed oxidative damage and kidney dysfunction without affecting CYP2E1 induction. Neutrophilic inflammation was responsible for ethanol-induced kidney damage, because loss of neutrophil myeloperoxidase in MPO(-/-) mice was similarly protective. We conclude that ethanol catabolism in renal tubules results in a self-perpetuating cycle of CYP2E1 induction, local PTAFR ligand formation, and neutrophil infiltration and activation that leads to myeloperoxidase-dependent oxidation and damage to kidney function. Hepatocytes do not express PTAFR, so this oxidative cycle is a local response to ethanol catabolism in the kidney.

  3. 肾损伤分子1在急性肾损伤与修复中的作用研究进%Kidney injury molecule-1 in acute kidney injury and renal repair: a review

    Institute of Scientific and Technical Information of China (English)

    Takaharu ICHIMURA; 牟姗

    2008-01-01

    @@ 1 Introduction Ac1ute kidney injury is very important in clinic [1,2].The primary etiologies of acute kidney injury and its severe condition,acute renal failure(ARF), are ischemia,sepsis and nephrotoxicity associated with therapeutic agents.In addition,nephrotoxicity is a central concern in pharmaceutical developmerit because of its implications for patient safety.

  4. SODIUM BICARBONATE INFUSION: TO PREVENT CARDIAC SURGERY - ASSOCIATED ACUTE KIDNEY INJURY

    Directory of Open Access Journals (Sweden)

    Ramesh

    2015-02-01

    Full Text Available OBJECTIVES: The incidence of cardiac surgery – associated acute kidney injury is 50% of patients and is associated with increased mortality and morbidity. This study aimed to determine if perioperative urinary and plasma alkalization with sodium bicarbonate infusion re duces the incidence of cardiac surgery – associated acute kidney injury. SETTING AND DESIGN: This study is double blind randomized control trial conducted at U N Mehta Institute of Cardiology and Research Center , India. METHOD S AND RESULT: A total of 140 pat ients scheduled to undergo elective cardiac surgery , who were at increased risk of development of cardiac surgery – associated acute kidney injury using recognized risk factors. Patients were randomly allocated to receive either sodium bicarbonate (n = 70 o r sodium chloride (n = 70 infusion , commencing at the start of anesthesia , in a dose of 4 mmol/kg over 24 hour. The primary outcome measure was the number of patients with development of CSA - AKI , defined as an increase in creatinine greater than 25% from baseline to peak value within the first three postoperative days. Significant differences among the groups in both plasma and urinary pH were achieved 6 hours after commencement of the infusion , and these changes persisted for more than 24 hours. A total o f 7 out of 70(10% patients in the sodium bicarbonate group and 16 out of 70(22.85% patients in the sodium chloride group developed acute kidney injury within the first three postoperative days with p value of 0.06 which is statistically not significant . There were also no significant differences in ventilation hours , ICU or hospital length of stay , or mortality. CONCLUSIONS: Perioperative alkalization of blood and urine using an infusion of sodium bicarbonate did not result in a decrease in the incidence of acute kidney injury in patients undergoing cardiac surgery. KEYWORDS: Acute kidney injury; Cardiac surgery; Cardiopulmonary bypass; Creatinine

  5. Tyrosol attenuates ischemia-reperfusion-induced kidney injury via inhibition of inducible nitric oxide synthase.

    Science.gov (United States)

    Wang, Pengqi; Zhu, Qingjun; Wu, Nan; Siow, Yaw L; Aukema, Harold; O, Karmin

    2013-04-17

    Tyrosol is a natural phenolic antioxidant compound. Oxidative stress represents one of the important mechanisms underlying ischemia-reperfusion-induced kidney injury. The aim of this study was to investigate the effect of tyrosol against ischemia-reperfusion-induced acute kidney injury. The left kidney of Sprague-Dawley rats was subjected to 45 min of ischemia followed by reperfusion for 6 h. Ischemia-reperfusion caused an increase in peroxynitrite formation and lipid peroxidation. The level of nitric oxide (NO) metabolites and the mRNA of inducible nitric oxide synthase (iNOS) were elevated in ischemia-reperfused kidneys. Administration of tyrosol (100 mg/kg body weight) to rats prior to the induction of ischemia significantly reduced peroxynitrite formation, lipid peroxidation, and the level of NO metabolites. Tyrosol administration also attenuated ischemia-reperfusion-induced NF-κB activation and iNOS expression. Such a treatment improved kidney function. Results suggest that tyrosol may have a protective effect against acute kidney injury through inhibition of iNOS-mediated oxidative stress.

  6. Biopsy series of acute kidney injury from a tertiary care referral center in south India

    Science.gov (United States)

    Sujatha, Siddappa; Ramprasad, Kowalya

    2015-01-01

    Acute kidney injury (AKI) is common in hospital patients and more so in critically ill patients. It is frequent, harmful and potentially treatable condition. In a total of 243 renal biopsies 130 cases fulfilled the criteria of acute kidney injury. The usual mode of presentation was renal failure followed by acute nephritis. Histopathologically acute interstitial nephritis was the usual finding followed by post infectious-glomerular nephritis. The acute renal failure (ARF) prognosis is influenced by the co-morbidity states and we had a high mortality of 8.46% in our referral centre.

  7. DISSOCIATION OF STRUCTURE AND FUNCTION AFTER ISCHAEMIA-REPERFUSION INJURY IN THE ISOLATED PERFUSED RAT KIDNEYS

    Directory of Open Access Journals (Sweden)

    M. Kadkhodaee

    1999-08-01

    Full Text Available Oxygen-derived free radical* (OFR involvement in ischacmia-rcpcrfusion (IR injury was investigated in a rat isolated kidney model, using 20 minutes iscliaemia followed by 15 or 60 minutes reperfusion. Two antioxidants, the xanthine oxidase inhibitor allopurinol and the hydroxyl radical scavenger dimcthylthiourca (DMTU, were uscit to try and prevent OFR-relatcd damage. Renal function was estimated from the inulin clearance, fractional soiiium excretion and renal vascular resistance, location and extent of tubular damage, and type of cell death (apoptosis vs necrosis were used as morphological parameters of IR-iiuluced change. Cell damage was most extensive in the nephron segments of the outer zone of the outer medulla (straight proximal tubule and thick ascending limb (TAL. I're-treatment with allopttrinol or DMTU did not Improve renal function. Less structural damage was observed in the TAL of allopuriol - or DMTU - treated kidneys compared with IR alone. In allopurinol - treated kidneys, luminal debris was less extensive than that seen in IR kidneys. Most cell death was necrotic in type and morphological features of apoptosis were seen infrequently. Tlic beneficial effects of allopurinol and DMTU on structural change did not correlate with functional improvement during the reperfusion period, litis may require longer repcrfusion or multiple treatments. Tlie results suggest that OFR ■ injury is of limited significance in this model of renal IR injury. Targeting OFR injury may only be useful after very brief periods of iscliaemia where necrosis is minimal ami the potential for recover}- is greater, Tiie results confirm the different susccptibilitcs of individual nephron segments to injury within the intact kidney. Understanding the molecular response to injury in each segment should facilitate development of methods to accelerate repair after [R injury.

  8. Renal functional reserve and renal recovery after acute kidney injury.

    Science.gov (United States)

    Sharma, Aashish; Mucino, Marìa Jimena; Ronco, Claudio

    2014-01-01

    Renal functional reserve (RFR) represents the capacity of the kidney to increase glomerular filtration rate (GFR) in response to certain physiological or pathological stimuli or conditions. Once baseline GFR is determined, RFR can be assessed clinically after an oral protein load or intravenous amino acid infusion. In clinical practice, baseline GFR displays variable levels due to diet or other factors. RFR is the difference between peak 'stress' GFR induced by the test (p.o. or i.v.) and the baseline GFR. In clinical scenarios where hyperfiltration is present (high baseline GFR due to pregnancy, hypertension or diabetic nephropathy, in solitary kidney or kidney donors), RFR may be fully or partially used to achieve normal or supranormal renal function. Since commonly used renal function markers, such as GFR, may remain within normal ranges until 50% of nephrons are lost or in patients with a single remnant kidney, the RFR test may represent a sensitive and early way to assess the functional decline in the kidney. RFR assessment may become an important tool to evaluate the ability of the kidney to recover completely or partially after a kidney attack. In case of healing with a defect and progressive fibrosis, recovery may appear complete clinically, but a reduced RFR may be a sign of a maladaptive repair or subclinical loss of renal mass. Thus, a reduction in RFR may represent the equivalent of renal frailty or susceptibility to insults. The main aim of this article is to review the concept of RFR, its utility in different clinical scenarios, and future perspective for its use.

  9. 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 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.

  10. Increased angiotensinogen expression, urinary angiotensinogen excretion, and tissue injury in nonclipped kidneys of two-kidney, one-clip hypertensive rats.

    Science.gov (United States)

    Shao, Weijian; Miyata, Kayoko; Katsurada, Akemi; Satou, Ryousuke; Seth, Dale M; Rosales, Carla B; Prieto, Minolfa C; Mitchell, Kenneth D; Navar, L Gabriel

    2016-08-01

    In angiotensin II (ANG II)-dependent hypertension, there is an angiotensin type 1 receptor-dependent amplification mechanism enhancing intrarenal angiotensinogen (AGT) formation and secretion in the tubular fluid. To evaluate the role of increased arterial pressure, AGT mRNA, protein expression, and urinary AGT (uAGT) excretion and tissue injury were assessed in both kidneys of two-kidney, one-clip Sprague-Dawley hypertensive rats subjected to left renal arterial clipping (0.25-mm gap). By 18-21 days, systolic arterial pressure increased to 180 ± 3 mmHg, and uAGT increased. Water intake, body weights, 24-h urine volumes, and sodium excretion were similar. In separate measurements of renal function in anesthetized rats, renal plasma flow and glomerular filtration rate were similar in clipped and nonclipped kidneys and not different from those in sham rats, indicating that the perfusion pressure to the clipped kidneys remained within the autoregulatory range. The nonclipped kidneys exhibited increased urine flow and sodium excretion. The uAGT excretion was significantly greater in nonclipped kidneys compared with clipped and sham kidneys. AGT mRNA was 2.15-fold greater in the nonclipped kidneys compared with sham (1.0 ± 0.1) or clipped (0.98 ± 0.15) kidneys. AGT protein levels were also greater in the nonclipped kidneys. The nonclipped kidneys exhibited greater glomerular expansion and immune cell infiltration, medullary fibrosis, and cellular proliferation than the clipped kidneys. Because both kidneys have elevated ANG II levels, the greater tissue injury in the nonclipped kidneys indicates that an increased arterial pressure synergizes with increased intrarenal ANG II to stimulate AGT production and exert greater renal injury.

  11. Contrast-induced acute kidney injury in kidney transplant recipients: A systematic review and meta-analysis

    Science.gov (United States)

    Cheungpasitporn, Wisit; Thongprayoon, Charat; Mao, Michael A; Mao, Shennen A; D'Costa, Matthew R; Kittanamongkolchai, Wonngarm; Kashani, Kianoush B

    2017-01-01

    AIM To evaluate the incidence of contrast-induced acute kidney injury (CIAKI) in kidney transplant recipients. METHODS A literature search was performed using MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews from the inception of the databases through July 2016. Studies assessing the incidence of CIAKI in kidney transplant recipients were included. We applied a random-effects model to estimate the incidence of CIAKI. RESULTS Six studies of 431 kidney transplant recipients were included in the analyses to assess the incidence of CIAKI in kidney transplant recipients. The estimated incidence of CIAKI and CIAKI-requiring dialysis were 9.6% (95%CI: 4.5%-16.3%) and 0.4% (95%CI: 0.0%-1.2%), respectively. A sensitivity analysis limited only to the studies that used low-osmolar or iso-osmolar contrast showed the estimated incidence of CIAKI was 8.0% (95%CI: 3.5%-14.2%). The estimated incidences of CIAKI in recipients who received contrast media with cardiac catheterization, other types of angiogram, and CT scan were 16.1% (95%CI: 6.6%-28.4%), 10.1% (95%CI: 4.2%-18.0%), and 6.1% (95%CI: 1.8%-12.4%), respectively. No graft losses were reported within 30 d post-contrast media administration. However, data on the effects of CIAKI on long-term graft function were limited. CONCLUSION The estimated incidence of CIAKI in kidney transplant recipients is 9.6%. The risk stratification should be considered based on allograft function, indication, and type of procedure.

  12. Apoptosis of the thick ascending limb results in acute kidney injury.

    Science.gov (United States)

    Srichai, Manakan B; Hao, Chuanming; Davis, Linda; Golovin, Anastasia; Zhao, Min; Moeckel, Gilbert; Dunn, Steve; Bulus, Nada; Harris, Raymond C; Zent, Roy; Breyer, Matthew D

    2008-08-01

    Ischemia- or toxin-induced acute kidney injury is generally thought to affect the cells of the proximal tubule, but it has been difficult to define the involvement of other tubular segments because of the widespread damage caused by ischemia/reperfusion or toxin-induced injury in experimental models. For evaluation of whether thick ascending limb (TAL)-specific epithelial injury results in acute kidney injury, a novel transgenic mouse model that expresses the herpes simplex virus 1 thymidine kinase gene under the direction of the TAL-specific Tamm-Horsfall protein promoter was generated. After administration of gancyclovir, these mice demonstrated apoptosis only in TAL cells, with little evidence of neutrophil infiltration. Compared with control mice, blood urea nitrogen and creatinine levels were at least five-fold higher in the transgenic mice, which also developed oliguria and impaired urinary concentrating ability. These findings suggest that acute injury targeted only to the TAL is sufficient to cause severe acute kidney injury in mice with features similar to those observed in humans.

  13. Dexamethasone pretreatment attenuates lung and kidney injury in cholestatic rats induced by hepatic ischemia/reperfusion.

    Science.gov (United States)

    Zhou, Liangyi; Yao, Xiangqing; Chen, Yanling

    2012-02-01

    Hepatic ischemia followed by reperfusion (IR) results in mild to severe organ injury, in which tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) seem to be involved. Thus, we aim to assess the influence of hepatic ischemia/reperfusion injury on remote organs in addition to cholestasis and consider the possible efficacy of steroid pretreatment in reducing the injury. A common bile duct ligation model was done on 24 male Sprague-Dawley rats. After 7 days, the rats were divided randomly into control group, IR group, and dexamethasone (DEX) group. The IR group showed significant increases in serum alanine aminotransferase, aspartate aminotransferase, and creatinine levels compared with the control and DEX groups. By ELISA techniques, higher levels of TNF-α and IL-1β in lung and kidney tissues were measured in the IR group than in the control and DEX groups, these were verified by immunohistochemistry. The lung histology of the IR group rats showed neutrophil infiltration, interstitial edema, and alveolar wall thickening. Kidney histology of the IR group rats showed vacuolization of the proximal tubular epithelial cells and tubular dilatation with granular eosinophilic casts. Better morphological aspects were observed in the DEX-pretreated animals. Minimal lesions were observed in the control. The results suggest that hepatic ischemia/reperfusion injury in cholestatic rats induced lung and kidney injuries. Pretreatment with dexamethasone reduced the IR-induced injury in addition to cholestasis.

  14. 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.

  15. Effects of sodium citrate on salt sensitivity and kidney injury in chronic renal failure.

    Science.gov (United States)

    Kim, Sejoong; Yang, Jin Young; Jung, Eun Sook; Lee, Jeonghwan; Heo, Nam Ju; Lee, Jae Wook; Na, Ki Young; Han, Jin Suk

    2014-12-01

    Metabolic acidosis, which is observed in salt-sensitive hypertension, is also associated with kidney injury. Alkali therapy in chronic renal failure (CRF) may ameliorate the progression of kidney disease; however, few studies have examined the effects of alkali therapy on salt sensitivity and kidney injury in CRF. We randomly administered standard diet (SD), sodium chloride with 20% casein diet (NACL), or sodium citrate with 20% casein diet (NACT) to Sprague-Dawley rats after a CRF or a sham operation. Four weeks after 5/6 nephrectomy, serum bicarbonate levels were higher in the NACT-treated group. On the pressure-natriuresis curve, NACT-treated CRF rats were more salt-resistant than NACL-treated CRF rats. Additionally, the NACT-treated CRF group showed less tubulointerstitial damage than the NACL-treated CRF group. The expression and immunoreactivity of NHE3 in the kidney in the NACT-treated CRF group were lower than those in the NACL-treated CRF group. We observed that dietary NACT as alkali therapy in CRF might improve the altered salt-sensitivity and ameliorate the progression of kidney injury compared to the NACL diet, which may be related to reduced renal NHE3 expression.

  16. Acute kidney injury: intravenous fluid to prevent contrast-induced AKI.

    Science.gov (United States)

    Weisbord, Steven D; Palevsky, Paul M

    2009-05-01

    Trials that compared sodium bicarbonate and sodium chloride for the prevention of contrast-induced acute kidney injury have yielded highly conflicting results. The authors of a recent meta-analysis endeavored to provide a definitive assessment of the relative efficacy of these two intravenous fluids.

  17. Comparison and clinical suitability of eight prediction models for cardiac surgery-related acute kidney injury

    NARCIS (Netherlands)

    Kiers, H.D.; Boogaard, M.H.W.A. van den; Schoenmakers, M.C.J.; Hoeven, J.G. van der; Swieten, H.A. van; Heemskerk, S.; Pickkers, P.

    2013-01-01

    BACKGROUND: Cardiac surgery-related acute kidney injury (CS-AKI) results in increased morbidity and mortality. Different models have been developed to identify patients at risk of CS-AKI. While models that predict dialysis and CS-AKI defined by the RIFLE criteria are available, their predictive powe

  18. Urinary neutrophil gelatinase-associated lipocalin and acute kidney injury after cardiac surgery

    DEFF Research Database (Denmark)

    Wagener, G.; Gubitosa, G.; Wang, S.;

    2008-01-01

    for cardiopulmonary bypass time and aortic cross-clamp time to predict AKI were 0.592 (95% CI, 0.518 to 0.666) and 0.593 (95% CI, 0.523 to 0.665), respectively. LIMITATIONS: Limited sensitivity of changes in serum creatinine levels for kidney injury. CONCLUSIONS: Urinary NGAL has limited diagnostic accuracy...

  19. Tubular kidney injury molecule-1 (KIM-1) in human renal disease

    NARCIS (Netherlands)

    van Timmeren, M. M.; van den Heuvel, M. C.; Bailly, V.; Bakker, S. J. L.; van Goor, H.; Stegeman, C. A.

    2007-01-01

    KIM-1, a transmembrane tubular protein with unknown function, is undetectable in normal kidneys, but is markedly induced in experimental renal injury. The KIM-1 ectodomain is cleaved, detectable in urine, and reflects renal damage. KIM-1 expression in human renal biopsies and its correlation with ur

  20. Prevention of acute kidney injury and protection of renal function in the intensive care unit

    NARCIS (Netherlands)

    Joannidis, Michael; Druml, Wilfred; Forni, Lui G.; Groeneveld, A. B. Johan; Honore, Patrick; Oudemans-van Straaten, Heleen M.; Ronco, Claudio; Schetz, Marie R. C.; Woittiez, Arend Jan

    2010-01-01

    Acute renal failure on the intensive care unit is associated with significant mortality and morbidity. To determine recommendations for the prevention of acute kidney injury (AKI), focusing on the role of potential preventative maneuvers including volume expansion, diuretics, use of inotropes, vasop

  1. Serum and urine cystatin C are poor biomarkers for acute kidney injury and renal replacement therapy

    NARCIS (Netherlands)

    Royakkers, A.A.N.M.; Korevaar, J.C.; van Suijlen, J.D.E.; Hofstra, L.S.; Kuiper, M.A.; Spronk, P.E.; Schultz, M.J.; Bouman, C.S.C.

    2011-01-01

    To evaluate whether cystatin C in serum (sCyC) and urine (uCyC) can predict early acute kidney injury (AKI) in a mixed heterogeneous intensive care unit (ICU), and also whether these biomarkers can predict the need for renal replacement therapy (RRT). Multicenter prospective observational cohort stu

  2. Protective effects of amifostine on ischemia-reperfusion injury of rat kidneys

    Directory of Open Access Journals (Sweden)

    Ayse Arducoglu Merter

    2015-01-01

    Conclusion: Amifostine could decrease the degree and severity of necrosis after reperfusion. Amifostine could not prevent membrane lipid peroxidation caused by superoxide anion radicals in kidney but they could protect tissues from the harmful effects of ischemia/reperfusion injury by increasing the level of reduced GSH which is a well-known oxygen radical eliminator.

  3. Serum and urine cystatin C are poor biomarkers for acute kidney injury and renal replacement therapy.

    NARCIS (Netherlands)

    Royakkers, A.A.N.M.; Korevaar, J.C.; Suijlen, J.D.E. van; Hofstra, L.S.; Kuiper, M.A.; Spronk, P.E.; Schultz, M.J.; Bouman, C.S.C.

    2011-01-01

    Purpose : To evaluate whether cystatin C in serum (sCyC) and urine (uCyC) can predict early acute kidney injury (AKI) in a mixed heterogeneous intensive care unit (ICU), and also whether these biomarkers can predict the need for renal replacement therapy (RRT). Methods: Multicenter prospective obser

  4. 76 FR 42716 - Effects of Ischemia Reperfusion Injury on Outcomes in Kidney Transplantation; Public Workshop

    Science.gov (United States)

    2011-07-19

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Effects of Ischemia Reperfusion Injury on Outcomes in Kidney... Food and Drug Administration (FDA) is announcing a public workshop to discuss the effects of...

  5. 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...

  6. 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.

  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. Angiogenin Mediates Cell-Autonomous Translational Control under Endoplasmic Reticulum Stress and Attenuates Kidney Injury.

    Science.gov (United States)

    Mami, Iadh; Bouvier, Nicolas; El Karoui, Khalil; Gallazzini, Morgan; Rabant, Marion; Laurent-Puig, Pierre; Li, Shuping; Tharaux, Pierre-Louis; Beaune, Philippe; Thervet, Eric; Chevet, Eric; Hu, Guo-Fu; Pallet, Nicolas

    2016-03-01

    Endoplasmic reticulum (ER) stress is involved in the pathophysiology of kidney disease and aging, but the molecular bases underlying the biologic outcomes on the evolution of renal disease remain mostly unknown. Angiogenin (ANG) is a ribonuclease that promotes cellular adaptation under stress but its contribution to ER stress signaling remains elusive. In this study, we investigated the ANG-mediated contribution to the signaling and biologic outcomes of ER stress in kidney injury. ANG expression was significantly higher in samples from injured human kidneys than in samples from normal human kidneys, and in mouse and rat kidneys, ANG expression was specifically induced under ER stress. In human renal epithelial cells, ER stress induced ANG expression in a manner dependent on the activity of transcription factor XBP1, and ANG promoted cellular adaptation to ER stress through induction of stress granules and inhibition of translation. Moreover, the severity of renal lesions induced by ER stress was dramatically greater in ANG knockout mice (Ang(-/-)) mice than in wild-type mice. These results indicate that ANG is a critical mediator of tissue adaptation to kidney injury and reveal a physiologically relevant ER stress-mediated adaptive translational control mechanism.

  9. Urinary levels of early kidney injury molecules in children with vitamin B12 deficiency.

    Science.gov (United States)

    Güneş, Ali; Aktar, Fesih; Tan, İlhan; Söker, Murat; Uluca, Ünal; Balık, Hasan; Mete, Nuriye

    2016-10-01

    The aim of this study was to investigate urine early kidney injury molecules, including human kidney injury molecule-1 (KIM-1), liver-type fatty-acid binding protein (L-FABP), N-acetyl-b-D-glucosaminidase A (NAG), and neutrophil gelatinase-associated lipocalin (NGAL) in children with vitamin B12 (cobalamin) deficiency (CD). Twelve children with vitamin B12 deficiency and 20 healthy matched controls were included. Hematologic parameters, serum urea, creatinine (Cr), electrolytes, B12 and folate levels were recorded. Estimated glomerular filtration rate (eGFR) was calculated. Urine protein, electrolytes, andurinary early markers were measured. Patients with CD had significantly higher urine electrolyte/Cr ratios (p B12 and urinary markers in the patients (p B12 deficiency suggest a possible subclinical renal dysfunction, which cannot be determined by conventional kidney function tests.

  10. Kidney injury biomarkers in hypertensive, diabetic, and nephropathy rat models treated with contrast media.

    Science.gov (United States)

    Rouse, Rodney L; Stewart, Sharron R; Thompson, Karol L; Zhang, Jun

    2013-01-01

    Contrast-induced nephropathy (CIN) refers to a decline in renal function following exposure to iodinated contrast media (CM). The present study was initiated to explore the role of known human risk factors (spontaneous hypertension, diabetes, protein-losing nephropathy) on CIN development in rodent models and to determine the effect of CM administration on kidney injury biomarkers in the face of preexisting kidney injury. Spontaneously hypertensive rats (hypertension), streptozotocin-treated Sprague Dawley rats (diabetes), and Dahl salt-sensitive rats (protein-losing nephropathy) were given single intravenous injections of the nonionic, low osmolar contrast medium, iohexol. Blood urea nitrogen (BUN), serum creatinine (sCr), and urinary biomarkers; albumin, lipocalin 2 (Lcn-2), osteopontin (Opn), kidney injury molecule 1 (Kim-1), renal papillary antigen 1 (Rpa-1), α-glutathione S-transferase (α-Gst), µ-glutathione S-transferase (µ-Gst), and beta-2 microglobulin (β2m) were measured in disease models and appropriate controls to determine the response of these biomarkers to CM administration. Each disease model produced elevated biomarkers of kidney injury without CM. Preexisting histopathology was exacerbated by CM but little or no significant increases in biomarkers were observed. When 1.5-fold or greater sCr increases from pre-CM were used to define true positives, receiver-operating characteristic curve analysis of biomarker performance showed sCr was the best predictor of CIN across disease models. β2m, Lcn-2, and BUN were the best predictors of histopathology defined kidney injury.

  11. How effective are alprostadil and hydrocortisone on reperfusion injury in kidney after distant organ ischemia?

    Directory of Open Access Journals (Sweden)

    Ali Ebrahimi

    2013-01-01

    Full Text Available Background: After reestablishment of blood flow to ischemic limb recirculation of free radicals may cause ischemia-reperfusion injury in many organs. This study designed to investigate effects of hydrocortisone and alprostadil distant injury to kidneys by both measuring biochemical markers of oxidative stress and histopathologic examination in an experimental rat model of hind limb ischemia-reperfusion. Materials and Methods: This study conducted in Isfahan University of Medical Sciences during 2011-2012. Ischemia was established by infra renal aortic clamping for 60 min in 32 male Wistar rats. Animals were divided into those receiving alprostadil (group ischemia-reperfusion plus alprostadil (IR/A, n = 8, those receiving hydrocortisone (group ischemia-reperfusion plus hydrocortisone (IR/H, n = 8, control group (group ischemia-reperfusion (IR, n = 8, and sham group (n = 8. After 120 min of reperfusion both kidneys were removed. Levels of superoxide dismutase (SOD, malondialdehyde (MDA, and glutathione (GSH as indirect markers of oxidative injury was measured. Finally all data in different groups were compared using the analysis of variance (ANOVA test by Statistical Package for Social Sciences (SPSS version 16. Results: Administration of alprostadil or hydrocortisone does not improve the biochemical parameters of oxidative injury including MDA and SOD. However, statistically significant difference was seen in GSH level among sham and IR groups. Mean (΁ standard deviation (SD concentration of GSH in IR, IR/A, IR/H, and sham groups were 1028.77 (72.65, 924.82 (70.66, 1000.28 (108.77, and 846.69 (163.52, respectively (P = 0.015. Histopathological study of specimens did not show any significant changes between groups. Conclusion: Alprostadil and hydrocortisone do not improve the kidney GSH, SOD, and MDA level and kidney releases its GSH reserve during ischemia-reperfusion event, and another point is that, 3 h of ischemia-reperfusion does not develop

  12. 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...

  13. Design of Clinical Trials in Acute Kidney Injury: Lessons from the Past and Future Directions.

    Science.gov (United States)

    Weisbord, Steven D; Palevsky, Paul M

    2016-01-01

    Acute kidney injury (AKI) is a common condition with multiple etiologies and variable clinical findings and pathologic manifestations. AKI is associated with serious adverse clinical outcomes, including the development of de novo chronic kidney disease, accelerated progression of pre-existing chronic kidney disease, end-stage kidney disease, and increased mortality. Past research has advanced our understanding of the pathophysiology, epidemiology, and outcomes of AKI significantly, however, little progress has been made in the development of evidence-based interventions for its prevention and treatment. In this review, we discuss key considerations in the design of clinical trials in AKI and highlight significant methodologic limitations that precluded many past studies from determining the effectiveness of preventive and therapeutic strategies for this common and serious condition.

  14. Kidney Injury Molecule-1 is an Early Noninvasive Indicator for Donor Brain Death-Induced Injury Prior to Kidney Transplantation

    NARCIS (Netherlands)

    Nijboer, W. N.; Schuurs, T. A.; Damman, J.; van Goor, H.; Vaidya, V. S.; van der Heide, J. J. Homan; Leuvenink, H. G. D.; Bonventre, J. V.; Ploeg, R. J.

    2009-01-01

    In rat kidney, real-time PCR revealed a 46-fold Kim-1 gene upregulation after 4 h of brain death. In situ hybridization showed proximal tubular Kim-1 localization, which was confirmed by immunohistochemistry. Also, Luminex assay showed a 6.6-fold Kim-1 rise in urine after 4 h of brain death. In huma

  15. Renal Vein Reconstruction for Harvesting Injury in Kidney Transplantation

    Directory of Open Access Journals (Sweden)

    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.

  16. Acute kidney injury in the setting of AIDS, bland urine sediment, minimal proteinuria and normal-sized kidneys: a presentation of renal lymphoma.

    Science.gov (United States)

    Sandhu, Gagangeet; Ranade, Aditi; Mankal, Pavan; Herlitz, Leal C; Jones, James; Cortell, Stanley

    2011-02-01

    Acute kidney injury in HIV patients is primarily related to HIV-mediated viral or immunological disease or to treatment-related toxicity (tenofovir). Neoplasms are a rare cause of non-obstructive acute kidney injury, primarily because when they occur, they manifest as discrete masses and not as diffuse infiltration of the renal parenchyma. Diffusely infiltrating tumors include carcinoma of the renal pelvis invading the renal parenchyma, renal lymphoma, squamous cell carcinoma (from lung) metastasizing to the kidney and infiltrating sarcomatous type of renal cell carcinoma. To be classified as a true case of renal lymphoma, the tumor should have escaped detection on routine imaging preceding biopsy, and lymphoma-associated renal failure/nephrotic proteinuria should have given rise to the indication for kidney biopsy. We present here a case of an acute kidney injury due to renal lymphoma in a patient with acquired immune deficiency syndrome that manifested clinically as bland urine sediment, minimal proteinuria and normal-sized kidneys. Chemotherapy resulted in complete reversal of acute kidney injury.

  17. Circulating Mitochondrial DAMPs Are Not Effective Inducers of Proteinuria and Kidney Injury in Rodents.

    Science.gov (United States)

    He, Jing; Lu, Yuqiu; Xia, Hong; Liang, Yaojun; Wang, Xiao; Bao, Wenduona; Yun, Shifeng; Ye, Yuting; Zheng, Chunxia; Liu, Zhihong; Shi, Shaolin

    2015-01-01

    Mitochondria in eukaryotic cells are derived from bacteria in evolution. Like bacteria, mitochondria contain DNA with unmethylated CpG motifs and formyl peptides, both of which have recently been shown to be damage associated molecular patterns (DAMPs) and induce immune response and cell injury. Based on the facts that circulating mitochondrial DAMPs (mtDAMPs) are increased in the patients of trauma or burn injury who also have proteinuria, that mtDAMPs can activate immune cells which in turn secrete glomerular permeability factors, that renal intrinsic cells express a variety of DAMP receptors, and that mtDAMPs can directly increase endothelial cell permeability in vitro, we hypothesized that mtDAMPs may be novel circulating factors inducing proteinuria and kidney injury. We tested this hypothesis by directly injecting mtDAMPs into rodents and examining urinary protein and kidney histology. We prepared mtDAMP samples, including mitochondrial DNA (mtDNA) and mitochondrial debris (MTD), from rodent liver. In mice, injection of mtDNA for 20 μg/ml initial concentration in circulation (much higher than the clinical range), did not cause any renal manifestations. However, an increased dose leading to 45 μg/ml initial concentration in circulation resulted in a transient, slight increase in urinary albumin. In rats, MTD injection resulting in 450 μg/ml initial concentration of MTD protein in circulation, which was much higher than the clinical range, caused mild, transient proteinuria and lung lesions. Multiple injections of such large amount of either mtDNA or MTD into rodents on 3 consecutive days also failed in inducing proteinuria and kidney injury. In summary, clinical levels of circulating mtDAMPs do not induce proteinuria and clinically irrelevant high levels of mtDAMPs cause only a transient and slight increase in urinary protein in rodents, suggesting that circulating mtDAMPs may not be responsible for the proteinuria and kidney injury in patients with trauma

  18. 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.

  19. Adhesion molecules involved in neutrophil recruitment during sepsis-induced acute kidney injury.

    Science.gov (United States)

    Herter, Jan M; Rossaint, Jan; Spieker, Tilmann; Zarbock, Alexander

    2014-01-01

    Acute kidney injury (AKI) is a common complication in critically ill patients and is associated with high mortality. Recruitment of neutrophils is a hallmark in the pathogenesis of AKI. Although ischemia-reperfusion injury (IRI) is a frequently used research model of AKI, the clinical relevance of IRI-induced AKI is limited. Epidemiologically, sepsis is the prevailing cause of kidney injury. However, it is still unknown whether these distinct entities of AKI share the same pathophysiological mechanisms. This study was initiated to investigate the molecular mechanisms of neutrophil recruitment into the kidney in a murine model of sepsis-induced AKI. By using a flow cytometry-based method, we show that the two β2-integrins Mac-1 and LFA-1 as well as E-selectin and P-selectin are involved in neutrophil recruitment into the kidney after induction of sepsis. The molecular mechanisms of neutrophil recruitment were further investigated using intravital microscopy, demonstrating that blocking one of these four molecules reduces the number of adherent leukocytes. This was accompanied by a renal upregulation of E-selectin, P-selectin and ICAM-1 (the counter-receptor of β2-integrins on endothelial cells) after sepsis induction. We conclude that blocking P-selectin, E-selectin, Mac-1 or LFA-1 protects mice from sepsis-induced AKI.

  20. Interleukin-19 mediates tissue damage in murine ischemic acute kidney injury.

    Directory of Open Access Journals (Sweden)

    Yu-Hsiang Hsu

    Full Text Available Inflammation and renal tubular injury are major features of acute kidney injury (AKI. Many cytokines and chemokines are released from injured tubular cells and acts as proinflammatory mediators. However, the role of IL-19 in the pathogenesis of AKI is not defined yet. In bilateral renal ischemia/reperfusion injury (IRI-induced and HgCl2-induced AKI animal models, real-time quantitative (RTQ-PCR showed that the kidneys, livers, and lungs of AKI mice expressed significantly higher IL-19 and its receptors than did sham control mice. Immunohistochemical staining showed that IL-19 and its receptors were strongly stained in the kidney, liver, and lung tissue of AKI mice. In vitro, IL-19 upregulated MCP-1, TGF-β1, and IL-19, and induced mitochondria-dependent apoptosis in murine renal tubular epithelial M-1 cells. IL-19 upregulated TNF-α and IL-10 in cultured HepG2 cells, and it increased IL-1β and TNF-α expression in cultured A549 cells. In vivo, after renal IRI or a nephrotoxic dose of HgCl2 treatment, IL-20R1-deficient mice (the deficiency blocks IL-19 signaling showed lower levels of blood urea nitrogen (BUN in serum and less tubular damage than did wild-type mice. Therefore, we conclude that IL-19 mediates kidney, liver, and lung tissue damage in murine AKI and that blocking IL-19 signaling may provide a potent therapeutic strategy for treating AKI.

  1. 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.

  2. Ouabain Contributes to Kidney Damage in a Rat Model of Renal Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Luca Villa

    2016-10-01

    Full Text Available Warm renal ischemia performed during partial nephrectomy has been found to be associated with kidney disease. Since endogenous ouabain (EO is a neuro-endocrine hormone involved in renal damage, we evaluated the role of EO in renal ischemia-reperfusion injury (IRI. We measured plasma and renal EO variations and markers of glomerular and tubular damage (nephrin, KIM-1, Kidney-Injury-Molecule-1, α1 Na-K ATPase and the protective effect of the ouabain inhibitor, rostafuroxin. We studied five groups of rats: (1 normal; (2 infused for eight weeks with ouabain (30 µg/kg/day, OHR or (3 saline; (4 ouabain; or (5 saline-infused rats orally treated with 100 µg/kg/day rostafuroxin for four weeks. In group 1, 2–3 h after IRI, EO increased in ischemic kidneys while decreased in plasma. Nephrin progressively decreased and KIM-1 mRNA increased starting from 24 h. Ouabain infusion (group 2 increased blood pressure (from 111.7 to 153.4 mmHg and ouabain levels in plasma and kidneys. In OHR ischemic kidneys at 120 h from IRI, nephrin, and KIM-1 changes were greater than those detected in the controls infused with saline (group 3. All these changes were blunted by rostafuroxin treatment (groups 4 and 5. These findings support the role of EO in IRI and suggest that rostafuroxin pre-treatment of patients before partial nephrectomy with warm ischemia may reduce IRI, particularly in those with high EO.

  3. Sodium nitrite protects against kidney injury induced by brain death and improves post-transplant function.

    Science.gov (United States)

    Kelpke, Stacey S; Chen, Bo; Bradley, Kelley M; Teng, Xinjun; Chumley, Phillip; Brandon, Angela; Yancey, Brett; Moore, Brandon; Head, Hughston; Viera, Liliana; Thompson, John A; Crossman, David K; Bray, Molly S; Eckhoff, Devin E; Agarwal, Anupam; Patel, Rakesh P

    2012-08-01

    Renal injury induced by brain death is characterized by ischemia and inflammation, and limiting it is a therapeutic goal that could improve outcomes in kidney transplantation. Brain death resulted in decreased circulating nitrite levels and increased infiltrating inflammatory cell infiltration into the kidney. Since nitrite stimulates nitric oxide signaling in ischemic tissues, we tested whether nitrite therapy was beneficial in a rat model of brain death followed by kidney transplantation. Nitrite, administered over 2 h of brain death, blunted the increased inflammation without affecting brain death-induced alterations in hemodynamics. Kidneys were transplanted after 2 h of brain death and renal function followed over 7 days. Allografts collected from nitrite-treated brain-dead rats showed significant improvement in function over the first 2 to 4 days after transplantation compared with untreated brain-dead animals. Gene microarray analysis after 2 h of brain death without or with nitrite therapy showed that the latter significantly altered the expression of about 400 genes. Ingenuity Pathway Analysis indicated that multiple signaling pathways were affected by nitrite, including those related to hypoxia, transcription, and genes related to humoral immune responses. Thus, nitrite therapy attenuates brain death-induced renal injury by regulating responses to ischemia and inflammation, ultimately leading to better post-transplant kidney function.

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

    Science.gov (United States)

    Andreucci, Michele; Faga, Teresa; Riccio, Eleonora; Sabbatini, Massimo; Pisani, Antonio; Michael, Ashour

    2016-01-01

    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. PMID:27672338

  5. Ouabain Contributes to Kidney Damage in a Rat Model of Renal Ischemia-Reperfusion Injury

    Science.gov (United States)

    Villa, Luca; Buono, Roberta; Ferrandi, Mara; Molinari, Isabella; Benigni, Fabio; Bettiga, Arianna; Colciago, Giorgia; Ikehata, Masami; Messaggio, Elisabetta; Rastaldi, Maria Pia; Montorsi, Francesco; Salonia, Andrea; Manunta, Paolo

    2016-01-01

    Warm renal ischemia performed during partial nephrectomy has been found to be associated with kidney disease. Since endogenous ouabain (EO) is a neuro-endocrine hormone involved in renal damage, we evaluated the role of EO in renal ischemia-reperfusion injury (IRI). We measured plasma and renal EO variations and markers of glomerular and tubular damage (nephrin, KIM-1, Kidney-Injury-Molecule-1, α1 Na-K ATPase) and the protective effect of the ouabain inhibitor, rostafuroxin. We studied five groups of rats: (1) normal; (2) infused for eight weeks with ouabain (30 µg/kg/day, OHR) or (3) saline; (4) ouabain; or (5) saline-infused rats orally treated with 100 µg/kg/day rostafuroxin for four weeks. In group 1, 2–3 h after IRI, EO increased in ischemic kidneys while decreased in plasma. Nephrin progressively decreased and KIM-1 mRNA increased starting from 24 h. Ouabain infusion (group 2) increased blood pressure (from 111.7 to 153.4 mmHg) and ouabain levels in plasma and kidneys. In OHR ischemic kidneys at 120 h from IRI, nephrin, and KIM-1 changes were greater than those detected in the controls infused with saline (group 3). All these changes were blunted by rostafuroxin treatment (groups 4 and 5). These findings support the role of EO in IRI and suggest that rostafuroxin pre-treatment of patients before partial nephrectomy with warm ischemia may reduce IRI, particularly in those with high EO. PMID:27754425

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

    Science.gov (United States)

    Leventhal, Jeremy S; Ni, Jie; Osmond, Morgan; Lee, Kyung; Gusella, G Luca; Salem, Fadi; Ross, Michael J

    2016-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Fungal granulomatous interstitial nephritis presenting as acute kidney injury diagnosed by renal histology including PCR assay.

    Science.gov (United States)

    Ogura, Makoto; Kagami, Shino; Nakao, Masatsugu; Kono, Midori; Kanetsuna, Yukiko; Hosoya, Tatsuo

    2012-10-01

    We describe two cases of fungal granulomatous interstitial nephritis (GIN) presenting as acute kidney injury (AKI). Increased serum creatinine was detected in Patient 1 after chemotherapy for pharyngeal cancer and in Patient 2 after steroid pulse therapy for bronchial asthma. Renal histology of both patients revealed GIN. Polymerase chain reaction (PCR)-based detection of fungal DNA sequences from kidney tissue demonstrated Trichosporon laibachii and Candida albicans, respectively. When AKI occurs in an immunocompromised host, differential diagnosis of fungal interstitial nephritis should be considered. Furthermore, PCR-based detection of fungal DNA sequences from renal specimens can be useful for rapid diagnosis.

  9. A new model to predict acute kidney injury requiring renal replacement therapy after cardiac surgery

    Science.gov (United States)

    Pannu, Neesh; Graham, Michelle; Klarenbach, Scott; Meyer, Steven; Kieser, Teresa; Hemmelgarn, Brenda; Ye, Feng; James, Matthew

    2016-01-01

    Background: Acute kidney injury after cardiac surgery is associated with adverse in-hospital and long-term outcomes. Novel risk factors for acute kidney injury have been identified, but it is unknown whether their incorporation into risk models substantially improves prediction of postoperative acute kidney injury requiring renal replacement therapy. Methods: We developed and validated a risk prediction model for acute kidney injury requiring renal replacement therapy within 14 days after cardiac surgery. We used demographic, and preoperative clinical and laboratory data from 2 independent cohorts of adults who underwent cardiac surgery (excluding transplantation) between Jan. 1, 2004, and Mar. 31, 2009. We developed the risk prediction model using multivariable logistic regression and compared it with existing models based on the C statistic, Hosmer–Lemeshow goodness-of-fit test and Net Reclassification Improvement index. Results: We identified 8 independent predictors of acute kidney injury requiring renal replacement therapy in the derivation model (adjusted odds ratio, 95% confidence interval [CI]): congestive heart failure (3.03, 2.00–4.58), Canadian Cardiovascular Society angina class III or higher (1.66, 1.15–2.40), diabetes mellitus (1.61, 1.12–2.31), baseline estimated glomerular filtration rate (0.96, 0.95–0.97), increasing hemoglobin concentration (0.85, 0.77–0.93), proteinuria (1.65, 1.07–2.54), coronary artery bypass graft (CABG) plus valve surgery (v. CABG only, 1.25, 0.64–2.43), other cardiac procedure (v. CABG only, 3.11, 2.12–4.58) and emergent status for surgery booking (4.63, 2.61–8.21). The 8-variable risk prediction model had excellent performance characteristics in the validation cohort (C statistic 0.83, 95% CI 0.79–0.86). The net reclassification improvement with the prediction model was 13.9% (p < 0.001) compared with the best existing risk prediction model (Cleveland Clinic Score). Interpretation: We have developed

  10. Amino acid metabolism inhibits antibody-driven kidney injury by inducing autophagy.

    Science.gov (United States)

    Chaudhary, Kapil; Shinde, Rahul; Liu, Haiyun; Gnana-Prakasam, Jaya P; Veeranan-Karmegam, Rajalakshmi; Huang, Lei; Ravishankar, Buvana; Bradley, Jillian; Kvirkvelia, Nino; McMenamin, Malgorzata; Xiao, Wei; Kleven, Daniel; Mellor, Andrew L; Madaio, Michael P; McGaha, Tracy L

    2015-06-15

    Inflammatory kidney disease is a major clinical problem that can result in end-stage renal failure. In this article, we show that Ab-mediated inflammatory kidney injury and renal disease in a mouse nephrotoxic serum nephritis model was inhibited by amino acid metabolism and a protective autophagic response. The metabolic signal was driven by IFN-γ-mediated induction of indoleamine 2,3-dioxygenase 1 (IDO1) enzyme activity with subsequent activation of a stress response dependent on the eIF2α kinase general control nonderepressible 2 (GCN2). Activation of GCN2 suppressed proinflammatory cytokine production in glomeruli and reduced macrophage recruitment to the kidney during the incipient stage of Ab-induced glomerular inflammation. Further, inhibition of autophagy or genetic ablation of Ido1 or Gcn2 converted Ab-induced, self-limiting nephritis to fatal end-stage renal disease. Conversely, increasing kidney IDO1 activity or treating mice with a GCN2 agonist induced autophagy and protected mice from nephritic kidney damage. Finally, kidney tissue from patients with Ab-driven nephropathy showed increased IDO1 abundance and stress gene expression. Thus, these findings support the hypothesis that the IDO-GCN2 pathway in glomerular stromal cells is a critical negative feedback mechanism that limits inflammatory renal pathologic changes by inducing autophagy.

  11. The influence of warm ischemia elimination on kidney injury during transplantation – clinical and molecular study

    Science.gov (United States)

    Kamińska, Dorota; Kościelska-Kasprzak, Katarzyna; Chudoba, Paweł; Hałoń, Agnieszka; Mazanowska, Oktawia; Gomółkiewicz, Agnieszka; Dzięgiel, Piotr; Drulis-Fajdasz, Dominika; Myszka, Marta; Lepiesza, Agnieszka; Polak, Wojciech; Boratyńska, Maria; Klinger, Marian

    2016-01-01

    Kidney surface cooling was used during implantation to assess the effect of warm ischemia elimination on allograft function, histological changes and immune-related gene expression. 23 recipients were randomly assigned to a group operated on with kidney surface cooling during implantation (ice bag technique, IBT group), and the other 23 recipients receiving the contralateral kidney from the same donor were operated on with a standard technique. Three consecutive kidney core biopsies were obtained during the transplantation procedure: after organ recovery, after cold ischemia and after reperfusion. Gene expression levels were determined using low-density arrays (Format 32, TaqMan). The IBT group showed a significantly lower rate of detrimental events (delayed graft function and/or acute rejection, p = 0.015) as well as higher glomerular filtration rate on day 14 (p = 0.026). A greater decrease of MMP9 and LCN2 gene expression was seen in the IBT group during total ischemia (p = 0.003 and p = 0.018). Elimination of second warm ischemia reduced the number of detrimental events after kidney transplantation, and thus had influence on the short-term but not long-term allograft function. Surface cooling of the kidney during vascular anastomosis may reduce some detrimental effects of immune activation resulting from both brain death and ischemia-reperfusion injury. PMID:27808277

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

    Directory of Open Access Journals (Sweden)

    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.

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

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    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.

  14. The role of medications and their management in acute kidney injury

    Directory of Open Access Journals (Sweden)

    McDaniel BL

    2015-05-01

    Full Text Available Bradford L McDaniel,1 Michael L Bentley1,2 1Department of Pharmacy, Carilion Clinic, Roanoke, VA, USA; 2Department of Biomedical Science, Virginia Tech Carilion School of Medicine, Roanoke, VA, USA Abstract: Prior to 2002, the incidence of acute renal failure (ARF varied as there was no standard definition. To better understand its incidence and etiology and to develop treatment and prevention strategies, while moving research forward, the Acute Dialysis Quality Initiative workgroup developed the RIFLE (risk, injury, failure, loss, end-stage kidney disease classification. After continued data suggesting that even small increases in serum creatinine lead to worse outcomes, the Acute Kidney Injury Network (AKIN modified the RIFLE criteria and used the term acute kidney injury (AKI instead of ARF. These classification and staging systems provide the clinician and researcher a starting point for refining the understanding and treatment of AKI. An important initial step in evaluating AKI is determining the likely location of injury, generally classified as prerenal, renal, or postrenal. There is no single biomarker or test that definitively defines the mechanism of the injury. Identifying the insult(s requires a thorough assessment of the patient and their medical and medication histories. Prerenal injuries arise primarily due to renal hypoperfusion. This may be the result of systemic or focal conditions or secondary to the effects of drugs such as nonsteroidal anti-inflammatory drugs, calcineurin inhibitors (CIs, and modulators of the renin–angiotensin–aldosterone system. Renal, or intrinsic, injury is an overarching term that represents complex conditions leading to considerable damage to a component of the intrinsic renal system (renal tubules, glomerulus, vascular structures, interstitium, or renal tubule obstruction. Acute tubular necrosis and acute interstitial nephritis are the more common types of intrinsic renal injury. Each type of

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

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    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.

  16. Acute kidney injury, hyperbilirubinemia, and ischemic skin necrosis due to massive sulindac overdose.

    Science.gov (United States)

    Vaughn, John L; Shah, Kejal V; Ghossein, Maroun M; Meyer, William L; Kirkpatrick, Robert B

    2015-01-01

    Sulindac is a long-acting nonsteroidal anti-inflammatory drug (NSAID) widely used for the management of osteoarthritis, rheumatoid arthritis, ankylosing sponydlitis, and acute gouty arthritis. Reports of sulindac toxicity in the literature are rare. We report the case of a 22-year old male with a history of bipolar disorder who was brought to the emergency department after ingesting approximately 15 g of sulindac in a suicide attempt. He was found to have acute kidney injury and hyperbilirubinemia. Despite aggressive fluid resuscitation, his renal function progressively worsened requiring the initiation of hemodialysis. Ten days following ingestion of sulindac, he began to develop ischemic skin changes with a gangrenous appearance in his hands and feet. He continued to receive supportive treatment, and his acute kidney injury, hyperbillirubinemia, and ischemic skin necrosis eventually resolved. Clinicians should be aware of this long-acting NSAID and its ability to cause prolonged multisystem organ dysfunction.

  17. Forced diuresis with the RenalGuard system: impact on contrast induced acute kidney injury.

    Science.gov (United States)

    Solomon, Richard

    2014-01-01

    Kidney injury following the administration of iodinated contrast media occurs particularly in patients with reduced kidney and cardiac function and when large doses of contrast are used. There is little compelling evidence that vasodilators and anti-oxidants prevent this injury. Most prevention trials have employed intravenous volume loading as a central strategy. However, the success of this approach depends upon maintaining euvolemia while producing a vigorous diuresis. A novel strategy for maintaining euvolemia and inducing a vigorous diuresis has been developed using the RenalGuard system. In this review; the mechanism of protective action is reviewed. The trials of the RenalGuard device are reviewed and future uses of the device are discussed.

  18. A feasible strategy for preventing blood clots in critically ill patients with acute kidney injury (FBI)

    DEFF Research Database (Denmark)

    Robinson, Sian I.; Zincuk, A.; Larsen, U. L.;

    2014-01-01

    urine output prior to discontinuing dialysis, and low neutrophil gelatinase-associated lipocalin in dialysis-free intervals, as markers of renal recovery. METHODS/DESIGN: In a multicenter, double-blind randomized controlled trial in progress at three intensive care units across Denmark, we randomly......BACKGROUND: Previous pharmacokinetic trials suggested that 40 mg subcutaneous enoxaparin once daily provided inadequate thromboprophylaxis for intensive care unit patients. Critically ill patients with acute kidney injury are at increased risk of venous thromboembolism and yet are often excluded...... from these trials. We hypothesized that for critically ill patients with acute kidney injury receiving continuous renal replacement therapy, a dose of 1 mg/kg enoxaparin subcutaneously once daily would improve thromboprophylaxis without increasing the risk of bleeding. In addition, we seek to utilize...

  19. 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.

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

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    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

  1. Using pRIFLE criteria for acute kidney injury in critically ill children

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    Rina Amalia C. Saragih

    2013-01-01

    Full Text Available Background Incidence of acute kidney injury (AKI in critically ill children and its mortality rate is high. The lack of a uniform definition for AKI leads to failure in determining kidney injury, delayed treatment, and the inability to generalize research results. Objectives To evaluate the pediatric RIFLE (pRIFLE criteria (risk for renal dysfunction, injury to the kidney, failure of kidney function, loss of kidney function, and end-stage renal disease for diagnosing and following the clinical course of AKI in critically ill children. We also aimed to compare AKI severity on days 1 and 3 of pediatric intensive care unit (PICUu stay in critically ill pediatric patients. Methods This prospective cohort study was performed in PICU patients. Urine output (UOP, serum creatinine (SCr, and glomerular filtration rate on days 1 and 3 of PICU stay were recorded. Classification of AKI was determined according to pRIFLE criteria. We also recorded subjects’ immune status, pediatric logistic organ dysfunction (PELOD score, admission diagnosis, the use of vasoactive medications, diuretics, and ventilators, as well as PICU length of stay and mortality. Results Forty patients were enrolled in this study. AKI was found in 13 patients (33%. A comparison of AKI severity on day 1 and day 3 revealed no statistically significant differences for attainment of pRIFLE criteria by urine output only (pRIFLE UOP; P=0.087 and by both UOP and SCr (pRIFLECr+UOP; P=0.577. However, attainment of pRIFLE criteria by SCr only (pRIFLECr was significantly improved between days 1 and 3 (P=0.026. There was no statistically significant difference in mortality or length of stay between subjects with AKI and those without AKI. Conclusion The pRIFLE criteria is feasible for use in diagnosing and following the clinical course of AKI in critically ill children.[Paediatr Indones. 2013;53:32-6.

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

    Science.gov (United States)

    Cárdenas-González, M; Osorio-Yáñez, C; Gaspar-Ramírez, O; Pavković, M; Ochoa-Martínez, A; López-Ventura, D; Medeiros, M; Barbier, O C; Pérez-Maldonado, I N; Sabbisetti, V S; Bonventre, J V; Vaidya, V S

    2016-10-01

    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 (45.6ppb) and chromium (61.7ppb) 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: 467pg/mL; T3: 615pg/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 (372pg/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.

  3. Early Stage of Chronic Kidney Disease with Renal Injury Caused by Hypertension in a Dog

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    Akira Yabuki

    2011-01-01

    Full Text Available A 10-year-old spayed female Papillon weighing 4.0 kg presented with a history of persistent hematuria and pollakiuria. Concurrent bladder calculi, a mammary gland tumor, and nonazotemic early stage of chronic kidney disease with contracted kidneys were noted in this dog. The dog underwent cystectomy, unilateral mastectomy, and intraoperative renal biopsy. On the basis of histopathological analysis of renal biopsy results, it was suspected that renal injury of the dog was caused by persistent hypertension, and a follow-up examination revealed severe hypertension. The dog was treated with a combination of an angiotensin-converting enzyme inhibitor and calcium channel blocker. The treatment produced a good outcome in the dog, and there has been no progression of the chronic kidney disease for over 2 years.

  4. Heme Oxygenase 1 as a Therapeutic Target in Acute Kidney Injury.

    Science.gov (United States)

    Bolisetty, Subhashini; Zarjou, Abolfazl; Agarwal, Anupam

    2017-04-01

    A common clinical condition, acute kidney injury (AKI) significantly influences morbidity and mortality, particularly in critically ill patients. The pathophysiology of AKI is complex and involves multiple pathways, including inflammation, autophagy, cell-cycle progression, and oxidative stress. Recent evidence suggests that a single insult to the kidney significantly enhances the propensity to develop chronic kidney disease. Therefore, the generation of effective therapies against AKI is timely. In this context, the cytoprotective effects of heme oxygenase 1 (HO-1) in animal models of AKI are well documented. HO-1 modulates oxidative stress, autophagy, and inflammation and regulates the progression of cell cycle via direct and indirect mechanisms. These beneficial effects of HO-1 induction during AKI are mediated in part by the by-products of the HO reaction (iron, carbon monoxide, and bile pigments). This review highlights recent advances in the molecular mechanisms of HO-1-mediated cytoprotection and discusses the translational potential of HO-1 induction in AKI.

  5. Malnutrition and inflammation in acute kidney injury due to earthquake-related crush syndrome

    OpenAIRE

    2010-01-01

    Abstract Background Malnutrition and inflammation are common and serious complications in patients with acute kidney injury (AKI). However, the profile of these complications in patients with AKI caused by crush syndrome (CS) remains unclear. This study describes the clinical characteristics of malnutrition and inflammation in patients with AKI and CS due to the Wenchuan earthquake. Methods One thousand and twelve victims and eighteen healthy adults were recruited to the study. They were divi...

  6. Definition and Classification of Acute Kidney Injury:Contributions and Problems in the Clinical Practice

    Institute of Scientific and Technical Information of China (English)

    CHEN Yi-pu

    2010-01-01

    @@ Definition and Classification of Acute Kidney Injury Before the RIFLE classification system of acute renal failure (ARF) was proposed in the Second Conference of Acute Dialysis Quality Initiative (ADQI, an international volunteer organization mainly composed of intensivists and nephrologists in developed countries) in 2002, there were more than 35 diagnostic criteria of ARF in different literatures, which led to confusion in clinical practice and epidemiological investigation(1).

  7. Measuring biomarkers of acute kidney injury during renal replacement therapy: wisdom or folly?

    Science.gov (United States)

    Ostermann, Marlies; Forni, Lui G

    2014-06-19

    Early data are now appearing relating to the measurement of biomarkers of acute kidney injury during renal replacement therapy. These data go some way in describing the clearance of these molecules during renal support. Understanding the potential clearance, or otherwise, of these proteins may lead to directing our therapies in the future particularly with regard to cessation of renal support. We describe a recent study which has provided data that may aid in addressing this issue.

  8. Value of joint detecion of multiple biomarkers on early diagnosis of acute kidney injury in critical patients

    Institute of Scientific and Technical Information of China (English)

    许光银

    2014-01-01

    Objective To assess the value of joint detection of serum cysteine proteinase inhibitors C(sCys-C),urinary kidney injury molecule 1(uKIM-1),urinary neutrophil gelatinase-associated lipocalin(uNGAL)and urinary interleukin 18(uIL-18)for early diagnosis of acute kidney injury(AKI)in critically ill patients.Methods A total of256 adult patients who stayed in Intensive Care Unit for

  9. Hemodialysis among pregnancy related acute kidney injury patients: A single center experience in North-Western Nigeria

    OpenAIRE

    A M Makusidi; Liman, H. M.; Yakubu, A.; Hassan, M; Isah, M. D.; Chijioke, A.

    2016-01-01

    Pregnancy related acute kidney injury (PRAKI) patients that underwent hemodialysis (HD) between May 2007 and April 2015 were studied with specific reference to clinical features, laboratory values, duration of pregnancy at the diagnosis of acute kidney injury and outcome. It involved 38 patients aged between 15 and 30 years. The main clinical features were fever, edema and oliguria. The leading etiological factors included ante/postpartum hemorrhage, septic abortion, and toxemia of pregnancy....

  10. Protective effect of propolis on methotrexate-induced kidney injury in the rat.

    Science.gov (United States)

    Ulusoy, Hasan Basri; Öztürk, İsmet; Sönmez, Mehmet Fatih

    2016-06-01

    Objectives Propolis is a potent antioxidant and a free radical scavenger. Pharmacological induction of heat shock proteins (HSPs) has been investigated for restoring normal cellular function following an injury. In this study, effect of propolis on HSP-70 expression in methotrexate-induced nephrotoxicity and direct preventive effect of propolis in this toxicity were investigated. Material and methods A total of 40 male Wistar albino rats were divided into four groups: Group 1 was the untreated control. On the eighth day of the experiment, groups 2 and 3 received single intraperitoneal injections of methotrexate (MTX) at 20 mg/kg. Groups 3 and 4 received 100 mg/kg/day propolis (by oral gavage) for 15 d by the first day of the experimental protocol. Then the rats were decapitated under ketamine esthesia and their kidney tissues were removed. HSP-70 expression, apoptosis, and histopathological damage scores were then compared. Results MTX caused epithelial desquamation into the lumen of the tubules, dilatation, and congestion of the peritubular vessels and renal corpuscles with obscure Bowman's space. The number of apoptotic cells (p = 0.000) and HSP-70 (p = 0.002) expression were increased in group 2. Propolis prevented the rise in number of apoptotic cells (p = 0.017), HSP-70 (p = 0.000) expression, and improved kidney morphology. Conclusions It was found that methotrexate gives rise to serious damage in the kidney and propolis is a potent antioxidant agent in preventing kidney injury.

  11. 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.

  12. Difficulties in diagnosing acute kidney injury post liver transplantation using serum creatinine based diagnostic criteria

    Institute of Scientific and Technical Information of China (English)

    Banwari; Agarwal; Andrew; Davenport

    2014-01-01

    Renal function in patients with advanced cirrhosis is an important prognostic factor for survival both prior to and following liver transplantation. The importance of renal function is reflected by the introduction of the model for end stage liver disease(MELD) score, which includes serum creatinine. The MELD score has been shown to predict the short term risk of death for transplant wait listed patients and is currently used by many countries to allocate liver transplants on the basis of severity of underlying illness. Changes in serum creatinine are also used to stage acute kidney injury. However prior to liver transplantation the serum creatinine typically over estimates underlying renal function, particularly when a colorimetric Jaffe based assay is used, and paradoxically then under estimates renal function post liver transplantation, particularly when immunophyllins are started early as part of transplant immunosuppression. As acute kidney injury is defined by changes in serum creatinine, this potentially leads to over estimation of the incidence and severity of acute kidney injury in the immediate post-operative period.

  13. Potential advantages of acute kidney injury management by mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Francesca; Bianchi; Elisa; Sala; Chiara; Donadei; Irene; Capelli; Gaetano; La; Manna

    2014-01-01

    Mesenchymal stem cells are currently considered as a promising tool for therapeutic application in acute kidney injury(AKI) management. AKI is characterized by acute tubular injury with rapid loss of renal function. After AKI, inflammation, oxidative stress and excessive deposition of extracellular matrix are the molecular events that ultimately cause the end-stage renal disease. Despite numerous improvement of supportive therapy, the mortality and morbidity among patients remain high. Therefore, exploring novel therapeutic options to treat AKI is mandatory. Numerous evidence in animal models has demonstrated the capability of mesenchymal stem cells(MSCs) to restore kidney function after induced kidney injury. After infusion, MSCs engraft in the injured tissue and release soluble factors and microvesicles that promote cell survival and tissue repairing. Indeed, the main mechanism of action of MSCs in tissue regeneration is the paracrine/endocrine secretion of bioactive molecules. MSCs can be isolated from several tissues, including bone marrow, adipose tissue, and blood cord; pre-treatment procedures to improve MSCs homing and their paracrine function have been also described. This review will focus on the application of cell therapy in AKI and it will summarize preclinical studies in animal models and clinical trials currently ongoing about the use of mesenchymal stem cells after AKI.

  14. Vitamin D deficiency contributes to vascular damage in sustained ischemic acute kidney injury.

    Science.gov (United States)

    de Bragança, Ana C; Volpini, Rildo A; Mehrotra, Purvi; Andrade, Lúcia; Basile, David P

    2016-07-01

    Reductions in renal microvasculature density and increased lymphocyte activity may play critical roles in the progression of chronic kidney disease (CKD) following acute kidney injury (AKI) induced by ischemia/reperfusion injury (IRI). Vitamin D deficiency is associated with tubulointerstitial damage and fibrosis progression following IRI-AKI We evaluated the effect of vitamin D deficiency in sustained IRI-AKI, hypothesizing that such deficiency contributes to the early reduction in renal capillary density or alters the lymphocyte response to IRI Wistar rats were fed vitamin D-free or standard diets for 35 days. On day 28, rats were randomized into four groups: control, vitamin D deficient (VDD), bilateral IRI, and VDD+IRI Indices of renal injury and recovery were evaluated for up to 7 days following the surgical procedures. VDD rats showed reduced capillary density (by cablin staining), even in the absence of renal I/R. In comparison with VDD and IRI rats, VDD+IRI rats manifested a significant exacerbation of capillary rarefaction as well as higher urinary volume, kidney weight/body weight ratio, tissue injury scores, fibroblast-specific protein-1, and alpha-smooth muscle actin. VDD+IRI rats also had higher numbers of infiltrating activated CD4(+) and CD8(+) cells staining for interferon gamma and interleukin-17, with a significant elevation in the Th17/T-regulatory cell ratio. These data suggest that vitamin D deficiency impairs renal repair responses to I/R injury, exacerbates changes in renal capillary density, as well as promoting fibrosis and inflammation, which may contribute to the transition from AKI to CKD.

  15. Evaluation of stem cell administration in a model of kidney ischemia-reperfusion injury.

    Science.gov (United States)

    da Silva, Léa Bueno Lucas; Palma, Patrícia Viana Bonini; Cury, Patrícia Maluf; Bueno, Valquiria

    2007-12-15

    Ischemia-reperfusion injury is a common early event in kidney transplantation and contributes to a delay in organ function. Acute tubular necrosis, impaired kidney function and organ leukocyte infiltration are the major findings. The therapeutic potential of stem cells has been the focus of recent research as these cells possess capabilities such as self-renewal, multipotent differentiation and aid in regeneration after organ injury. FTY720 is a new synthetic compound that has been associated with preferential migration of blood lymphocytes to peripheral lymph nodes instead of inflammatory sites. Bone marrow stem cells (BMSC) and/or FTY720 were used as therapy to promote recovery of tubule cells and avoid inflammation at the renal site, respectively. Mice were submitted to renal ischemia-reperfusion injury and were either treated with two doses of FTY720, 10x10(6) BMSC, or both in order to compare the therapeutic effect with non-treated and control animals. Renal function and structure were investigated as were cell numbers in peripheral blood and spleen. Activation and apoptosis markers were also evaluated in splenocytes using flow cytometry. We found that the combined therapy (FTY720+BMSC) was associated with more significant changes in renal function and structure after ischemia-reperfusion injury when compared with the other groups. Also a decrease at cell numbers and prevention of spleen cells activation and apoptosis was observed. In conclusion, in our model it was not possible to demonstrate the potential of stem cells alone or in combination with FTY720 to promote early kidney recovery after ischemia-reperfusion injury.

  16. Soluble epoxide hydrolase activity determines the severity of ischemia-reperfusion injury in kidney.

    Directory of Open Access Journals (Sweden)

    Jung Pyo Lee

    Full Text Available Soluble epoxide hydrolase (sEH in endothelial cells determines the plasma concentrations of epoxyeicosatrienoic acids (EETs, which may act as vasoactive agents to control vascular tone. We hypothesized that the regulation of sEH activity may have a therapeutic value in preventing acute kidney injury by controlling the concentration of EETs. In this study, we therefore induced ischemia-reperfusion injury (IRI in C57BL/6 mice and controlled sEH activity by intraperitoneal administration of the sEH inhibitor 12-(3-adamantan-1-ylureido-dodecanoic acid (AUDA. The deterioration of kidney function induced by IRI was partially moderated and prevented by AUDA treatment. In addition, AUDA treatment significantly attenuated tubular necrosis induced by IRI. Ischemic injury induced the down-regulation of sEH, and AUDA administration had no effect on the expression pattern of sEH induced by IRI. In vivo sEH activity was assessed by measuring the substrate epoxyoctadecenoic acid (EpOME and its metabolite dihydroxyoctadec-12-enoic acid (DHOME. Ischemic injury had no effects on the plasma concentrations of EpOME and DHOME, but inhibition of sEH by AUDA significantly increased plasma EpOME and the EpOME/DHOME ratio. The protective effect of the sEH inhibitor was achieved by suppression of proinflammatory cytokines and up-regulation of regulatory cytokines. AUDA treatment prevented the intrarenal infiltration of inflammatory cells, but promoted endothelial cell migration and neovascularization. The results of this study suggest that treatment with sEH inhibitors can reduce acute kidney injury.

  17. Nephroprotective effect ofCroton zambesicus root extract against gentimicin-induced kidney injury

    Institute of Scientific and Technical Information of China (English)

    Jude E Okokon; Paul A Nwafor; Kufre Noah

    2011-01-01

    Objective:To evaluate the kidney protective effect of ethanolic root extract ofCroton zambesicus (C. zambesicus) against gentimicin-induced kidney injury in rats.Methods: The root extract (27 -81 mg/kg) was administered to rats for eight days with concurrent administration of gentimicin (100mg/kg) daily for the same period of time. Protective effect of the extract was evaluated in serum levels of creatinine, urea, and uric acid as well as some ions like sodium, potassium and chloride. Histological examination of the kidneys from different treatment groups were also carried out.Results: Administration of the root extract significantly reduced histopathological changes in the kidneys of the extract-treated rats especially in the rats treated with lower doses of the extract (27and54 mg/kg). The levels of serum urea and creatinine were also reduced significantly (P<0.01) at these doses with no observable effect on the levels of uric acid and ions. Conclusions: The kidney - protective activity of this extract could be due to its antioxidant and free radical scavenging activities.

  18. A European Renal Best Practice (ERBP) position statement on the Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guidelines on Acute Kidney Injury: part 2: renal replacement therapy.

    Science.gov (United States)

    Jörres, Achim; John, Stefan; Lewington, Andrew; ter Wee, Pieter M; Vanholder, Raymond; Van Biesen, Wim; Tattersall, James

    2013-12-01

    This paper provides an endorsement of the KDIGO guideline on acute kidney injury; more specifically, on the part that concerns renal replacement therapy. New evidence that has emerged since the publication of the KDIGO guideline was taken into account, and the guideline is commented on from a European perspective. Advice is given on when to start and stop renal replacement therapy in acute kidney injury; which modalities should be preferentially be applied, and in which conditions; how to gain access to circulation; how to measure adequacy; and which dose can be recommended.

  19. Ischemia/reperfusion-induced Kidney Injury in Heterozygous PACAP-deficient Mice.

    Science.gov (United States)

    Laszlo, E; Varga, A; Kovacs, K; Jancso, G; Kiss, P; Tamas, A; Szakaly, P; Fulop, B; Reglodi, D

    2015-09-01

    Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with very diverse distribution and functions. Among others, PACAP is a potent cytoprotective peptide due to its antiapoptotic, anti-inflammatory, and antioxidant actions. This also has been shown in different kidney pathologies, including ischemia/reperfusion-induced kidney injury. Similar protective effects of the endogenous PACAP are confirmed by the increased vulnerability of PACAP-deficient mice to different harmful stimuli. Kidneys of homozygous PACAP-deficient mice have more severe damages in renal ischemia/reperfusion and kidney cell cultures isolated from these mice show increased sensitivity to renal oxidative stress. In our present study we raised the question of whether the partial lack of the PACAP gene is also deleterious, i.e. whether heterozygous PACAP-deficient mice also display more severe damage after renal ischemia/reperfusion. Mice underwent 45 or 60 minutes of ischemia followed by 2 weeks reperfusion. Histological evaluation of the kidneys was performed and individual histopathological parameters were graded. Furthermore, we investigated apoptotic markers, cytokine expression, and the activity of superoxide dismutase (SOD) enzyme 24 hours after 60 minutes of renal ischemia/reperfusion. We found no difference between the intact kidneys of wild-type and heterozygous mice, but marked differences could be observed following ischemia/reperfusion. Heterozygous PACAP-deficient mice had more severe histological alterations, with significantly higher histopathological scores for most of the tested parameters. Higher level of the proapoptotic pp38 MAPK and of some proinflammatory cytokines, as well as lower activity of the antioxidant SOD could be found in these mice. In conclusion, the partial lack of the PACAP gene results in worse outcomes in cases of renal ischemia/reperfusion, confirming that PACAP functions as an endogenous protective factor in the kidney.

  20. The Effects of Vitamin D on Gentamicin-Induced Acute Kidney Injury in Experimental Rat Model

    Directory of Open Access Journals (Sweden)

    Ender Hur

    2013-01-01

    Full Text Available Introduction. Acute kidney injury (AKI pathogenesis is complex. Findings of gentamicin nephrotoxicity are seen in 30% of the AKI patients. Vitamin D has proven to be effective on renin expression, inflammatory response, oxidative stress, apoptosis, and atherosclerosis. We aimed to investigate the effect of vitamin D in an experimental rat model of gentamicin-induced AKI. Methods. Thirty nonuremic Wistar albino rats were divided into 3 groups: Control group, 1 mL saline intramuscular (im daily; Genta group, gentamicin 100 mg/kg/day (im; Genta + vitamin D, gentamicin 100 mg/kg/day (im in addition to 1α, 25 (OH2D3 0.4 mcg/kg/day subcutaneously for 8 days. Blood pressures and 24-hour urine were measured. Blood urea and creatinine levels and urine tubular injury markers were measured. Renal histology was semiquantitatively assessed. Results. Urea, creatinine and urine neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1 were all increased in Genta group indicating AKI model. Systolic blood pressure decreased, but urine volume and glutathione increased in Genta + Vit D group compared to Control group. Histological scores indicating tubular injury increased in Genta and Genta + Vit D groups. Conclusions. Vitamin D does not seem to be effective on histological findings although it has some beneficial effects via RAS system and a promising effect on antioxidant system.

  1. Novel biomarkers for cardiac surgery-associated acute kidney injury: a skeptical assessment of their role.

    Science.gov (United States)

    Sidebotham, David

    2012-12-01

    Cardiac surgery-associated acute kidney injury (AKI) is common and is associated with a high mortality rate. Traditional biomarkers of AKI (creatinine and urea) increase slowly in response to renal injury, are insensitive to mild degrees of AKI, and are influenced by nonrenal factors. There is considerable interest in novel biomarkers of AKI such as neutrophil gelatinase-associated lipocalin that increase rapidly after renal injury, detect mild degrees of AKI, and are less subject to nonrenal factors. It has been postulated that the early diagnosis of cardiac surgery-associated AKI using novel biomarkers will result in improved outcomes. However, there is little evidence that interventions started early in the course of evolving AKI enhance renal recovery. Until effective therapies are developed that significantly improve the outcome from AKI, there is little benefit from early diagnosis using novel biomarkers.

  2. Circulating Mitochondrial DAMPs Are Not Effective Inducers of Proteinuria and Kidney Injury in Rodents.

    Directory of Open Access Journals (Sweden)

    Jing He

    Full Text Available Mitochondria in eukaryotic cells are derived from bacteria in evolution. Like bacteria, mitochondria contain DNA with unmethylated CpG motifs and formyl peptides, both of which have recently been shown to be damage associated molecular patterns (DAMPs and induce immune response and cell injury. Based on the facts that circulating mitochondrial DAMPs (mtDAMPs are increased in the patients of trauma or burn injury who also have proteinuria, that mtDAMPs can activate immune cells which in turn secrete glomerular permeability factors, that renal intrinsic cells express a variety of DAMP receptors, and that mtDAMPs can directly increase endothelial cell permeability in vitro, we hypothesized that mtDAMPs may be novel circulating factors inducing proteinuria and kidney injury. We tested this hypothesis by directly injecting mtDAMPs into rodents and examining urinary protein and kidney histology. We prepared mtDAMP samples, including mitochondrial DNA (mtDNA and mitochondrial debris (MTD, from rodent liver. In mice, injection of mtDNA for 20 μg/ml initial concentration in circulation (much higher than the clinical range, did not cause any renal manifestations. However, an increased dose leading to 45 μg/ml initial concentration in circulation resulted in a transient, slight increase in urinary albumin. In rats, MTD injection resulting in 450 μg/ml initial concentration of MTD protein in circulation, which was much higher than the clinical range, caused mild, transient proteinuria and lung lesions. Multiple injections of such large amount of either mtDNA or MTD into rodents on 3 consecutive days also failed in inducing proteinuria and kidney injury. In summary, clinical levels of circulating mtDAMPs do not induce proteinuria and clinically irrelevant high levels of mtDAMPs cause only a transient and slight increase in urinary protein in rodents, suggesting that circulating mtDAMPs may not be responsible for the proteinuria and kidney injury in

  3. Farnesoid X Receptor Protects against Kidney Injury in Uninephrectomized Obese Mice.

    Science.gov (United States)

    Gai, Zhibo; Gui, Ting; Hiller, Christian; Kullak-Ublick, Gerd A

    2016-01-29

    Activation of the farnesoid X receptor (FXR) has indicated a therapeutic potential for this nuclear bile acid receptor in the prevention of diabetic nephropathy and obesity-induced renal damage. Here, we investigated the protective role of FXR against kidney damage induced by obesity in mice that had undergone uninephrectomy, a model resembling the clinical situation of kidney donation by obese individuals. Mice fed a high-fat diet developed the core features of metabolic syndrome, with subsequent renal lipid accumulation and renal injury, including glomerulosclerosis, interstitial fibrosis, and albuminuria. The effects were accentuated by uninephrectomy. In human renal biopsies, staining of 4-hydroxynonenal (4-HNE), glucose-regulated protein 78 (Grp78), and C/EBP-homologous protein, markers of endoplasmic reticulum stress, was more prominent in the proximal tubules of 15 obese patients compared with 16 non-obese patients. In mice treated with the FXR agonist obeticholic acid, renal injury, renal lipid accumulation, apoptosis, and changes in lipid peroxidation were attenuated. Moreover, disturbed mitochondrial function was ameliorated and the mitochondrial respiratory chain recovered following obeticholic acid treatment. Culturing renal proximal tubular cells with free fatty acid and FXR agonists showed that FXR activation protected cells from free fatty acid-induced oxidative stress and endoplasmic reticulum stress, as denoted by a reduction in the level of reactive oxygen species staining and Grp78 immunostaining, respectively. Several genes involved in glutathione metabolism were induced by FXR activation in the remnant kidney, which was consistent with a decreased glutathione disulfide/glutathione ratio. In summary, FXR activation maintains endogenous glutathione homeostasis and protects the kidney in uninephrectomized mice from obesity-induced injury.

  4. Biochemical and histological study of rat liver and kidney injury induced by Cisplatin.

    Science.gov (United States)

    Palipoch, Sarawoot; Punsawad, Chuchard

    2013-09-01

    Cisplatin is a chemotherapeutic agent widely used in treatment of several cancers. It is documented as a major cause of clinical nephrotoxicity and hepatotoxicity. The purpose of this study was to investigate the involvement of oxidative stress in the pathogenesis of cisplatin-induced liver and kidney injury. Wistar rats were divided into four groups. Group 1 (control) was intraperitoneally (IP) injected with a single dose of 0.85% normal saline. Groups 2, 3 and 4 were IP injected with single doses of cisplatin at 10, 25 and 50 mg/kg body weight (BW), respectively. At 24, 48, 72, 96 and 120 h after injection, BW, levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), and activity of superoxide dismutase (SOD) and histology of the liver and kidney were evaluated. Cisplatin caused a reduction in BW of rats in groups 2, 3 and 4 at all post injection intervals. The levels of serum ALT, AST, BUN and creatinine and MDA of the kidney and liver were markedly increased especially at 48 and 72 h, whereas the activity of SOD was decreased after cisplatin injection. Liver sections revealed moderate to severe congestion with dilation of the hepatic artery, portal vein and bile duct and disorganization of hepatic cords at 50 mg/kg of cisplatin. Kidney sections illustrated mild to moderate tubular necrosis at 25 and 50 mg/kg of cisplatin. Therefore, oxidative stress was implicated in the pathogenesis of liver and kidney injury causing biochemical and histological alterations.

  5. Pregnancy-related acute kidney injury: An analysis of 165 cases

    Science.gov (United States)

    Mahesh, E.; Puri, S.; Varma, V.; Madhyastha, P. R.; Bande, S.; Gurudev, K. C.

    2017-01-01

    Pregnancy-related acute kidney injury (PRAKI) contributes to 3–7% of overall acute kidney injury (AKI) cases in Indian subcontinent. The aim of this study was to determine the outcomes of PRAKI and risk factors associated with renal injury and maternal mortality. One hundred and sixty-five patients with PRAKI, seen at M. S. Ramaiah Medical College between 2005 and 2014, were included in this, observational study. AKI was analyzed in terms of maximal stage of renal injury attained as per Risk, Injury, Failure, Loss of function, and End-stage renal disease (RIFLE) criteria. Outcomes included requirement for renal replacement therapy (RRT), maternal, and fetal mortality. Incidence of PRAKI was 1.56%, and the mean age of the study population was 25 years. Fifty percent of the patients were diagnosed with PRAKI during their first pregnancy. PRAKI was observed most commonly in the postpartum period (60%), followed by third trimester (32%); as per RIFLE criteria, failure was seen in 36% and injury in 34%. Thirty percent of cases required RRT. Sepsis (59%), pre-eclampsia, and eclampsia (56%) were the leading causes of PRAKI, while sepsis was the leading cause of maternal mortality. Maternal and fetal mortality were 20% and 22%, respectively. In univariate analysis, shock, hemorrhage requiring transfusion of >5 units packed red blood cells, oliguria, and “Loss” category of RIFLE were significantly associated with mortality. Majority of the patients (57%) required Intensive Care Unit care with a mean duration of admission at 7.3 days, and 75% was diagnosed with AKI at the time of admission. We report the lowest incidence of PRAKI in contemporary Indian literature. PRAKI was associated with high maternal and fetal mortality, with sepsis being the leading cause. No association was noted between mortality and initial stages of RIFLE criteria. PMID:28356662

  6. Clinical analysis of acute kidney injury in chroinc kidney disease%慢性肾脏病发生急性肾损伤临床分析

    Institute of Scientific and Technical Information of China (English)

    贺禄碧; 周利

    2012-01-01

    Objective To investigate the cause, clinial characteristics, treatment and improvment of chroinc kidney disease occurring acute kidney injury, in order to improve the prevention level of acute kidney injury. Methods The clinical characteristics of 68 cases of chroinc kidney disease occurring acute kidney injury patients in our hospital were retrospectively analyzed. Results The clinical characteristics of 68 cases of chroinc kidney disease occurring acute kidney injury patients were kidney function acutely worsen. All patients were treated with hormones and cytotoxic drugs given to infection control, diuresis, anticoagulation therapy, including 32 cases of hemodialysis treatment, 27 cases of kidney function improved. Conclusion Patients with chronic kidney disease complicated by acute renal injury is not uncommon clinical Once diagnosed and treated promptly, most patients with good prognosis, return to normal renal function.%目的 探讨慢性肾脏病合并急性肾损伤的病因、临床特点及治疗与转归情况,提高急性肾损伤的防治水平.方法 对慢性肾脏病发生急性肾损伤68例住院患者的临床特点进行回顾性分析.结果 慢性肾脏病合并急性肾损伤的临床特征表现为短时间内肾功能急剧恶化.所有患者均给予激素和细胞毒药物,同时给予控制感染、利尿、抗凝等综合治疗,其中32例进行血液透析治疗,27例肾功能恢复.结论 慢性肾病并发急性肾损伤临床并不少见,一旦确定诊断并给予及时治疗,多数患者预后较好,肾功能可恢复正常.

  7. Protective effect of chenodeoxycholic acid against lipid kidney injury induced by high-fructose feeding in rats and the underlying mechanism

    Institute of Scientific and Technical Information of China (English)

    胡志娟

    2013-01-01

    Objective To study the intervention of chenodeoxycholic acid(CDCA) on kidney of high-fructose-fed rats,and investigate the mechanism of CDCA on lipid kidney injury.Methods Forty-eight healthy male Wistar

  8. Peptidyl arginine deiminase-4 activation exacerbates kidney ischemia-reperfusion injury.

    Science.gov (United States)

    Ham, Ahrom; Rabadi, May; Kim, Mihwa; Brown, Kevin M; Ma, Zhe; D'Agati, Vivette; Lee, H Thomas

    2014-11-01

    Peptidyl arginine deiminase (PAD)4 is a nuclear enzyme that catalyzes the posttranslational conversion of arginine residues to citrulline. Posttranslational protein citrullination has been implicated in several inflammatory autoimmune diseases, including rheumatoid arthritis, colitis, and multiple sclerosis. Here, we tested the hypothesis that PAD4 contributes to ischemic acute kidney injury (AKI) by exacerbating the inflammatory response after renal ischemia-reperfusion (I/R). Renal I/R injury in mice increased PAD4 activity as well as PAD4 expression in the mouse kidney. After 30 min of renal I/R, vehicle-treated mice developed severe AKI with large increases in plasma creatinine. In contrast, mice pretreated with PAD4 inhibitors (2-chloroamidine or streptonigrin) had significantly reduced renal I/R injury. Further supporting a critical role for PAD4 in generating ischemic AKI, mice pretreated with recombinant human PAD4 (rPAD4) protein and subjected to mild (20 min) renal I/R developed exacerbated ischemic AKI. Consistent with the hypothesis that PAD4 regulates renal tubular inflammation after I/R, mice treated with a PAD4 inhibitor had significantly reduced renal neutrophil chemotactic cytokine (macrophage inflammatory protein-2 and keratinocyte-derived cytokine) expression and had decreased neutrophil infiltration. Furthermore, mice treated with rPAD4 had significantly increased renal tubular macrophage inflammatory protein-2 and keratinocyte-derived cytokine expression as well as increased neutrophil infiltration and necrosis. Finally, cultured mouse kidney proximal tubules treated with rPAD4 had significantly increased proinflammatory chemokine expression compared with vehicle-treated cells. Taken together, our results suggest that PAD4 plays a critical role in renal I/R injury by increasing renal tubular inflammatory responses and neutrophil infiltration after renal I/R.

  9. Toll-like receptor 4 contributes to acute kidney injury after cardiopulmonary resuscitation in mice

    Science.gov (United States)

    Zhang, Qingsong; Li, Gang; Xu, Li; Li, Qian; Wang, Qianyan; Zhang, Yue; Zhang, Qing; Sun, Peng

    2016-01-01

    Toll-like receptor 4 (TLR4) activation mediates renal injury in regional ischemia and reperfusion (I/R) models generated by clamping renal pedicles. However, it remains unclear whether TLR4 is causal in the kidney injury following global I/R induced by cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). The present study used wild-type (C3H/HeN) and TLR4-mutant (C3H/HeJ) mice to produce the CA/CPR model. CA was induced by injection of cold KCl and left untreated for different time periods. After resuscitation (72 h), the level of blood urea nitrogen (BUN) and serum creatinine (Scr), as well as histological changes in renal tissue were assessed to evaluate the severity of acute kidney injury (AKI). The expression of TLR4, intercellular adhesion molecule-1 (ICAM-1), myeloperoxidase (MPO) and growth-regulated oncogene-β (GRO-β) in kidney tissues was detected. The results demonstrated that the levels of Scr and BUN increased significantly in C3H/HeN and C3H/HeJ mice after CPR. CPR also resulted in increased expression of TLR4, ICAM-1, GRO-β and MPO in a CA-duration dependent manner. However, there was decreased expression of ICAM-1, GRO-β and MPO in C3H/HeJ mice compared with that in C3H/HeN mice. C3H/HeJ mice were resistant to AKI as demonstrated by the minor changes in renal histology and function following CPR. In conclusion, mice suffered from AKI after successful CPR and severe AKI occurred in mice with prolonged CA duration. TLR4 and its downstream signaling events that promote neutrophil infiltration via ICAM-1 and GRO-β may be important in mediating inflammatory responses to renal injury after CPR. PMID:27510583

  10. Determining the Incidence of Drug-Associated Acute Kidney Injury in Nursing Home Residents

    Science.gov (United States)

    Handler, Steven M.; Cheung, Pui Wen; Culley, Colleen M.; Perera, Subashan; Kane-Gill, Sandra L.; Kellum, John A.; Marcum, Zachary A.

    2015-01-01

    Objective Although acute kidney injury (AKI) is well-studied in the acute care setting, investigation of AKI in the nursing home (NH) setting is virtually nonexistent. The goal of this study was to determine the incidence of drug-associated AKI using the RIFLE (Risk, Injury, Failure, Loss of kidney function or End-Stage kidney disease) criteria in NH residents. Design/Setting/Participants/Measurements We conducted a retrospective study between February 9, 2012 and February 8, 2013 for all residents at four UPMC NHs located in Southwest Pennsylvania. The TheraDoc™ Clinical Surveillance System, which monitors laboratory and medication data and fires alerts when patients have a sufficient increase in serum creatinine, was used for automated case detection. An increase in serum creatinine in the presence of an active medication order identified to potentially cause AKI triggered an alert, and drug-associated AKI was staged according to the RIFLE criteria. Data were analyzed by frequency and distribution of alert type by risk, injury, and failure. Results Of the 249 residents who had a drug-associated AKI alert fire, 170 (68.3%) were female, and the mean age was 74.2 years. Using the total number of alerts (n=668), the rate of drug-associated AKI was 0.35 events per 100 resident-months. Based on the RIFLE criteria, there were 191, 70, and 44 residents who were classified as AKI risk, injury, and failure, respectively. The most common medication classes included in the AKI alerts were diuretics, ACEIs/ARBs, and antibiotics. Conclusion Drug-associated AKI was a common cause of potential adverse drug events. The vast majority of the cases were related to the use of diuretics, ACEIs/ARBs and antibiotics. Future studies are needed to better understand patient, provider and facility risk factors as well as strategies to enhance the detection and management of drug-associated AKI in the NH. PMID:24814042

  11. Design of clinical trials in acute kidney injury: report from an NIDDK workshop on trial methodology.

    Science.gov (United States)

    Palevsky, Paul M; Molitoris, Bruce A; Okusa, Mark D; Levin, Adeera; Waikar, Sushrut S; Wald, Ron; Chertow, Glenn M; Murray, Patrick T; Parikh, Chirag R; Shaw, Andrew D; Go, Alan S; Faubel, Sarah G; Kellum, John A; Chinchilli, Vernon M; Liu, Kathleen D; Cheung, Alfred K; Weisbord, Steven D; Chawla, Lakhmir S; Kaufman, James S; Devarajan, Prasad; Toto, Robert M; Hsu, Chi-yuan; Greene, Tom; Mehta, Ravindra L; Stokes, John B; Thompson, Aliza M; Thompson, B Taylor; Westenfelder, Christof S; Tumlin, James A; Warnock, David G; Shah, Sudhir V; Xie, Yining; Duggan, Emily G; Kimmel, Paul L; Star, Robert A

    2012-05-01

    Acute kidney injury (AKI) remains a complex clinical problem associated with significant short-term morbidity and mortality and lacking effective pharmacologic interventions. Patients with AKI experience longer-term risks for progressive chronic ESRD, which diminish patients' health-related quality of life and create a larger burden on the healthcare system. Although experimental models have yielded numerous promising agents, translation into clinical practice has been unsuccessful, possibly because of issues in clinical trial design, such as delayed drug administration, masking of therapeutic benefit by adverse events, and inadequate sample size. To address issues of clinical trial design, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored a workshop titled "Clinical Trials in Acute Kidney Injury: Current Opportunities and Barriers" in December 2010. Workshop participants included representatives from academia, industry, and government agencies whose areas of expertise spanned basic science, clinical nephrology, critical care medicine, biostatistics, pharmacology, and drug development. This document summarizes the discussions of collaborative workgroups that addressed issues related to patient selection, study endpoints, the role of novel biomarkers, sample size and power calculations, and adverse events and pilot/feasibility studies in prevention and treatment of AKI. Companion articles outline the discussions of workgroups for model trials related to prevention or treatment of established AKI in different clinical settings, such as in patients with sepsis.

  12. Contrast-induced acute kidney injury: short- and long-term implications.

    Science.gov (United States)

    Weisbord, Steven D; Palevsky, Paul M

    2011-05-01

    The intravascular administration of iodine-based contrast media remains a common cause of acute kidney injury and a leading cause of iatrogenic renal disease. Past research has elucidated the principal risk factors for contrast-induced acute kidney injury (CIAKI) and helped to establish the efficacy of various interventions for the prevention of this condition. The importance of preventing CIAKI has been underscored by a growing number of studies showing strong associations of CIAKI with serious adverse short- and long-term outcomes. However, it remains unclear whether these associations are causal. This is important because considerable health care resources are used to prevent CIAKI. If CIAKI is a marker, but not a mediator, of serious adverse downstream outcomes, more judicious and selective use of preventive care may be appropriate. Moreover, with an increasing number of studies reporting the underuse of coronary angiography in patients with acute coronary syndrome and underlying chronic kidney disease, presumably in part because of a fear of CIAKI, a clear understanding of whether this condition directly results in adverse downstream outcomes is essential. Careful inspection of past studies that investigated the association of CIAKI with adverse short- and long-term events sheds light on their strengths and weaknesses and provides insight into how future research may be better able to characterize the short- and long-term implications of this iatrogenic condition.

  13. The ischemic/nephrotoxic acute kidney injury and the use of renal biomarkers in clinical practice.

    Science.gov (United States)

    Andreucci, Michele; Faga, Teresa; Pisani, Antonio; Perticone, Maria; Michael, Ashour

    2017-04-01

    The term Acute Renal Failure (ARF) has been replaced by the term Acute Kidney Injury (AKI). AKI indicates an abrupt (within 24-48h) decrease in Glomerular Filtraton Rate, due to renal damage, that causes fluid and metabolic waste retention and alteration of electrolyte and acid-base balance. The renal biomarkers of AKI are substances or processes that are indicators of normal or impaired function of the kidney. The most used renal biomarker is still serum creatinine that is inadequate for several reasons, one of which is its inability to differentiate between hemodynamic changes of renal function ("prerenal azotemia") from intrinsic renal failure or obstructive nephropathy. Cystatin C is no better in this respect. After the description of the pathophysiology of "prerenal azotemia" and of Acute Kidney Injury (AKI) due to ischemia or nephrotoxicity, the renal biomarkers are listed and described: urinary NAG, urinary and serum KIM-1, serum and urinary NGAL, urinary IL-18, urinary L-FABP, serum Midkine, urinary IGFBP7 and TIMP2, urinary α-GST and π-GST, urinary ɣGT and AP, urinary β2M, urinary RBP, serum and urinary miRNA. All have been shown to appear much earlier than the rise of serum Creatinine. Some of them have been demonstrated to predict the clinical outcomes of AKI, such as the need for initiation of dialysis and mortality.

  14. Outcome assessment of pregnancy-related acute kidney injury in Morocco: A national prospective study

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    Nadia Kabbali

    2015-01-01

    Full Text Available Acute kidney injury (AKI is a rare but life-threatening complication of pregnancy. The aim of this paper is to study the characteristics of acute AKI in pregnancy and to emphasize on its management modalities in Moroccan hospitals. This is a national prospective study performed over six months from July 1 to December 31 2010 on AKI developing in pregnant patients, both preand post-partum period. Patients with pre-existing kidney disease were excluded from the study. Outcome was considered unfavorable when complete recovery of renal function was not achieved and/or maternal death occurred. Forty-four patients were included in this study. They were 29.6 ± 6 years old and mostly illiterate (70.6%. Most AKI occurred in the post-partum period, with 66% of the cases occurring in those who did not receive antenatal care. The main etiologies were pre-eclampsia (28 cases, hemorrhagic shock (six cases and septic events (five cases. We noted three cases of acute fatty liver, one case of obstructive kidney injury and one case of lupus nephritis. Hemodialysis was necessary in 17 (38.6% cases. The outcome was favorable in 29 patients. The maternal mortality rate was 11.4%. Two poor prognostic factors were identified: Age over 38 years and sepsis. AKI is a severe complication of pregnancy in developing countries. Its prevention necessitates the improvement of the sanitary infrastructure and the establishment of the obligatory antenatal care.

  15. Outcome assessment of pregnancy-related acute kidney injury in Morocco: A national prospective study.

    Science.gov (United States)

    Kabbali, Nadia; Tachfouti, Nabil; Arrayhani, Mohammed; Harandou, Mustapha; Tagnaouti, Mounia; Bentata, Yassamine; Laouad, Inass; Ramdani, Benyounes; Bayahia, Rabia; Oualim, Zouhair; Houssaini, Tarik Sqalli

    2015-01-01

    Acute kidney injury (AKI) is a rare but life-threatening complication of pregnancy. The aim of this paper is to study the characteristics of acute AKI in pregnancy and to emphasize on its management modalities in Moroccan hospitals. This is a national prospective study performed over six months from July 1 to December 31 2010 on AKI developing in pregnant patients, both preand post-partum period. Patients with pre-existing kidney disease were excluded from the study. Outcome was considered unfavorable when complete recovery of renal function was not achieved and/or maternal death occurred. Forty-four patients were included in this study. They were 29.6 ± 6 years old and mostly illiterate (70.6%). Most AKI occurred in the post-partum period, with 66% of the cases occurring in those who did not receive antenatal care. The main etiologies were pre-eclampsia (28 cases), hemorrhagic shock (six cases) and septic events (five cases). We noted three cases of acute fatty liver, one case of obstructive kidney injury and one case of lupus nephritis. Hemodialysis was necessary in 17 (38.6%) cases. The outcome was favorable in 29 patients. The maternal mortality rate was 11.4%. Two poor prognostic factors were identified: Age over 38 years and sepsis. AKI is a severe complication of pregnancy in developing countries. Its prevention necessitates the improvement of the sanitary infrastructure and the establishment of the obligatory antenatal care.

  16. 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.

  17. Acute kidney injury after using contrast during cardiac catheterization in children with heart disease.

    Science.gov (United States)

    Hwang, Young Ju; Hyun, Myung Chul; Choi, Bong Seok; Chun, So Young; Cho, Min Hyun

    2014-08-01

    Acute kidney injury (AKI) is closely associated with the mortality of hospitalized patients and long-term development of chronic kidney disease, especially in children. The purpose of our study was to assess the evidence of contrast-induced AKI after cardiac catheterization in children with heart disease and evaluate the clinical usefulness of candidate biomarkers in AKI. A total of 26 children undergoing cardiac catheterization due to various heart diseases were selected and urine and blood samples were taken at 0 hr, 6 hr, 24 hr, and 48 hr after cardiac catheterization. Until 48 hr after cardiac catheterization, there was no significant increase in serum creatinine level in all patients. Unlike urine kidney injury molecule-1, IL-18 and neutrophil gelatinase-associated lipocalin, urine liver-type fatty acid-binding protein (L-FABP) level showed biphasic pattern and the significant difference in the levels of urine L-FABP between 24 and 48 hr. We suggest that urine L-FABP can be one of the useful biomarkers to detect subclinical AKI developed by the contrast before cardiac surgery.

  18. Increased urinary levels of podocyte glycoproteins, matrix metallopeptidases, inflammatory cytokines, and kidney injury biomarkers in women with preeclampsia.

    Science.gov (United States)

    Wang, Yuping; Gu, Yang; Loyd, Susan; Jia, Xiuyue; Groome, Lynn J

    2015-12-15

    To investigate kidney injury in preeclampsia, we analyzed 14 biomarkers in urine specimen from 4 groups of pregnant women (normotensive pregnant women and those with pregnancy complicated with chronic hypertension or mild or severe preeclampsia). These biomarkers included 1) podocyte glycoproteins nephrin and podocalyxin, 2) matrix metallopeptidase (MMP)-2 and MMP-9 and their inhibitor tissue inhibitor of metalloproteinase-2, 3) inflammatory molecules and cytokines soluble VCAM-1, TNF-α, soluble TNF receptor receptor-1, IL-6, IL-8, IL-10, and IL-18, and 4) kidney injury biomarkers neutrophil gelatinase-associated lipocalin and kidney injury molecule-1. Postpartum urine specimens (6-8 wk) from normotensive women and those with severe preeclampsia were also evaluated. We found that, first, urine levels of nephrin, MMP-2, MMP-9, and kidney injury molecule-1 were significantly higher before delivery in severe preeclampsia than normotensive groups. The increased levels were all reduced to levels similar to those of the normotensive control group in postpartum specimens from the severe preeclampsia group. Second, soluble VCAM-1, soluble TNF receptor-1, and neutrophil gelatinase-associated lipocalin levels were significantly increased in the severe preeclampsia group compared with the normotensive control group before delivery, but levels of these molecules were significantly reduced in postpartum specimens in both groups. Third, IL-6 and IL-8 levels were not different between preeclampsia and normotensive groups but significantly increased in pregnancy complicated with chronic hypertension. Finally, tissue inhibitor of metalloproteinase-2 and IL-18 levels were not different among the study groups before delivery but were significantly reduced in postpartum specimens from normotensive controls. Our results indicate that the kidney experiences an increased inflammatory response during pregnancy. Most interestingly, tubular epithelial cell injury may also occur in severe

  19. Myeloid cell-derived HIF attenuates inflammation in UUO-induced kidney injury

    Science.gov (United States)

    Kobayashi, Hanako; Gilbert, Victoria; Liu, Qingdu; Kapitsinou, Pinelopi P.; Unger, Travis L.; Rha, Jennifer; Rivella, Stefano; Schlöndorff, Detlef; Haase, Volker H.

    2012-01-01

    Renal fibrosis and inflammation are associated with hypoxia, and tissue pO2 plays a central role in modulating the progression of chronic kidney disease. Key mediators of cellular adaptation to hypoxia are hypoxia-inducible factor (HIF)-1 and -2. In the kidney they are expressed in a cell type-specific manner; to what degree activation of each homolog modulates renal fibrogenesis and inflammation has not been established. To address this issue, we used Cre-loxP recombination to activate or to delete both Hif-1 and Hif-2 either globally or cell type-specifically in myeloid cells. Global activation of Hif suppressed inflammation and fibrogenesis in mice subjected to unilateral ureteral obstruction, while activation of Hif in myeloid cells suppressed inflammation only. Suppression of inflammatory cell infiltration was associated with down-regulation of CC chemokine receptors in renal macrophages. Conversely, global deletion or myeloid-specific inactivation of Hif promoted inflammation. Furthermore, prolonged hypoxia suppressed the expression of multiple inflammatory molecules in non-injured kidneys. Collectively, we provide experimental evidence that hypoxia and/or myeloid cell-specific HIF activation attenuates renal inflammation associated with chronic kidney injury. PMID:22490864

  20. Intravenous injection of Xuebijing attenuates acute kidney injury in rats with paraquat intoxication

    Science.gov (United States)

    Xu, Jia-jun; Zhen, Jian-tao; Tang, Li; Lin, Qing-ming

    2017-01-01

    BACKGROUND: The study aimed to investigate the therapeutic benefits of intravenous Xuebijing on acute kidney injury (AKI) in rats with paraquat intoxication. METHODS: Male Sprague-Dawley rats were randomly divided equally into three groups: sham group (n=8), paraquat group (n=8) and Xuebijing-treated group (n=8) using a random number table. The rats were intraperitoneally injected with 50 mg/kg of paraquat. One hour after paraquat administration, the rats were treated intravenously with Xuebijing (8 mL/kg). At 12 hours after paraquat administration, serum was collected to evaluate kidney function, then the rats were sacrificed and kidney samples were immediately harvested. AKI scores were evaluated by renal histopathology and pro-inflammatory cytokines mRNA levels in kidney were assayed using real-time RT-PCR. RESULTS: Serum urea nitrogen, creatinine and AKI scores were significantly higher in the paraquat group, compared with the sham group (Pparaquat group (Pparaquat group (Pparaquat poisoning by suppressing inflammatory response. PMID:28123623

  1. Toll-like receptor 4 regulates early endothelial activation during ischemic acute kidney injury

    Science.gov (United States)

    Chen, Jianlin; John, Reji; Richardson, James A.; Shelton, John M.; Zhou, Xin J.; Wang, Yanxia; Wu, Qing Qing; Hartono, John R.; Winterberg, Pamela D.; Lu, Christopher Y.

    2012-01-01

    Ischemic acute kidney injury (AKI) triggers an inflammatory response which exacerbates injury that requires increased expression of endothelial adhesion molecules. To study this further, we used in situ hybridization, immunohistology, and isolated endothelial cells, and found increased Toll-like receptor 4 (TLR4) expression on endothelial cells of the vasa rectae of the inner stripe of the outer medulla of the kidney 4 h after reperfusion. This increase was probably due to reactive oxygen species, known to be generated early during ischemic AKI, because the addition of hydrogen peroxide increased TLR4 expression in MS1 microvascular endothelial cells in vitro. Endothelial TLR4 may regulate adhesion molecule (CD54 and CD62E) expression as they were increased on endothelia of wild-type but not TLR4 knockout mice in vivo. Further, the addition of high-mobility group protein B1, a TLR4 ligand released by injured cells, increased adhesion molecule expression on endothelia isolated from wild-type but not TLR4 knockout mice. TLR4 was localized to proximal tubules in the cortex and outer medulla after 24 h of reperfusion. Thus, at least two different cell types express TLR4, each of which contributes to renal injury by temporally different mechanisms during ischemic AKI. PMID:20927041

  2. Non-Hodgkin's Lymphoma Primarily Presenting with Fanconi Syndrome and Acute Kidney Injury

    Institute of Scientific and Technical Information of China (English)

    Wen-ling Ye; Bing Han; Bing-yan Liu; Chan Meng; Wei Ye; Yu-bing Wen; Hang Li; Xue-mei Li

    2010-01-01

    @@ KIDNEY involvement is common in non-Hodg-kin's lymphoma (NHL) with incidence up to 30%-40% in autopsy studies. However, it us-ually occurs late in the course of the disease and is clinically silent. Clinically overt renal disease in-cluding acute kidney injury (AKI) as its primary manifes-tation is rarely reported, moreover, Fanconi syndrome (FS) is extremely rare as the main manifestation in NHL. In this report, we presented a case of NHL primarily presenting with FS and AKI due to diffuse interstitial infiltration of NHL cells and emphasized the important role of renal biopsy, especially renal immunohistochemical analysis in the di-agnosis of renal diffuse lymphoma.

  3. Acute kidney injury due to bilateral urolithiasis in pregnancy: a case report

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    Vineet Mishra

    2016-12-01

    Full Text Available Kidney stones are very common and unfortunately do not spare the pregnant population. Anatomical and pathophysiological changes occur in the pregnant females that alter the risk for development of urolithiasis. Acute renal colic during pregnancy is associated with significant potential risks to both mother and fetus. Diagnosis is often challenging because good imaging options without radiation use are limited. Management of diagnosed urolithiasis is unique in the pregnant population and requires multi-disciplinary care. Herein, we report a case of pregnancy which occurred in a state of pre-existing bilateral renal calculi with compromised renal function which subsequently developed into acute kidney injury, and requiring definitive management in the form of PCNL after termination of pregnancy. [Int J Reprod Contracept Obstet Gynecol 2016; 5(12.000: 4486-4490

  4. Acute kidney injury biomarkers: renal angina and the need for a renal troponin I

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    Goldstein Stuart L

    2011-12-01

    Full Text Available Abstract Acute kidney injury (AKI in hospitalized patients is independently associated with increased morbidity and mortality in pediatric and adult populations. Continued reliance on serum creatinine and urine output to diagnose AKI has resulted in our inability to provide successful therapeutic and supportive interventions to prevent and mitigate AKI and its effects. Research efforts over the last decade have focused on the discovery and validation of novel urinary biomarkers to detect AKI prior to a change in kidney function and to aid in the differential diagnosis of AKI. The aim of this article is to review the AKI biomarker literature with a focus on the context in which they should serve to add to the clinical context facing physicians caring for patients with, or at-risk for, AKI. The optimal and appropriate utilization of AKI biomarkers will only be realized by understanding their characteristics and placing reasonable expectations on their performance in the clinical arena.

  5. Thrombotic microangiopathies and acute kidney injury induced by artificial termination of pregnancy.

    Science.gov (United States)

    Wu, H; Zou, H B; Xu, Y; Zhang, L

    2014-01-01

    Thrombotic microangiopathy (TMA) is a rare, but potentially lethal condition requiring rapid recognition, diagnosis and initiation of therapy. Here, we present two cases of women with hemolytic anemia, thrombocytopenia and acute kidney injury shortly after surgical termination of pregnancy. Histological examination of their kidneys revealed endothelial cell swelling and luminal stenosis or fibrin-containing thrombi in the glomeruli and arterioles, which support the diagnosis of TMA. The patients were treated with hemodialysis, plasma infusion and corticosteroids with or without immunosuppressive agents. Three weeks after treatment, one patient was cured and symptoms of the other patient markedly improved. Reporting of more cases of TMA associated with surgical termination of pregnancy will provide further insights into this rare disease, possibly aiding in identifying risk factors and improving time to clinical diagnosis, treatment and prognosis.

  6. Foetal serum but not urinary β2-microglobulin correlates with histological injury to the kidney.

    Science.gov (United States)

    Luton, D; Delezoide, A L; Leguy, M C; Gobeaux, C; Vuillard, E; Grangé, G; Guibourdenche, J

    2013-10-01

    In a context of foetal obstructive uropathies, biochemical markers can be helpful to assess the renal function, but most studies to date have focused on their correlation with ultrasound findings and neonatal outcome. Our aim was to evaluate foetal β2-microglobulin as an index of histological injury to the kidney. β2-microglobulin was measured in serum and/or urine from 27 foetuses with bilateral obstructive uropathy, and compared to the findings of kidney examination following the termination of pregnancy. In serum, increased β2-microglobulin levels correlated to a decreased number of glomeruli, a reduction in the blastema and the presence of primitive ducts reflecting renal hypoplasia and dysplasia. However, elevated β2-microglobulin levels in the urine correlated only to a decreased number of glomeruli.

  7. 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.

  8. Quantification and localization of M2 macrophages in human kidneys with acute tubular injury

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    Palmer MB

    2014-11-01

    Full Text Available Matthew B Palmer,1 Alfred A Vichot,2 Lloyd G Cantley,2 Gilbert W Moeckel1 1Department of Pathology, Yale University School of Medicine, New Haven, CT, USA; 2Department of Medicine, Yale University School of Medicine, New Haven, CT, USA Abstract: This study addresses for the first time the question whether there is significant macrophage population in human kidney sections from patients with acute tubular injury (ATI. We examined therefore the interstitial macrophage population in human kidney tissue with biopsy-proven diagnosis of ATI, minimal change disease (MCD, and MCD with ATI. Kidney biopsies from patients with the above diagnoses were stained with antibodies directed against CD68 (general macrophage marker, CD163 (M2 marker, and HLA-DR (M1 marker and their respective electron microscopy samples were evaluated for the presence of interstitial macrophages. Our study shows that patients with ATI have significantly increased numbers of interstitial CD68+ macrophages, with an increase in both HLA-DR+ M1 macrophages and CD163+ M2 macrophages as compared to patients with MCD alone. Approximately 75% of macrophages were M2 (CD163+ whereas only 25% were M1 (HLA-DR+. M2 macrophages, which are believed to be critical for wound healing, were found to localize close to the tubular basement membrane of injured proximal tubule cells. Ultra structural examination showed close adherence of macrophages to the basement membrane of injured tubular epithelial cells. We conclude that macrophages accumulate around injured tubules following ATI and exhibit predominantly an M2 phenotype. We further speculate that macrophage-mediated repair may involve physical contact between the M2 macrophage and the injured tubular epithelial cell. Keywords: macrophages, acute kidney injury, CD163, HLA-DR, CD68, electron microscopy

  9. Comparison of Plasma and Urine Biomarker Performance in Acute Kidney Injury

    Science.gov (United States)

    Schley, Gunnar; Köberle, Carmen; Manuilova, Ekaterina; Rutz, Sandra; Forster, Christian; Weyand, Michael; Formentini, Ivan; Kientsch-Engel, Rosemarie; Eckardt, Kai-Uwe; Willam, Carsten

    2015-01-01

    Background New renal biomarkers measured in urine promise to increase specificity for risk stratification and early diagnosis of acute kidney injury (AKI) but concomitantly may be altered by urine concentration effects and chronic renal insufficiency. This study therefore directly compared the performance of AKI biomarkers in urine and plasma. Methods This single-center, prospective cohort study included 110 unselected adults undergoing cardiac surgery with cardiopulmonary bypass between 2009 and 2010. Plasma and/or urine concentrations of creatinine, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), liver fatty acid-binding protein (L-FABP), kidney injury molecule 1 (KIM1), and albumin as well as 15 additional biomarkers in plasma and urine were measured during the perioperative period. The primary outcome was AKI defined by AKIN serum creatinine criteria within 72 hours after surgery. Results Biomarkers in plasma showed markedly better discriminative performance for preoperative risk stratification and early postoperative (within 24h after surgery) detection of AKI than urine biomarkers. Discriminative power of urine biomarkers improved when concentrations were normalized to urinary creatinine, but urine biomarkers had still lower AUC values than plasma biomarkers. Best diagnostic performance 4h after surgery had plasma NGAL (AUC 0.83), cystatin C (0.76), MIG (0.74), and L-FAPB (0.73). Combinations of multiple biomarkers did not improve their diagnostic power. Preoperative clinical scoring systems (EuroSCORE and Cleveland Clinic Foundation Score) predicted the risk for AKI (AUC 0.76 and 0.71) and were not inferior to biomarkers. Preexisting chronic kidney disease limited the diagnostic performance of both plasma and urine biomarkers. Conclusions In our cohort plasma biomarkers had higher discriminative power for risk stratification and early diagnosis of AKI than urine biomarkers. For preoperative risk stratification of AKI clinical models showed

  10. Comparison of Plasma and Urine Biomarker Performance in Acute Kidney Injury.

    Directory of Open Access Journals (Sweden)

    Gunnar Schley

    Full Text Available New renal biomarkers measured in urine promise to increase specificity for risk stratification and early diagnosis of acute kidney injury (AKI but concomitantly may be altered by urine concentration effects and chronic renal insufficiency. This study therefore directly compared the performance of AKI biomarkers in urine and plasma.This single-center, prospective cohort study included 110 unselected adults undergoing cardiac surgery with cardiopulmonary bypass between 2009 and 2010. Plasma and/or urine concentrations of creatinine, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL, liver fatty acid-binding protein (L-FABP, kidney injury molecule 1 (KIM1, and albumin as well as 15 additional biomarkers in plasma and urine were measured during the perioperative period. The primary outcome was AKI defined by AKIN serum creatinine criteria within 72 hours after surgery.Biomarkers in plasma showed markedly better discriminative performance for preoperative risk stratification and early postoperative (within 24h after surgery detection of AKI than urine biomarkers. Discriminative power of urine biomarkers improved when concentrations were normalized to urinary creatinine, but urine biomarkers had still lower AUC values than plasma biomarkers. Best diagnostic performance 4h after surgery had plasma NGAL (AUC 0.83, cystatin C (0.76, MIG (0.74, and L-FAPB (0.73. Combinations of multiple biomarkers did not improve their diagnostic power. Preoperative clinical scoring systems (EuroSCORE and Cleveland Clinic Foundation Score predicted the risk for AKI (AUC 0.76 and 0.71 and were not inferior to biomarkers. Preexisting chronic kidney disease limited the diagnostic performance of both plasma and urine biomarkers.In our cohort plasma biomarkers had higher discriminative power for risk stratification and early diagnosis of AKI than urine biomarkers. For preoperative risk stratification of AKI clinical models showed similar discriminative performance

  11. 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.

  12. Comprehensive microRNA profiling in acetaminophen toxicity identifies novel circulating biomarkers for human liver and kidney injury.

    Science.gov (United States)

    Vliegenthart, A D B; Shaffer, J M; Clarke, J I; Peeters, L E J; Caporali, A; Bateman, D N; Wood, D M; Dargan, P I; Craig, D G; Moore, J K; Thompson, A I; Henderson, N C; Webb, D J; Sharkey, J; Antoine, D J; Park, B K; Bailey, M A; Lader, E; Simpson, K J; Dear, J W

    2015-10-22

    Our objective was to identify microRNA (miRNA) biomarkers of drug-induced liver and kidney injury by profiling the circulating miRNome in patients with acetaminophen overdose. Plasma miRNAs were quantified in age- and sex-matched overdose patients with (N = 27) and without (N = 27) organ injury (APAP-TOX and APAP-no TOX, respectively). Classifier miRNAs were tested in a separate cohort (N = 81). miRNA specificity was determined in non-acetaminophen liver injury and murine models. Sensitivity was tested by stratification of patients at hospital presentation (N = 67). From 1809 miRNAs, 75 were 3-fold or more increased and 46 were 3-fold or more decreased with APAP-TOX. A 16 miRNA classifier model accurately diagnosed APAP-TOX in the test cohort. In humans, the miRNAs with the largest increase (miR-122-5p, miR-885-5p, miR-151a-3p) and the highest rank in the classifier model (miR-382-5p) accurately reported non-acetaminophen liver injury and were unaffected by kidney injury. miR-122-5p was more sensitive than ALT for reporting liver injury at hospital presentation, especially combined with miR-483-3p. A miRNA panel was associated with human kidney dysfunction. In mice, miR-122-5p, miR-151a-3p and miR-382-5p specifically reported APAP toxicity - being unaffected by drug-induced kidney injury. Profiling of acetaminophen toxicity identified multiple miRNAs that report acute liver injury and potential biomarkers of drug-induced kidney injury.

  13. Vitamin D3 pretreatment alleviates renal oxidative stress in lipopolysaccharide-induced acute kidney injury.

    Science.gov (United States)

    Xu, Shen; Chen, Yuan-Hua; Tan, Zhu-Xia; Xie, Dong-Dong; Zhang, Cheng; Xia, Mi-Zhen; Wang, Hua; Zhao, Hui; Xu, De-Xiang; Yu, De-Xin

    2015-08-01

    Increasing evidence demonstrates that reactive oxygen species plays important roles in sepsis-induced acute kidney injury. This study investigated the effects of VitD3 pretreatment on renal oxidative stress in sepsis-induced acute kidney injury. Mice were intraperitoneally injected with lipopolysaccharide (LPS, 2.0mg/kg) to establish an animal model of sepsis-induced acute kidney injury. In VitD3+LPS group, mice were orally pretreated with three doses of VitD3 (25 μg/kg) at 1, 24 and 48 h before LPS injection. As expected, oral pretreatment with three daily recommended doses of VitD3 markedly elevated serum 25(OH)D concentration and efficiently activated renal VDR signaling. Interestingly, LPS-induced renal GSH depletion and lipid peroxidation were markedly alleviated in VitD3-pretreated mice. LPS-induced serum and renal nitric oxide (NO) production was obviously suppressed by VitD3 pretreatment. In addition, LPS-induced renal protein nitration, as determined by 3-nitrotyrosine residue, was obviously attenuated by VitD3 pretreatment. Further analysis showed that LPS-induced up-regulation of renal inducible nitric oxide synthase (inos) was repressed in VitD3-pretreated mice. LPS-induced up-regulation of renal p47phox and gp91phox, two NADPH oxidase subunits, were normalized by VitD3 pretreatment. In addition, LPS-induced down-regulation of renal superoxide dismutase (sod) 1 and sod2, two antioxidant enzyme genes, was reversed in VitD3-pretreated mice. Finally, LPS-induced tubular epithelial cell apoptosis, as determined by TUNEL, was alleviated by VitD3 pretreatment. Taken together, these results suggest that VitD3 pretreatment alleviates LPS-induced renal oxidative stress through regulating oxidant and antioxidant enzyme genes.

  14. PLASMA NEUTROPHIL GELATINASE ASSOCIATED LIPOCALIN AS AN EARLY BIOMARKER OF ACUTE KIDNEY INJURY IN SNAKE BITE

    Directory of Open Access Journals (Sweden)

    Thamarai

    2014-12-01

    Full Text Available INTRODUCTION: Acute kidney injury due to snake bite represents a frequent and devastating problem. Currently, Acute Kidney Injury is diagnosed by biochemical monitoring of increase in serum creatinine. Increase in serum creatinine represents a late indication of a functional change in glomerular function rate. Studies have shown that Neutrophil Gelatinase Associated Lipocalin has been found to be very useful for the detection of acute kidney injury within few hours of nephrotoxic insult. Limited information, however, is available regarding the study of plasma Neutrophil Gelatinase-Associated Lipocalin in snake bite. AIM: The purpose of the study was to estimate the diagnostic accuracy of plasma Neutrophil Gelatinase-Associated Lipocalin as an early biomarker of Acute Kidney Injury in patients with snake bite and to correlate with serum creatinine. If early detection of Acute Kidney Injury occurs, it can be followed by effective treatment modalities to abort the development or limit the severity of AKI. Therefore this study was designed to explore the importance of pNGAL in cases of snake bite induced AKI. MATERIALS AND METHODS: A prospective observational study was designed to study the patients admitted for the treatment of snakebite within 6 hours in a tertiary care hospital. Patients admitted for snake bite were followed by estimation of pNGAL on day 1 and serum creatinine from the period of admission for up to 5 days. A total of 130 snake bite patients were enrolled and 100 were included in the final study. Snake bite patients were classified into two groups based on the occurrence and absence of AKI. Plasma NGAL and serum creatinine was estimated by solid phase Enzyme Linked Immunosorbent Assay method and Jaffe`s method respectively. Data were entered into the excel sheet and analyzed statistically using statistical package for the social sciences (SPSS version 17. RESULTS:Among 100 snake bite patients 64 individuals had elevated p

  15. Protective effect of moxonidine on ischemia/reperfusion-induced acute kidney injury through α2/imidazoline I1 receptor.

    Science.gov (United States)

    Tsutsui, Hidenobu; Sugiura, Takahiro; Hayashi, Kentaro; Yukimura, Tokihito; Ohkita, Mamoru; Takaoka, Masanori; Matsumura, Yasuo

    2013-10-15

    Enhancement of renal sympathetic nerve activity during renal ischemia and norepinephrine overflow from the kidney after reperfusion play important roles in the development of ischemic acute kidney injury. Recently, we have found that moxonidine, an α2/imidazoline Ι1-receptor agonist, has preventive effects on ischemic acute kidney injury by suppressing the excitation of renal sympathetic nervous system after reperfusion. In the present study, to clarify the renoprotective mechanisms of moxonidine (360 nmol/kg, i.v.) against ischemic acute kidney injury, we investigated the effect of intravenous (i.v.) and intracerebroventricular (i.c.v.) injection of efaroxan, an α2/Ι1 receptor antagonist, on the moxonidine-exhibited actions. Ischemic acute kidney injury was induced by clamping the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. The suppressive effect of moxonidine on enhanced renal sympathetic nerve activity during renal ischemia was not observed in the rat treated with either i.v. (360 nmol/kg) or i.c.v. (36 nmol/kg) of efaroxan. Furthermore, i.v. injection of efaroxan eliminated the preventive effect of moxonidine on ischemia/reperfusion-induced kidney injury and norepinephrine overflow, and i.c.v. injection of efaroxan did not completely inhibit the moxonidine's effects. These results indicate that moxonidine prevents the ischemic kidney injury by sympathoinhibitory effect probably via α2/Ι1 receptors in central nervous system and by suppressing the norepinephrine overflow through α2/Ι1 receptors on sympathetic nerve endings.

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

    Science.gov (United States)

    Dhanapriya, J.; Gopalakrishnan, N.; Arun, V.; Dineshkumar, T.; Sakthirajan, R.; Balasubramaniyan, T.; Haris, M.

    2016-01-01

    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. PMID:27194836

  17. Acute kidney injury on admission to the intensive care unit: where to go from here?

    Science.gov (United States)

    Ostermann, Marlies

    2008-01-01

    Acute kidney injury (AKI) is a common problem, especially in critically ill patients. In Critical Care, Kolhe and colleagues report that 6.3% of 276,731 patients in 170 intensive care units (ICUs) in the UK had evidence of severe AKI within the first 24 hours of admission to ICU. ICU and hospital mortality as well as length of stay in hospital were significantly increased. In light of this serious burden on individuals and the health system in general, the following commentary discusses the current state of knowledge of AKI in ICU and calls for more attention to preventive strategies.

  18. Cardiac surgery-associated acute kidney injury in a developing country: Prevalence, risk factors and outcome

    OpenAIRE

    2015-01-01

    Little is known about cardiac surgery-associated acute kidney injury (CS-AKI) in children in developing regions of the world. The study aimed to determine the prevalence of CSAKI, associated factors and its impact on mortality and utilization of hospital services. The hospital records of children aged 0-17 years who underwent CS at an Indian hospital were reviewed. CS-AKI was defined as a rise in serum creatinine of ≥0.3 mg/dL in any 48 h and or by urine output

  19. Snake Bite-Induced Acute Kidney Injury: Report of a Successful Outcome during Pregnancy.

    Science.gov (United States)

    Vikrant, Sanjay; Parashar, Anupam

    2017-02-06

    Snake bite is an important health hazard in tropics. Snake envenomation in pregnancy may cause fetal death and maternal mortality or morbidity. However, little is known about the toxic effects and optimal management during pregnancy after snake envenomation because of the rarity of cases. Herein, we report a case of a pregnant woman who was successfully treated for snake bite-induced acute kidney injury during the third trimester. She was treated with equine-derived polyvalent anti-snake venom without development of any adverse effects, hemodialysis, and supportive therapy. She fully recovered and subsequently gave birth to a healthy child.

  20. Herpes labialis in patients with Russell's viper bite and acute kidney injury: a single center experience.

    Science.gov (United States)

    Waikhom, Rajesh; Sapam, Ranjeeta; Patil, Krishna; Jadhav, Jaya Prada; Sircar, Dipankar; Roychowdhury, Arpita; Dasgupta, Sanjay; Pandey, Rajendra

    2011-06-01

    Snake bite is an important health hazard in tropical countries and is associated with significant morbidity and mortality. Herpes labialis is a common ailment caused by the Herpes simplex virus. There is no published data showing any association between the snake bite and development of Herpes labialis. Here, we present a series of patients who developed Herpes labialis after Russell's viper bite and had acute kidney injury. We attempted to find whether snake bite is an immunosuppressed state and whether it could have pre-disposed the patients to the development of these lesions.

  1. EARLY ALLOGRAFT DYSFUNCTION AND ACUTE KIDNEY INJURY AFTER LIVER TRANSPLANTATION: DEFINITIONS, RISK FACTORS AND CLINICAL SIGNIFICANCE

    Directory of Open Access Journals (Sweden)

    L. Y. Moysyuk

    2012-01-01

    Full Text Available This review discusses issues related to intensive care in recipients of transplanted liver in the early postoperative period, with an emphasis on contemporary conditions and attitudes that are specific for this group of patients. Early allograft dysfunction (EAD requires immediate diagnosis and appropriate treatment in case. The causes of the EAD and therapeutic tactics are discussed. Acute kidney injury (AKI and renal failure are common in patients after transplantation. We consider etiology, risk factors, diagnosis and treatment guidelines for AKI. The negative impact of EAD and AKI on the grafts survival and recipients is demonstrated. 

  2. Old drug new trick: levamisole-adulterated cocaine causing acute kidney injury.

    Science.gov (United States)

    Ammar, Abeer T; Livak, Mark; Witsil, Joanne C

    2015-02-01

    Levamisole is an agent previously used in humans and later withdrawn from the US drug market due to concerns of agranulocytosis.It is currently used as an adulterating agent in cocaine, bringing to light toxicities typically manifested by vasculitis and skin necrosis.We report a case of a 36-year-old crack cocaine user who presented with a purpuric rash on her face and limbs. Levamisole-induced vasculitis was suspected, and she therefore underwent an extensive work-up. In addition to these findings, she also presented with acute kidney injury of unknown etiology, which was later attributed to levamisoleadulterated cocaine.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Acute kidney injury mediated by oxidative stress in Egyptian horses with exertional rhabdomyolysis.

    Science.gov (United States)

    el-Ashker, Maged R

    2011-06-01

    The present study was carried out to evaluate the role of oxidative stress in the pathophysiologic process of acute renal failure associated with exertional rhabdomyolysis (ER) in Egyptian horses. ER was tentatively diagnosed in 31 Baladi horses based on case history, physical examination findings and confirmed by elevation of plasma creatine kinase (CK) and urine myoglobin concentrations. According to severity of the condition, the diseased horses were categorized into two main groups; the first group included 18 horses with minimal clinical signs and plasma CK horses with overt clinical signs and plasma CK >100 000 IU/L). It was found that plasma creatol (CTL) was positively correlated (p stress in renal injury associated with severe rhabdomyolysis in horses. It is suggested that exaggeration of oxidative stress associated with increased muscle membrane leakage plays a key role in acute kidney injury in Baladi horses with severe rhabdomyolysis.

  5. Acute Kidney Failure

    Science.gov (United States)

    ... out of balance. Acute kidney failure — also called acute renal failure or acute kidney injury — develops rapidly over ... 2015. Palevsky PM. Definition of acute kidney injury (acute renal failure). http://www.uptodate.com/home. Accessed April ...

  6. Topiramate as a rare cause of reversible Fanconi syndrome and acute kidney injury: a case report and literature review

    Directory of Open Access Journals (Sweden)

    Marcelle G. Meseeha

    2016-02-01

    Full Text Available Topiramate (TPM is a sulfa-derivative monosaccharide that has been used for multiple indications in the last several years. We describe a 53-year-old woman with known chronic kidney disease stage 2 and baseline creatinine of 1 mg/dL who developed acute kidney injury and proximal renal tubular dysfunction while on TPM for depression. The Naranjo Adverse Drug Reaction Probability Scale indicated a probable relationship (score of 6 between TPM and acute kidney injury as well as proximal tubular dysfunction; these renal conditions resolved on withdrawal of TPM. To our knowledge, this is the first report of such a scenario. Patients receiving TPM therapy should be closely monitored for evidence of kidney dysfunction and electrolyte abnormalities.

  7. Silencing of Histone Deacetylase 9 Expression in Podocytes Attenuates Kidney Injury in Diabetic Nephropathy

    Science.gov (United States)

    Liu, Feng; Zong, Ming; Wen, Xiaofei; Li, Xuezhu; Wang, Jun; Wang, Yi; Jiang, Wei; Li, Xiaojun; Guo, Zhongliang; Qi, Hualin

    2016-01-01

    Podocyte dysfunction is important in the onset and development of diabetic nephropathy (DN). Histone deacetylases (HDACs) have been recently proved to play critical roles in the pathogenesis of DN. As one subtype of the class IIa HDACs, HDAC9 is capable to repress/de-repress their target genes in tumor, inflammation, atherosclerosis and metabolic diseases. In the present study, we investigate whether HDAC9 is involved in the pathophysiologic process of DN, especially the podocyte injury. Firstly, we explored the expression patterns and localization of HDAC9 and found that HDAC9 expression was significantly up-regulated in high glucose (HG)-treated mouse podocytes, as well as kidney tissues from diabetic db/db mice and patients with DN. Secondly, knockdown of HDAC9 in mouse podocytes significantly suppressed HG-induced reactive oxygen species (ROS) generation, cell apoptosis and inflammation through JAK2/STAT3 pathway and reduced the podocytes injury by decreasing the expression levels of Nephrin and Podocin. Moreover, in diabetic db/db mice, silencing of HDAC9 attenuated the glomerulosclerosis, inflammatory cytokine release, podocyte apoptosis and renal injury. Collectively, these data indicate that HDAC9 may be involved in the process of DN, especially podocyte injury. Our study suggest that inhibition of HDAC9 may have a therapeutic potential in DN treatment. PMID:27633396

  8. Kidney injury molecule-1 expression is closely associated with renal allograft damage.

    Science.gov (United States)

    Song, Lianlian; Xue, Lijuan; Yu, Jinyu; Zhao, Jun; Zhang, Wenlan; Fu, Yaowen

    2013-08-01

    The aim of our study was to investigate the expression of kidney injury molecule-1 (KIM-1) in renal allograft biopsy samples and assess the clinical significance of its use as a biomarker for tissue damage. A total of 69 renal allograft biopsy samples from 17 patients with normal serum creatinine and 52 cases of increased serum creatinine were collected. They were divided into different groups according to the Banff 2007 diagnostic criteria. KIM-1 expression was detected by immunohistochemical methods and the association of KIM-1 and blood biochemical indexes was analyzed. KIM-1 expression increased as Banff 2007 classification grade increased and was positively correlated with tubular inflammation severity in the acute T-cell rejection group. Moreover, KIM-1 expression was strongly positive in the chronic active antibody-mediated rejection group. Interestingly, KIM-1 was weakly positive in the normal group without obvious acute rejection and injury of immunosuppressant toxicity. In this group, 27.3% (3/11) of the cases with normal serum creatinine level showed weakly positive KIM-1 expression in their renal tissues. KIM-1 expression level is positively correlated with renal allograft damage and tubular cell injury. KIM-1 is expressed in tubular epithelial cells before blood biochemical indexes become elevated and morphological changes occur. KIM-1 expression is an early, sensitive, and specific biomarker to determine renal tubular epithelial cell injury in renal allograft tissue.

  9. Systems Toxicology of Chemically Induced Liver and Kidney Injuries: Histopathology-Associated Gene Co-Expression Modules

    Science.gov (United States)

    2016-01-04

    Balanced Accuracy or ½ (Sen+ Spc). J. A. Te et al. 1144whereas triamterene is an acute nephrotoxicant known to cause nephropathy (Nasr et al., 2014...liver and kidney injuries and may provide a rational basis for identifying and developing poten- tial biomarkers for diagnosis or prognosis. For...10.1111/j.1440-1746.2009.06187.x. Nasr SH, Milliner DS, Wooldridge TD, Sethi S. 2014. Triamterene crystalline nephropathy . Am. J. Kidney Dis. 63: 148–152

  10. Contrast-Induced Acute Kidney Injury: Short and Long-term Implications

    Science.gov (United States)

    Weisbord, Steven D.; Palevsky, Paul M.

    2011-01-01

    The intravascular administration of iodine-based contrast media remains a common cause of acute kidney injury and a leading cause of iatrogenic renal disease. Past research has elucidated the principal risk factors for contrast-induced acute kidney injury (CIAKI) and helped to establish the efficacy of various interventions for the prevention of this condition. The importance of preventing CIAKI has been underscored by a growing number of studies demonstrating strong associations of CIAKI with serious, adverse short and long-term outcomes. However, it remains unclear whether these associations are causal. This is important as considerable healthcare resources are used to prevent CIAKI. If CIAKI is a marker, but not a mediator, of serious, adverse downstream outcomes, more judicious and selective utilization of preventive care may be appropriate. Moreover, with an increasing number of studies reporting the under-utilization of coronary angiography in patients with acute coronary syndrome and underlying CKD, presumably due in part out of a fear of CIAKI, a clear understanding of whether this condition directly results in adverse downstream outcomes is essential. Careful inspection of past studies that investigated the association of CIAKI with adverse short and long-term events sheds light on their strengths and weaknesses and provides insight into how future research may be better able to characterize the short and long-term implications of this iatrogenic condition. PMID:21784279

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

    Institute of Scientific and Technical Information of China (English)

    Fan Zhang

    2016-01-01

    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,BaxandCaspase3 mRNA also increased while the level ofBcl2 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. The postreperfusion syndrome is associated with acute kidney injury following donation after brain death liver transplantation.

    Science.gov (United States)

    Kalisvaart, Marit; de Haan, Jubi E; Hesselink, Dennis A; Polak, Wojciech G; Hansen, Bettina E; IJzermans, Jan N M; Gommers, Diederik; Metselaar, Herold J; de Jonge, Jeroen

    2016-11-19

    Acute kidney injury (AKI) is frequently observed after donation after brain death (DBD) liver transplantation (LT) and associated with impaired recipient survival and chronic kidney disease. Hepatic ischemia/reperfusion injury (IRI) is suggested to be an important factor in this process. The postreperfusion syndrome (PRS) is the first manifestation of severe hepatic IRI directly after reperfusion. We performed a retrospective study on the relation between hepatic IRI and PRS and their impact on AKI in 155 DBD LT recipients. Severity of hepatic IRI was measured by peak postoperative AST levels and PRS was defined as >30% decrease in MAP ≥1 min within 5 min after reperfusion. AKI was observed in 39% of the recipients. AKI was significantly more observed in recipients with PRS (53% vs. 32%; P = 0.013). Median peak AST level was higher in recipients with PRS (1388 vs. 771 U/l; P PRS as an independent factor for postoperative AKI (OR 2.28; 95% CI 1.06-4.99; P = 0.035). In conclusion, PRS reflects severe hepatic IRI and predicts AKI after DBD LT. PRS immediately after reperfusion is an early warning sign and creates opportunities to preserve postoperative renal function.

  13. Biphasic recruitment of microchimeric fetal mesenchymal cells in fibrosis following acute kidney injury.

    Science.gov (United States)

    Roy, Edwige; Seppanen, Elke; Ellis, Rebecca; Lee, Eddy S; Khosrotehrani, Kiarash; Khosroterani, Kiarash; Fisk, Nicholas M; Bou-Gharios, George

    2014-03-01

    Fetal microchimeric cells (FMCs) enter the maternal circulation and persist in tissue for decades. They have capacity to home to injured maternal tissue and differentiate along that tissue's lineage. This raises the question of the origin(s) of cells transferred to the mother during pregnancy. FMCs with a mesenchymal phenotype have been documented in several studies, which makes mesenchymal stem cells an attractive explanation for their broad plasticity. Here we assessed the recruitment and mesenchymal lineage contribution of FMCs in response to acute kidney fibrosis induced by aristolochic acid injection. Serial in vivo bioluminescence imaging revealed a biphasic recruitment of active collagen-producing FMCs during the repair process of injured kidney in post-partum wild-type mothers that had delivered transgenic pups expressing luciferase under the collagen type I-promoter. The presence of FMCs long-term post injury (day 60) was associated with profibrotic molecules (TGF-β/CTGF), serum urea levels, and collagen deposition. Immunostaining confirmed FMCs at short term (day 15) using post-partum wild-type mothers that had delivered green fluorescent protein-positive pups and suggested a mainly hematopoietic phenotype. We conclude that there is biphasic recruitment to, and activity of, FMCs at the injury site. Moreover, we identified five types of FMC, implicating them all in the reparative process at different stages of induced renal interstitial fibrosis.

  14. Pregnancy related acute kidney injury: A single center experience from the Kashmir Valley.

    Science.gov (United States)

    Najar, M Saleem; Shah, A Rashid; Wani, I A; Reshi, A Rashid; Banday, K A; Bhat, M Ashraf; Saldanha, C L

    2008-10-01

    All patients admitted with pregnancy related acute renal failure (PRAKI) from June 2005 to May 2007 were studied with respect to etiology, clinical features, and outcome of PRAKI. Of 569 cases of acute kidney injury (AKI), 40 (7.02%) cases were related to gestational problems; the age of the patients ranged from 15 to 45 years. Septic abortion was the most common cause of PRAKI, accounting for 20 (50%) cases of which 15 (75%) cases occurred in the first and five (25%) in the second trimester. Other causes were antepartum hemorrhage: six cases (15%), toxemia of pregnancy: six cases (15%), acute gastroenteritis: three cases (7.5%), postpartum hemorrhage: two cases (5%), acute pyelonephritis: two cases (5%), and postpartum, acute kidney injury: one case (2.5%). Dialysis was needed in 60% of the cases and mortality was observed in 20% of the cases. PRAKI continues to be a major concern in our society, causing a high maternal mortality. Septic abortion which has virtually disappeared from developed countries, continues to be a major cause of PRAKI in our society. Hence, there is a need to halt the practice of illegal abortions and improve antenatal care.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Sesamin Ameliorates High-Fat Diet–Induced Dyslipidemia and Kidney Injury by Reducing Oxidative Stress

    Science.gov (United States)

    Zhang, Ruijuan; Yu, Yan; Deng, Jianjun; Zhang, Chao; Zhang, Jinghua; Cheng, Yue; Luo, Xiaoqin; Han, Bei; Yang, Haixia

    2016-01-01

    The study explored the protective effect of sesamin against lipid-induced renal injury and hyperlipidemia in a rat model. An animal model of hyperlipidemia was established in Sprague-Dawley rats. Fifty-five adult Sprague-Dawley rats were divided into five groups. The control group was fed a standard diet, while the other four groups were fed a high-fat diet for 5 weeks to induce hyperlipidemia. Three groups received oral sesamin in doses of 40, 80, or 160 mg/(kg·day). Seven weeks later, the blood lipids, renal function, antioxidant enzyme activities, and hyperoxide levels in kidney tissues were measured. The renal pathological changes and expression levels of collagen type IV (Col-IV) and α-smooth muscle actin (α-SMA) were analyzed. The administration of sesamin improved the serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, apolipoprotein-B, oxidized-low-density lipoprotein, and serum creatinine levels in hyperlipidemic rats, while it increased the high-density lipoprotein cholesterol and apolipoprotein-A levels. Sesamin reduced the excretion of 24-h urinary protein and urinary albumin and downregulated α-SMA and Col-IV expression. Moreover, sesamin ameliorated the superoxide dismutase activity and reduced malondialdehyde levels in kidney tissue. Sesamin could mediate lipid metabolism and ameliorate renal injury caused by lipid metabolism disorders in a rat model of hyperlipidemia. PMID:27171111

  17. Sesamin Ameliorates High-Fat Diet-Induced Dyslipidemia and Kidney Injury by Reducing Oxidative Stress.

    Science.gov (United States)

    Zhang, Ruijuan; Yu, Yan; Deng, Jianjun; Zhang, Chao; Zhang, Jinghua; Cheng, Yue; Luo, Xiaoqin; Han, Bei; Yang, Haixia

    2016-05-09

    The study explored the protective effect of sesamin against lipid-induced renal injury and hyperlipidemia in a rat model. An animal model of hyperlipidemia was established in Sprague-Dawley rats. Fifty-five adult Sprague-Dawley rats were divided into five groups. The control group was fed a standard diet, while the other four groups were fed a high-fat diet for 5 weeks to induce hyperlipidemia. Three groups received oral sesamin in doses of 40, 80, or 160 mg/(kg·day). Seven weeks later, the blood lipids, renal function, antioxidant enzyme activities, and hyperoxide levels in kidney tissues were measured. The renal pathological changes and expression levels of collagen type IV (Col-IV) and α-smooth muscle actin (α-SMA) were analyzed. The administration of sesamin improved the serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, apolipoprotein-B, oxidized-low-density lipoprotein, and serum creatinine levels in hyperlipidemic rats, while it increased the high-density lipoprotein cholesterol and apolipoprotein-A levels. Sesamin reduced the excretion of 24-h urinary protein and urinary albumin and downregulated α-SMA and Col-IV expression. Moreover, sesamin ameliorated the superoxide dismutase activity and reduced malondialdehyde levels in kidney tissue. Sesamin could mediate lipid metabolism and ameliorate renal injury caused by lipid metabolism disorders in a rat model of hyperlipidemia.

  18. Sesamin Ameliorates High-Fat Diet–Induced Dyslipidemia and Kidney Injury by Reducing Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Ruijuan Zhang

    2016-05-01

    Full Text Available The study explored the protective effect of sesamin against lipid-induced renal injury and hyperlipidemia in a rat model. An animal model of hyperlipidemia was established in Sprague-Dawley rats. Fifty-five adult Sprague-Dawley rats were divided into five groups. The control group was fed a standard diet, while the other four groups were fed a high-fat diet for 5 weeks to induce hyperlipidemia. Three groups received oral sesamin in doses of 40, 80, or 160 mg/(kg·day. Seven weeks later, the blood lipids, renal function, antioxidant enzyme activities, and hyperoxide levels in kidney tissues were measured. The renal pathological changes and expression levels of collagen type IV (Col-IV and α-smooth muscle actin (α-SMA were analyzed. The administration of sesamin improved the serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, apolipoprotein-B, oxidized-low-density lipoprotein, and serum creatinine levels in hyperlipidemic rats, while it increased the high-density lipoprotein cholesterol and apolipoprotein-A levels. Sesamin reduced the excretion of 24-h urinary protein and urinary albumin and downregulated α-SMA and Col-IV expression. Moreover, sesamin ameliorated the superoxide dismutase activity and reduced malondialdehyde levels in kidney tissue. Sesamin could mediate lipid metabolism and ameliorate renal injury caused by lipid metabolism disorders in a rat model of hyperlipidemia.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. TRPC6 channel as an emerging determinant of the podocyte injury susceptibility in kidney diseases.

    Science.gov (United States)

    Ilatovskaya, Daria V; Staruschenko, Alexander

    2015-09-01

    Podocytes (terminally differentiated epithelial cells of the glomeruli) play a key role in the maintenance of glomerular structure and permeability and in the incipiency of various renal abnormalities. Injury to podocytes is considered a major contributor to the development of kidney disease as their loss causes proteinuria and progressive glomerulosclerosis. The physiological function of podocytes is critically dependent on proper intracellular calcium handling; excessive calcium influx in these cells may result in the effacement of foot processes, apoptosis, and subsequent glomeruli damage. One of the key proteins responsible for calcium flux in the podocytes is transient receptor potential cation channel, subfamily C, member 6 (TRPC6); a gain-of-function mutation in TRPC6 has been associated with the onset of the familial forms of focal segmental glomerulosclerosis (FSGS). Recent data also revealed a critical role of this channel in the onset of diabetic nephropathy. Therefore, major efforts of the research community have been recently dedicated to unraveling the TRPC6-dependent effects in the initiation of podocyte injury. This mini-review focuses on the TRPC6 channel in podocytes and colligates recent data in an attempt to shed some light on the mechanisms underlying the pathogenesis of TRPC6-mediated glomeruli damage and its potential role as a therapeutic target for the treatment of chronic kidney diseases.

  1. A Case of Primary Hypoparathyroidism Presenting with Acute Kidney Injury Secondary to Rhabdomyolysis

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    Abdullah Sumnu

    2016-01-01

    Full Text Available Hypoparathyroidism is the most common cause of symmetric calcification of the basal ganglia. Herein, a case of primary hypoparathyroidism with severe tetany, rhabdomyolysis, and acute kidney injury is presented. A 26-year-old male was admitted to the emergency clinic with leg pain and cramps, nausea, vomiting, and decreased amount of urine. He had been treated for epilepsy for the last 10 years. He was admitted to the emergency department for leg pain, cramping in the hands and legs, and agitation multiple times within the last six months. He was prescribed antidepressant and antipsychotic medications. He had a blood pressure of 150/90 mmHg, diffuse abdominal tenderness, and abdominal muscle rigidity on physical examination. Pathological laboratory findings were as follows: creatinine, 7.5 mg/dL, calcium, 3.7 mg/dL, alanine transaminase, 4349 U/L, aspartate transaminase, 5237 U/L, creatine phosphokinase, 262.000 U/L, and parathyroid hormone, 0 pg/mL. There were bilateral symmetrical calcifications in basal ganglia and the cerebellum on computerized tomography. He was diagnosed as primary hypoparathyroidism and acute kidney injury secondary to severe rhabdomyolysis. Brain calcifications, although rare, should be considered in dealing with patients with neurological symptoms, symmetrical cranial calcifications, and calcium metabolism abnormalities.

  2. Sex differences in ischemia/reperfusion-induced acute kidney injury are dependent on the renal sympathetic nervous system.

    Science.gov (United States)

    Tanaka, Ryosuke; Tsutsui, Hidenobu; Ohkita, Mamoru; Takaoka, Masanori; Yukimura, Tokihito; Matsumura, Yasuo

    2013-08-15

    Resistance to ischemic acute kidney injury has been shown to be higher in female rats than in male rats. We found that renal venous norepinephrine overflow after reperfusion played important roles in the development of ischemic acute kidney injury. In the present study, we investigated whether sex differences in the pathogenesis of ischemic acute kidney injury were derived from the renal sympathetic nervous system using male and female Sprague-Dawley rats. Ischemia/reperfusion-induced acute kidney injury was achieved by clamping the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal function was impaired after reperfusion in both male and female rats; however, renal dysfunction and histological damage were more severe in male rats than in female rats. Renal venous plasma norepinephrine levels after reperfusion were markedly elevated in male rats, but were not in female rats. These sex differences were eliminated by ovariectomy or treatment with tamoxifen, an estrogen receptor antagonist, in female rats. Furthermore, an intravenous injection of hexamethonium (25mg/kg), a ganglionic blocker, 5 min before ischemia suppressed the elevation in renal venous plasma norepinephrine levels after reperfusion, and attenuated renal dysfunction and histological damage in male rats, and ovariectomized and tamoxifen-treated female rats, but not in intact females. Thus, the present findings confirmed sex differences in the pathogenesis of ischemic acute kidney injury, and showed that the attenuation of ischemia/reperfusion-induced acute kidney injury observed in intact female rats may be dependent on depressing the renal sympathetic nervous system with endogenous estrogen.

  3. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury.

    Science.gov (United States)

    Palevsky, Paul M; Liu, Kathleen D; Brophy, Patrick D; Chawla, Lakhmir S; Parikh, Chirag R; Thakar, Charuhas V; Tolwani, Ashita J; Waikar, Sushrut S; Weisbord, Steven D

    2013-05-01

    In response to the recently released 2012 KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for acute kidney injury (AKI), the National Kidney Foundation organized a group of US experts in adult and pediatric AKI and critical care nephrology to review the recommendations and comment on their relevancy in the context of current US clinical practice and concerns. The first portion of the KDIGO guideline attempts to harmonize earlier consensus definitions and staging criteria for AKI. While the expert panel thought that the KDIGO definition and staging criteria are appropriate for defining the epidemiology of AKI and in the design of clinical trials, the panel concluded that there is insufficient evidence to support their widespread application to clinical care in the United States. The panel generally concurred with the remainder of the KDIGO guidelines that are focused on the prevention and pharmacologic and dialytic management of AKI, although noting the dearth of clinical trial evidence to provide strong evidence-based recommendations and the continued absence of effective therapies beyond hemodynamic optimization and avoidance of nephrotoxins for the prevention and treatment of AKI.

  4. Abrogation of plasminogen activator inhibitor-1-vitronectin interaction ameliorates acute kidney injury in murine endotoxemia.

    Directory of Open Access Journals (Sweden)

    Kamlesh K Gupta

    Full Text Available Sepsis-induced acute kidney injury (AKI contributes to the high mortality and morbidity in patients. Although the pathogenesis of AKI during sepsis is poorly understood, it is well accepted that plasminogen activator inhibitor-1 (PAI-1 and vitronectin (Vn are involved in AKI. However, the functional cooperation between PAI-1 and Vn in septic AKI has not been completely elucidated. To address this issue, mice were utilized lacking either PAI-1 (PAI-1-/- or expressing a PAI-1-mutant (PAI-1R101A/Q123K in which the interaction between PAI-1 and Vn is abrogated, while other functions of PAI-1 are retained. It was found that both PAI-1-/- and PAI-1R101A/Q123K mice are associated with decreased renal dysfunction, apoptosis, inflammation, and ERK activation as compared to wild-type (WT mice after LPS challenge. Also, PAI-1-/- mice showed attenuated fibrin deposition in the kidneys. Furthermore, a lack of PAI-1 or PAI-1-Vn interaction was found to be associated with an increase in activated Protein C (aPC in plasma. These results demonstrate that PAI-1, through its interaction with Vn, exerts multiple deleterious mechanisms to induce AKI. Therefore, targeting of the PAI-1-Vn interaction in kidney represents an appealing therapeutic strategy for the treatment of septic AKI by not only altering the fibrinolytic capacity but also regulating PC activity.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. The balance of powers: Redox regulation of fibrogenic pathways in kidney injury.

    Science.gov (United States)

    Okamura, Daryl M; Pennathur, Subramaniam

    2015-12-01

    Oxidative stress plays a central role in the pathogenesis of diverse chronic inflammatory disorders including diabetic complications, cardiovascular disease, aging, and chronic kidney disease (CKD). Patients with moderate to advanced CKD have markedly increased levels of oxidative stress and inflammation that likely contribute to the unacceptable high rates of morbidity and mortality in this patient population. Oxidative stress is defined as an imbalance of the generation of reactive oxygen species (ROS) in excess of the capacity of cells/tissues to detoxify or scavenge them. Such a state of oxidative stress may alter the structure/function of cellular macromolecules and tissues that eventually leads to organ dysfunction. The harmful effects of ROS have been largely attributed to its indiscriminate, stochastic effects on the oxidation of protein, lipids, or DNA but in many instances the oxidants target particular amino acid residues or lipid moieties. Oxidant mechanisms are intimately involved in cell signaling and are linked to several key redox-sensitive signaling pathways in fibrogenesis. Dysregulation of antioxidant mechanisms and overproduction of ROS not only promotes a fibrotic milieu but leads to mitochondrial dysfunction and further exacerbates kidney injury. Our studies support the hypothesis that unique reactive intermediates generated in localized microenvironments of vulnerable tissues such as the kidney activate fibrogenic pathways and promote end-organ damage. The ability to quantify these changes and assess response to therapies will be pivotal in understanding disease mechanisms and monitoring efficacy of therapy.

  7. Classical and remote post-conditioning effects on ischemia/reperfusion-induced acute oxidant kidney injury.

    Science.gov (United States)

    Kadkhodaee, Mehri; Najafi, Atefeh; Seifi, Behjat

    2014-11-01

    The present study aimed to analyze and compare the effects of classical and remote ischemic postconditioning (POC) on rat renal ischemia/reperfusion (IR)-induced acute kidney injury. After right nephrectomy, male rats were randomly assigned into four groups (n = 8). In the IR group, 45 min of left renal artery occlusion was induced followed by 24 h of reperfusion. In the classical POC group, after induction of 45 min ischemia, 4 cycles of 10 s of intermittent ischemia and reperfusion were applied to the kidney before complete restoring of renal blood. In the remote POC group, 4 cycles of 5 min ischemia and reperfusion of left femoral artery were applied after 45 min renal ischemia and right at the time of renal reperfusion. There was a reduction in renal function (increase in blood urea and creatinine) in the IR group. Application of both forms of POC prevented the IR-induced reduction in renal function and histology. There were also significant improvements in kidney oxidative stress status in both POC groups demonstrated by a reduction in malondialdehyde (MDA) formation and preservation of antioxidant levels comparing to the IR group. We concluded that both methods of POC have protective effects on renal function and histology possibly by a reduction in IR-induced oxidative stress.

  8. Vitamin D3 pretreatment regulates renal inflammatory responses during lipopolysaccharide-induced acute kidney injury.

    Science.gov (United States)

    Xu, Shen; Chen, Yuan-Hua; Tan, Zhu-Xia; Xie, Dong-Dong; Zhang, Cheng; Zhang, Zhi-Hui; Wang, Hua; Zhao, Hui; Yu, De-Xin; Xu, De-Xiang

    2015-12-22

    Vitamin D receptor (VDR) is highly expressed in human and mouse kidneys. Nevertheless, its functions remain obscure. This study investigated the effects of vitamin D3 (VitD3) pretreatment on renal inflammation during lipopolysaccharide (LPS)-induced acute kidney injury. Mice were intraperitoneally injected with LPS. In VitD3 + LPS group, mice were pretreated with VitD3 (25 μg/kg) at 48, 24 and 1 h before LPS injection. As expected, an obvious reduction of renal function and pathological damage was observed in LPS-treated mice. VitD3 pretreatment significantly alleviated LPS-induced reduction of renal function and pathological damage. Moreover, VitD3 pretreatment attenuated LPS-induced renal inflammatory cytokines, chemokines and adhesion molecules. In addition, pretreatment with 1,25(OH)2D3, the active form of VitD3, alleviated LPS-induced up-regulation of inflammatory cytokines and chemokines in human HK-2 cells, a renal tubular epithelial cell line, in a VDR-dependent manner. Further analysis showed that VitD3, which activated renal VDR, specifically repressed LPS-induced nuclear translocation of nuclear factor kappa B (NF-κB) p65 subunit in the renal tubules. LPS, which activated renal NF-κB, reciprocally suppressed renal VDR and its target gene. Moreover, VitD3 reinforced the physical interaction between renal VDR and NF-κB p65 subunit. These results provide a mechanistic explanation for VitD3-mediated anti-inflammatory activity during LPS-induced acute kidney injury.

  9. Epidemiology of acute kidney injury in intensive care septic patients based on the KDIGO guidelines

    Institute of Scientific and Technical Information of China (English)

    Peng Qianyi; Zhang Lina; Ai Yuhang; Zhang Lemeng

    2014-01-01

    Background Acute kidney injury (AKI) is a common complication of sepsis,which is associated with higher risks of adverse outcomes.Recently,kidney disease:improving global outcomes (KDIGO) recommended a new guideline forAKI,including a little modification on the AKI staging criteria.Methods This retrospective study included 211 septic patients admitted to the intensive care unit (ICU) at Xiangya Hospital,Central South University from January 2008 to January 2011.AKI was diagnosed and classified according to the KDIGO or acute kidney injury network (AKIN) criteria.Differences between the AKI and non-AKI groups for baseline characteristics,laboratory examinations,etiology,outcomes,as well as the risk factors for AKI and 28-day mortality were analyzed.The reliability of the KDIGO criteria was also evaluated by comparing it with the AKIN criteria.Results The overall incidence of AKI in septic patients was 47.9%,and the 28-day mortality was 32.7%.The incidence of AKI was significantly higher in patients with more severe sepsis.Indicators of hepatic and respiratory function were significantly worse in the AKI group.Furthermore,a higher proportion of patients were infected with Enterobacter cloacae in the AKI group.The independent risk factors for AKI were shock,the number of organ failures,blood urea nitrogen (BUN)levels,and the use of vasopressors.The independent risk factors for mortality were BUN and creatine kinase-MB (CK-MB)levels.Both the KDIGO criteria and the AKIN criteria were significantly associated with 28-day mortality.Conclusions The incidence and 28-day mortality of AKI were very high in ICU septic patients.Greater attention should be paid to AKI-induced hepatic and respiratory dysfunction in clinical practice.Patients with an intra-abdominal source of infection were more likely to develop AKI.KDIGO criteria are reliable in AKI staging.

  10. Hemodialysis among pregnancy related acute kidney injury patients: A single center experience in North-Western Nigeria.

    Science.gov (United States)

    Makusidi, A M; Liman, H M; Yakubu, A; Hassan, M; Isah, M D; Chijioke, A

    2016-09-01

    Pregnancy related acute kidney injury (PRAKI) patients that underwent hemodialysis (HD) between May 2007 and April 2015 were studied with specific reference to clinical features, laboratory values, duration of pregnancy at the diagnosis of acute kidney injury and outcome. It involved 38 patients aged between 15 and 30 years. The main clinical features were fever, edema and oliguria. The leading etiological factors included ante/postpartum hemorrhage, septic abortion, and toxemia of pregnancy. The majority of cases occurred during the third trimester. PRAKI is a dreaded complication of pregnancy with high morbidity and mortality. HD improved patient survival in our study.

  11. Metformin Protects Against Cisplatin-Induced Tubular Cell Apoptosis and Acute Kidney Injury via AMPKα-regulated Autophagy Induction.

    Science.gov (United States)

    Li, Jianzhong; Gui, Yuan; Ren, Jiafa; Liu, Xin; Feng, Ye; Zeng, Zhifeng; He, Weichun; Yang, Junwei; Dai, Chunsun

    2016-04-07

    Metformin, one of the most common prescriptions for patients with type 2 diabetes, is reported to protect the kidney from gentamicin-induced nephrotoxicity. However, the role and mechanisms for metformin in preventing cisplatin-induced nephrotoxicity remains largely unknown. In this study, a single intraperitoneal injection of cisplatin was employed to induce acute kidney injury (AKI) in CD1 mice. The mice exhibited severe kidney dysfunction and histological damage at day 2 after cisplatin injection. Pretreatment of metformin could markedly attenuate cisplatin-induced acute kidney injury, tubular cell apoptosis and inflammatory cell accumulation in the kidneys. Additionally, pretreatment of metformin could enhance both AMPKα phosphorylation and autophagy induction in the kidneys after cisplatin injection. In cultured NRK-52E cells, a rat kidney tubular cell line, metformin could stimulate AMPKα phosphorylation, induce autophagy and inhibit cisplatin-induced cell apoptosis. Blockade of either AMPKα activation or autophagy induction could largely abolish the protective effect of metformin in cisplatin-induced cell death. Together, this study demonstrated that metformin may protect against cisplatin-induced tubular cell apoptosis and AKI through stimulating AMPKα activation and autophagy induction in the tubular cells.

  12. Urinary L-FABP predicts poor outcomes in critically ill patients with early acute kidney injury.

    Science.gov (United States)

    Parr, Sharidan K; Clark, Amanda J; Bian, Aihua; Shintani, Ayumi K; Wickersham, Nancy E; Ware, Lorraine B; Ikizler, T Alp; Siew, Edward D

    2015-03-01

    Biomarker studies for early detection of acute kidney injury (AKI) have been limited by nonselective testing and uncertainties in using small changes in serum creatinine as a reference standard. Here we examine the ability of urine L-type fatty acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), and kidney injury molecule-1 (KIM-1) to predict injury progression, dialysis, or death within 7 days in critically ill adults with early AKI. Of 152 patients with known baseline creatinine examined, 36 experienced the composite outcome. Urine L-FABP demonstrated an area under the receiver-operating characteristic curve (AUC-ROC) of 0.79 (95% confidence interval 0.70-0.86), which improved to 0.82 (95% confidence interval 0.75-0.90) when added to the clinical model (AUC-ROC of 0.74). Urine NGAL, IL-18, and KIM-1 had AUC-ROCs of 0.65, 0.64, and 0.62, respectively, but did not significantly improve discrimination of the clinical model. The category-free net reclassification index improved with urine L-FABP (total net reclassification index for nonevents 31.0%) and urine NGAL (total net reclassification index for events 33.3%). However, only urine L-FABP significantly improved the integrated discrimination index. Thus, modest early changes in serum creatinine can help target biomarker measurement for determining prognosis with urine L-FABP, providing independent and additive prognostic information when combined with clinical predictors.

  13. bFGF and TGFβ expression in rat kidneys after ischemic/ reperfusional gut injury and its relationship with tissue repair

    Institute of Scientific and Technical Information of China (English)

    Yin Hui Yang; Xiao Bing Fu; Tong Zhu Sun; Li Xian Jiang; Xiao Man Gu

    2000-01-01

    @@ INTRODUCTION Intestinal ischemia/ reperfusion ( I/ R ) occur commonly in critically ill patients. It is well recognized that gut I/R may cause tissue damage and dysfunction of intestine, and induce remote organ injury including kidney, lung, and liver[1]. It may also lead to complications after severe burn or injury. Previous studies have focused on cellular elements, cytokines and inflammatory mediators.Relatively little attention has been paid endogenous protective mechanisms, I.e. The growth factors.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  15. A unified theory of sepsis-induced acute kidney injury: inflammation, microcirculatory dysfunction, bioenergetics, and the tubular cell adaptation to injury

    NARCIS (Netherlands)

    Gomez, H.; Ince, C.; Backer, D. de; Pickkers, P.; Payen, D.; Hotchkiss, J.; Kellum, J.A.

    2014-01-01

    Given that the leading clinical conditions associated with acute kidney injury (AKI), namely, sepsis, major surgery, heart failure, and hypovolemia, are all associated with shock, it is tempting to attribute all AKI to ischemia on the basis of macrohemodynamic changes. However, an increasing body of

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  18. PAX2与急慢性肾脏疾病研究进展%The role of PAX2 in acute kidney injury and chronic kidney disease

    Institute of Scientific and Technical Information of China (English)

    王秀丽; 赵成广(综述); 吴玉斌(审校)

    2016-01-01

    Paired box2 ( PAX2 ) is a transciption factor which mainly expressed in the developing kid-ney. Researches indicate that PAX2 promote the transcription through interactions with the adaptor PAX transac-tivation domain interacting protein(PTIP). Otherwise,PAX2 protein can lead to chromatin compaction and gene silencing through interactions with Grg4. PAX2 reexpressed in acute kidney injury and involved in promoting cell proliferation. Congenital PAX2 gene mutation is closely related to congenital abnormalies of the kidney and uri-nary tract. In chronic kidney disease,PAX2 promote proliferation and cyst formation. Here,the recent researches on the function of PAX2 and its role in acute kidney injury and chronic kidney disease are reviewed.%配对盒基因2(paired box2,PAX2)是一种核转录因子,表达在发育期肾脏。研究表明PAX2通过与PTIP的相互作用使染色质处于可转录状态,与Grg4的相互作用削弱了其与PTIP结合而抑制转录。 PAX2在急性肾损伤时再表达,参与促进细胞增殖修复。先天PAX2基因突变与先天性肾脏输尿管异常密切相关。在慢性肾脏疾病,PAX2起到促进增殖及囊肿形成的作用。该文就PAX2的功能及其在急性肾损伤和慢性肾脏疾病中作用的相关研究进行综述。

  19. Recovery of renal function after administration of adipose-tissue-derived stromal vascular fraction in rat model of acute kidney injury induced by ischemia/reperfusion injury.

    Science.gov (United States)

    Lee, Chunwoo; Jang, Myoung Jin; Kim, Bo Hyun; Park, Jin Young; You, Dalsan; Jeong, In Gab; Hong, Jun Hyuk; Kim, Choung-Soo

    2017-03-10

    Acute kidney injury (AKI) induced by ischemia/reperfusion (I/R) injury is a major challenge in critical care medicine. The purpose of this study is to determine the therapeutic effects of the adipose-tissue-derived stromal vascular fraction (SVF) and the optimal route for SVF delivery in a rat model of AKI induced by I/R injury. Fifty male Sprague-Dawley rats were randomly divided into five groups (10 animals per group): sham, nephrectomy control, I/R injury control, renal arterial SVF infusion and subcapsular SVF injection. To induce AKI by I/R injury, the left renal artery was clamped with a nontraumatic vascular clamp for 40 min, and the right kidney was removed. Rats receiving renal arterial infusion of SVF had a significantly reduced increase in serum creatinine compared with the I/R injury control group at 4 days after I/R injury. The glomerular filtration rate of the renal arterial SVF infusion group was maintained at a level similar to that of the sham and nephrectomy control groups at 14 days after I/R injury. Masson's trichrome staining showed significantly less fibrosis in the renal arterial SVF infusion group compared with that in the I/R injury control group in the outer stripe (P renal arterial SVF infusion and subcapsular SVF injection groups compared with the I/R injury control group in the outer stripe (P renal function is effectively rescued from AKI induced by I/R injury through the renal arterial administration of SVF in a rat model.

  20. 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

    2011-03-01

    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.

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

    Science.gov (United States)

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

    2014-05-15

    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 their homing patterns following administration to mice with ischemia-reperfusion (IR) injury using whole body bioluminescence imaging. The effect of MSCs on macrophage phenotype following direct and indirect coculture was assessed using qPCR. Human cytokine production was measured using multiplex arrays. After IR, MSCs homed to injured kidneys where they afforded protection indicated by decreased proximal tubule kidney injury molecule-1 expression, blood urea nitrogen, and serum creatinine levels. SDS-PAGE and immunofluorescence labeling revealed MSCs reduced collagen α1(I) and IV by day 7 post-IR. Gelatin zymography confirmed that MSC treatment significantly increased matrix metalloproteinase-9 activity in IR kidneys, which contributed to a reduction in total collagen. Following direct and indirect coculture, macrophages expressed genes indicative of an anti-inflammatory "M2" phenotype. MSC-derived human GM-CSF, EGF, CXCL1, IL-6, IL-8, MCP-1, PDGF-AA, and CCL5 were identified in culture supernatants. In conclusion, MSCs home to injured kidneys and promote repair, which may be mediated by their ability to promote M2 macrophage polarization.

  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. High Risk of Herpes Zoster among Patients with Advance Acute Kidney Injury--A Population-Based Study.

    Science.gov (United States)

    Yang, Wei-Shun; Hu, Fu-Chang; Chen, Meng-Kan; Ko, Wen-Je; Chen, Likwang; Wu, Kwan-Dun; Wu, Vin-Cent

    2015-09-03

    The risk for herpes zoster (HZ) in acute kidney injury (AKI) survivors was never explored. We identified 2,387 adults in the Taiwan National Health Insurance Research Database who recovered from dialysis-requiring AKI and matched them with non-recovery and non-AKI patients by propensity score. During a mean follow-up of 2.7 years, the incidences of HZ were 6.9, 8.2 and 4.8 episodes per 1,000 person-years in AKI-non-recovery, AKI-recovery and non-AKI group, respectively. The recovery group was more likely to develop herpes zoster than those without acute kidney injury [incidence-rate ratios 1.71, 95% confidence interval 1.16-2.52; p = 0.007]. Patients without acute kidney injury were less likely to develop herpes zoster than those AKI, recovered from dialysis or not (hazard ratio HR 0.66, 95% CI 0.46-0.95). Dialysis-requiring acute kidney injury poses a long-term risk of herpes zoster after hospital discharge. Even patients who have recovered from dialysis still carry a significantly higher risk of developing herpes zoster.

  4. Dialysis-requiring acute kidney injury in Denmark 2000-2012: time trends of incidence and prevalence of risk factors

    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...

  5. Trends in one-year outcomes of dialysis-requiring acute kidney injury in Denmark 2005-2012

    DEFF Research Database (Denmark)

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

    2016-01-01

    BACKGROUND: Dialysis-requiring acute kidney injury (AKI) is associated with substantial mortality and risk of end-stage renal disease (ESRD). Despite considerable growth in incidence of severe AKI, information pertaining to trends in outcomes remains limited. We evaluated time trends in one year ...

  6. A Meta-analysis of the Association of Estimated GFR, Albuminuria, Age, Race, and Sex With Acute Kidney Injury

    NARCIS (Netherlands)

    Grams, Morgan E.; Sang, Yingying; Ballew, Shoshana H.; Gansevoort, Ron T.; Kimm, Heejin; Kovesdy, Csaba P.; Naimark, David; Oien, Cecilia; Smith, David H.; Coresh, Josef; Sarnak, Mark J.; Stengel, Benedicte; Tonelli, Marcello; de Zeeuw, Dick; Bakker, Stephan J. L.; van der Harst, Pim; Heerspink, Hiddo J.; Hillege, Hans L.

    2015-01-01

    Background: Acute kidney injury (AKI) is a serious global public health problem. We aimed to quantify the risk of AKI associated with estimated glomerular filtration rate (eGFR), albuminuria (albumin-creatinine ratio [ACR]), age, sex, and race (African American and white). Study Design: Collaborativ

  7. Pharmacokinetics of cefotaxime in critically ill patients with acute kidney injury treated with continuous renal replacement therapy : a pilot study

    NARCIS (Netherlands)

    Koedijk, Joost B; Valk-Swinkels, Corinne G H; Rijpstra, Tom A; Touw, Daan J; Mulder, Paul G H; van der Voort, Peter H J; Van't Veer, Nils E; van der Meer, Nardo J M

    2016-01-01

    INTRODUCTION: The objective of this study is to describe the pharmacokinetics of cefotaxime (CTX) in critically ill patients with acute kidney injury (AKI) when treated with continuous renal replacement therapy (CRRT) in the Intensive Care Unit (ICU). MATERIALS AND METHODS: This single-center prospe

  8. Serum and urine cystatin C are poor biomarkers for acute kidney injury and renal replacement therapy

    NARCIS (Netherlands)

    A.A.N.M. Royakkers; J.C. Korevaar; J.D.E. van Suijlen; L.S. Hofstra; M.A. Kuiper; P.E. Spronk; M.J. Schultz; C.S.C. Bouman

    2011-01-01

    To evaluate whether cystatin C in serum (sCyC) and urine (uCyC) can predict early acute kidney injury (AKI) in a mixed heterogeneous intensive care unit (ICU), and also whether these biomarkers can predict the need for renal replacement therapy (RRT). Multicenter prospective observational cohort stu

  9. 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 thei

  10. Augmented inhibition from cannabinoid sensitive interneurons diminishes CA1 output after traumatic brain injury

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    Brian Neal Johnson

    2014-12-01

    Full Text Available The neurological impairments associated with traumatic brain injury include learning and memory deficits and increased risk of seizures. The hippocampus is critically involved in both of these phenomena and highly susceptible to damage by traumatic brain injury. To examine network activity in the hippocampal CA1 region after lateral fluid percussion injury, we used a combination of voltage sensitive dye, field potential and patch clamp recording in mouse hippocampal brain slices. When the stratum radiatum was stimulated in slices from injured mice we found decreased depolarization in stratum radiatum and increased hyperpolarization in stratum oriens, together with a decrease in the percentage of pyramidal neurons firing stimulus-evoked action potentials. Increased hyperpolarization in stratum oriens persisted when glutamatergic transmission was blocked. However, we found no changes in stratum oriens responses when the alveus was stimulated to directly activate stratum oriens. These results suggest that the increased stratum oriens hyperpolarization evoked by stratum radiatum stimulation was mediated by interneurons that have cell bodies and/or axons in stratum radiatum, and form synapses in stratum pyramidale and stratum oriens. A low concentration (100 nM of the synthetic cannabinoid WIN55,212-2,restored CA1 output in slices from injured animals. These findings support the hypothesis that increased GABAergic signaling by cannabinoid sensitive interneurons contributes to the reduced CA1 output following traumatic brain injury.

  11. Adenovirus-mediated eNOS expression augments liver injury after ischemia/reperfusion in mice.

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    Arun P Palanisamy

    Full Text Available Hepatic ischemia/reperfusion (l/R injury continues to be a critical problem. The role of nitric oxide in liver I/R injury is still controversial. This study examines the effect of endothelial nitric oxide synthase (eNOS over-expression on hepatic function following I/R. Adenovirus expressing human eNOS (Ad-eNOS was administered by tail vein injection into C57BL/6 mice. Control mice received either adenovirus expressing LacZ or vehicle only. Sixty minutes of total hepatic ischemia was performed 3 days after adenovirus treatment, and mice were sacrificed after 6 or 24 hrs of reperfusion to assess hepatic injury. eNOS over expression caused increased liver injury as evidenced by elevated AST and ALT levels and decreased hepatic ATP content. While necrosis was not pervasive in any group, TUNEL demonstrated significantly increased apoptosis in Ad-eNOS infected livers. Western blotting demonstrated increased levels of protein nitration and upregulation of the pro-apoptotic proteins bax and p53. Our data suggest that over-expression of eNOS is detrimental in the setting of hepatic I/R.

  12. Hantavirus: an infectious cause of acute kidney injury in the UK.

    Science.gov (United States)

    Adams, Kate; Jameson, Lisa; Meigh, Rolf; Brooks, Tim

    2014-07-17

    We present a case of an undifferentiated febrile illness in a 59-year-old man from East Yorkshire. He was initially treated for leptospirosis due to the fact that he had farm exposure and the findings of acute kidney injury (AKI), thrombocytopenia and a raised alanine transferase (ALT) on his initial blood results. Serology tests later proved him to have had another rodent-borne illness: hantavirus. An investigation by Public Health England (formerly known as Health Protection Agency) (PHE) went on to prove the presence of the same serotype of hantavirus in rats caught on the patient's property. After an initial deterioration, the patient made a relatively uneventful recovery and all his blood tests returned to normal levels.

  13. Reversible anuric acute kidney injury secondary to acute renal autoregulatory dysfunction.

    Science.gov (United States)

    Imbriano, Louis J; Maesaka, John K; Drakakis, James; Mattana, Joseph

    2014-02-01

    Autoregulation of glomerular capillary pressure via regulation of the resistances at the afferent and efferent arterioles plays a critical role in maintaining the glomerular filtration rate over a wide range of mean arterial pressure. Angiotensin II and prostaglandins are among the agents which contribute to autoregulation and drugs which interfere with these agents may have a substantial impact on afferent and efferent arteriolar resistance. We describe a patient who suffered an episode of anuric acute kidney injury following exposure to a nonsteroidal anti-inflammatory agent while on two diuretics, an angiotensin-converting enzyme inhibitor, and an angiotensin receptor blocker. The episode completely resolved and we review some of the mechanisms by which these events may have taken place and suggest the term "acute renal autoregulatory dysfunction" to describe this syndrome.

  14. [Disseminated intravascular coagulation and acute kidney injury requiring renal replacement therapy after diagnostic amniocentesis].

    Science.gov (United States)

    Ratković, Marina; Bašić-Jukić, Nikolina; Gledović, Branka; Radunović, Danilo

    2014-04-01

    Disseminated intravascular coagulation (DIC) is a very rare complication of amniocentesis. We present a case of a 33-year-old patient who developed DIC with acute respiratory distress syndrome and acute kidney injury after diagnostic amniocentesis. The patient required replacement of renal function for 59 days with continuous venovenous hemodiafiltration and later with hemodialysis. She was treated with heparin, fresh frozen plasma, platelets and cryoprecipitate. Her condition was further complicated with the development of intracranial hematoma. After 67 days of hospitalization, she was discharged from the hospital with serum creatinine 337 μmol/L. Three years later, her serum creatinine was 102 μmol/L, and she is currently in the 7th month of pregnancy.

  15. Acute kidney injury associated with androgenic steroids and nutritional supplements in bodybuilders†

    Science.gov (United States)

    Almukhtar, Safa E.; Abbas, Alaa A.; Muhealdeen, Dana N.; Hughson, Michael D.

    2015-01-01

    Four bodybuilders who injected anabolic steroids and ingested commercial protein (78–104 g/day) and creatine (15 g/day) products presented with serum creatinine levels between 229.84 and 335.92 µmol/L (2.6–3.8 mg/dL). Renal biopsies revealed acute tubular necrosis. Four weeks after discontinuing injections and supplements, serum creatinine was in the normal range and estimated glomerular filtration rate > 1.00 mL/s (60 mL/min), including two patients with biopsies showing >30% interstitial fibrosis and tubular atrophy. The findings highlight a risk for acute and potentially chronic kidney injury among young men abusing anabolic steroids and using excessive amounts of nutritional supplements. PMID:26251708

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

    Science.gov (United States)

    Keller, Anna K.; Hansen, Rie Schultz; Nørregaard, Rikke; Krag, Søren Palmelund; Møldrup, Ulla; Pedersen, Michael; Jespersen, Bente; Birn, Henrik

    2016-01-01

    Introduction 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. Methods 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. Results 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. Conclusions 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. PMID:27760220

  17. Defining the cause of death in hospitalised patients with acute kidney injury.

    Directory of Open Access Journals (Sweden)

    Nicholas M Selby

    Full Text Available BACKGROUND: The high mortality rates that follow the onset of acute kidney injury (AKI are well recognised. However, the mode of death in patients with AKI remains relatively under-studied, particularly in general hospitalised populations who represent the majority of those affected. We sought to describe the primary cause of death in a large group of prospectively identified patients with AKI. METHODS: All patients sustaining AKI at our centre between 1(st October 2010 and 31(st October 2011 were identified by real-time, hospital-wide, electronic AKI reporting based on the Acute Kidney Injury Network (AKIN diagnostic criteria. Using this system we are able to generate a prospective database of all AKI cases that includes demographic, outcome and hospital coding data. For those patients that died during hospital admission, cause of death was derived from the Medical Certificate of Cause of Death. RESULTS: During the study period there were 3,930 patients who sustained AKI; 62.0% had AKI stage 1, 20.6% had stage 2 and 17.4% stage 3. In-hospital mortality rate was 21.9% (859 patients. Cause of death could be identified in 93.4% of cases. There were three main disease categories accounting for three quarters of all mortality; sepsis (41.1%, cardiovascular disease (19.2% and malignancy (12.9%. The major diagnosis leading to sepsis was pneumonia, whilst cardiovascular death was largely a result of heart failure and ischaemic heart disease. AKI was the primary cause of death in only 3% of cases. CONCLUSIONS: Mortality associated with AKI remains high, although cause of death is usually concurrent illness. Specific strategies to improve outcomes may therefore need to target not just the management of AKI but also the most relevant co-existing conditions.

  18. 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.

  19. Acute kidney injury biomarkers for patients in a coronary care unit: a prospective cohort study.

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    Tien-Hsing Chen

    Full Text Available BACKGROUND: Renal dysfunction is an established predictor of all-cause mortality in intensive care units. This study analyzed the outcomes of coronary care unit (CCU patients and evaluated several biomarkers of acute kidney injury (AKI, including neutrophil gelatinase-associated lipocalin (NGAL, interleukin-18 (IL-18 and cystatin C (CysC on the first day of CCU admission. METHODOLOGY/PRINCIPAL FINDINGS: Serum and urinary samples collected from 150 patients in the coronary care unit of a tertiary care university hospital between September 2009 and August 2010 were tested for NGAL, IL-18 and CysC. Prospective demographic, clinical and laboratory data were evaluated as predictors of survival in this patient group. The most common cause of CCU admission was acute myocardial infarction (80%. According to Acute Kidney Injury Network criteria, 28.7% (43/150 of CCU patients had AKI of varying severity. Cumulative survival rates at 6-month follow-up following hospital discharge differed significantly (p<0.05 between patients with AKI versus those without AKI. For predicting AKI, serum CysC displayed an excellent areas under the receiver operating characteristic curve (AUROC (0.895 ± 0.031, p < 0.001. The overall 180-day survival rate was 88.7% (133/150. Multiple Cox logistic regression hazard analysis revealed that urinary NGAL, serum IL-18, Acute Physiology, Age and Chronic Health Evaluation II (APACHE II and sodium on CCU admission day one were independent risk factors for 6-month mortality. In terms of 6-month mortality, urinary NGAL had the best discriminatory power, the best Youden index, and the highest overall correctness of prediction. CONCLUSIONS: Our data showed that serum CysC has the best discriminative power for predicting AKI in CCU patients. However, urinary NGAL and serum IL-18 are associated with short-term mortality in these critically ill patients.

  20. Defining the incidence and risk factors of colistin-induced acute kidney injury by KDIGO criteria

    Science.gov (United States)

    Shields, Ryan K.; Anand, Rohit; Clarke, Lloyd G.; Paronish, Julie A.; Weirich, Matthew; Perone, Hanna; Kieserman, Jake; Freedy, Henry; Andrzejewski, Christina; Bonilla, Hector

    2017-01-01

    Background Acute kidney injury (AKI) remains a treatment-limiting toxicity of colistin. Recently developed clinical practice guidelines from the Kidney Disease: Improving Global Outcomes (KDIGO) group have harmonized definitions of AKI, but have not been widely applied to patients receiving colistin. Methods We retrospectively defined AKI by KDIGO definitions among adult patients receiving intravenous colistin for ≥ 3 days. Risk factors for AKI within 48 hours and 7 days of initiating colistin were determined by multivariable logistic regression. Results Among 249 patients treated with colistin, rates of AKI were 12% and 29% at 48 hours and 7 days, respectively. At 48 hours, patients in the intensive care unit were at increased risk for AKI. Within 7 days, colistin daily doses >5mg/kg, chronic liver disease, and concomitant vancomycin were independent predictors. Seven percent of patients required renal replacement therapy at a median of 5 days (range: 3–7) following colistin initiation. Conclusion Safe use of colistin is promoted by early detection of AKI with KDIGO criteria, avoiding nephrotoxins, and limiting duration of therapy. PMID:28267779

  1. SIRT1/3 Activation by Resveratrol Attenuates Acute Kidney Injury in a Septic Rat Model

    Science.gov (United States)

    Xu, Siqi; Wei, Siwei; Dai, Xingui

    2016-01-01

    Sepsis often results in damage to multiple organ systems, possibly due to severe mitochondrial dysfunction. Two members of the sirtuin family, SIRT1 and SIRT3, have been implicated in the reversal of mitochondrial damage. The aim of this study was to determine the role of SIRT1/3 in acute kidney injury (AKI) following sepsis in a septic rat model. After drug pretreatment and cecal ligation and puncture (CLP) model reproduction in the rats, we performed survival time evaluation and kidney tissue extraction and renal tubular epithelial cell (RTEC) isolation. We observed reduced SIRT1/3 activity, elevated acetylated SOD2 (ac-SOD2) levels and oxidative stress, and damaged mitochondria in RTECs following sepsis. Treatment with resveratrol (RSV), a chemical SIRT1 activator, effectively restored SIRT1/3 activity, reduced acetylated SOD2 levels, ameliorated oxidative stress and mitochondrial function of RTECs, and prolonged survival time. However, the beneficial effects of RSV were greatly abrogated by Ex527, a selective inhibitor of SIRT1. These results suggest a therapeutic role for SIRT1 in the reversal of AKI in septic rat, which may rely on SIRT3-mediated deacetylation of SOD2. SIRT1/3 activation could therefore be a promising therapeutic strategy to treat sepsis-associated AKI. PMID:28003866

  2. 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.

  3. 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.

  4. Serum metabolomic profiles from patients with acute kidney injury: a pilot study.

    Science.gov (United States)

    Sun, Jinchun; Shannon, Melissa; Ando, Yosuke; Schnackenberg, Laura K; Khan, Nasim A; Portilla, Didier; Beger, Richard D

    2012-04-15

    Low sensitivity of current clinical markers (serum creatinine and blood urea nitrogen (BUN)) in early stages of the development of acute kidney injury (AKI) limits their utility. Rapid LC/MS-based metabolic profiling of serum demonstrated in a pilot study that metabolomics could provide novel indicators of AKI. Metabolic profiles of serum samples from seventeen hospitalized patients with newly diagnosed AKI were compared with the profiles of serum from age-matched subjects with normal kidney function. Increases in acylcarnitines and amino acids (methionine, homocysteine, pyroglutamate, asymmetric dimethylarginine (ADMA), and phenylalanine) and a reduction in serum levels of arginine and several lysophosphatidyl cholines were observed in patients with AKI compared to healthy subjects. Increases in homocysteine, ADMA and pyroglutamate have been recognized as biomarkers of cardiovascular and renal disease, and acylcarnitines represent biomarkers of defective fatty acid oxidation. The results of this pilot study demonstrate the utility of metabolomics in the discovery of novel serum biomarkers that can facilitate the diagnosis and determine prognosis of AKI in hospitalized patients.

  5. 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.

  6. 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.

  7. Adipose-Derived Mesenchymal Stem Cell Protects Kidneys against Ischemia-Reperfusion Injury through Suppressing Oxidative Stress and Inflammatory Reaction

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    Chua Sarah

    2011-05-01

    Full Text Available Abstract Background Reactive oxygen species are important mediators exerting toxic effects on various organs during ischemia-reperfusion (IR injury. We hypothesized that adipose-derived mesenchymal stem cells (ADMSCs protect the kidney against oxidative stress and inflammatory stimuli in rat during renal IR injury. Methods Adult male Sprague-Dawley (SD rats (n = 24 were equally randomized into group 1 (sham control, group 2 (IR plus culture medium only, and group 3 (IR plus immediate intra-renal administration of 1.0 × 106 autologous ADMSCs, followed by intravenous ADMSCs at 6 h and 24 h after IR. The duration of ischemia was 1 h, followed by 72 hours of reperfusion before the animals were sacrificed. Results Serum creatinine and blood urea nitrogen levels and the degree of histological abnormalities were markedly lower in group 3 than in group 2 (all p Conclusion ADMSC therapy minimized kidney damage after IR injury through suppressing oxidative stress and inflammatory response.

  8. Professor Eric G.L. Bywaters, Acute Kidney Injury and the "forgotten" letter.

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    Almond, Michael

    2016-02-01

    The Bywaters seminal 1941 British Medical Journal paper on the crush syndrome was important both for its written content and for using a photomicrograph demonstrating pigmented casts in the renal tubules. He appeared to be reporting the first cases of renal failure secondary to crushing injuries. Most at this point would have been content yet Bywaters demonstrated both determination and humility by publishing a letter in the BMJ 4 months later. This letter, now almost forgotten and rarely referenced, significantly corrected his original paper. He identified that descriptions of the syndrome had been made before, not least by German pathologists in World War 1. The letter recognised various pathologists and surgeons, Colmers (1909) reporting on casualties from the Messina earthquake suffering from acute pressure necrosis and Frankenthal (1916) describing soldiers who had been buried in the trenches showing oedema, bloody urine and post mortem ischaemic muscle necrosis. Others were credited as describing similar cases in inaccessible journals or in "inaugural dissertations". Hackradt (1917) described injuries from burial with oedema of the leg and bloody urine containing albumin and casts, necropsy showed muscle necrosis and tubular degeneration in the kidneys with blood casts and Lewin (1919) described 3 similar cases. Bywaters subsequently credits Minami (1923) a Japanese dermatologist working in Germany for summarizing the literature and providing a description that tallied exactly with his own. Finally Bywaters puzzles why the standard textbooks on war surgery available in Great Britain and the U.S.A. in 1941 make no mention of this entity.

  9. Effects of salt restriction on renal growth and glomerular injury in rats with remnant kidneys.

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    Lax, D S; Benstein, J A; Tolbert, E; Dworkin, L D

    1992-06-01

    Male Munich-Wistar rats underwent right nephrectomy and infarction of two thirds of the left kidney. Rats were randomly assigned to ingest standard chow (REM) or a moderately salt restricted chow (LS). A third group of rats were fed the low salt diet and were injected with an androgen (LSA). Eight weeks after ablation, glomerular volume and glomerular capillary radius were markedly increased in REM. This increase was prevented by the low salt diet, however, the antihypertrophic effect of the diet was overcome by androgen. Values for glomerular volume and capillary radius were similar in LSA and REM. Morphologic studies revealed that approximately 25% of glomeruli were abnormal in REM. Much less injury was observed in salt restricted rats, however, the protective effect of the low salt diet was significantly abrogated when renal growth was stimulated in salt restricted rats by androgen. Micropuncture studies revealed that glomerular pressure was elevated in all three groups and not affected by diet or androgen. Serum cholesterol was also similar in the three groups. These findings indicate that renal and glomerular hypertrophy are correlated with the development of glomerular injury after reduction in renal mass and suggest that dietary salt restriction lessens renal damage, at least in part, by inhibiting compensatory renal growth.

  10. The role of tubuloglomerular feedback in the pathogenesis of acute kidney injury.

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    Singh, Prabhleen; Okusa, Mark D

    2011-01-01

    The mechanisms involved in reduction in glomerular filtration rate (GFR) in prerenal and intrarenal acute kidney injury (AKI) are not mutually exclusive and prerenal mechanisms continue to play a role in the pathogenesis of established intrarenal AKI. In nearly all forms of AKI, glomeruli are morphologically normal; therefore, the investigative efforts have focused on systemic and intrarenal mechanisms that lead to the failure of filtration at the glomerulus. There is observed and/or deductive evidence supporting the role of tubuloglomerular feedback in mediating the reduction in GFR in various forms of AKI. In prerenal AKI, the activation of various neurohormonal renal vasoconstrictors can increase the sensitivity and responsiveness of tubuloglomerular feedback. In different forms of intrarenal AKI, the varying degree of tubular injury is linked to filtration failure directly by mechanisms such as tubular obstruction or tubular backleak of solutes, or indirectly via the activation of tubuloglomerular feedback. Tubular obstruction or backleak of solutes, while readily understood, do not appear to be consistent features in experimental AKI and have a limited role in explaining the degree of impairment of GFR in human AKI. The functional connection between tubular damage and filtration failure mediated by tubuloglomerular feedback via alterations in nephron plasma flow and glomerular capillary hydrostatic pressure is more consistently observed or deduced from experimental data. It also explains the principal abnormality of increased preglomerular resistances, a pathogenic characteristic of both experimental and human AKI.

  11. Kidney injury biomarkers and urinary creatinine variability in nominally healthy adults.

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    Stiegel, M A; Pleil, J D; Sobus, J R; Angrish, M M; Morgan, M K

    2015-01-01

    Environmental exposure diagnostics use creatinine concentrations in urine aliquots as the internal standard for dilution normalization of all other excreted metabolites when urinary excretion rate data are not available. This is a reasonable approach for healthy adults as creatinine is a human metabolite that is continually produced in skeletal muscles and presumably excreted in the urine at a stable rate. However, creatinine also serves as a biomarker for glomerular filtration rate (efficiency) of the kidneys, so undiagnosed kidney function impairment could affect this commonly applied dilution calculation. The United States Environmental Protection Agency (US EPA) has recently conducted a study that collected approximately 2600 urine samples from 50 healthy adults, aged 19-50 years old, in North Carolina in 2009-2011. Urinary ancillary data (creatinine concentration, total void volume, elapsed time between voids), and participant demographic data (race, gender, height, and body weight) were collected. A representative subset of 280 urine samples from 29 participants was assayed using a new kidney injury panel (KIP). In this article, we investigated the relationships of KIP biomarkers within and between subjects and also calculated their interactions with measured creatinine levels. The aims of this work were to document the analytical methods (procedures, sensitivity, stability, etc.), provide summary statistics for the KIP biomarkers in "healthy" adults without diagnosed disease (distribution, fold range, central tendency, variance), and to develop an understanding as to how urinary creatinine level varies with respect to the individual KIP proteins. Results show that new instrumentation and data reduction methods have sufficient sensitivity to measure KIP levels in nominally healthy urine samples, that linear regression between creatinine concentration and urinary excretion explains only about 68% of variability, that KIP markers are poorly correlated with

  12. 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

  13. Changing picture of renal cortical necrosis in acute kidney injury in developing country.

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    Prakash, Jai; Singh, Vijay Pratap

    2015-11-06

    Renal cortical necrosis (RCN) is characterized by patchy or diffuse ischemic destruction of all the elements of renal cortex resulting from significantly diminished renal arterial perfusion due to vascular spasm and microvascular injury. In addition, direct endothelial injury particularly in setting of sepsis, eclampsia, haemolytic uremic syndrome (HUS) and snake bite may lead to endovascular thrombosis with subsequent renal ischemia. Progression to end stage renal disease is a rule in diffuse cortical necrosis. It is a rare cause of acute kidney injury (AKI) in developed countries with frequency of 1.9%-2% of all patients with AKI. In contrast, RCN incidence is higher in developing countries ranging between 6%-7% of all causes of AKI. Obstetric complications (septic abortion, puerperal sepsis, abruptio placentae, postpartum haemorrhage and eclampsia) are the main (60%-70%) causes of RCN in developing countries. The remaining 30%-40% cases of RCN are caused by non-obstetrical causes, mostly due to sepsis and HUS. The incidence of RCN ranges from 10% to 30% of all cases of obstetric AKI compared with only 5% in non-gravid patients. In the developed countries, RCN accounts for 2% of all cases of AKI in adults and more than 20% of AKI during the third trimester of pregnancy. The reported incidence of RCN in obstetrical AKI varies between 18%-42.8% in different Indian studies. However, the overall incidence of RCN in pregnancy related AKI has decreased from 20%-30% to 5% in the past two decades in India. Currently RCN accounts for 3% of all causes of AKI. The incidence of RCN in obstetrical AKI was 1.44% in our recent study. HUS is most common cause of RCN in non-obstetrical group, while puerperal sepsis is leading cause of RCN in obstetric group. Because of the catastrophic sequelae of RCN, its prevention and aggressive management should always be important for the better renal outcome and prognosis of the patients.

  14. Outcomes of acute kidney injury in children at Muhammad Husin Hospital, Palembang

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    Hertanti Indah Lestari

    2014-09-01

    Full Text Available Background Acute kidney injury (AKI is a common problem in hospitalized pediatric patients, with effects on morbidity and mortality. Objectives To assess for the incidence and common etiologies of AKI, as well as to review factors that affect patient outcomes at Muhammad Husin Hospital, Palembang. Methods We reviewed data from our nephrology registry from January 2010 to June 2013. Independent variables were age, stage and etiology of AKI, requirement of renal replacement therapy (RRT, and PICU admission. The dependent variable was patient outcomes, categorized as survived or died. Association between clinical data and outcomes were analyzed by Chi-square test. Results The incidence of AKI was 28.3%. Using the pediatric risk, injury, failure, loss, end stage renal disease (pRrIFLEle criteria, 65 (36.7% patients were in the risk stage, 56 (31.6% in the injury stage, and 56 (31.6% in the failure stage. Twelve (6.8% patients required RRT and 29 (16.4% patients were admitted to the PICU. The mortality rate from AKI was 20.9%. The common etiologies of AKI were acute glomerulonephritis (55 subjects; 31.1%, multiple organ dysfunction (24 subjects; 13.6%, dehydration (23 subjects; 13.0%, hypoalbuminemia (20 subjects; 11.3%, heart failure (11 subjects; 6.2% and nephrotoxic agents (12 subjects; 6.8%. The mortality rate was significantly higher in children of younger age (<5 years (P=0.0001, in the failure stage of AKI (P=0.014, with non-renal origin of illness (P=0.0001 and those with an indication for PICU admission (P=0.0001. Conclusion AKI is found in one-third of nephrology patients. The most common etiology of AKI is acute glomerulonephritis. One-fifth of patients with AKI do not survive. Recognition of risk factors and detection of AKI in early stages might improve patient outcomes. [Paediatr Indones. 2014;54:266-72.].

  15. Involvement of the Hippo pathway in regeneration and fibrogenesis after ischaemic acute kidney injury: YAP is the key effector.

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    Xu, Jing; Li, Pei-Xue; Wu, Jun; Gao, Yi-Jun; Yin, Meng-Xin; Lin, Ye; Yang, Ming; Chen, Dong-Ping; Sun, Hai-Peng; Liu, Zeng-Bo; Gu, Xiang-Chen; Huang, Hong-Ling; Fu, Li-Li; Hu, Hui-Min; He, Liang-Liang; Wu, Wen-Qing; Fei, Zhao-Liang; Ji, Hong-Bin; Zhang, Lei; Mei, Chang-Lin

    2016-03-01

    Renal tubule cells can recover after they undergo AKI (acute kidney injury). An incomplete repair of renal tubules can result in progressive fibrotic CKD (chronic kidney disease). Studies have revealed the relationship between tubular epithelial cells and kidney fibrogenesis. However, the underlying mechanism remains unclear. Hippo pathway components were evaluated in complete/incomplete repair of I/R (ischaemia/reperfusion) AKI rat models, HK-2 cells and AKI human renal biopsy samples. We found that the expression levels of the Hippo pathway components changed dynamically during kidney regeneration and fibrogenesis in rat models of I/R-induced AKI and human renal biopsy samples. The transcription cofactor YAP (Yes-associated protein) might be a key effector of renal regeneration and fibrogenesis. Our results showed further that YAP might elicit both beneficial and detrimental effects on I/R AKI. After I/R injury occurred, YAP could promote the repair of the injured epithelia. The constant YAP increase and activation might be related to interstitial fibrosis and abnormal renal tubule differentiation. These results indicate that the proper modulation of the Hippo pathway, specifically the transcription cofactor YAP, during repair might be a potent therapeutic target in AKI-CKD transition after I/R injury.

  16. The evolution of nonimmune histological injury and its clinical relevance in adult-sized kidney grafts in pediatric recipients.

    Science.gov (United States)

    Naesens, M; Kambham, N; Concepcion, W; Salvatierra, O; Sarwal, M

    2007-11-01

    To describe the evolution, risk factors and impact of nonimmune histological injury after pediatric kidney transplantation, we analyzed 245 renal allograft protocol biopsies taken regularly from the time of transplantation to 2 years thereafter in 81 consecutive rejection-free pediatric recipients of an adult-sized kidney. Isometric tubular vacuolization was present early after transplantation was not progressive, and was associated with higher tacrolimus pre-dose trough levels. Chronic tubulo-interstitial damage and tubular microcalcifications were already noted at 3 months, were progressive and had a greater association with small recipient size, male donor gender, higher donor age and female recipient gender, but not with tacrolimus exposure. Renal function assessment showed that older recipients had a significant increase in absolute glomerular filtration rate with time after transplantation, which differed from small recipients who showed no increase. It is concluded that progressive, functionally relevant, nonimmune injury is detected early after adult-sized kidney transplantation in pediatric recipients. Renal graft ischemia associated with the donor-recipient size discrepancy appears to be a greater risk factor for this chronic histological injury, suggesting that the exploration of additional therapeutic approaches to increase allograft perfusion could further extend the graft survival benefit of adult-sized kidneys transplanted into small children.

  17. Correlation of serum neutrophil gelatinase-associated lipocalin with acute kidney injury in hypertensive disorders of pregnancy.

    Science.gov (United States)

    Patel, Ml; Sachan, Rekha; Gangwar, Radheyshyam; Sachan, Pushpalata; Natu, Sm

    2013-01-01

    Hypertensive disorders of pregnancy (HDP) remain one of the largest single causes of maternal and fetal morbidity and mortality, accounting for 16.1% of maternal deaths in developed countries. The aim of the study was to evaluate acute kidney injury (AKI) in hypertensive disorders of pregnancy and to examine the correlation of serum neutrophil gelatinase-associated lipocalin (NGAL) with acute kidney injury. This prospective case control study was carried out over a period of 1 year. After written, informed consent and ethical clearance, 149 cases of hypertensive disorders of pregnancy were screened, and seven were lost to follow-up. Acute kidney injury was detected in 88 cases and acute renal failure in 30 cases of HDP. Thirty-one healthy pregnant nonhypertensive women were enrolled as controls. Quantitative measurement of serum NGAL levels was done by enzyme linked immunosorbent assay technique using a sandwich enzyme-linked immunosorbent assay kit. As per the Kidney Diseases Improving Global Outcomes International guidelines acute kidney injury network (AKIN), 50 cases (42.37%) of AKI stage I, 38 (32.2%) cases of AKI stage II, and 30 (25.42%) cases of renal failure were detected. Serum NGAL had a positive association with increasing proteinuria. It also had a positive correlation with systolic blood pressure (r∼0.36), diastolic blood pressure (r∼0.37), and serum creatinine (r∼0.4). NGAL was found to be significantly correlated with creatinine in the cases with the value of the correlation coefficient being 0.4. This direct correlation might be a consequence of endothelial dysfunction on which hypertension and proteinuria probably depends.

  18. Sildenafil citrate for prophylaxis of nephropathy in an animal model of contrast-induced acute kidney injury.

    Science.gov (United States)

    Lauver, D Adam; Carey, E Grant; Bergin, Ingrid L; Lucchesi, Benedict R; Gurm, Hitinder S

    2014-01-01

    Contrast-induced acute kidney injury (CIAKI) is one of the commonest complications associated with contrast media (CM). Although the exact etiology of CIAKI remains unclear, one hypothesis involves vasoconstriction of afferent arterioles resulting in renal ischemia. Increased renal blood flow, therefore, might represent an attractive target for the treatment of CIAKI. In this study we evaluated the protective effects of the phosphodiesterase type 5 (PDE5) inhibitor, sildenafil citrate, in a rabbit model of CIAKI. New Zealand white rabbits were used due to their susceptibility to CIAKI. To evaluate the effects of sildenafil, the drug was administered before CM infusion and repeatedly throughout the remainder of the experiment (6 mg/kg, p.o.). Animals were sacrificed after 48 hours and kidneys were prepared for histological evaluation. Intravenous administration of CM produced marked kidney injury. Serum creatinine concentrations were elevated within two hours of the infusion and remained elevated for the duration of the experiment. Histological evaluation of the kidneys revealed significant tubular necrosis. The effects of the CM were dose dependent. Treatment with sildenafil was associated with lesser degree of histological injury, attenuation in markers of acute kidney injury (48 hour creatinine 1.54±0.21 versus 4.42±1.31 mg/dl, p<0.05) and reduction in electrolyte derangement (percent change in serum K+ at 48 hours 2.55±3.80% versus 15.53±4.47%, p<0.05; serum Na+ at 48 hours -0.14±0.26% versus -1.97±1.29%, p = 0.20). The results suggest a possible role for PDE5 inhibitors in the treatment of CIAKI and warrant further evaluation to determine the exact mechanism of protection.

  19. Hypomagnesemia is a risk factor for nonrecovery of renal function and mortality in AIDS patients with acute kidney injury.

    Science.gov (United States)

    Santos, M S Biagioni; Seguro, A C; Andrade, L

    2010-03-01

    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 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.

  20. 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.

  1. 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

  2. Deletion of Rac1GTPase in the Myeloid Lineage Protects against Inflammation-Mediated Kidney Injury in Mice.

    Science.gov (United States)

    Nagase, Miki; Kurihara, Hidetake; Aiba, Atsu; Young, Morag J; Sakai, Tatsuo

    2016-01-01

    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 suppressing

  3. Maximising Acute Kidney Injury Alerts--A Cross-Sectional Comparison with the Clinical Diagnosis.

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    Simon Sawhney

    Full Text Available Acute kidney injury (AKI is serious and widespread across healthcare (1 in 7 hospital admissions but recognition is often delayed causing avoidable harm. Nationwide automated biochemistry alerts for AKI stages 1-3 have been introduced in England to improve recognition. We explored how these alerts compared with clinical diagnosis in different hospital settings.We used a large population cohort of 4464 patients with renal impairment. Each patient had case-note review by a nephrologist, using RIFLE criteria to diagnose AKI and chronic kidney disease (CKD. We identified and staged AKI alerts using the new national NHS England AKI algorithm and compared this with nephrologist diagnosis across hospital settings.Of 4464 patients, 525 had RIFLE AKI, 449 had mild AKI, 2185 had CKD (without AKI and 1305 were of uncertain chronicity. NHS AKI algorithm criteria alerted for 90.5% of RIFLE AKI, 72.4% of mild AKI, 34.1% of uncertain cases and 14.0% of patients who actually had CKD.The algorithm identified AKI particularly well in intensive care (95.5% and nephrology (94.6%, but less well on surgical wards (86.4%. Restricting the algorithm to stage 2 and 3 alerts reduced the over-diagnosis of AKI in CKD patients from 14.0% to 2.1%, but missed or delayed alerts in two-thirds of RIFLE AKI patients.Automated AKI detection performed well across hospital settings, but was less sensitive on surgical wards. Clinicians should be mindful that restricting alerts to stages 2-3 may identify fewer CKD patients, but including stage 1 provides more sensitive and timely alerting.

  4. 4-Phenylbutyrate inhibits tunicamycin-induced acute kidney injury via CHOP/GADD153 repression.

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    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.

  5. Herbal Medicines for Acute Kidney Injury:Evidence, Gaps and Frontiers

    Institute of Scientific and Technical Information of China (English)

    Vale´ rian Bunel; Fan Qu; Pierre Duez; Qi-he Xu

    2015-01-01

    Acute kidney injury (AKI) is a major health threat worldwide. The literature on herbal intervention in AKI was searched from English and Chinese databases and reports were critically analyzed in terms of preventing AKI, promoting repair and regeneration, enhancing extrarenal clearance of uremic toxins, and preventing progression to chronic kidney disease (CKD). Altogether, 16 herbal formulae and a few extracts derived from individual herbs were reported to prevent or mitigate AKI in animal models induced by renal ischemia/reperfusion, cisplastin, gentamicin, glycerol, adenine, sepsis or physical exhaustion. Four formulae and six individual herbs were reported to accelerate recovery and/or to prevent CKD in established AKI animal models. Intrarectal herbal medicines, with or without simultaneous oral administration, were reported in six clinical trials and in an animal model to increase extrarenal clearance of uremic toxins. Additional 13 clinical trials reported oral or intravenous herbal interventions in AKI of different etiologies. Despite recurring problems, notably poor compliance with good practice guidelines for clinical trials and for authentication, naming and quality control of herbal materials, accumulating experimental data on the preventive effects of herbal medicines in AKI look encouraging and urge for better, definitive trials to guide clinical practice. Herbal enemas promoting extrarenal clearance of uremic toxins seem cost-effective, but better clinical evidence is certainly needed before any affirmative recommendation be made for AKI patients without access to dialysis. New frontiers, however, lie in those herbal remedies that promote repair/regeneration and prevent chronicity after AKI. Recent experimental data suggest that this may be possible.

  6. Acute kidney injury in Hemiscorpius lepturus scorpion stung children: Risk factors and clinical features

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    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.

  7. Epoxyeicosatrienoic acid analogue mitigates kidney injury in a rat model of radiation nephropathy.

    Science.gov (United States)

    Hye Khan, Md Abdul; Fish, Brian; Wahl, Geneva; Sharma, Amit; Falck, John R; Paudyal, Mahesh P; Moulder, John E; Imig, John D; Cohen, Eric P

    2016-04-01

    Arachidonic acid is metabolized to epoxyeicosatrienoic acids (EETs) by CYP epoxygenases, and EETs are kidney protective in multiple pathologies. We determined the ability of an EET analogue, EET-A, to mitigate experimental radiation nephropathy. The kidney expression of the EET producing enzyme CYP2C11 was lower in rats that received total body irradiation (TBI rat) compared with non-irradiated control. At 12 weeks after TBI, the rats had higher systolic blood pressure and impaired renal afferent arteriolar function compared with control, and EET-A or captopril mitigated these abnormalities. The TBI rats had 3-fold higher blood urea nitrogen (BUN) compared with control, and EET-A or captopril decreased BUN by 40-60%. The urine albumin/creatinine ratio was increased 94-fold in TBI rats, and EET-A or captopril attenuated that increase by 60-90%. In TBI rats, nephrinuria was elevated 30-fold and EET-A or captopril decreased it by 50-90%. Renal interstitial fibrosis, tubular and glomerular injury were present in the TBI rats, and each was decreased by EET-A or captopril. We further demonstrated elevated renal parenchymal apoptosis in TBI rats, which was mitigated by EET-A or captopril. Additional studies revealed that captopril or EET-A mitigated renal apoptosis by acting on the p53/Fas/FasL (Fas ligand) apoptotic pathway. The present study demonstrates a novel EET analogue-based strategy for mitigation of experimental radiation nephropathy by improving renal afferent arteriolar function and by decreasing renal apoptosis.

  8. Prehospitalization Risk Factors for Acute Kidney Injury during Hospitalization for Serious Infections in the REGARDS Cohort

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    Henry E. Wang

    2015-11-01

    Full Text Available Background/Aims: Acute kidney injury (AKI frequently occurs in hospitalized patients. In this study, we determined prehospitalization characteristics associated with AKI in community-dwelling adults hospitalized for a serious infection. Methods: We used prospective data from 30,239 participants of the Reasons for Geographic and Racial Differences in Stroke (REGARDS study, a national cohort of community-dwelling adults ≥45 years old. We identified serious infection hospitalizations between 2003 and 2012. Using the Kidney Disease Improving Global Outcomes (KDIGO criteria, we defined AKI as an increase in serum creatinine (sCr ≥0.3 mg/dl from the first inpatient sCr measurement during the first 7 hospitalization days. We excluded individuals with a history of renal transplant or preexisting end-stage renal disease as well as individuals with Results: Over a median follow-up of 4.5 years (interquartile range 2.4-6.3, we included 2,074 serious infection hospitalizations among 1,543 individuals. AKI occurred in 296 of 2,074 hospitalizations (16.5%. On multivariable analysis, prehospitalization characteristics independently associated with AKI among individuals hospitalized for a serious infection included a history of diabetes [odds ratio (OR 1.38; 95% CI 1.02-1.89], increased cystatin C (OR 1.73 per SD; 95% CI 1.20-2.50, and increased albumin-to-creatinine ratio (OR 1.19 per SD; 95% CI 1.007-1.40. Sex, race, hypertension, myocardial infarction, estimated glomerular filtration rate, high-sensitivity C-reactive protein, and the use of nonsteroidal anti-inflammatory, statin, or antihypertensive medications were not associated with AKI. Conclusions: Community-dwelling adults with a history of diabetes or increased cystatin C or albumin-to-creatinine ratio are at increased risk for AKI after hospitalization for a serious infection. These findings may be used to identify individuals at high risk for AKI.

  9. Urinary biomarkers in hexachloro-1:3-butadiene-induced acute kidney injury in the female Hanover Wistar rat; correlation of α-glutathione S-transferase, albumin and kidney injury molecule-1 with histopathology and gene expression.

    Science.gov (United States)

    Swain, Aubrey; Turton, John; Scudamore, Cheryl L; Pereira, Ines; Viswanathan, Neeti; Smyth, Rosemary; Munday, Michael; McClure, Fiona; Gandhi, Mitul; Sondh, Surjit; York, Malcolm

    2011-05-01

    Hexachloro-1:3-butadiene (HCBD) causes kidney injury specific to the pars recta of the proximal tubule. In the present studies, injury to the nephron was characterized at 24 h following a single dose of HCBD, using a range of quantitative urinary measurements, renal histopathology and gene expression. Multiplexed renal biomarker measurements were performed using both the Meso Scale Discovery (MSD) and Rules Based Medicine platforms. In a second study, rats were treated with a single nephrotoxic dose of HCBD and the time course release of a range of traditional and newer urinary biomarkers was followed over a 25 day period. Urinary albumin (a marker of both proximal tubular function and glomerular integrity) and α-glutathione S-transferase (α-GST, a proximal tubular cell marker of cytoplasmic leakage) showed the largest fold change at 24 h (day 1) after dosing. Most other markers measured on either the MSD or RBM platforms peaked on day 1 or 2 post-dosing, whereas levels of kidney injury molecule-1 (KIM-1), a marker of tubular regeneration, peaked on day 3/4. Therefore, in rat proximal tubular nephrotoxicity, the measurement of urinary albumin, α-GST and KIM-1 is recommended as they potentially provide useful information about the function, degree of damage and repair of the proximal tubule. Gene expression data provided useful confirmatory information regarding exposure of the kidney and liver to HCBD, and the response of these tissues to HCBD in terms of metabolism, oxidative stress, inflammation, and regeneration and repair.

  10. Correlation of serum neutrophil gelatinase-associated lipocalin with acute kidney injury in hypertensive disorders of pregnancy

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    Patel ML

    2013-10-01

    Full Text Available ML Patel,1 Rekha Sachan,2 Radheyshyam Gangwar,3 Pushpalata Sachan,4 SM Natu51Department of Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India; 2Department of Obstetrics and Gynaecology, King George's Medical University, Lucknow, Uttar Pradesh, India; 3Department of Critical Care, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India; 4Department of Physiology, King George's Medical University, Lucknow, Uttar Pradesh, India; 5Department of Pathology, King George's Medical University, Lucknow, Uttar Pradesh, IndiaAbstract: Hypertensive disorders of pregnancy (HDP remain one of the largest single causes of maternal and fetal morbidity and mortality, accounting for 16.1% of maternal deaths in developed countries. The aim of the study was to evaluate acute kidney injury (AKI in hypertensive disorders of pregnancy and to examine the correlation of serum neutrophil gelatinase-associated lipocalin (NGAL with acute kidney injury. This prospective case control study was carried out over a period of 1 year. After written, informed consent and ethical clearance, 149 cases of hypertensive disorders of pregnancy were screened, and seven were lost to follow-up. Acute kidney injury was detected in 88 cases and acute renal failure in 30 cases of HDP. Thirty-one healthy pregnant nonhypertensive women were enrolled as controls. Quantitative measurement of serum NGAL levels was done by enzyme linked immunosorbent assay technique using a sandwich enzyme-linked immunosorbent assay kit. As per the Kidney Diseases Improving Global Outcomes International guidelines acute kidney injury network (AKIN, 50 cases (42.37% of AKI stage I, 38 (32.2% cases of AKI stage II, and 30 (25.42% cases of renal failure were detected. Serum NGAL had a positive association with increasing proteinuria. It also had a positive correlation with systolic blood pressure (r~0.36, diastolic blood pressure (r~0.37, and serum creatinine (r~0

  11. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE of urinary protein in acute kidney injury

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    Sufi M Suhail

    2011-01-01

    Full Text Available Recent experimental and clinical studies have shown the importance of urinary proteomics in acute kidney injury (AKI. We analyzed the protein in urine of patients with clinical AKI using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE for its diagnostic value, and followed them up for 40 months to evaluate prognosis. Urine from 31 consecutive cases of AKI was analyzed with SDS-PAGE to determine the low, middle and high molecular weight proteins. Fractional excretion of sodium (FENa was estimated from serum and urine creatinine and sodium (Na. The cases were followed-up for 40 months from the end of the recruitment of study cases. Glomerular protein was higher in the hematuria group when compared with the non-hematuria group (P <0.04 and in the AKI group than in the acute on chronic renal failure (AKI-on-CRF group (P <0.002. Tubular protein was higher in the AKI-on-CRF group (P <0.003 than in the AKI group. Tubular protein correlated with FENa in groups with diabetes mellitus (DM, AKI-on-CRF, and without hematuria (P <0.03, P <0.02 and P <0.004, respectively. Pattern of protein did not differ between groups with and without DM and clinical acute tubular necrosis (ATN. At the end of 40 months follow-up, category with predominantly glomerular protein progressed to chronic renal failure (CRF or end-stage renal failure in higher proportion (P <0.05. In clinical AKI, we observed that glomerular protein dominated in cases with glomerular insult, as indicated by hematuria. Tubular protein was common in the study cases with CRF, DM and cases without hematuria. This indicates tubulo-interstitial injury for AKI in these cases. Patients with predominantly glomerular protein had an adverse outcome.

  12. Clinical value of renal injury biomarkers in diagnosis of chronic kidney disease

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    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.

  13. Hydrogen sulfide in posthemorrhagic shock mesenteric lymph drainage alleviates kidney injury in rats

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    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.

  14. Acute Lymphoblastic Leukemia in a Young Adult Presenting as Hepatitis and Acute Kidney Injury

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    Heincelman, Marc; Karakala, Nithin; Rockey, Don C.

    2016-01-01

    Acute lymphoblastic leukemia (ALL) in adults is a relatively rare malignancy. The typical presentation includes signs and symptoms associated with bone marrow failure, including fevers, infections, fatigue, and excessive bruising. In this article, we report an unusual systemic presentation of ALL in a previously healthy 18-year-old man. He initially presented with several-day history of nausea and vomiting, 10-pound weight loss, and right upper quadrant abdominal pain with evidence of acute hepatocellular liver injury (elevations in aspartate aminotransferase/alanine aminotransferase) and elevation in serum creatinine. Further history revealed that he just joined the Marine Corp; in preparation, he had been lifting weights and taking protein and creatine supplements. A complete serological evaluation for liver disease was negative and creatine phosphokinase was normal. His aspartate aminotransferase and alanine aminotransferase declined, and he was discharged with expected improvement. However, he returned one week later with continued symptoms and greater elevation of aminotransferases. Liver biopsy was nondiagnostic, revealing scattered portal and lobular inflammatory cells (primarily lymphocytes) felt to be consistent with drug-induced liver injury or viral hepatitis. Given his elevated creatinine, unresponsive to aggressive volume expansion, a kidney biopsy was performed, revealing normal histology. He subsequently developed an extensive left lower extremity deep venous thrombosis. Given his deep venous thrombosis, his peripheral blood was sent for flow cytometry, which revealed lymphoblasts. Bone marrow biopsy revealed 78% blasts with markers consistent with acute B-cell lymphoblastic leukemia. This report emphasizes that right upper quadrant abdominal pain with liver test abnormalities may be the initial presentation of a systemic illness such as ALL.

  15. Complete Blood Cell and HCO3 as a Predictor of Developing Acute Kidney Injury in Children

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    Yousefichaijan

    2016-11-01

    Full Text Available Background Acute kidney injury (AKI due to hypovolemia and gastroenteritis is still a common disease, especially among children in developing countries. The risk, injury, failure, loss, and end-stage renal disease (RIFLE classification is used as the estimated indicator of outcomes and incidence of AKI. Leukocytosis may be seen with systemic infectious, inflammatory diseases, and pyelonephritis. However, the cell blood count is unspecific. Some studies have shown the role of complete blood count in AKI as a useful predictive factor for mortality. We aimed at investigating cell blood count indexes and HCO3 in the prognosis of children with RIFLE criteria of AKI. Methods In this prospective study, 206 patients with AKI, who were admitted to Amir-Kabir emergency department, were investigated. The complete blood count, erythrocyte sedimentation rate, serum HCO3, and electrolytes of the patients were measured and compared. All patients were followed monthly for 4 months for renal function test and clinical manifestation. Data analysis was performed by SPSS Version 18 (IBM Corp., NY, US.. Mean, standard deviation, standard error, and frequency were used for descriptive analysis; and t-test, Chi-square, Mann-Whitney and Friedman tests were used for data analysis. Results There were no significant differences between the 4 groups in white blood cell count, hemoglobin, hematocrit, and ESR at baseline (P > 0.05. The number of platelet units was remarkably higher, but the number of MPV and HCO3 was considerably lower in patients with loss/ failure criteria. Conclusions MPV is higher in the case of platelets destruction, and this is commonly observed in inflammatory diseases. Metabolic acidosis is related to AKI and may lead to disorders such as hypotension, cardiac dysfunction, and mortality. HCO3, and MPV are likely to act as a predictor of the development of AKI. Conducting a multicenter study with a larger sample size and longer follow-up is suggested

  16. Hydrogen sulfide in posthemorrhagic shock mesenteric lymph drainage alleviates kidney injury in rats.

    Science.gov (United States)

    Han, B; Zhao, Z G; Zhang, L M; Li, S G; Niu, C Y

    2015-07-01

    Posthemorrhagic shock mesenteric lymph (PHSML) is a key factor in multiple organ injury following hemorrhagic shock. We investigated the role of hydrogen sulfide (H2S) 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 H2S, 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 H2S, CSE, TLR4, IL-10, IL-12, and TNF-α levels in renal tissue. PHSML drainage significantly reduced urea, creatinine, H2S, CSE, and TNF-α but not TLR4, IL-10, or IL-12. PPG decreased creatinine, H2S, 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 H2S and H2S-mediated inflammation.

  17. Hydrogen sulfide in posthemorrhagic shock mesenteric lymph drainage alleviates kidney injury in rats

    Directory of Open Access Journals (Sweden)

    B. Han

    2015-07-01

    Full Text Available Posthemorrhagic shock mesenteric lymph (PHSML is a key factor in multiple organ injury following hemorrhagic shock. We investigated the role of hydrogen sulfide (H2S 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 H2S, 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 H2S, CSE, TLR4, IL-10, IL-12, and TNF-α levels in renal tissue. PHSML drainage significantly reduced urea, creatinine, H2S, CSE, and TNF-α but not TLR4, IL-10, or IL-12. PPG decreased creatinine, H2S, 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 H2S and H2S-mediated inflammation.

  18. Mediation of calcium oxalate crystal growth on human kidney epithelial cells with different degrees of injury

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    Zhang Shen [Graduate School of Southern Medical University, Guangzhou 510515 (China); Institute of Biomineralization and Lithiasis Research, Jinan University, Guangzhou 510632 (China); Su Zexuan, E-mail: suz2008@126.com [The First Affiliated Hospital, Jinan University, Guangzhou 510632 (China); Yao Xiuqiong; Peng Hua; Deng Suiping [Institute of Biomineralization and Lithiasis Research, Jinan University, Guangzhou 510632 (China); Ouyang Jianming, E-mail: toyjm@jnu.edu.cn [Institute of Biomineralization and Lithiasis Research, Jinan University, Guangzhou 510632 (China)

    2012-05-01

    The current study examined the role of injured human kidney tubular epithelial cell (HKC) in the mediation of formation of calcium oxalate (CaOxa) crystals by means of scanning electronic microscopy and X-ray diffraction. HKC was injured using different concentrations of H{sub 2}O{sub 2}. Cell injury resulted in a significant decrease in cell viability and superoxide dismutase (SOD) concentration and an increase in the level of malondialdehyde (MDA) and expression of osteopontin (OPN). Injured cells not only promote nucleation and aggregation of CaOxa crystals, but also induce the formation of calcium oxalate monohydrate (COM) crystals that strongly adhere to cells. These results imply that injured HKCs promote stone formation by providing more nucleating sites for crystals, promoting the aggregation of crystals, and inducing the formation of COM crystals. - Graphical abstract: Injured cells promote nucleation and aggregation of CaOxa crystals, induce the formation of calcium oxalate monohydrate (COM) crystals. Highlights: Black-Right-Pointing-Pointer A direct nucleation and growth of CaOxa crystals on both normal and injured cells. Black-Right-Pointing-Pointer Stronger green fluorescence, i.e. OPN expression, was seen on the injury cell surface Black-Right-Pointing-Pointer Injured cells promote nucleation and aggregation of CaOxa crystals. Black-Right-Pointing-Pointer Injured cells induce the formation of calcium oxalate monohydrate crystals. Black-Right-Pointing-Pointer H{sub 2}O{sub 2} decrease cell viability in a dose-dependent manner at 0.1-1 mmol/L.

  19. 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.

  20. The first description of severe anemia associated with acute kidney injury and adult minimal change disease: a case report

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    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.

  1. High temporal resolution parametric MRI monitoring of the initial ischemia/reperfusion phase in experimental acute kidney injury.

    Science.gov (United States)

    Pohlmann, Andreas; Hentschel, Jan; Fechner, Mandy; Hoff, Uwe; Bubalo, Gordana; Arakelyan, Karen; Cantow, Kathleen; Seeliger, Erdmann; Flemming, Bert; Waiczies, Helmar; Waiczies, Sonia; Schunck, Wolf-Hagen; Dragun, Duska; Niendorf, Thoralf

    2013-01-01

    Ischemia/reperfusion (I/R) injury, a consequence of kidney hypoperfusion or temporary interruption of blood flow is a common cause of acute kidney injury (AKI). There is an unmet need to better understand the mechanisms operative during the initial phase of ischemic AKI. Non-invasive in vivo parametric magnetic resonance imaging (MRI) may elucidate spatio-temporal pathophysiological changes in the kidney by monitoring the MR relaxation parameters T2* and T2, which are known to be sensitive to blood oxygenation. The aim of our study was to establish the technical feasibility of fast continuous T2*/T2 mapping throughout renal I/R. MRI was combined with a remotely controlled I/R model and a segmentation model based semi-automated quantitative analysis. This technique enabled the detailed assessment of in vivo changes in all kidney regions during ischemia and early reperfusion. Significant changes in T2* and T2 were observed shortly after induction of renal ischemia and during the initial reperfusion phase. Our study demonstrated for the first time that continuous and high temporal resolution parametric MRI is feasible for in-vivo monitoring and characterization of I/R induced AKI in rats. This technique may help in the identification of the timeline of key events responsible for development of renal damage in hypoperfusion-induced AKI.

  2. High temporal resolution parametric MRI monitoring of the initial ischemia/reperfusion phase in experimental acute kidney injury.

    Directory of Open Access Journals (Sweden)

    Andreas Pohlmann

    Full Text Available Ischemia/reperfusion (I/R injury, a consequence of kidney hypoperfusion or temporary interruption of blood flow is a common cause of acute kidney injury (AKI. There is an unmet need to better understand the mechanisms operative during the initial phase of ischemic AKI. Non-invasive in vivo parametric magnetic resonance imaging (MRI may elucidate spatio-temporal pathophysiological changes in the kidney by monitoring the MR relaxation parameters T2* and T2, which are known to be sensitive to blood oxygenation. The aim of our study was to establish the technical feasibility of fast continuous T2*/T2 mapping throughout renal I/R. MRI was combined with a remotely controlled I/R model and a segmentation model based semi-automated quantitative analysis. This technique enabled the detailed assessment of in vivo changes in all kidney regions during ischemia and early reperfusion. Significant changes in T2* and T2 were observed shortly after induction of renal ischemia and during the initial reperfusion phase. Our study demonstrated for the first time that continuous and high temporal resolution parametric MRI is feasible for in-vivo monitoring and characterization of I/R induced AKI in rats. This technique may help in the identification of the timeline of key events responsible for development of renal damage in hypoperfusion-induced AKI.

  3. Cisplatin-Induced Non-Oliguric Acute Kidney Injury in a Pediatric Experimental Animal Model in Piglets.

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    Maria José Santiago

    Full Text Available To design an experimental pediatric animal model of acute kidney injury induced by cisplatin.Prospective comparative observational animal study in two different phases. Acute kidney injury was induced using three different doses of cisplatin (2, 3 and 5 mg/kg. The development of nephrotoxicity was assessed 2 to 4 days after cisplatin administration by estimating biochemical parameters, diuresis and renal morphology. Analytical values and renal morphology were compared between 15 piglets treated with cisplatin 3 mg/kg and 15 control piglets in the second phase of the study.41 piglets were studied. The dose of 3 mg/kg administered 48 hours before the experience induced a significant increase in serum creatinine and urea without an increase in potassium levels. Piglets treated with cisplatin 3 mg/kg had significantly higher values of creatinine, urea, phosphate and amylase, less diuresis and lower values of potassium, sodium and bicarbonate than control piglets. Histological findings showed evidence of a dose-dependent increase in renal damage.a dose of 3 mg/kg of cisplatin induces a significant alteration in renal function 48 hours after its administration, so it can be used as a pediatric animal model of non-oliguric acute kidney injury.

  4. 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.

  5. Thioredoxin-Interacting Protein Mediates NLRP3 Inflammasome Activation Involved in the Susceptibility to Ischemic Acute Kidney Injury in Diabetes

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    Ye Da Xiao

    2016-01-01

    Full Text Available Kidney in diabetic state is more sensitive to ischemic acute kidney injury (AKI. However, the underlying mechanisms remain unclear. Herein, we examined the impact of diabetes mellitus on thioredoxin-interacting protein (TXNIP expression and whether mediated NLRP3 activation was associated with renal ischemia/reperfusion- (I/R- induced AKI. In an in vivo model, streptozotocin-induced diabetic rats showed higher susceptibility to I/R injury with increased TXNIP expression, which was significantly attenuated by resveratrol (RES treatment (10 mg/kg intraperitoneal daily injection for 7 consecutive days prior to I/R induction. RES treatment significantly inhibited TXNIP binding to NLRP3 in diabetic rats subjected to renal I/R injury. Furthermore, RES treatment significantly reduced cleaved caspase-1 expression and production of IL-1β and IL-18. In an in vitro study using cultured human kidney proximal tubular cell (HK-2 cells in high glucose condition (HG, 30 mM subjected to hypoxia/reoxygenation (H/R, HG combined H/R (HH/R stimulated TXNIP expression which was accompanied by increased NLRP3 expression, ROS generation, caspase-1 activity and IL-1β levels, and aggravated HK-2 cells apoptosis. All these changes were significantly attenuated by TXNIP RNAi and RES treatment. In conclusion, our results demonstrate that TXNIP-mediated NLRP3 activation through oxidative stress is a key signaling mechanism in the susceptibility to AKI in diabetic models.

  6. Contrast-induced acute kidney injury: how much contrast is safe?

    LENUS (Irish Health Repository)

    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.

  7. Kidney injury, fluid, electrolyte and acid-base abnormalities in alcoholics.

    Science.gov (United States)

    Adewale, Adebayo; Ifudu, Onyekachi

    2014-03-01

    In the 21(st) century, alcoholism and the consequences of ethyl alcohol abuse are major public health concerns in the United States, affecting approximately 14 million people. Pertinent to the global impact of alcoholism is the World Health Organisation estimate that 140 million people worldwide suffer from alcohol dependence. Alcoholism and alcohol abuse are the third leading causes of preventable death in the United States. Alcohol dependence and alcohol abuse cost the United State an estimated US$220 billion in 2005, eclipsing the expense associated with cancer (US$196 billion) or obesity (US$133 billion). Orally ingested ethyl alcohol is absorbed rapidly without chemical change from the stomach and intestine, reaching maximum blood concentration in about an hour. Alcohol crosses capillary membranes by simple diffusion, affecting almost every organ system in the body by impacting a wide range of cellular functions. Alcohol causes metabolic derangements either directly, via its chemical by-product or secondarily through alcohol-induced disorders. Many of these alcohol-related metabolic disturbances are increased in severity by the malnutrition that is common in those with chronic alcoholism. This review focuses on the acute and chronic injurious consequences of alcohol ingestion on the kidney, as well as the fluid, electrolyte and acid-base abnormalities associated with acute and chronic ingestion of alcohol.

  8. 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.

  9. Effects of Ischemic Acute Kidney Injury on Lung Water Balance: Nephrogenic Pulmonary Edema?

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    Rajit K. Basu

    2011-01-01

    Full Text Available Pulmonary edema worsens the morbidity and increases the mortality of critically ill patients. Mechanistically, edema formation in the lung is a result of net flow across the alveolar capillary membrane, dependent on the relationship of hydrostatic and oncotic pressures. Traditionally, the contribution of acute kidney injury (AKI to the formation of pulmonary edema has been attributed to bulk fluid accumulation, increasing capillary hydrostatic pressure and the gradient favoring net flow into the alveolar spaces. Recent research has revealed more subtle, and distant, effects of AKI. In this review we discuss the concept of nephrogenic pulmonary edema. Pro-inflammatory gene upregulation, chemokine over-expression, altered biochemical channel function, and apoptotic dysregulation manifest in the lung are now understood as “extra-renal” and pulmonary effects of AKI. AKI should be counted as a disease process that alters the endothelial integrity of the alveolar capillary barrier and has the potential to overpower the ability of the lung to regulate fluid balance. Nephrogenic pulmonary edema, therefore, is the net effect of fluid accumulation in the lung as a result of both the macroscopic and microscopic effects of AKI.

  10. Dialysis for acute kidney injury associated with influenza a (H1N1 infection

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    Augusto Vallejos

    2013-01-01

    Full Text Available In June 2009, the World Health Organization declared a novel influenza A, S-OIV (H1N1, pandemic. We observed 44 consecutive patients during the "first wave" of the pandemic. 70.5% of them showed co-morbidities (hypertension, obesity, chronic respiratory diseases, chronic renal disease, diabetes, pregnancy. Serious cases were admitted to the intensive care unit (ICU, particularly those with severe acute respiratory failure. Some of them developed acute kidney injury (AKI and required renal replacement therapy (RRT. The average time between admission to the ICU and initiation of RRT was 3.16 ± 2.6 days. At initiation of RRT, most patients required mechanical ventilation. No relationship was found with creatinine-kinase levels. Seventy-five percent of the cases were observed during a 3-week period and mortality, related to respiratory failure, doubling of alanine amino transferase and use of inotropics was 81.8%. In conclusion, the H1N1-infected patients who developed RRT-requiring AKI, in the context of multi-organ failure, showed a high mortality rate. Thus, it is mandatory that elaborate strategies aimed at anticipating potential renal complications associated to future pandemics are implemented.

  11. Maternal, fetal and renal outcomes of pregnancy-associated acute kidney injury requiring dialysis.

    Science.gov (United States)

    Krishna, A; Singh, R; Prasad, N; Gupta, A; Bhadauria, D; Kaul, A; Sharma, R K; Kapoor, D

    2015-01-01

    Pregnancy-associated acute kidney injury (PAKI) is encountered frequently in developing countries. We evaluated the maternal, fetal and renal outcomes in women with PAKI who needed at least one session of dialysis. Of the total of 98 cases (mean age 28.85 ± 5.13 years; mean parity 2.65 ± 1.28) of PAKI, the most common cause of PAKI was postabortal sepsis. Eighteen patients died; those with oligoanuria, sepsis and central nervous system (CNS) involvement were at greater risk of mortality. The relative risk (RR) of neonatal mortality was lower after with full-term delivery (RR: 0.17, 95% confidence interval (CI): 0.03-0.96, P = 0.02) compared to preterm delivery. Of the 80 surviving patients, 60 (75%) patients achieved complete recovery of renal function at the end of 3 months; and of the remaining 14 had presumed (n = 4) or, biopsy-proven (n = 10) acute patchy cortical necrosis. The RR of non-recovery of renal function was high (RR: 24.7, 95% CI: 3.4- 179.5) in patients who did not recover at 6 weeks. Of the 14 patients with cortical necrosis, 3 (21.42%) became independent of dialysis at 6 months. PAKI patients should be watched for dialysis independency for 6 months.

  12. Dialysis for acute kidney injury associated with influenza a (H1N1) infection.

    Science.gov (United States)

    Vallejos, Augusto; Arias, Marcelo; Cusumano, Ana; Coste, Eduardo; Simon, Miguel; Martinez, Ricardo; Mendez, Sandra; Raño, Miguel; Sintado, Luis; Lococo, Bruno; Blanco, Carlos; Cestari, Jorge

    2013-05-01

    In June 2009, the World Health Organization declared a novel influenza A, S-OIV (H1N1), pandemic. We observed 44 consecutive patients during the "first wave" of the pandemic. 70.5% of them showed co-morbidities (hypertension, obesity, chronic respiratory diseases, chronic renal disease, diabetes, pregnancy). Serious cases were admitted to the intensive care unit (ICU), particularly those with severe acute respiratory failure. Some of them developed acute kidney injury (AKI) and required renal replacement therapy (RRT). The average time between admission to the ICU and initiation of RRT was 3.16 ± 2.6 days. At initiation of RRT, most patients required mechanical ventilation. No relationship was found with creatinine-kinase levels. Seventy-five percent of the cases were observed during a 3-week period and mortality, related to respiratory failure, doubling of alanine amino transferase and use of inotropics was 81.8%. In conclusion, the H1N1-infected patients who developed RRT-requiring AKI, in the context of multi-organ failure, showed a high mortality rate. Thus, it is mandatory that elaborate strategies aimed at anticipating potential renal complications associated to future pandemics are implemented.

  13. Utility of serum creatinine/cystatin C ratio in diagnosis of postrenal acute kidney injury

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    Salih Inal

    2014-01-01

    Full Text Available Background: In obstructive uropathy, despite a severe increase in the serum creatinine (Cr levels, only a mild cystatin C (CysC increase was previously reported. Therefore, we aimed to determine the availability of serum Cr/CysC ratio in predicting postrenal acute kidney injury (AKI. Materials and Methods: This was a cross-sectional study involving 61-adult patients with heterogeneous AKI cases. Patients with bilateral pelvicalyceal dilatation in renal sonography were considered as postrenal AKI group (n = 15 and others were intrinsic AKI group (n = 46. Venous blood sampling for blood urea nitrogen, Cr and CysC measurements were performed on admission. Results: The mean age of study population was 66.3 ± 15.5 years; 38 (62% of which were male. Two groups were similar regarding age, gender, and comorbidities. Cr/CysC ratio was significantly higher in postrenal AKI group (6.9 ± 3.1 vs. 4.4 ± 2.1, P = 0.007. Conclusion: We suggest that serum Cr/CysC ratio seems to be a useful diagnostic tool for detection of postrenal AKI cases, especially for the cases without definite hydronephrosis.

  14. Role of markers for acute kidney injury in surgical management of patients with renal cancer

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    O. I. Kit

    2015-01-01

    Full Text Available The paper gives the results of studying the urinary levels of markers of acute kidney injury (AKI in 46 patients with renal cancer during separate ureteral catheterization before the surgery and 24 hours after laparoscopic partial nephrectomy performed due to elective indications under warm ischemia. The levels of cystatin C, neutrophil gelatinase-associated lipocalin (NGAL, liver-type fatty acid-binding protein (L-FABP, and interleukin-18 were examined by enzyme immunoassay. It has been established that the risk of early postoperative AKI may be predicted from the baseline urinary levels of cystatin C and LFABP in patients with renal cancer resulting from 15-20-min warm ischemia time during the partial nephrectomy. An approach based on estimation of the baseline urinary levels of cystatin C and L-FABP to be incorporated into a preoperative examination scheme is proposed for surgical treatment policy choosing in patients with renal cancer. A scheme for examining patients with renal cancer is also suggested for the risk of complications and the degree of AKI assessing in the early post-operative period.

  15. Organophosphate Poisoning and Subsequent Acute Kidney Injury Risk: A Nationwide Population-Based Cohort Study.

    Science.gov (United States)

    Lee, Feng-You; Chen, Wei-Kung; Lin, Cheng-Li; Lai, Ching-Yuan; Wu, Yung-Shun; Lin, I-Ching; Kao, Chia-Hung

    2015-11-01

    Small numbers of the papers have studied the association between organophosphate (OP) poisoning and the subsequent acute kidney injury (AKI). Therefore, we used the National Health Insurance Research Database (NHIRD) to study whether patients with OP poisoning are associated with a higher risk to have subsequent AKI.The retrospective cohort study comprised patients aged ≥20 years with OP poisoning and hospitalized diagnosis during 2000-2011 (N = 8924). Each OP poisoning patient was frequency-matched to 4 control patients based on age, sex, index year, and comorbidities of diabetes, hypertension, hyperlipidemia, chronic obstructive pulmonary disease, coronary artery disease, and stroke (N = 35,696). We conducted Cox proportional hazard regression analysis to estimate the effects of OP poisoning on AKI risk.The overall incidence of AKI was higher in the patients with OP poisoning than in the controls (4.85 vs 3.47/1000 person-years). After adjustment for age, sex, comorbidity, and interaction terms, patients with OP poisoning were associated with a 6.17-fold higher risk of AKI compared with the comparison cohort. Patients with highly severe OP poisoning were associated with a substantially increased risk of AKI.The study found OP poisoning is associated with increased risk of subsequent AKI. Future studies are encouraged to evaluate whether long-term effects exist and the best guideline to prevent the continuously impaired renal function.

  16. Association of oliguria with the development of acute kidney injury in the critically ill.

    Science.gov (United States)

    Vaara, Suvi T; Parviainen, Ilkka; Pettilä, Ville; Nisula, Sara; Inkinen, Outi; Uusaro, Ari

    2016-01-01

    Urine output (UO) criterion may increase the sensitivity of the definition of acute kidney injury (AKI). We determined whether the empirically derived definition for oliguria(<0.5 ml/kg/h) is independently associated with adverse outcome. Data analysis included hourly recorded UO from the prospective, multicenter FINNAKI study conducted in 16 Finnish intensive care units. Confounder-adjusted association of oliguria of different severity and duration primarily with the development of AKI defined by creatinine criterion (Cr-AKI) or renal replacement therapy(RRT) was assessed. Secondarily, we determined the association of oliguria with 90-day mortality. Of the 1966 patients analyzed for the development of AKI, 454 (23.1%) reached this endpoint. Within this AKI cohort, 312 (68.7%)developed Cr-AKI, 21 (4.6%) commenced RRT without Cr-AKI, and 121 (26.7%) commenced RRT with Cr-AKI. Episodes of severe oliguria (<0.1 ml/kg/h) for more than 3 h were independently associated with the development of Cr-AKI or RRT. The shortest periods of consecutive oliguria independently associated with an increased risk for 90-day mortality were 6–12 h of oliguria from 0.3 to <0.5 ml/kg/h, over 6 h of oliguria from 0.1 to <0.3 ml/kg/h, and severe oliguria lasting over 3 h.Thus, our findings underlie the importance of hourly UO measurements.

  17. Profile of acute kidney injury after open heart surgeries in a tertiary care hospital.

    Science.gov (United States)

    Rather, Fayaz A; Najar, Saleem M; Malla, Hilal A; Ahangar, A G; Bhat, Hilal M; Wani, Imtiyaz A

    2015-11-01

    Our objective is to determine the incidence, etiology, risk factors and outcome of acute kidney injury (AKI) after open heart surgery. A prospective study was conducted on 62 patients who underwent open heart surgery and were followed-up for the development of AKI and to determine its incidence, etiology and outcome. Post-operative AKI was considered when the post-operative serum creatinine was >1.5 mg/dL or there was doubling of serum creatinine above the baseline (pre-operative) with a prior normal renal function. The incidence of AKI in the post-operative period in our study was 17.7%. The common etiological factors for AKI in our study were sepsis, hypotension, prolonged need for ventilator and inotropic support and drugs given in the post-operative period. The important risk factors for the development of AKI in the post-operative period were hypertension, diabetes mellitus, gout, prolonged total bypass time and prolonged aortic cross-clamp time. The overall mortality in our study subjects was 11.3% (seven of 62 died) and the mortality in the patients who developed post-operative AKI was 71.4%.

  18. Metabolomics as an extension of proteomic analysis: study of acute kidney injury.

    Science.gov (United States)

    Portilla, Didier; Schnackenberg, Laura; Beger, Richard D

    2007-11-01

    Although proteomics studies the global expression of proteins, metabolomics characterizes and quantifies their end products: the metabolites, produced by an organism under a certain set of conditions. From this perspective it is apparent that proteomics and metabolomics are complementary and when joined allow a fuller appreciation of an organism's phenotype. Our studies using (1)H-nuclear magnetic resonance spectroscopic analysis showed the presence of glucose, amino acids, and trichloroacetic acid cycle metabolites in the urine after 48 hours of cisplatin administration. These metabolic alterations precede changes in serum creatinine. Biochemical studies confirmed the presence of glucosuria, but also showed the accumulation of nonesterified fatty acids, and triglycerides in serum, urine, and kidney tissue, despite increased levels of plasma insulin. These metabolic alterations were ameliorated by the use of fibrates. We propose that the injury-induced metabolic profile may be used as a biomarker of cisplatin-induced nephrotoxicity. These studies serve to illustrate that metabolomic studies add insight into pathophysiology not provided by proteomic analysis alone.

  19. 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.

  20. 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.

  1. Rosiglitazone Did Not Induce Acute Kidney Injury in Normocholesterolemic Rats Despite Reduction in Glomerular Filtration Rate

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    Cristiano Dias

    2014-04-01

    Full Text Available Background/Aims: Rosiglitazone (RGL has been used to ameliorate lipids homeostasis and also to treat inflammatory diseases. However, RGL may reduce renal blood flow and glomerular filtration rate (GFR predisposing to acute kidney injury (AKI. We investigated whether the treatment with RGL induces AKI in normocholesterolemic (NC and hypercholesterolemic (HC rats. Methods: We measured GFR by inulin clearance technique and we quantified urinary neutrophil gelatinase-associated lipocalin (uNGAL in all groups at baseline and during Ang II-stimulated vasoconstriction. Moreover, we evaluated the presence of renal damaged by histologic examination. Results: At baseline, NC and HC had normal and similar GFR. RGL treatment reduced GFR only in NC+RGL. Unexpectedly, HC+RGL showed high levels of uNGAL although GFR was at normal range. During Ang II-stimulated vasoconstriction, all groups showed reduction in GFR to the same range and we found high levels of uNGAL and high score of renal damage in HC and HC+RGL. Conclusion: RGL acts distinctly in normocholesterolemia and in hypercholesterolemia. Reduction in GFR provoked by RGL treatment did not allow the diagnosis of AKI in NC even in the presence of ANG II-stimulated vasoconstriction. However, AKI was diagnosed in HC+RGL at baseline although GFR was within normal range.

  2. Acute kidney failure

    Science.gov (United States)

    Kidney failure; Renal failure; Renal failure - acute; ARF; Kidney injury - acute ... There are many possible causes of kidney damage. They include: ... cholesterol (cholesterol emboli) Decreased blood flow due to very ...

  3. Raised plasma Robo4 and cardiac surgery-associated acute kidney injury.

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    Anne Burke-Gaffney

    Full Text Available OBJECTIVE: Endothelial dysfunction associated with systemic inflammation can contribute to organ injury/failure following cardiac surgery requiring cardiopulmonary bypass (CPB. Roundabout protein 4 (Robo4, an endothelial-expressed transmembrane receptor and regulator of cell activation, is an important inhibitor of endothelial hyper-permeability. We investigated the hypothesis that plasma levels of Robo4 are indicative of organ injury, in particular acute kidney injury (AKI, after cardiac surgery. METHODS: Patients (n = 32 undergoing elective cardiac surgery with CPB were enrolled, prospectively. Plasma Robo4 concentrations were measured pre-, 2 and 24 h post-operatively, using a commercially available ELISA. Plasma and endothelial markers of inflammation [interleukin (IL -6, -8, -10: von Willibrand factor (vWF and angiopoeitin-2 (Ang-2] and the AKI marker, neutrophil gelatinase-associated lipocalin (NGAL, were also measured by ELISA. RESULTS: Plasma Robo4 increased significantly (p<0.001 from pre-operative levels of 2515 ± 904 pg/ml to 4473 ± 1915 pg/ml, 2 h after surgery; and returned to basal levels (2682 ± 979 pg/ml by 24 h. Plasma cytokines, vWF and NGAL also increased 2 h post-operatively and remained elevated at 24 h. Ang-2 increased 24 h post-operatively, only. There was a positive, significant correlation (r = 0.385, p = 0.0298 between Robo-4 and IL-10, but not other cytokines, 2 h post-operatively. Whilst raised Robo4 did not correlate with indices of lung dysfunction or other biomarkers of endothelial activation; there was a positive, significant correlation between raised (2 h plasma NGAL and Robo4 (r = 0.4322, p = 0.0135. When patients were classed as AKI or non-AKI either using NGAL cut-off of 150 ng/ml, or the AKI Network (AKIN clinical classification; plasma Robo4 was significantly higher (p = 0.0073 and 0.003, respectively in AKI vs. non-AKI patients (NGAL cut-off: 5350 ± 2191 ng/ml, n = 16 vs. 3595 ± 1068 pg/ml, n = 16

  4. 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.

  5. Gradual Rewarming with Gradual Increase in Pressure during Machine Perfusion after Cold Static Preservation Reduces Kidney Ischemia Reperfusion Injury.

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    Paria Mahboub

    Full Text Available In this study we evaluated whether gradual rewarming after the period of cold ischemia would improve organ quality in an Isolated Perfused Kidney Model. Left rat kidneys were statically cold stored in University of Wisconsin solution for 24 hours at 4°C. After cold storage kidneys were rewarmed in one of three ways: perfusion at body temperature (38°C, or rewarmed gradually from 10°C to 38°C with stabilization at 10°C for 30 min and rewarmed gradually from 10°C to 38°C with stabilization at 25°C for 30 min. In the gradual rewarming groups the pressure was increased stepwise to 40 mmHg at 10°C and 70 mmHg at 25°C to counteract for vasodilatation leading to low perfusate flows. Renal function parameters and injury biomarkers were measured in perfusate and urine samples. Increases in injury biomarkers such as aspartate transaminase and lactate dehydrogenase in the perfusate were lower in the gradual rewarming groups versus the control group. Sodium re-absorption was improved in the gradual rewarming groups and reached significance in the 25°C group after ninety minutes of perfusion. HSP-70, ICAM-1, VCAM-1 mRNA expressions were decreased in the 10°C and 25°C groups. Based on the data kidneys that underwent gradual rewarming suffered less renal parenchymal, tubular injury and showed better endothelial preservation. Renal function improved in the gradual rewarming groups versus the control group.

  6. Urinary retention and acute kidney injury in a tetraplegic patient using condom catheter after partying: a preventable complication

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    Vaidyanathan S

    2015-10-01

    Full Text Available Subramanian Vaidyanathan,1 Fahed Selmi,1 Peter L Hughes,2 Gurpreet Singh,3 Bakul M Soni11Regional Spinal Injuries Centre, 2Department of Radiology, 3Department of Urology, Southport and Formby District General Hospital, Town Lane, Southport, UKBackground: Spinal cord injury patients, who manage their bladder using a condom catheter, are at risk of developing urine retention when they consume large volumes of alcoholic drinks within a short period of time.Case presentation: A male tetraplegic patient had been managing satisfactorily penile sheath drainage for 8 years. He went out socializing during which he consumed large volumes of alcohol but did not take any recreational drugs. The following morning, he noticed distension of the lower abdomen and passed urine in dribbles. He then developed a temperature and became unwell. He was seen by district nurses and a doctor, who prescribed antibiotics. He continued to feel unwell. After 8 days, he referred himself to a spinal unit at Regional Spinal Injuries Centre, Southport. The blood test results showed the following: blood urea: 19.8 mmol/L; creatinine: 172 µmol/L; and C-reactive protein: 336.4 mg/L. Urethral catheterization led to immediate drainage of 1,400 mL of urine. A computed tomography scan revealed an enlarged, swollen left kidney, indicating acute bacterial nephritis. He was prescribed intravenous fluids and Meropenem. Creatinine decreased to 46 µmol/L.Conclusion: Spinal cord injury patients using condom catheters should be made aware of the risk of urine retention when they consume large amounts of alcoholic drinks in a short period of time. Patients and caregivers should be informed to consider intermittent catheterizations for 24–48 hours or insert indwelling urethral catheter when planning for an evening out.Keywords: spinal cord injury, tetraplegia, neuropathic urinary bladder, acute kidney injury 

  7. Systems toxicology of chemically induced liver and kidney injuries: histopathology-associated gene co-expression modules.

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    Te, Jerez A; AbdulHameed, Mohamed Diwan M; Wallqvist, Anders

    2016-09-01

    Organ injuries caused by environmental chemical exposures or use of pharmaceutical drugs pose a serious health risk that may be difficult to assess because of a lack of non-invasive diagnostic tests. Mapping chemical injuries to organ-specific histopathology outcomes via biomarkers will provide a foundation for designing precise and robust diagnostic tests. We identified co-expressed genes (modules) specific to injury endpoints using the Open Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System (TG-GATEs) - a toxicogenomics database containing organ-specific gene expression data matched to dose- and time-dependent chemical exposures and adverse histopathology assessments in Sprague-Dawley rats. We proposed a protocol for selecting gene modules associated with chemical-induced injuries that classify 11 liver and eight kidney histopathology endpoints based on dose-dependent activation of the identified modules. We showed that the activation of the modules for a particular chemical exposure condition, i.e., chemical-time-dose combination, correlated with the severity of histopathological damage in a dose-dependent manner. Furthermore, the modules could distinguish different types of injuries caused by chemical exposures as well as determine whether the injury module activation was specific to the tissue of origin (liver and kidney). The generated modules provide a link between toxic chemical exposures, different molecular initiating events among underlying molecular pathways and resultant organ damage. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. Journal of Applied Toxicology published by John Wiley & Sons, Ltd.

  8. Hypomagnesemia is a risk factor for nonrecovery of renal function and mortality in AIDS patients with acute kidney injury

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    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.

  9. Protocatechuic aldehyde attenuates cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammation

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    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.

  10. Cell Therapy Using Human Induced Pluripotent Stem Cell-Derived Renal Progenitors Ameliorates Acute Kidney Injury in Mice

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    Toyohara, Takafumi; Mae, Shin-Ichi; Sueta, Shin-Ichi; Inoue, Tatsuyuki; Yamagishi, Yukiko; Kawamoto, Tatsuya; Kasahara, Tomoko; Hoshina, Azusa; Toyoda, Taro; Tanaka, Hiromi; Araoka, Toshikazu; Sato-Otsubo, Aiko; Takahashi, Kazutoshi; Sato, Yasunori; Yamaji, Noboru; Ogawa, Seishi; Yamanaka, Shinya

    2015-01-01

    Acute kidney injury (AKI) is defined as a rapid loss of renal function resulting from various etiologies, with a mortality rate exceeding 60% among intensive care patients. Because conventional treatments have failed to alleviate this condition, the development of regenerative therapies using human induced pluripotent stem cells (hiPSCs) presents a promising new therapeutic option for AKI. We describe our methodology for generating renal progenitors from hiPSCs that show potential in ameliorating AKI. We established a multistep differentiation protocol for inducing hiPSCs into OSR1+SIX2+ renal progenitors capable of reconstituting three-dimensional proximal renal tubule-like structures in vitro and in vivo. Moreover, we found that renal subcapsular transplantation of hiPSC-derived renal progenitors ameliorated the AKI in mice induced by ischemia/reperfusion injury, significantly suppressing the elevation of blood urea nitrogen and serum creatinine levels and attenuating histopathological changes, such as tubular necrosis, tubule dilatation with casts, and interstitial fibrosis. To our knowledge, few reports demonstrating the therapeutic efficacy of cell therapy with renal lineage cells generated from hiPSCs have been published. Our results suggest that regenerative medicine strategies for kidney diseases could be developed using hiPSC-derived renal cells. Significance This report is the first to demonstrate that the transplantation of renal progenitor cells differentiated from human induced pluripotent stem (iPS) cells has therapeutic effectiveness in mouse models of acute kidney injury induced by ischemia/reperfusion injury. In addition, this report clearly demonstrates that the therapeutic benefits come from trophic effects by the renal progenitor cells, and it identifies the renoprotective factors secreted by the progenitors. The results of this study indicate the feasibility of developing regenerative medicine strategy using iPS cells against renal diseases

  11. Malnutrition and inflammation in acute kidney injury due to earthquake-related crush syndrome

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    Zhang Yue

    2010-03-01

    Full Text Available Abstract Background Malnutrition and inflammation are common and serious complications in patients with acute kidney injury (AKI. However, the profile of these complications in patients with AKI caused by crush syndrome (CS remains unclear. This study describes the clinical characteristics of malnutrition and inflammation in patients with AKI and CS due to the Wenchuan earthquake. Methods One thousand and twelve victims and eighteen healthy adults were recruited to the study. They were divided into five groups: Group A was composed of victims without CS and AKI (904 cases; Group B was composed of patients with CS and AKI who haven't received renal replacement therapy (RRT (57 cases; and Group C was composed of patients with CS and AKI receiving RRT (25 cases; Group D was composed of earthquake victims with AKI but without CS (26 cases; and Group E was composed of 18 healthy adult controls. The C-reactive protein (CRP, prealbumin, transferrin, interleukin-6 and TNF-α were measured and compared between Group E and 18 patients from Group C. Results The results indicate that participants in Group C had the highest level of serum creatinine, blood urea nitrogen and uric acid. Approximately 92% of patients with CS who had RRT were suffering from hypoalbuminemia. The interleukin-6 and CRP levels were significantly higher in patients with CS AKI receiving RRT than in the control group. Patients in Group C received the highest dosages of albumin, plasma or red blood cell transfusions. One patient in Group C died during treatment. Conclusions Malnutrition and inflammation was common in patients with earthquake-related CS and had a negative impact on the prognosis of these subjects. The results of this study indicate that the use of RRT, intensive nutritional supplementation and transfusion alleviated the degree of malnutrition and inflammation in hemodialysis patients with crush syndrome.

  12. Early Trends in Cystatin C and Outcomes in Patients with Cirrhosis and Acute Kidney Injury

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    Justin M. Belcher

    2014-01-01

    Full Text Available Background. Acute kidney injury (AKI is a common and severe complication in patients with cirrhosis. Progression of AKI to a higher stage associates with increased mortality. Intervening early in AKI when renal dysfunction is worsening may improve outcomes. However, serum creatinine correlates poorly with glomerular filtration in patients with cirrhosis and fluctuations may mask progression early in the course of AKI. Cystatin C, a low-molecular-weight cysteine proteinase inhibitor, is a potentially more accurate marker of glomerular filtration. Methods. We conducted a prospective multicenter study in patients with cirrhosis comparing changes in cystatin and creatinine immediately following onset of AKI as predictors of a composite endpoint of dialysis or mortality. Results. Of 106 patients, 37 (35% met the endpoint. Cystatin demonstrated less variability between samples than creatinine. Patients were stratified into four groups reflecting changes in creatinine and cystatin: both unchanged or decreased 38 (36% (Scr−/CysC−; only cystatin increased 25 (24% (Scr−/CysC+; only creatinine increased 15 (14% (Scr+/CysC−; and both increased 28 (26% (Scr+/CysC+. With Scr−/CysC− as the reference, in both instances where cystatin rose, Scr−/CysC+ and Scr+/CysC+, the primary outcome was significantly more frequent in multivariate analysis, P=0.02 and 0.03, respectively. However, when only creatinine rose, outcomes were similar to the reference group. Conclusions. Changes in cystatin levels early in AKI are more closely associated with eventual dialysis or mortality than creatinine and may allow more rapid identification of patients at risk for adverse outcomes.

  13. Cardiac surgery-associated acute kidney injury in a developing country: Prevalence, risk factors and outcome.

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    Ekure, Ekanem Nsikak; Esezobor, Christopher Imokhuede; Sridhar, Anuradha; Vasudevan, Jyothi; Subramanyan, Rajhavan; Cherian, Kotturathu Mammen

    2015-01-01

    Little is known about cardiac surgery-associated acute kidney injury (CS-AKI) in children in developing regions of the world. The study aimed to determine the prevalence of CSAKI, associated factors and its impact on mortality and utilization of hospital services. The hospital records of children aged 0-17 years who underwent CS at an Indian hospital were reviewed. CS-AKI was defined as a rise in serum creatinine of ≥0.3 mg/dL in any 48 h and or by urine output CS. The study included 323 children with a median age of one year (0.04-17), of whom 22 (6.8%) were neonates and 18.3% had a single ventricle. About 60% of the children had Risk Adjusted Congenital Heart Surgery-I category 1 or 2 interventions. CS-AKI occurred in 39 children (12.1%). Factors associated with CS-AKI were sepsis and intraand post-operative hypotension. In-hospital mortality was six-fold higher in children who developed CS-AKI. CS-AKI was associated with two to three days more of mechanical ventilation and Intensive care unit stay. CS-AKI occurs in children in developing countries, but at a lower frequency mainly due to the predominance of post-neonatal children undergoing less-complex CSs. CS-AKI was associated with higher in-hospital mortality and increased utilization of hospital services. Factors associated with CS-AKI included intraand post-operative hypotension and sepsis.

  14. Incidence of acute kidney injury in the neonatal intensive care unit.

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    Youssef, Doaa; Abd-Elrahman, Hadeel; Shehab, Mohamed M; Abd-Elrheem, Mohamed

    2015-01-01

    The aim of this work is to study the incidence of acute kidney injury (AKI) in neonates admitted to the neonatal intensive care unit (NICU) over a six-month period from September 2011 to March 2012. This prospective study was performed on 250 neonates admitted to the NICU at the Children's Hospital, Faculty of Medicine, Zagazig University. All neonates were subjected to detailed history taking, including pre-natal, natal and post-natal history, with stress on symptoms suggestive of AKI. All neonates were examined thoroughly and the following investigations were performed: Blood urea nitrogen (BUN), serum creatinine, sodium, potassium, calcium, complete blood count, C-reactive protein, arterial blood gases, urine sodium and urine creatinine. AKI was diagnosed in 27 cases (10.8%), including 12 females and 15 males. 40.7% of the AKI cases were born after full-term pregnancy while 59.3% were pre-term babies. 29.6% of the AKI cases had oliguria, and there was male sex predominance, with a male-female ratio of 1.3:1. The cause of AKI was pre-renal in 96.3% and intrinsic renal in 3.7% of the cases. The predisposing factors for AKI were sepsis in 63% of the cases, respiratory distress syndrome in 55.6%, mechanical ventilation in 51.9%, peri-natal asphyxia in 18.5%, dehydration in 14.8%, surgical operation in 11.1%, congenital heart disease in 7.4%, sub-galeal hematoma in 3.7%, polycythemia in 3.7% and intra-ventricular hemorrhage in 3.7% of the cases. Our data suggest that pre-renal failure was the most common form of AKI in our patients. Early recognition of risk factors such as sepsis, peri-natal asphyxia or peri-operative problems and rapid effective treatment of contributing conditions will reduce the incidence of AKI in the neonatal period.

  15. Epidemiology of acute kidney injury in Hungarian intensive care units: a multicenter, prospective, observational study

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    Bencsik Gabor

    2011-09-01

    Full Text Available Abstract Background Despite the substantial progress in the quality of critical care, the incidence and mortality of acute kidney injury (AKI continues to rise during hospital admissions. We conducted a national, multicenter, prospective, epidemiological survey to evaluate the importance of AKI in intensive care units (ICUs in Hungary. The objectives of this study were to determine the incidence of AKI in ICU patients; to characterize the differences in aetiology, illness severity and clinical practice; and to determine the influencing factors of the development of AKI and the patients' outcomes. Methods We analysed the demographic, morbidity, treatment modality and outcome data of patients (n = 459 admitted to ICUs between October 1st, 2009 and November 30th, 2009 using a prospectively filled in electronic survey form in 7 representative ICUs. Results The major reason for ICU admission was surgical in 64.3% of patients and medical in the remaining 35.7%. One-hundred-twelve patients (24.4% had AKI. By AKIN criteria 11.5% had Stage 1, 5.4% had Stage 2 and 7.4% had Stage 3. In 44.0% of patients, AKI was associated with septic shock. Vasopressor treatment, SAPS II score, serum creatinine on ICU admission and sepsis were the independent risk factors for development of any stage of AKI. Among the Stage 3 patients (34 50% received renal replacement therapy. The overall utilization of intermittent renal replacement therapy was high (64.8%. The overall in-hospital mortality rate of AKI was 49% (55/112. The ICU mortality rate was 39.3% (44/112. The independent risk factors for ICU mortality were age, mechanical ventilation, SOFA score and AKI Stage 3. Conclusions For the first time we have established the incidence of AKI using the AKIN criteria in Hungarian ICUs. Results of the present study confirm that AKI has a high incidence and is associated with high ICU and in-hospital mortality.

  16. Acute kidney injury in cirrhotic patients undergoing contrast-enhanced computed tomography

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    Filomia, Roberto; Maimone, Sergio; Caccamo, Gaia; Saitta, Carlo; Visconti, Luca; Alibrandi, Angela; Caloggero, Simona; Bottari, Antonio; Franzè, Maria Stella; Gambino, Carmine Gabriele; Lembo, Tindaro; Oliva, Giovanni; Cacciola, Irene; Raimondo, Giovanni; Squadrito, Giovanni

    2016-01-01

    Abstract Contrast medium administration is one of the leading causes of acute kidney injury (AKI) in different clinical settings. The aim of the study was to investigate occurrence and predisposing factors of AKI in cirrhotic patients undergoing contrast-enhanced computed tomography (CECT). Datasets of 1279 consecutively hospitalized cirrhotic patients were retrospectively analyzed. Two hundred forty-nine of 1279 patients (mean age 64 ± 11 years, 165 male) who had undergone CECT were selected on the basis of the availability of serum creatinine (sCr) values evaluated before and after CECT (CECT group). In analogy, 203/1279 cases (mean age 66 ± 10 years, 132 male) who had not undergone CECT and had been tested twice for sCr in 7 days were also included as controls (Control group). AKI network criteria were employed to assess contrast-induced AKI (CI-AKI) development. Apart from lack of narrowed double sCr measurements, additional exclusion criteria were active bacterial infections, nephrotoxic drugs intake, and estimated glomerular filtration rate sCr values (OR: 0.124, 95% CI: 0.016–0.975; P = 0.047). In the CECT group, presence of ascites (OR: 2.796, 95% CI: 1.109–7.052; P = 0.029), female sex (OR: 0.192, 95% CI: 0.073–0.510; P = 0.001), and hyperazotemia (OR: 1.018, 95% CI: 1.001–1.037; P = 0.043) correlated with CI-AKI development at multivariate analysis. CI-AKI is a quite frequent occurrence in cirrhotic patients with female sex, presence of ascites, and hyperazotemia being the predisposing factors. PMID:27661025

  17. Meta-analysis for outcomes of acute kidney injury after cardiac surgery

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    Shi, Qiankun; Hong, Liang; Mu, Xinwei; Zhang, Cui; Chen, Xin

    2016-01-01

    Abstract This study aimed to investigate the outcomes of acute kidney injury (AKI) after cardiac surgery by the meta-analysis. Electronic databases PubMed and Embase were searched for relative studies from December 2008 to June 2015. For eligible studies, the R software was conducted to meta-analyze outcomes of AKI patients (AKI group) and none-AKI patients after cardiac surgery (NO AKI group). The chi-square-based Q test and I2 statistic were used for heterogeneity analysis. P  50% revealed significant heterogeneity among studies, and then a random effects model was used; otherwise a fixed effect model was performed. Egger's test was performed for publication bias assessment. Subgroup analysis was performed by stratifying AKI definitions and study type. Totally 17 studies with 9656 subjects (2331 in the AKI group and 7325 in the NO AKI group) were enrolled. Significantly higher renal replacement therapy (RRT) (OR=23.67, 95%CI: 12.58–44.55), mortality (OR = 6.27, 95%CI: 3.58–11.00), serum creatinine (SMD = 1.42, 95%CI: 1.01–1.83), and hospital length of stay (LOS) (SMD = 0.45, 95%CI: 0.02–0.88) were shown in the AKI group compared with patients in the NO AKI group. Subgroup analysis showed that results of only 3 subgroups were reversed indicating that the definition of AKI did not affect its outcomes. Publication bias was only found among studies involving mortality and serum creatinine, but the 2 outcomes were not reversed after correction. This meta-analysis confirmed the worse outcomes of AKI in patients after cardiac surgery, including higher RRT rates, mortality, and longer hospital LOS than those of NO AKI patients. PMID:27930561

  18. Design of clinical trials in acute kidney injury: a report from an NIDDK workshop--prevention trials.

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    Okusa, Mark D; Molitoris, Bruce A; Palevsky, Paul M; Chinchilli, Vernon M; Liu, Kathleen D; Cheung, Alfred K; Weisbord, Steven D; Faubel, Sarah; Kellum, John A; Wald, Ron; Chertow, Glenn M; Levin, Adeera; Waikar, Sushrut S; Murray, Patrick T; Parikh, Chirag R; Shaw, Andrew D; Go, Alan S; Chawla, Lakhmir S; Kaufman, James S; Devarajan, Prasad; Toto, Robert M; Hsu, Chi-yuan; Greene, Tom H; Mehta, Ravindra L; Stokes, John B; Thompson, Aliza M; Thompson, B Taylor; Westenfelder, Christof S; Tumlin, James A; Warnock, David G; Shah, Sudhir V; Xie, Yining; Duggan, Emily G; Kimmel, Paul L; Star, Robert A

    2012-05-01

    AKI is an important clinical problem that has become increasingly more common. Mortality rates associated with AKI remain high despite advances in supportive care. Patients surviving AKI have increased long-term mortality and appear to be at increased risk of developing CKD and progressing to ESRD. No proven effective pharmacologic therapies are currently available for the prevention or treatment of AKI. Advances in addressing this unmet need will require the development of novel therapeutic agents based on precise understanding of key pathophysiological events and the implementation of well designed clinical trials. To address this need, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored the "Clinical Trials in Acute Kidney Injury: Current Opportunities and Barriers" workshop in December 2010. The event brought together representatives from academia, industry, the National Institutes of Health, and the US Food and Drug Administration. We report the discussions of workgroups that developed outlines of clinical trials for the prevention of AKI in two patient populations: patients undergoing elective surgery who are at risk for or who develop AKI, and patients who are at risk for contrast-induced AKI. In both of these populations, primary prevention or secondary therapy can be delivered at an optimal time relative to kidney injury. The workgroups detailed primary and secondary endpoints for studies in these groups, and explored the use of adaptive clinical trial designs for trials of novel preventive strategies to improve outcomes of patients with AKI.

  19. Fractal analysis and Gray level co-occurrence matrix method for evaluation of reperfusion injury in kidney medulla.

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    Pantic, Igor; Nesic, Zorica; Paunovic Pantic, Jovana; Radojević-Škodrić, Sanja; Cetkovic, Mila; Basta Jovanovic, Gordana

    2016-05-21

    Fractal analysis and Gray level co-occurrence matrix method represent two novel mathematical algorithms commonly used in medical sciences as potential parts of computer-aided diagnostic systems. In this study, we tested the ability of these methods to discriminate the kidney medullar tissue suffering from reperfusion injury, from normal tissue. A total of 320 digital micrographs of Periodic acid-Schiff (PAS) - stained kidney medulla from 16 Wistar albino mice (20 per animal), were analyzed using National Institutes of Health ImageJ software (NIH, Bethesda, MD) and its plugins. 160 micrographs were obtained from the experimental group with induced reperfusion injury, and another 160 were obtained from the controls. For each micrograph we calculated the values of fractal dimension, lacunarity, as well as five GLCM features: angular second moment, entropy, inverse difference moment, GLCM contrast, and GLCM correlation. Discriminatory value of the parameters was tested using receiver operating characteristic (ROC) analysis, by measuring the area below ROC curve. The results indicate that certain features of GLCM algorithm have excellent discriminatory ability in evaluation of damaged kidney tissue. Fractal dimension and lacunarity as parameters of fractal analysis also had a relatively good discriminatory value in differentiation of injured from the normal tissue. Both methods have potentially promising application in future design of novel techniques applicable in cell physiology, histology and pathology.

  20. Ear Injury

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    ... Fundamentals Heart and Blood Vessel Disorders Hormonal and Metabolic Disorders Immune Disorders Infections Injuries and Poisoning Kidney and ... Fundamentals Heart and Blood Vessel Disorders Hormonal and Metabolic Disorders Immune Disorders Infections Injuries and Poisoning Kidney and ...

  1. Acute Kidney Injury, Recurrent Seizures, and Thrombocytopenia in a Young Patient with Lupus Nephritis: A Diagnostic Dilemma

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    Hector Alvarado Verduzco

    2016-01-01

    Full Text Available Introduction. Posterior reversible encephalopathy syndrome (PRES is a constellation of clinical and radiologic findings. Fluctuations in blood pressure, seizures, and reversible brain MRI findings mainly in posterior cerebral white matter are the main manifestations. PRES has been associated with multiple conditions such as autoimmune disorders, pregnancy, organ transplant, and thrombotic microangiopathy (TMA. Case Presentation. A 22-year-old woman with history of Systemic Lupus Erythematous complicated with chronic kidney disease secondary to lupus nephritis class IV presented with recurrent seizures and uncontrolled hypertension. She was found to have acute kidney injury and thrombocytopenia. Repeat kidney biopsy showed diffuse endocapillary and extracapillary proliferative and membranous lupus nephritis (ISN-RPS class IV-G+V and endothelial swelling secondary to severe hypertension but no evidence of TMA. Brain MRI showed reversible left frontal and parietal lesions that resolved after controlling the blood pressure, making PRES the diagnosis. Conclusion. PRES is an important entity that must be recognized and treated early due to the potential reversibility in the early stages. Physicians must have high suspicion for these unusual presentations. We present a case where performing kidney biopsy clinched the diagnosis in our patient with multiple confounding factors.

  2. Myeloid cell-derived hypoxia-inducible factor attenuates inflammation in unilateral ureteral obstruction-induced kidney injury.

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    Kobayashi, Hanako; Gilbert, Victoria; Liu, Qingdu; Kapitsinou, Pinelopi P; Unger, Travis L; Rha, Jennifer; Rivella, Stefano; Schlöndorff, Detlef; Haase, Volker H

    2012-05-15

    Renal fibrosis and inflammation are associated with hypoxia, and tissue pO(2) plays a central role in modulating the progression of chronic kidney disease. Key mediators of cellular adaptation to hypoxia are hypoxia-inducible factor (HIF)-1 and -2. In the kidney, they are expressed in a cell type-specific manner; to what degree activation of each homolog modulates renal fibrogenesis and inflammation has not been established. To address this issue, we used Cre-loxP recombination to activate or to delete both Hif-1 and Hif-2 either globally or cell type specifically in myeloid cells. Global activation of Hif suppressed inflammation and fibrogenesis in mice subjected to unilateral ureteral obstruction, whereas activation of Hif in myeloid cells suppressed inflammation only. Suppression of inflammatory cell infiltration was associated with downregulation of CC chemokine receptors in renal macrophages. Conversely, global deletion or myeloid-specific inactivation of Hif promoted inflammation. Furthermore, prolonged hypoxia suppressed the expression of multiple inflammatory molecules in noninjured kidneys. Collectively, we provide experimental evidence that hypoxia and/or myeloid cell-specific HIF activation attenuates renal inflammation associated with chronic kidney injury.

  3. Protective effect of low potassium dextran solution on acute kidney injury following acute lung injury induced by oleic acid in piglets

    Institute of Scientific and Technical Information of China (English)

    WU Rui-ping; LIANG Xiu-bin; GUO Hui; ZHOU Xiao-shuang; ZHAO Li; WANG Chen; LI Rong-shan

    2012-01-01

    Background Low potassium dextran (LPD) solution can attenuate acute lung injury (ALI).However,LPD solution for treating acute kidney injury secondary to ALI has not been reported.The present study was performed to examine the renoprotective effect of LPD solution in ALI induced by oleic acid (OA) in piglets.Methods Twelve animals that suffered an ALI induced by administration of OA into the right atrium were divided into two groups:the placebo group (n=6) pretreated with normal saline and the LPD group (n=6),pretreated with LPD solution.LPD solution was injected intravenously at a dose of 12.5 ml/kg via the auricular vein 1 hour before OA injection.Results All animals survived the experiments with mild histopathological injury to the kidney.There were no significant differences in mean arterial pressure (MAP),creatinin and renal damage scores between the two groups.Compared with the placebo group,the LPD group had better gas exchange parameters at most of the observation points ((347.0±12.6)mmHg vs.(284.3±11.3) mmHg at 6 hours after ALI,P<0.01).After 6 hours of treatment with OA,the plasma concentrations of NGAL and interleukin (IL)-6 in both groups increased dramatically compared to baseline ((6.0±0.6) and (2.50±0.08) folds in placebo group; and (2.5±0.5) and (1.40±0.05) folds in LPD group),but the change of both parameters in the LPD group was significantly lower (P <0.01) than in the placebo group.And 6 hours after ALl the kidney tissue concentration of IL-6 in the LPD group ((165.7 ± 22.5) pg.ml-1.g-1 protein) was significantly lower (P <0.01) than that in placebo group ((67.2± 25.3) pg.ml-1.g-1 protein).Conclusion These findings suggest that pretreatment with LPD solution via systemic administration might attenuate acute kidney injury and the cytokine response of IL-6 in the ALl piglet model induced by OA injection.

  4. Evaluation of the usefulness of novel biomarkers for drug-induced acute kidney injury in beagle dogs.

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    Zhou, Xiaobing; Ma, Ben; Lin, Zhi; Qu, Zhe; Huo, Yan; Wang, Jufeng; Li, Bo

    2014-10-01

    As kidney is a major target organ affected by drug toxicity, early detection of renal injury is critical in preclinical drug development. In past decades, a series of novel biomarkers of drug-induced nephrotoxicity were discovered and verified in rats. However, limited data regarding the performance of novel biomarkers in non-rodent species are publicly available. To increase the applicability of these biomarkers, we evaluated the performance of 4 urinary biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), clusterin, total protein, and N-acetyl-β-D-glucosaminidase (NAG), relative to histopathology and traditional clinical chemistry in beagle dogs with acute kidney injury (AKI) induced by gentamicin. The results showed that urinary NGAL and clusterin levels were significantly elevated in dogs on days 1 and 3 after administration of gentamicin, respectively. Gene expression analysis further provided mechanistic evidence to support that NGAL and clusterin are potential biomarkers for the early assessment of drug-induced renal damage. Furthermore, the high area (both AUCs=1.000) under receiver operator characteristics (ROC) curve also indicated that NGAL and clusterin were the most sensitive biomarkers for detection of gentamicin-induced renal proximal tubular toxicity. Our results also suggested that NAG may be used in routine toxicity testing due to its sensitivity and robustness for detection of tissue injury. The present data will provide insights into the preclinical use of these biomarkers for detection of drug-induced AKI in non-rodent species.

  5. Renal HIV expression is unaffected by serum LPS levels in an HIV transgenic mouse model of LPS induced kidney injury.

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    Jeremy S Leventhal

    Full Text Available Acute kidney injury (AKI is associated with increased rates of mortality. For unknown reasons, HIV infected individuals have a higher risk of AKI than uninfected persons. We tested our hypothesis that increased circulating LPS increases renal expression of HIV and that HIV transgenic (Tg26 mice have increased susceptibility to AKI. Tg26 mice harbor an HIV transgene encoding all HIV genes except gag and pol, and develop a phenotype analogous to HIVAN. Mice were used at 4-6 weeks of age before the onset of gross renal disease. Mice were injected i.p. with LPS or sterile saline. Renal function, tubular injury, cytokine expression, and HIV transcription were evaluated in Tg26 and wild type (WT mice. LPS injection induced a median 60.1-fold increase in HIV expression in spleen but no change in kidney. There was no significant difference in renal function, cytokine expression, or tubular injury scores at baseline or 24 hours after LPS injection. HIV transcription was also analyzed in vitro using a human renal tubular epithelial cell (RTEC line. HIV transcription increased minimally in human RTEC, by 1.47 fold, 48 hours after LPS exposure. We conclude that Tg26 mice do not increase HIV expression or have increased susceptibility to LPS induced AKI. The increased risk of AKI in HIV infected patients is not mediated via increased renal expression of HIV in the setting of sepsis. Moreover, renal regulation of HIV transcription is different to that in the spleen.

  6. Renal Doppler and Novel Biomarkers to Assess Acute Kidney Injury in a Swine Model of Ventricular Fibrillation Cardiac Arrest

    Institute of Scientific and Technical Information of China (English)

    Xue Mei; Chen-Chen Hang; Shuo Wang; Chun-Sheng Li; Ze-Xing Yu

    2015-01-01

    Background: Majority of the research on cardiac arrest (CA) have focused on post-CA brain injury and myocardial dysfunction, the renal dysfunction and acute kidney injury (AKI) in other critical illnesses after CA have not been well described.This study was designed to assess AKI with renal Doppler and novel AKI biomarkers in a swine model ofventricular fibrillation cardiac arrest (VFCA).Methods: Thirty healthy piglets were divided into VFCA group (n =22) and Sham group (n =8) in a blinded manner.Mean arterial pressure, heart rate, and cardiac output were recorded continuously.Cardiac arrest (CA) was induced by programmed electric stimulation in the VFCA group, and then cardiopulmonary resuscitation was performed.Twenty piglets retumed of spontaneous circulation (ROSC) and received intensive care.Blood and urine samples were collected for AKI biomarkers testing, and Color Doppler flow imaging was performed at baseline, 6 h, 12 h, and 24 h,respectively after ROSC.At ROSC 24 h, the animals were sacrificed and a semi-quantitative evaluation of pathologic kidney injury was performed.Results: In the VFCA group, corrected resistive index (cRI) increased from 0.47 ± 0.03 to 0.64 ± 0.06, and pulsatility index (PI) decreased from 0.82 ± 0.03 to 0.68 ± 0.04 after ROSC.Cystatin C (CysC) in both serum and urine samples increased at ROSC 6 h, but neutrophil gelatinase-associated lipocalin (NGAL) in serum increased to 5.34 ± 1.68 ng/ml at ROSC 6 h, and then decreased to 3.16 ± 0.69 ng/ml at ROSC 24 h while CysC increasing constantly.According to the renal histopathology, 18 of 20 animals suffered from kidney injury.The grade of renal injury was highly correlated with RI, cRI, NGAL, and CysC.Linear regression equation was established: Grade of renal injury =0.002 × serum CysC + 6.489 × PI + 4.544 × cRI-8.358 (r2 =0.698, F =18.506, P < 0.001).Conclusions: AKI is common in post-CA syndrome.Renal Doppler and novel AKI biomarkers in serum and urine are of significant

  7. A nationwide survey of clinical characteristics, management, and outcomes of acute kidney injury (AKI) - patients with and without preexisting chronic kidney disease have different prognoses.

    Science.gov (United States)

    Pan, Heng-Chih; Wu, Pei-Chen; Wu, Vin-Cent; Yang, Ya-Fei; Huang, Tao-Min; Shiao, Chih-Chung; Chen, Te-Chuan; Tarng, Der-Cherng; Lin, Jui-Hsiang; Yang, Wei-Shun; Sun, Chiao-Yin; Lin, Chan-Yu; Chu, Tzong-Shinn; Wu, Mai-Szu; Wu, Kwan-Dun; Chen, Yung-Chang; Huang, Chiu-Ching

    2016-09-01

    Acute kidney injury (AKI) is a common complication in hospitalized patients. The International Society of Nephrology implemented the "0 by 25" initiative aimed at preventing deaths from treatable AKI worldwide by 2025 and conducted a global snapshot survey in 2014. We joined in the project and conducted this study to compare the epidemiology, risk factors, and prognosis between patients with pure AKI and those with acute-on-chronic kidney disease (ACKD). In this study, we prospectively collected demographic parameters and data on clinical characteristics, baseline comorbidities, management, and outcomes of 201 AKI patients in 18 hospitals in Taiwan from September 2014 to November 2014. The in-hospital mortality rate was 16%. AKI was mostly attributed to sepsis (52%). Multivariate logistic regression indicated that oliguria was a positive independent predictor of in-hospital mortality, whereas preexisting CKD and exposure to nephrotoxic agents were negative independent predictors. The prevalence of vasopressor use, intensive care unit care, and mortality were significantly higher in pure AKI patients than in ACKD patients. Moreover, serum creatinine (SCr) levels significantly increased within 7 days after AKI diagnosis in nonsurvivors but not in survivors in the pure AKI group. By contrast, SCr levels were persistently lower in nonsurvivors than in survivors in the ACKD group during the same period. We thus determined that the prognosis of ACKD patients differed from that of pure AKI patients. Considering the CKD history in the future AKI staging system may improve prognosis prediction.

  8. Thalidomide Ameliorates Inflammation and Vascular Injury but Aggravates Tubular Damage in the Irradiated Mouse Kidney

    NARCIS (Netherlands)

    Scharpfenecker, Marion; Floot, Ben; Russell, Nicola S.; Coppes, Rob P.; Stewart, Fiona A.

    2014-01-01

    Purpose: The late side effects of kidney irradiation include vascular damage and fibrosis, which are promoted by an irradiation-induced inflammatory response. We therefore treated kidney-irradiated mice with the anti-inflammatory and angiogenesis-modulating drug thalidomide in an attempt to prevent

  9. Frequency of Acute Kidney Injury in Patients Treated With Normal Saline after Off-Pump Coronary Artery Bypass Grafting

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    Shima Sheybani

    2017-03-01

    Full Text Available Introduction: Acute kidney injury (AKI is a common postoperative complication of cardiac surgery, which is associated with an increased risk of morbidity and mortality. This study investigated the frequency of postoperative AKI in low risk adult patients undergoing off-pump coronary artery bypass grafting (CABG.Materials & Methods: All consecutive adult patients of American Society of Anesthesiologists (ASA class II and III, who were transferred to the post-operative cardiac surgery ICU after off-pump CABG and were low risk for AKI from October 2013 to September 2014 at Emam Reza Hospital, Mashhad, Iran were enrolled in this prospective cohort study at a teaching hospital. The patients were explored for AKI development, based on risk-injury-failure-loss- end stage kidney disease (RIFLE and acute kidney injury network (AKIN criteria, frequency of metabolic acidosis, hypernatremia, hyperchloremia, and length of stay in ICU.Results: According to the results of the present study, 479 patients with the mean age of 60.8±10.75 yrs were included. AKI occurred in 22 (4.4% and23 (4.8% patients, based on both the RIFLE and AKIN criteria, respectively with the highest rate of AKI, reported on the third and fourth post-operative days. Additionally, hyperchloremia and hypernatremia were observed in 71 (14.8% and 76 (15.9% patients, respectively. Only one case of mortality occurred during the study. Metabolic acidosis was reported in 112 (23.4% patients with a high anion gap in 60 (12.5% cases.Conclusion: The current study demonstrated that hypernatremia and metabolic acidosis but not AKI are frequently seen in patients receiving normal saline following off pump CABG with low risk for AKI.

  10. No increase in kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin excretion following intravenous contrast enhanced-CT

    Energy Technology Data Exchange (ETDEWEB)

    Kooiman, Judith [Leiden University Medical Center, Department of Thrombosis and Haemostasis, Leiden (Netherlands); Leiden University Medical Center, Department of Nephrology, Leiden (Netherlands); Peppel, Wilke R. van de; Huisman, Menno V. [Leiden University Medical Center, Department of Thrombosis and Haemostasis, Leiden (Netherlands); Sijpkens, Yvo W.J. [Bronovo Hospital, Department of Nephrology, The Hague (Netherlands); Brulez, Harald F.H. [Sint Lucas Andreas Hospital, Department of Nephrology, Amsterdam (Netherlands); Vries, P.M. de [St. Antonius Hospital, Department of Vascular Surgery, Nieuwegein (Netherlands); Nicolaie, Mioara A.; Putter, H. [Leiden University Medical Center, Department of Medical Statistics and Bioinformatics, Leiden (Netherlands); Kooij, W. van der; Kooten, Cees van; Rabelink, Ton J. [Leiden University Medical Center, Department of Nephrology, Leiden (Netherlands)

    2015-07-15

    To analyze kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (N-GAL) excretion post-intravenous contrast enhanced-CT (CE-CT) in patients with chronic kidney disease (CKD). Patients were enrolled in a trial on hydration regimes to prevent contrast-induced acute kidney injury (CI-AKI). Blood and urine samples were taken at baseline, 4 - 6, and 48 - 96 h post CE-CT. Urinary KIM-1 and N-GAL values were normalized for urinary creatinine levels, presented as medians with 2.5 - 97.5 percentiles. Of the enrolled 511 patients, 10 (2 %) were lost to follow-up. CI-AKI occurred in 3.9 % of patients (20/501). Median KIM-1 values were 1.2 (0.1 - 7.7) at baseline, 1.3 (0.1 - 8.6) at 4 - 6 h, and 1.3 ng/mg (0.1 - 8.1) at 48 - 96 h post CE-CT (P = 0.39). Median N-GAL values were 41.0 (4.4 - 3,174.4), 48.9 (5.7 - 3,406.1), and 37.8 μg/mg (3.5 - 3,200.4), respectively (P = 0.07). The amount of KIM-1 and N-GAL excretion in follow-up was similar for patients with and without CI-AKI (P-value KIM-1 0.08, P-value N-GAL 0.73). Neither patient characteristics at baseline including severe CKD, medication use, nor contrast dose were associated with increased excretion of KIM-1 or N-GAL during follow-up. KIM-1 and N-GAL excretion were unaffected by CE-CT both in patients with and without CI-AKI, suggesting that CI-AKI was not accompanied by tubular injury. (orig.)

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

    DEFF Research Database (Denmark)

    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......-regression controlling for illness severity (Acute Physiology And Chronic Health Evaluation II (APACHE II)), baseline creatinine and urea did not impact the overall summary estimate for mortality. Of studies reporting secondary outcomes, five studies (out of seven) reported greater renal recovery, seven (out of eight...

  12. Comparison of Effects of Different Statins on Contrast-Induced Acute Kidney Injury in Rats: Histopathological and Biochemical Findings

    OpenAIRE

    Xiao-lei Wang; Tuo Zhang; Liu-hua Hu; Shi-qun Sun; Wei-feng Zhang; Zhe Sun; Ling-hong Shen; Ben He

    2017-01-01

    Statins are a promising new strategy to prevent contrast-induced acute kidney injury (CI-AKI). In this study we compared the ameliorative effect of different statins in a rat model of CI-AKI. Sprague-Dawley rats were divided into five groups: control group; CI-AKI group; CI-AKI + rosuvastatin group (10 mg/kg/day); CI-AKI + simvastatin group (80 mg/kg/day); and CI-AKI + atorvastatin group (20 mg/kg/day). CI-AKI was induced by dehydration for 72 hours, followed by furosemide intramuscular injec...

  13. The provision of thromboprophylaxis and the prediction of renal recovery in critically ill patients with acute kidney injury

    DEFF Research Database (Denmark)

    Robinson, Sian; Larsen, Ulla L.; Zincuk, Aleksander

    2015-01-01

    Background: It is unknown whether the dose of enoxaparin can be optimised, without increasing the risk of bleeding, in critically ill patients with acute kidney injury (AKI). Neutrophil gelatinase-associated lipocalin (NGAL) is associated with AKI, and the subsequent need for continuous renal rep...... be able to predict renal recovery in critically ill patients, and allow proper utilization of resources. (EU Clinical Trials Register EudraCT Number: 2012-004368-23; URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-004368-23/DK)....

  14. Prognosis of acute kidney injury in dogs using RIFLE (Risk, Injury, Failure, Loss and End-stage renal failure)-like criteria.

    Science.gov (United States)

    Lee, Y-J; Chang, C-C; Chan, J P-W; Hsu, W-L; Lin, K-W; Wong, M-L

    2011-03-12

    A retrospective case-series study evaluated the prognosis of 853 dogs with acute kidney injury (AKI) based on the RIFLE (Risk, Injury, Failure, Loss and End-stage renal failure) criteria, derived from human medicine. The 30-day mortality of dogs with AKI in each class was found to be 23.8 per cent (40 of 168) dogs for Risk, 41.0 per cent (107 of 261) dogs for Injury and 78.5 per cent (333 of 424) dogs for Failure. Using the dogs in the Risk class as the reference, the mortality of dogs in either the Injury or Failure class was significantly higher than that of dogs in the Risk class (PFailure class (three days). Using a multiple logistic regression model, a new score that simultaneously considered RIFLE class, diarrhoea status and serum phosphorus level was calculated to predict prognosis. Evaluation using the area under the receiver-operating characteristic curve (AUROC) indicated that the new scoring method (AUROC 0.80) was a better prognostic indicator than using RIFLE criteria alone (AUROC 0.73).

  15. Effects of continuous and intermittent renal replacement therapies among adult patients with acute kidney injury.

    Science.gov (United States)

    Schoenfelder, Tonio; Chen, Xiaoyu; Bleß, Hans-Holger

    2017-01-01

    Background: Dialysis-dependent acute kidney injury (AKI) can be treated using continuous (CRRT) or intermittent renal replacement therapies (IRRT). Although some studies suggest that CRRT may have advantages over IRRT, study findings are inconsistent. This study assessed differences between CRRT and IRRT regarding important clinical outcomes (such as mortality and renal recovery) and cost-effectiveness. Additionally, ethical aspects that are linked to renal replacement therapies in the intensive care setting are considered. Methods: Systematic searches in MEDLINE, EMBASE, and Cochrane Library including RCTs, observational studies, and cost-effectiveness studies were performed. Results were pooled using a random effects-model. Results: Forty-nine studies were included. Findings show a higher rate of renal recovery among survivors who initially received CRRT as compared with IRRT. This advantage applies to the analysis of all studies with different observation periods (Relative Risk (RR) 1.10; 95% Confidence Interval (CI) [1.05, 1.16]) and to a selection of studies with observation periods of 90 days (RR 1.07; 95% CI [1.04, 1.09]). Regarding observation periods beyond there are no differences when only two identified studies were analyzed. Patients initially receiving CRRT have higher mortality as compared to IRRT (RR 1.17; 95% CI [1.06, 1.28]). This difference is attributable to observational studies and may have been caused by allocation bias since seriously ill patients more often initially receive CRRT instead of IRRT. CRRT do not significantly differ from IRRT with respect to change of mean arterial pressure, hypotensive episodes, hemodynamic instability, and length of stay. Data on cost-effectiveness is inconsistent. Recent analyzes indicate that initial CRRT is cost-effective compared to initial IRRT due to a reduction of the rate of long-term dialysis dependence. As regards a short time horizon, this cost benefit has not been shown. Conclusion: Findings of

  16. Incidence of acute kidney injury in the neonatal intensive care unit

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    Doaa Youssef

    2015-01-01

    Full Text Available The aim of this work is to study the incidence of acute kidney injury (AKI in neonates admitted to the neonatal intensive care unit (NICU over a six-month period from September 2011 to March 2012. This prospective study was performed on 250 neonates admitted to the NICU at the Children′s Hospital, Faculty of Medicine, Zagazig University. All neonates were subjected to detailed history taking, including pre-natal, natal and post-natal history, with stress on symptoms suggestive of AKI. All neonates were examined thoroughly and the following investigations were performed: Blood urea nitrogen (BUN, serum creatinine, sodium, potassium, calcium, complete blood count, C-reactive protein, arterial blood gases, urine sodium and urine creatinine. AKI was diagnosed in 27 cases (10.8%, including 12 females and 15 males. 40.7% of the AKI cases were born after full-term pregnancy while 59.3% were pre-term babies. 29.6% of the AKI cases had oliguria, and there was male sex predominance, with a male-female ratio of 1.3:1. The cause of AKI was pre-renal in 96.3% and intrinsic renal in 3.7% of the cases. The predisposing factors for AKI were sepsis in 63% of the cases, respiratory distress syndrome in 55.6%, mechanical ventilation in 51.9%, peri-natal asphyxia in 18.5%, dehydration in 14.8%, surgical operation in 11.1%, congenital heart disease in 7.4%, sub-galeal hematoma in 3.7%, polycythemia in 3.7% and intra-ventricular hemorrhage in 3.7% of the cases. Our data suggest that pre-renal failure was the most common form of AKI in our patients. Early recognition of risk factors such as sepsis, peri-natal asphyxia or peri-operative problems and rapid effective treatment of contributing conditions will reduce the incidence of AKI in the neonatal period.

  17. Thalidomide Ameliorates Inflammation and Vascular Injury but Aggravates Tubular Damage in the Irradiated Mouse Kidney

    Energy Technology Data Exchange (ETDEWEB)

    Scharpfenecker, Marion, E-mail: m.scharpfenecker@nki.nl [Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam (Netherlands); Floot, Ben [Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam (Netherlands); Russell, Nicola S. [Division of Radiotherapy, The Netherlands Cancer Institute, Amsterdam (Netherlands); Coppes, Rob P. [Departments of Radiation Oncology and Cell Biology, University Medical Centre Groningen, University of Groningen, Groningen (Netherlands); Stewart, Fiona A. [Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam (Netherlands)

    2014-07-01

    Purpose: The late side effects of kidney irradiation include vascular damage and fibrosis, which are promoted by an irradiation-induced inflammatory response. We therefore treated kidney-irradiated mice with the anti-inflammatory and angiogenesis-modulating drug thalidomide in an attempt to prevent the development of late normal tissue damage and radiation nephropathy in the mouse kidney. Methods and Materials: Kidneys of C57Bl/6 mice were irradiated with a single dose of 14 Gy. Starting from week 16 after irradiation, the mice were fed with thalidomide-containing chow (100 mg/kg body weight/day). Gene expression and kidney histology were analyzed at 40 weeks and blood samples at 10, 20, 30, and 40 weeks after irradiation. Results: Thalidomide improved the vascular structure and vessel perfusion after irradiation, associated with a normalization of pericyte coverage. The drug also reduced infiltration of inflammatory cells but could not suppress the development of fibrosis. Irradiation-induced changes in hematocrit and blood urea nitrogen levels were not rescued by thalidomide. Moreover, thalidomide worsened tubular damage after irradiation and also negatively affected basal tubular function. Conclusions: Thalidomide improved the inflammatory and vascular side effects of kidney irradiation but could not reverse tubular toxicity, which probably prevented preservation of kidney function.

  18. Angiotensin II induces kidney inflammatory injury and fibrosis through binding to myeloid differentiation protein-2 (MD2)

    Science.gov (United States)

    Xu, Zheng; Li, Weixin; Han, Jibo; Zou, Chunpeng; Huang, Weijian; Yu, Weihui; Shan, Xiaoou; Lum, Hazel; Li, Xiaokun; Liang, Guang

    2017-01-01

    Growing evidence indicates that angiotensin II (Ang II), a potent biologically active product of RAS, is a key regulator of renal inflammation and fibrosis. In this study, we tested the hypothesis that Ang II induces renal inflammatory injury and fibrosis through interaction with myeloid differentiation protein-2 (MD2), the accessory protein of toll-like receptor 4 (TLR4) of the immune system. Results indicated that in MD2−/− mice, the Ang II-induced renal fibrosis, inflammation and kidney dysfunction were significantly reduced compared to control Ang II-infused wild-type mice. Similarly, in the presence of small molecule MD2 specific inhibitor L6H21 or siRNA-MD2, the Ang II-induced increases of pro-fibrotic and pro-inflammatory molecules were prevented in tubular NRK-52E cells. MD2 blockade also inhibited activation of NF-κB and ERK. Moreover, MD2 blockade prevented the Ang II-stimulated formation of the MD2/TLR4/MyD88 signaling complex, as well as the increased surface binding of Ang II in NRK-52E cells. In addition, Ang II directly bound recombinant MD2 protein, rather than TLR4 protein. We conclude that MD2 is a significant contributor in the Ang II-induced kidney inflammatory injury in chronic renal diseases. Furthermore, MD2 inhibition could be a new and important therapeutic strategy for preventing progression of chronic renal diseases.

  19. Identification of hantavirus infection by Western blot assay and TaqMan PCR in patients hospitalized with acute kidney injury.

    Science.gov (United States)

    Oldal, Miklós; Németh, Viktória; Madai, Mónika; Kemenesi, Gábor; Dallos, Bianka; Péterfi, Zoltán; Sebők, Judit; Wittmann, István; Bányai, Krisztián; Jakab, Ferenc

    2014-06-01

    Hantaviruses, one of the causative agents of viral hemorrhagic fevers, represent a considerable healthcare threat. In Hungary, Dobrava-Belgrade virus (DOBV) and Puumala virus (PUUV) are the main circulating hantavirus species, responsible for the clinical picture known as hemorrhagic fever with renal syndrome, a disease that may be accompanied by acute kidney injury (AKI), requiring hospitalization with occasionally prolonged recovery phase. A total of 20 patient sera were collected over a 2-year period from persons hospitalized with AKI, displaying clinical signs and laboratory findings directly suggestive for hantavirus infection. Samples were tested using an immunoblot assay, based on complete viral nucleocapsid proteins to detect patients' IgM and IgG antibodies against DOBV and PUUV. In parallel, all specimens were also tested by 1-step real-time TaqMan reverse-transcriptase polymerase chain reaction to confirm infection and to determine the causative hantavirus genotype. We present here the first Hungarian clinical study spanning across 2 years and dedicated specifically to assess acute kidney injuries, in the context of hantavirus prevalence.

  20. Successful Antiviral Triple Therapy in a Longstanding Refractory Hepatitis C Virus Infection with an Acute Kidney Injury

    Directory of Open Access Journals (Sweden)

    David Callau Monje

    2014-01-01

    Full Text Available Introduction. The HCV infection is a common disease with many chronically infected patients worldwide. So far, the standard therapy of a chronic HCV infection consisted of interferon as single therapy or in combination with ribavirin. After approval of the two protease inhibitors, boceprevir and telaprevir, the standard therapy for patients with genotype 1 changed. In patients with acute kidney injury (AKI these therapies are not approved and have so far not been evaluated in studies. Case Report. In April 2012, a 58-year-old female was admitted due to a cryoglobulin-positive chronic HCV infection which had been treated with interferon and ribavirin. Currently, the patient was admitted because of severe complications with an acute kidney injury. We treated our patient successfully with a boceprevir based triple therapy. Conclusion. Limited data suggests that a therapy with ribavirin in patients with AKI seems to be safe under close monitoring. Our patient was treated successfully with a protease inhibitor based triple therapy. Nevertheless, it is necessary to plan an interventional study to evaluate the exact risk-benefit profile of triple therapy regimens in patients with AKI and hepatitis C.

  1. Hydrogen Sulfide Inhibits High-Salt Diet-Induced Renal Oxidative Stress and Kidney Injury in Dahl Rats

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    Pan Huang

    2016-01-01

    Full Text Available Background. The study was designed to investigate if H2S could inhibit high-salt diet-induced renal excessive oxidative stress and kidney injury in Dahl rats. Methods. Male salt-sensitive Dahl and SD rats were used. Blood pressure (BP, serum creatinine, urea, creatinine clearance rate, and 24-hour urine protein were measured. Renal ultra- and microstructures were observed. Collagen-I and -III contents the oxidants and antioxidants levels in renal tissue were detected. Keap1/Nrf2 association and Keap1 s-sulfhydration were detected. Results. After 8 weeks of high-salt diet, BP was significantly increased, renal function and structure were impaired, and collagen deposition was abundant in renal tissues with increased renal MPO activity, H2O2, MDA, GSSG, and •OH contents, reduced renal T-AOC and GSH contents, CAT, GSH-PX and SOD activity, and SOD expressions in Dahl rats. Furthermore, endogenous H2S in renal tissues was decreased in Dahl rats. H2S donor, however, decreased BP, improved renal function and structure, and inhibited collagen excessive deposition in kidney, in association with increased antioxidative activity and reduced oxidative stress in renal tissues. H2S activated Nrf2 by inducing Keap1 s-sulfhydration and subsequent Keap1/Nrf2 disassociation. Conclusions. H2S protected against high-salt diet-induced renal injury associated with enhanced antioxidant capacity and inhibited renal oxidative stress.

  2. Fish Oil-Based Fat Emulsion Reduces Acute Kidney Injury and Inflammatory Response in Antibiotic-Treated Polymicrobial Septic Mice.

    Science.gov (United States)

    Shih, Juey-Ming; Shih, Yao-Ming; Pai, Man-Hui; Hou, Yu-Chen; Yeh, Chiu-Li; Yeh, Sung-Ling

    2016-03-15

    Acute kidney injury (AKI) is a common complication in sepsis. This study compared the effects of a fish oil-based with a mixed oil fat emulsion on remote renal injury in an antibiotic-treated septic murine model. Mice were randomly assigned to a normal control (NC) group and three septic groups. Sepsis was induced by cecal ligation and puncture (CLP). The antibiotic was injected intraperitoneally (IP) after CLP and then daily till the time of sacrifice. Three hours after antibiotic treatment, one of the septic groups was injected IP with a fish oil-based emulsion (FO), while the other two groups were given either a mixed oil emulsion (MO) or saline (SC). The septic groups were further divided into two separate time groups, with blood and kidneys samples collected at 24 h or 72 h post-CLP. The results showed that sepsis leads to the activation of neutrophils, T helper (Th)1/Th-2/Th-17 and Treg cells (p oil-based emulsion had decreased plasma NGAL by 22% and Treg by 33%. Furthermore, renal gene expressions of MyD88 and TLR4 reduced by 46% and 62%, respectively, whereas heat shock protein 70 and peroxisome proliferator-activated receptor-γ increased by 158% and 69%, respectively (p oil-based emulsion has favorable effects, maintaining blood T cell percentage, downregulating Treg expression, attenuating systemic and local inflammation and offering renal protection under conditions of antibiotic-treated polymicrobial sepsis.

  3. The duration of hypotension determines the evolution of bacteremia-induced acute kidney injury in the intensive care unit.

    Directory of Open Access Journals (Sweden)

    Karin Janssen van Doorn

    Full Text Available BACKGROUND: Exploration of the impact of severe hypotension on the evolution of acute kidney injury in septic patients. METHODS AND RESULTS: We reviewed the hemodynamic parameters of 137 adults with septic shock and proven blood stream infection in the ICU. Severe hypotension was defined as a mean arterial blood pressure (MAP ≤65 mmHg. The influence of the duration of severe hypotension on the evolution of acute kidney injury was evaluated according to the RIFLE classification, with day 0 defined as the day of a positive blood stream infection. After bloodstream infection, the probability for a patient to be in Failure was significantly higher than before blood stream infection (OR = 1.94, p = 0.0276. Patients have a significantly higher risk of evolving to Failure if the duration of severe hypotension is longer (OR = 1.02 for each 10 minutes increase in duration of a MAP <65 mmHg, p = 0.0472. A cut-off of at least 51 minutes of severe hypotension (<65 mmHg or at least 5.5 periods of severe hypotension within 1 day identified patients with increased risk to evolve to Failure. CONCLUSIONS: There is a significant influence of both the duration and the number of periods of severe hypotension on the evolution to Failure. Blood stream infection has a significantly negative effect on the relationship between severe hypotension and Failure.

  4. Predictors for nephrology outpatient care and recurrence of acute kidney injury (AKI) after an in-hospital AKI episode.

    Science.gov (United States)

    Xie, Mingyang; Iqbal, Sameena

    2014-10-01

    Acute kidney injury (AKI) is associated with increased long-term risk of end-stage kidney disease (ESKD) and mortality. Nephrology care following discharge from hospital may improve survival through prevention of recurrent AKI events. In this study, we examined the factors that were associated with outpatient nephrology follow-up after the development of AKI on patients who had a nephrology in-hospital consultation and were discharged from McGill University Health Centre between January 1, 2006 and December 31, 2010. The associated factors for AKI-free survival postdischarge were assessed applying multivariate Cox hazard proportional models. Of 170 patients, only 22% of the AKI admissions studied were booked with nephrology follow-up after discharge. The unadjusted hazard ratio (HR) of outpatient nephrology care postdischarge was 1.82 (95% confidence interval [CI] 0.93-3.56) for AKI-free survival postdischarge. The adjusted HR was 2.04 (95% CI 1.01-4.12) when we adjusted for follow-up with other medical clinics, significant stage 4 and stage 5 chronic kidney disease and diabetes status. Patients with less comorbidities and higher serum creatinine on discharge received outpatient nephrology care. Nephrology outpatient care is associated with decreased risk of recurrence of AKI after discharge from hospital.

  5. Decreased Tissue COX5B Expression and Mitochondrial Dysfunction during Sepsis-Induced Kidney Injury in Rats

    Science.gov (United States)

    Böhm, Lennert; Braunecker, Stefan; Adler, Christoph; De Robertis, Edoardo; Cirillo, Fabrizio

    2017-01-01

    Background. Sepsis is defined as a life-threatening organ dysfunction due to a dysregulated host response to infection. Sepsis is the dominant cause of acute kidney injury (AKI), accounting for nearly 50% of episodes of acute renal failure. Signaling cascades and pathways within the kidney are largely unknown and analysis of these molecular mechanisms may enhance knowledge on pathophysiology and possible therapeutic options. Material and Methods. 26 male Wistar rats were assigned to either a sham group (control, N = 6) or sepsis group (N = 20; cecal ligature and puncture model, 24 and 48 hours after CLP). Surviving rats (n = 12) were decapitated at 24 hours (early phase; n = 6) or 48 hours (late phase; n = 6) after CLP and kidneys removed for proteomic analysis. 2D-DIGE and DeCyder 2D software (t-test, P cytochrome c oxidase subunit B (COX5b), myosin-6 (MYH6), and myosin-7 (MYH7). A significant correlation with the proteins was found for mitochondrial energy production and electron transport. Conclusions. COX5B could be a promising biomarker candidate since a significant association was found during experimental sepsis in the present study. For future research, COX5B should be evaluated as a biomarker in both human urine and serum to identify sepsis. PMID:28246552

  6. Health status, renal function, and quality of life after multiorgan failure and acute kidney injury requiring renal replacement therapy

    Directory of Open Access Journals (Sweden)

    Faulhaber-Walter R

    2016-05-01

    Full Text Available Robert Faulhaber-Walter,1,2 Sebastian Scholz,1,3 Herrmann Haller,1 Jan T Kielstein,1,* Carsten Hafer1,4,* 1Department of Renal and Hypertensive Disease, Medical School Hannover, Hannover, Germany; 2Facharztzentrum Aarberg, Waldshut-Tiengen, Germany; 3Sanitaetsversorgungszentrum Wunstorf, Wunstorf, Germany; 4HELIOS Klinikum Erfurt, Erfurt, Germany *These authors contributed equally to this work Background: Critically ill patients with acute kidney injury (AKI in need of renal replacement therapy (RRT may have a protracted and often incomplete rehabilitation. Their long-term outcome has rarely been investigated. Study design: Survivors of the HANnover Dialysis OUTcome (HANDOUT study were evaluated after 5 years for survival, health status, renal function, and quality of life (QoL. The HANDOUT study had examinded mortality and renal recovery of patients with AKI receiving either standard extendend or intensified dialysis after multi organ failure. Results: One hundred fifty-six former HANDOUT participants were analyzed. In-hospital mortality was 56.4%. Five-year survival after AKI/RRT was 40.1% (86.5% if discharged from hospital. Main causes of death were cardiovascular complications and sepsis. A total of 19 survivors presented to the outpatient department of our clinic and had good renal recovery (mean estimated glomerular filtration rate 72.5±30 mL/min/1.73 m2; mean proteinuria 89±84 mg/d. One person required maintenance dialysis. Seventy-nine percent of the patients had a pathological kidney sonomorphology. The Charlson comorbidity score was 2.2±1.4 and adjusted for age 3.3±2.1 years. Numbers of comorbid conditions averaged 2.38±1.72 per patient (heart failure [52%] > chronic kidney disease/myocardial infarction [each 29%]. Median 36-item short form health survey (SF-36™ index was 0.657 (0.69 physical health/0.66 mental health. Quality-adjusted life-years after 5 years were 3.365. Conclusion: Mortality after severe AKI is higher than

  7. Oxidative stress and modification of renal vascular permeability are associated with acute kidney injury during P. berghei ANKA infection.

    Science.gov (United States)

    Elias, Rosa Maria; Correa-Costa, Matheus; Barreto, Claudiene Rodrigues; Silva, Reinaldo Correia; Hayashida, Caroline Y; Castoldi, Angela; Gonçalves, Giselle Martins; Braga, Tarcio Teodoro; Barboza, Renato; Rios, Francisco José; Keller, Alexandre Castro; Cenedeze, Marcos Antonio; Hyane, Meire Ioshie; D'Império-Lima, Maria Regina; Figueiredo-Neto, Antônio Martins; Reis, Marlene Antônia; Marinho, Cláudio Romero Farias; Pacheco-Silva, Alvaro; Câmara, Niels Olsen Saraiva

    2012-01-01

    Malaria associated-acute kidney injury (AKI) is associated with 45% of mortality in adult patients hospitalized with severe form of the disease. However, the causes that lead to a framework of malaria-associated AKI are still poorly characterized. Some clinical studies speculate that oxidative stress products, a characteristic of Plasmodium infection, as well as proinflammatory response induced by the parasite are involved in its pathophysiology. Therefore, we aimed to investigate the development of malaria-associated AKI during infection by P. berghei ANKA, with special attention to the role played by the inflammatory response and the involvement of oxidative stress. For that, we took advantage of an experimental model of severe malaria that showed significant changes in the renal pathophysiology to investigate the role of malaria infection in the renal microvascular permeability and tissue injury. Therefore, BALB/c mice were infected with P. berghei ANKA. To assess renal function, creatinine, blood urea nitrogen, and ratio of proteinuria and creatininuria were evaluated. The products of oxidative stress, as well as cytokine profile were quantified in plasma and renal tissue. The change of renal microvascular permeability, tissue hypoxia and cellular apoptosis were also evaluated. Parasite infection resulted in renal dysfunction. Furthermore, we observed increased expression of adhesion molecule, proinflammatory cytokines and products of oxidative stress, associated with a decrease mRNA expression of HO-1 in kidney tissue of infected mice. The measurement of lipoprotein oxidizability also showed a significant increase in plasma of infected animals. Together, our findings support the idea that products of oxidative stress, as well as the immune response against the parasite are crucial to changes in kidney architecture and microvascular endothelial permeability of BALB/c mice infected with P. berghei ANKA.

  8. Cholestatic jaundice, acute kidney injury and acute pancreatitis secondary to the recreational use of methandrostenolone: a case report

    Directory of Open Access Journals (Sweden)

    Kwan Peter

    2011-04-01

    Full Text Available Abstract Introduction Over the last few years the use of anabolic steroids has become increasingly common amongst amateur athletes and for aesthetic purposes. As a result, the adverse events related to their use are being seen more frequently. Methandrostenolone is an anabolic steroid which is widely available and has been used for both performance enhancement and aesthetic purposes. This drug has also been reported to cause cholestasis of the intra-hepatic bile ducts resulting in elevated aminotransferases, hyperbilirubinemia and clinical jaundice. However, to the best of our knowledge this agent has not been previously reported to cause pancreatitis or acute kidney injury. Case presentation In this paper, we report the case of a 50-year-old man of Indian descent who presented with a six week history of diffuse abdominal pain, anorexia and weight loss following an eight week cycle of methandrostenolone use. At initial presentation, his lipase level was 785 U/L, bilirubin was 922 μmol/L and creatinine was 200 U/L while his aspartate aminotransferase and alanine aminotransferase levels were only mildly elevated at 61 U/L and 56 U/L respectively. His lipase peaked on day nine at >3000 U/L whilst his creatinine level was 299 U/L. Imaging was consistent with acute pancreatitis while a liver biopsy was consistent with intra-hepatic cholestasis and a kidney biopsy revealed evidence of acute tubular necrosis. Conclusion Both acute pancreatitis and acute kidney injury have rarely been reported with anabolic steroid use and they have not been previously reported to occur in the same patient. This case demonstrates some potentially new and serious adverse consequences occurring with the use of anabolic steroids, of which physicians need to be aware.

  9. Effects of Carperitide on Contrast-Induced Acute Kidney Injury with a Minimum Volume of Contrast in Chronic Kidney Disease Patients

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    Naoki Okumura

    2012-12-01

    Full Text Available Background/Aims: Although contrast-induced acute kidney injury (CIAKI is a major complication associated with angiography, the prophylaxis is not well established. Use of a low dose of carperitide for preventing CIAKI remains controversial. We examined the protective effect of carperitide on CIAKI after coronary angiography with a small contrast volume in chronic kidney disease (CKD patients with coronary artery disease. Methods: We randomly assigned 112 consecutive patients to a carperitide or a control group. The contrast volume was kept under 150 ml. The primary endpoint was the incidence of CIAKI defined by a serum creatinine of ≥25% or a serum creatinine of ≥0.5 mg/dl from baseline within 48 h. The secondary endpoint was a change in renal function at 1 week after the procedure. Results: The baseline characteristics and contrast volumes (carperitide group: 67.4 ± 38.2 ml vs. control group: 64.8 ± 20.5 ml, p = 0.661 were comparable in the two groups. The incidence of CIAKI was similar in the two groups (carperitide group: 8.5% vs. control group: 5.7%, p = 0.564. A multivariate analysis revealed that a hypotension ≥20 mm Hg was a significant predictor of developing CIAKI in the carperitide group (p = 0.015. The incidence of CIAKI in the carperitide group without hypotension was rare, but not significantly different (carperitide group: 2.4% vs. control group: 5.7%, p = 0.432. Conclusions: This study indicated that the use of a small contrast volume suppressed the incidence of CIAKI and that carperitide had no prophylactic effect against CIAKI. Our results also revealed the impact of hypotension on the development of CIAKI in the carperitide group.

  10. Systemic over-release of interleukin-17 in acute kidney injury after septic shock: Clinical and experimental evidence.

    Science.gov (United States)

    Maravitsa, Panagiota; Adamopoulou, Maria; Pistiki, Aikaterini; Netea, Mihai G; Louis, Konstantinos; Giamarellos-Bourboulis, Evangelos J

    2016-10-01

    In order to investigate the role of T-helper 17 (Th17) cell activation in acute kidney injury (AKI) after septic shock, a two-stage approach was used. Firstly, peripheral blood mononuclear cells (PBMCs) and CD4-lymphocytes were isolated the first 24h after septic shock from 26 patients with AKI and 18 patients with chronic renal disease (CRD) without AKI and stimulated for the release of tumour necrosis factor-alpha (TNFα), interleukin (IL)-10, IL-17, IL-22 and interferon-gamma (IFNγ). Results were compared with 15 healthy volunteers and 13 patients with uncomplicated sepsis. Secondly, a murine model of multiple organ dysfunction (MODS) complicated with AKI and bacterial gut translocation was studied, and IL-10, IL-17, IL-22 and IFNγ were measured in kidney homogenates. IL-17 was the only cytokine produced at greater quantities from PBMCs and CD4-lymphocytes of patients with septic shock and AKI than comparators. When PBMCs of patients with septic shock and AKI were ex-vivo stimulated, intracellular staining for IL-17 was greater in CD3(+)/CD4(+)/CD196(+) cells compared to patients with septic shock and CRD. IL-17 was released at greater amounts from PBMCs of non-survivors by septic shock and AKI but not of septic shock and CRD. In the murine model of MODS, a gradual decrease of IL-17, but not of IL-10, IL-22 and IFNγ, of kidney homogenates was found indicating over-consumption. These results suggest that AKI after septic shock is driven through IL-17 release by Th17 cells; this is gradually consumed in the kidney.

  11. Unilateral Renal Ischemia-Reperfusion as a Robust Model for Acute to Chronic Kidney Injury in Mice.

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    Nathalie Le Clef

    Full Text Available Acute kidney injury (AKI is an underestimated, yet important risk factor for development of chronic kidney disease (CKD. Even after initial total recovery of renal function, some patients develop progressive and persistent deterioration of renal function and these patients are more likely to progress to end-stage renal disease (ESRD. Animal models are indispensable for unravelling the mechanisms underlying this progression towards CKD and ESRD and for the development of new therapeutic strategies in its prevention or treatment. Ischemia (i.e. hypoperfusion after surgery, bleeding, dehydration, shock, or sepsis is a major aetiology in human AKI, yet unilateral ischemia-reperfusion is a rarely used animal model for research on CKD and fibrosis. Here, we demonstrate in C57Bl/6J mice, by both histology and gene expression, that unilateral ischemia-reperfusion without contralateral nephrectomy is a very robust model to study the progression from acute renal injury to long-term tubulo-interstitial fibrosis, i.e. the histopathological hallmark of CKD. Furthermore, we report that the extent of renal fibrosis, in terms of Col I, TGFβ, CCN2 and CCN3 expression and collagen I immunostaining, increases with increasing body temperature during ischemia and ischemia-time. Thus, varying these two main determinants of ischemic injury allows tuning the extent of the long-term fibrotic outcome in this model. Finally, in order to cover the whole practical finesse of ischemia-reperfusion and allow model and data transfer, we provide a referenced overview on crucial technical issues (incl. anaesthesia, analgesia, and pre- and post-operative care with the specific aim of putting starters in the right direction of implementing ischemia in their research and stimulate them, as well as the community, to have a critical view on ischemic literature data.

  12. Unilateral Renal Ischemia-Reperfusion as a Robust Model for Acute to Chronic Kidney Injury in Mice.

    Science.gov (United States)

    Le Clef, Nathalie; Verhulst, Anja; D'Haese, Patrick C; Vervaet, Benjamin A

    2016-01-01

    Acute kidney injury (AKI) is an underestimated, yet important risk factor for development of chronic kidney disease (CKD). Even after initial total recovery of renal function, some patients develop progressive and persistent deterioration of renal function and these patients are more likely to progress to end-stage renal disease (ESRD). Animal models are indispensable for unravelling the mechanisms underlying this progression towards CKD and ESRD and for the development of new therapeutic strategies in its prevention or treatment. Ischemia (i.e. hypoperfusion after surgery, bleeding, dehydration, shock, or sepsis) is a major aetiology in human AKI, yet unilateral ischemia-reperfusion is a rarely used animal model for research on CKD and fibrosis. Here, we demonstrate in C57Bl/6J mice, by both histology and gene expression, that unilateral ischemia-reperfusion without contralateral nephrectomy is a very robust model to study the progression from acute renal injury to long-term tubulo-interstitial fibrosis, i.e. the histopathological hallmark of CKD. Furthermore, we report that the extent of renal fibrosis, in terms of Col I, TGFβ, CCN2 and CCN3 expression and collagen I immunostaining, increases with increasing body temperature during ischemia and ischemia-time. Thus, varying these two main determinants of ischemic injury allows tuning the extent of the long-term fibrotic outcome in this model. Finally, in order to cover the whole practical finesse of ischemia-reperfusion and allow model and data transfer, we provide a referenced overview on crucial technical issues (incl. anaesthesia, analgesia, and pre- and post-operative care) with the specific aim of putting starters in the right direction of implementing ischemia in their research and stimulate them, as well as the community, to have a critical view on ischemic literature data.

  13. Evaluation of the usefulness of novel biomarkers for drug-induced acute kidney injury in beagle dogs

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Xiaobing [National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, A8 Hongda Middle Street, Beijing Economic-Technological Development Area, Beijing 100176 (China); Graduate School of Peking Union Medical College, Dongcheng District, Beijing, 100730 (China); Ma, Ben; Lin, Zhi; Qu, Zhe; Huo, Yan; Wang, Jufeng [National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, A8 Hongda Middle Street, Beijing Economic-Technological Development Area, Beijing 100176 (China); Li, Bo, E-mail: libo@nifdc.org.cn [National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, A8 Hongda Middle Street, Beijing Economic-Technological Development Area, Beijing 100176 (China); Graduate School of Peking Union Medical College, Dongcheng District, Beijing, 100730 (China)

    2014-10-01

    As kidney is a major target organ affected by drug toxicity, early detection of renal injury is critical in preclinical drug development. In past decades, a series of novel biomarkers of drug-induced nephrotoxicity were discovered and verified in rats. However, limited data regarding the performance of novel biomarkers in non-rodent species are publicly available. To increase the applicability of these biomarkers, we evaluated the performance of 4 urinary biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), clusterin, total protein, and N-acetyl-β-D-glucosaminidase (NAG), relative to histopathology and traditional clinical chemistry in beagle dogs with acute kidney injury (AKI) induced by gentamicin. The results showed that urinary NGAL and clusterin levels were significantly elevated in dogs on days 1 and 3 after administration of gentamicin, respectively. Gene expression analysis further provided mechanistic evidence to support that NGAL and clusterin are potential biomarkers for the early assessment of drug-induced renal damage. Furthermore, the high area (both AUCs = 1.000) under receiver operator characteristics (ROC) curve also indicated that NGAL and clusterin were the most sensitive biomarkers for detection of gentamicin-induced renal proximal tubular toxicity. Our results also suggested that NAG may be used in routine toxicity testing due to its sensitivity and robustness for detection of tissue injury. The present data will provide insights into the preclinical use of these biomarkers for detection of drug-induced AKI in non-rodent species. - Highlights: • Urinary NGAL, clusterin and NAG levels were significantly elevated in canine AKI. • NGAL and clusterin gene expression were increased following treatment with gentamicin. • NGAL and clusterin have high specificity and sensitivity for detection of AKI.

  14. Optimizing Mouse Surgery with Online Rectal Temperature Monitoring and Preoperative Heat Supply. Effects on Post-Ischemic Acute Kidney Injury.

    Science.gov (United States)

    Marschner, Julian A; Schäfer, Hannah; Holderied, Alexander; Anders, Hans-Joachim

    2016-01-01

    Body temperature affects outcomes of tissue injury. We hypothesized that online body core temperature recording and selective interventions help to standardize peri-interventional temperature control and the reliability of outcomes in experimental renal ischemia reperfusion injury (IRI). We recorded core temperature in up to seven mice in parallel using a Thermes USB recorder and ret-3-iso rectal probes with three different protocols. Setup A: Heating pad during ischemia time; Setup B: Heating pad from incision to wound closure; Setup C: A ventilated heating chamber before surgery and during ischemia time with surgeries performed on a heating pad. Temperature profile recording displayed significant declines upon installing anesthesia. The profile of the baseline experimental setup A revealed that temperature readings were within the target range of 36.5 to 38.5°C. Setup B and C increased the target range readings to 34.6 ± 28.0% and 99.3 ± 1.5%, respectively. Setup C significantly increased S3 tubular necrosis, neutrophil influx, and mRNA expression of kidney injury markers. In addition, using setup C different ischemia times generated a linear correlation with acute tubular necrosis parameters at a low variability, which further correlated with the degree of kidney atrophy 5 weeks after surgery. Changing temperature control setup A to C was equivalent to 10 minutes more ischemia time. We conclude that body temperature drops quickly in mice upon initiating anesthesia. Immediate heat supply, e.g. in a ventilated heating chamber, and online core temperature monitoring can help to standardize and optimize experimental outcomes.

  15. Levels of protein C and soluble thrombomodulin in critically ill patients with acute kidney injury: a multicenter prospective observational study.

    Directory of Open Access Journals (Sweden)

    Josée Bouchard

    Full Text Available Endothelial dysfunction contributes to the development of acute kidney injury (AKI in animal models of ischemia reperfusion injury and sepsis. There are limited data on markers of endothelial dysfunction in human AKI. We hypothesized that Protein C (PC and soluble thrombomodulin (sTM levels could predict AKI. We conducted a multicenter prospective study in 80 patients to assess the relationship of PC and sTM levels to AKI, defined by the AKIN creatinine (AKI Scr and urine output criteria (AKI UO. We measured marker levels for up to 10 days from intensive care unit admission. We used area under the curve (AUC and time-dependent multivariable Cox proportional hazard model to predict AKI and logistic regression to predict mortality/non-renal recovery. Protein C and sTM were not different in patients with AKI UO only versus no AKI. On intensive care unit admission, as PC levels are usually lower with AKI Scr, the AUC to predict the absence of AKI was 0.63 (95%CI 0.44-0.78. The AUC using log10 sTM levels to predict AKI was 0.77 (95%CI 0.62-0.89, which predicted AKI Scr better than serum and urine neutrophil gelatinase-associated lipocalin (NGAL and cystatin C, urine kidney injury molecule-1 and liver-fatty acid-binding protein. In multivariable models, PC and urine NGAL levels independently predicted AKI (p=0.04 and 0.02 and PC levels independently predicted mortality/non-renal recovery (p=0.04. In our study, PC and sTM levels can predict AKI Scr but are not modified during AKI UO alone. PC levels could independently predict mortality/non-renal recovery. Additional larger studies are needed to define the relationship between markers of endothelial dysfunction and AKI.

  16. Danshen (Salvia miltiorrhiza injection suppresses kidney injury induced by iron overload in mice.

    Directory of Open Access Journals (Sweden)

    Shengjiang Guan

    Full Text Available OBJECTIVES: Excessive iron can accumulate in the kidney and induce tissue damage. Danshen (Salvia miltiorrhiza injection is a traditional Chinese medicinal preparation used for preventing and treating chronic renal failure. The aim of the present study was to evaluate the effects of treatment with Danshen injection on iron overload-induced kidney damage. METHODS: Mice were mock-treated with saline (control group or given a single dose of iron dextran without treatment (iron overload group, 50 mg/kg/day for 2 weeks or with daily treatments of low-dose Danshen (3 g/kg/day, high-dose Danshen (6 g/kg/day or deferoxamine (100 mg/kg/day. RESULTS: Treatment of iron-overloaded mice with Danshen injection led to significant improvements of body weight and decreased iron levels in the kidney. Danshen injection treatment also reduced concentrations of blood urea nitrogen, creatinine and malondialdehyde and enhanced glutathione peroxidase and superoxide dismutase activities. Histopathological examinations showed that Danshen injection ameliorated pathological changes and reduced iron deposition in kidneys of iron overloaded mice. Furthermore, the treatment was demonstrated to suppress apoptosis in nephrocytes. CONCLUSIONS: These results indicated that Danshen injection exerted significant renal protective effects in iron-overloaded mice, which were closely associated with the decrease of iron deposition and suppression of lipid peroxidation and apoptosis in the kidney.

  17. Continuous Venovenous Hemofiltration in Severely Burned Patients with Acute Kidney Injury: A Cohort Study

    Science.gov (United States)

    2009-05-01

    FiO2: fraction of inspired oxygen; IHD: intermittent hemodialysis ; IQR: interquartile range; ISS: injury severity score; MODS: multiple organ...were compared. Definitions During the period after November 2005 our staff intensivists utilized the RIFLE (Risk, Injury, Failure, Loss, End-stage...for acute renal fail- ure which included: fluid resuscitation, minimization of nephro- toxic agents, and utilization of hemodialysis if classic

  18. Monitoring of urinary L-type fatty acid-binding protein predicts histological severity of acute kidney injury.

    Science.gov (United States)

    Negishi, Kousuke; Noiri, Eisei; Doi, Kent; Maeda-Mamiya, Rui; Sugaya, Takeshi; Portilla, Didier; Fujita, Toshiro

    2009-04-01

    The present study aimed to evaluate whether levels of urinary L-type fatty acid-binding protein (L-FABP) could be used to monitor histological injury in acute kidney injury (AKI) induced by cis-platinum (CP) injection and ischemia reperfusion (IR). Different degrees of AKI severity were induced by several renal insults (CP dose and ischemia time) in human L-FABP transgenic mice. Renal histological injury scores increased with both CP dose and ischemic time. In CP-induced AKI, urinary L-FABP levels increased exponentially even in the lowest dose group as early as 2 hours, whereas blood urea nitrogen (BUN) levels increased at 48 hours. In IR-induced AKI, BUN levels increased only in the 30-minute ischemia group 24 hours after reperfusion; however, urinary L-FABP levels increased more than 100-fold, even in the 5-minute ischemia group after 1 hour. In both AKI models, urinary L-FABP levels showed a better correlation with final histological injury scores and glomerular filtration rates measured by fluorescein isothiocyanate-labeled inulin injection than with levels of BUN and urinary N-acetyl-D-glucosaminidase, especially at earlier time points. Receiver operating characteristic curve analysis demonstrated that urinary L-FABP was superior to other biomarkers for the detection of significant histological injuries and functional declines. In conclusion, urinary L-FABP levels are better suited to allow the accurate and earlier detection of both histological and functional insults in ischemic and nephrotoxin-induced AKI compared with conventional renal markers.

  19. Limitations of early serum creatinine variations for the assessment of kidney injury in neonates and infants with cardiac surgery.

    Directory of Open Access Journals (Sweden)

    Mirela Bojan

    Full Text Available BACKGROUND: Changes in kidney function, as assessed by early and even small variations in serum creatinine (ΔsCr, affect survival in adults following cardiac surgery but such associations have not been reported in infants. This raises the question of the adequate assessment of kidney function by early ΔsCr in infants undergoing cardiac surgery. METHODOLOGY: The ability of ΔsCr within 2 days of surgery to assess the severity of kidney injury, accounted for by the risk of 30-day mortality, was explored retrospectively in 1019 consecutive neonates and infants. Patients aged ≤ 10 days were analyzed separately because of the physiological improvement in glomerular filtration early after birth. The Kml algorithm, an implementation of k-means for longitudinal data, was used to describe creatinine kinetics, and the receiver operating characteristic and the reclassification methodology to assess discrimination and the predictive ability of the risk of death. RESULTS: Three clusters of ΔsCr were identified: in 50% of all patients creatinine decreased, in 41.4% it increased slightly, and in 8.6% it rose abruptly. Mortality rates were not significantly different between the first and second clusters, 1.6% [0.0-4.1] vs 5.9% [1.9-10.9], respectively, in patients aged ≤ 10 days, and 1.6% [0.5-3.0] vs 3.8% [1.9-6.0] in older ones. Mortality rates were significantly higher when creatinine rose abruptly, 30.3% [15.1-46.2] in patients aged ≤ 10 days, and 15.1% [5.9-25.5] in older ones. However, only 41.3% of all patients who died had an abrupt increase in creatinine. ΔsCr improved prediction in survivors, but not in patients who died, and did not improve discrimination over a clinical mortality model. CONCLUSIONS: The present results suggest that a postoperative decrease in creatinine represents the normal course in neonates and infants with cardiac surgery, and that early creatinine variations lack sensitivity for the assessment of the severity of

  20. Remote Ischemic Preconditioning for the Prevention of Contrast-Induced Acute Kidney Injury in Diabetics Receiving Elective Percutaneous Coronary Intervention

    Science.gov (United States)

    Balbir Singh, Gillian; Ann, Soe Hee; Park, Jongha; Chung, Hyun Chul; Lee, Jong Soo; Kim, Eun-Sook; Choi, Jung Il; Lee, Jiho; Kim, Shin-Jae; Shin, Eun-Seok

    2016-01-01

    Objective Remote ischemic preconditioning (RIPC) induces transient episodes of ischemia by the occlusion of blood flow in non-target tissue, before a subsequent ischemia-reperfusion injury. When RIPC is applied before percutaneous coronary intervention (PCI), the kidneys may be protected against ischemia-reperfusion injury and subsequently contrast-induced acute kidney injury (CI-AKI). The aim of this study was to evaluate the efficacy of RIPC for the prevention of CI-AKI in patients with diabetes with pre-existing chronic kidney disease (CKD) undergoing elective PCI. Methods This randomized, double-blind, sham-controlled study enrolled patients with diabetes scheduled for elective PCI with eGFR ≤60 ml/min/1.73 m2 or urinary albumin creatinine ratio of >300 mg/g to receive either RIPC or the sham ischemic preconditioning. Results One hundred and two patients (68.9 ± 8.2 years old, 47.1% men) were included. Baseline eGFR, creatinine and serum NGAL was similar between RIPC and control groups (48.5 ± 12 ml/min vs. 46.6 ± 10 ml/min, p = 0.391; 1.42 ± 0.58 mg/dl vs. 1.41 ± 0.34 mg/dl, p = 0.924; and 136.0 ± 45.0 ng/ml vs. 137.6 ± 43.3 ng/ml, p = 0.961, respectively). CI-AKI occurred in 13.7% (14/102) of the total subjects, with both RIPC and control groups having an equal incidence of 13.7% (7/51). No significant differences were seen in creatinine, NGAL, cardiac enzymes (troponin T, CKMB) and hs-CRP between the groups post-procedure. Conclusions In this study, RIPC applied prior to elective PCI was not effective in preventing CI-AKI in patients with diabetes with pre-existing CKD. Trial Registration ClinicalTrials.gov NCT02329444 PMID:27723839

  1. Evaluation of acute kidney injury as defined by the risk, injury,failure, loss, and end-stage criteria in critically ill patients undergoing abdominal aortic aneurysm repair

    Institute of Scientific and Technical Information of China (English)

    YUE Jia-ning; LUO Zhe; GUO Da-qiao; XU Xin; CHEN Bin; JIANG Jun-hao; YANG Jue

    2013-01-01

    Background Acute kidney injury (AKI) is considered as a common and significant complication following abdominal aortic aneurysm (AAA) repair.This study aimed to assess the associated risk factors of AKI in the critically ill patients undergoing AAA repair and to evaluate the appropriate AKI management in the specific population.Methods We retrospectively examined data from all critically ill patients undergoing AAA repairs at our institution from April 2007 to March 2012.Multivariable analysis was used to identify factors associated with postoperative AKI,which was defined by risk,injury,failure,loss and end-stage (RIFLE) kidney disease criteria.The goal-directed hemodynamic optimization (maintenance of optimal hemodynamics and neutral or negative fluid balance) and renal outcomes were also reviewed.Results Of the 71 patients enrolled,32 (45.1%) developed AKI,with 30 (93.8%) cases diagnosed on admission to surgical intensive care unit (SICU).Risk factors for AKI were ruptured AAA (odds ratio (OR)=5.846,95% confidence interval (Cl):1.346-25.390),intraoperative hypotension (OR=6.008,95% CI:1.176 to 30.683),and perioperative blood transfusion (OR=4.611,95% CI:1.307-16.276).Goal-directed hemodynamic optimization resulted in 75.0% complete and 18.8% partial renal recovery.Overall in-hospital mortality was 2.8% AKI was associated with significantly increased length of stay ((136.9±24.5) hours vs.(70.4±11.3) hours)in Surgical Intensive Care Unit.Conclusions Critically ill patients undergoing AAA repair have a high incidence of AKI,which can be early recognized by RIFLE criteria.Rupture,hypotension,and blood transfusion are the significant associated risk factors.Application of goal-directed hemodynamic optimization in this cohort appeared to be effective in improving renal outcome.

  2. Acute kidney injury with hydroxyethyl starch 130/0.42 in severe sepsis

    DEFF Research Database (Denmark)

    Müller, Rasmus Gamborg; Haase, Nicolai; Lange, T;

    2015-01-01

    BACKGROUND: We aimed to detail the effects of hydroxyethyl starch (HES) vs. Ringer's on kidney function including the interaction with mortality in post-hoc analyses as resuscitation with HES 130/0.42 increased mortality in the Scandinavian Starch for Severe Sepsis/Septic Shock (6S) trial. METHODS...

  3. Drug-related Kidney Injury and Safe Pharmacotherapy in the Elderly

    NARCIS (Netherlands)

    J.C. van Blijderveen (Nico)

    2014-01-01

    markdownabstract__Abstract__ The kidney performs two functions that are essential for life. First, it participates in the homeostasis of the extracellular environment that is required for adequate functioning of the cells. This is achieved by excretion of some of the waste products of metabolism an

  4. Adenovirus-mediated interteukin-13 gene therapy attenuates acute kidney allograft injury

    NARCIS (Netherlands)

    Sandovici, Maria; Deelmani, Leo E.; van Goor, Harry; Helfrich, Wijnand; de Zeeuw, Dick; Henning, Robert H.

    2007-01-01

    Background Kidney transplantation is possible by virtue of systemic immunosuppression, which is in turn accompanied by serious side effects. The search for novel therapeutic agents and strategies is ongoing. Here we investigate the effects of adenovirus-mediated gene therapy with interleukin (IL)-13

  5. Acute arterial occlusion - kidney

    Science.gov (United States)

    Acute renal arterial thrombosis; Renal artery embolism; Acute renal artery occlusion; Embolism - renal artery ... kidney can often result in permanent kidney failure. Acute arterial occlusion of the renal artery can occur after injury or trauma to ...

  6. Functional imaging of acute kidney injury at 3 Tesla. Investigating multiple parameters using DCE-MRI and a two-compartment filtration model

    Energy Technology Data Exchange (ETDEWEB)

    Zoellner, Frank G.; Zimmer, Fabian; Schad, Lothar R. [Heidelberg Univ., Mannheim (Germany). Computer Assisted Clinical Medicine; Klotz, Sarah; Hoeger, Simone [Heidelberg Univ., Mannheim (Germany). Dept. of Medicine V

    2015-05-01

    To investigate how MR-based parameters reflect functional changes in kidneys with acute kidney injury (AKI) using dynamic contrast enhanced MRI and a two-compartment renal filtration model. MRI data of eight male Lewis rats were analyzed retrospectively. Five animals were subjected to AKI, three native rats served as control. All animals underwent perfusion imaging by dynamic contrast-enhanced MRI. Renal blood volume, glomerular filtration rate (GFR) as well as plasma and tubular mean transit times were estimated from regions-of-interest drawn in the renal cortex. Differences between healthy kidneys and kidneys subjected to AKI were analyzed using a paired t-test. Significant differences between ischemic and healthy kidneys could only be detected for the glomerular filtration rate. For all other calculated parameters, differences were present, however not significant. In rats with AKI, average single kidney GFR was 0.66 ± 0.37 ml/min for contralateral and 0.26 ± 0.12 ml/ min for diseased kidneys (P = 0.0254). For the healthy control group, the average GFR was 0.39 ± 0.06 ml/min and 0.41 ± 0.11 ml/min, respectively. Differences between diseased kidneys of AKI rats and ipsilateral kidneys of the healthy control group were significant (P=0.0381). Significant differences of functional parameters reflecting damage of the renal tissue of kidneys with AKI compared to the contralateral, healthy kidneys could only be detected by GFR. GFR might be a useful parameter that allows for a spatially resolved detection of abnormal changes of renal tissue by AKI.

  7. Reduction of proteinuria in adriamycin-induced nephropathy is associated with reduction of renal kidney injury molecule (Kim-1) over time

    NARCIS (Netherlands)

    Kramer, Andrea B.; van Timmeren, Mirjan M.; Schuurs, Theo A.; Vaidya, Vishal S.; Bonventre, Joseph V.; van Goor, Harry; Navis, Gerjan

    2009-01-01

    Kramer AB, van Timmeren MM, Schuurs TA, Vaidya VS, Bonventre JV, van Goor H, Navis G. Reduction of proteinuria in adriamycin-induced nephropathy is associated with reduction of renal kidney injury molecule (Kim-1) over time. Am J Physiol Renal Physiol 296: F1136-F1145, 2009. First published February

  8. Invasive mechanical ventilation as a risk factor for acute kidney injury in the critically ill: A systematic review and meta-analysis

    NARCIS (Netherlands)

    J.P. van den Akker (Johannes); M. Egal (Mohamud); J. Groeneveld (Johan)

    2013-01-01

    textabstractIntroduction: Mechanical ventilation (MV) is commonly regarded as a risk factor for acute kidney injury (AKI) in the critically ill. We investigated the strength of this association and whether settings of tidal volume (Vt) and positive end-expiratory pressure (PEEP) affect the risk for

  9. The effect of acute kidney injury on long-term health-related quality of life : a prospective follow-up study

    NARCIS (Netherlands)

    Hofhuis, Jose G. M.; van Stel, Henk F.; Schrijvers, Augustinus J. P.; Rommes, Johannes H.; Spronk, Peter E.

    2013-01-01

    Introduction: Acute kidney injury (AKI) is a serious complication in critically ill patients admitted to the Intensive Care Unit (ICU). We hypothesized that ICU survivors with AKI would have a worse health-related quality of life (HRQOL) outcome than ICU survivors without AKI. Methods: We performed

  10. Urinary neutrophil gelatinase-associated lipocalin identifies critically ill young children with acute kidney injury following intensive care admission: A prospective cohort study

    NARCIS (Netherlands)

    A.J.M. Zwiers (Alexandra); S.N. de Wildt (Saskia); J.M. van Rosmalen (Joost); Y.B. de Rijke (Yolanda); E.A.B. Buijs (Erik ); D. Tibboel (Dick); K. Cransberg (Karlien)

    2015-01-01

    textabstractIntroduction: Children admitted to a pediatric intensive care unit (ICU) are at high risk of developing acute kidney injury (AKI). Although serum creatinine (SCr) levels are used in clinical practice, they are insensitive for early diagnosis of AKI. Urinary neutrophil gelatinase-associat

  11. Urinary neutrophil gelatinase-associated lipocalin identifies critically ill young children with acute kidney injury following intensive care admission: A prospective cohort study

    NARCIS (Netherlands)

    A.J.M. Zwiers (Alexandra); S.N. de Wildt (Saskia); J.M. van Rosmalen (Joost); Y.B. de Rijke (Yolanda); E.A.B. Buijs (Erik ); D. Tibboel (Dick); K. Cransberg (Karlien)

    2015-01-01

    markdownabstract#### Introduction Children admitted to a pediatric intensive care unit (ICU) are at high risk of developing acute kidney injury (AKI). Although serum creatinine (SCr) levels are used in clinical practice, they are insensitive for early diagnosis of AKI. Urinary neutrophil gelatinase

  12. Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Kidney Injury Molecule 1 (KIM1) in patients with diabetic nephropathy: a cross-sectional study and the effects of lisinopril

    DEFF Research Database (Denmark)

    Nielsen, S E; Schjoedt, K J; Astrup, A S

    2010-01-01

    Our aim was to evaluate the markers of tubulointerstitial damage, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule1 (KIM1) in Type 1 diabetic patients with different levels of albuminuria and in control subjects. In addition, the effect of renoprotective treatment...... on urinary NGAL was evaluated in diabetic nephropathy....

  13. Pilot Study of the Pharmacokinetics of Cefotaxime in Critically Ill Patients with Acute Kidney Injury Treated with Continuous Renal Replacement Therapy

    NARCIS (Netherlands)

    Koedijk, Joost B.; Valk-Swinkels, Corinne G. H.; Rijpstra, Tom A.; Touw, Daan J.; Mulder, Paul G. H.; Van Der Voort, Peter H. J.; Van 't Veer, Nils E.; Van Der Meer, Nardo J. M.

    2016-01-01

    The objective of this study was to describe the pharmacokinetics of cefotaxime (CTX) in critically ill patients with acute kidney injury (AKI) when treated with continuous renal replacement therapy (CRRT) in the intensive care unit (ICU). This single-center prospective observational pilot study was

  14. The effect of atorvastatin combined with probucol on contrast-induced acute kidney injury and serum uric acid in elderly patients

    Institute of Scientific and Technical Information of China (English)

    李作成

    2013-01-01

    Objective To observe the effect of different doses of atorvastatin combined with probucol on contrast-induced acute kidney injury(CIAKI) and serum uric acid in elderly patients. Methods Totally 121 cases admitted for coronary angioplasty were randomly divided into three

  15. An elderly 'kawara' craftsman with acute kidney injury and haemoptysis: a case of silica-induced autoimmunity.

    Science.gov (United States)

    Matsui, Satoshi; Tsuji, Hiroko; Ono, Shinji

    2011-02-01

    A 62-year-old Japanese 'kawara' (ceramic roof tile) craftsman presented with acute kidney injury and haemoptysis. This case met the systemic lupus erythematosus and microscopic polyangiitis criteria, with high titres of myeloperoxidase-antineutrophil cytoplasmic antibody (570 EU). Results showed the presence of antinuclear antibody at a high titre (1:2560), but detection of rheumatoid factor, anti-dsDNA, anti-SSA and anti-SSB antibodies was not apparent. This serology was similar to drug-induced, silicon-induced or silica-induced autoimmunity. The patient had been exposed to silica for > 40 years. The environmental aetiology of autoimmune diseases should be considered in cases that show atypical epidemiology and serology.

  16. Leveraging Big Data and Electronic Health Records to Enhance Novel Approaches to Acute Kidney Injury Research and Care.

    Science.gov (United States)

    Sutherland, Scott M; Goldstein, Stuart L; Bagshaw, Sean M

    2017-03-08

    While acute kidney injury (AKI) has been poorly defined historically, a decade of effort has culminated in a standardized, consensus definition. In parallel, electronic health records (EHRs) have been adopted with greater regularity, clinical informatics approaches have been refined, and the field of EHR-enabled care improvement and research has burgeoned. Although both fields have matured in isolation, uniting the 2 has the capacity to redefine AKI-related care and research. This article describes how the application of a consistent AKI definition to the EHR dataset can accurately and rapidly diagnose and identify AKI events. Furthermore, this electronic, automated diagnostic strategy creates the opportunity to develop predictive approaches, optimize AKI alerts, and trace AKI events across institutions, care platforms, and administrative datasets.

  17. Demographic data for urinary Acute Kidney Injury (AKI marker [IGFBP7]·[TIMP2] reference range determinations

    Directory of Open Access Journals (Sweden)

    Nandkishor S. Chindarkar

    2015-12-01

    Full Text Available This data in brief describes characteristics of chronic stable comorbid patients who were included in reference range studies of [IGFBP7]·[TIMP-2] “Reference Intervals of Urinary Acute Kidney Injury (AKI Markers [IGFBP7]·[TIMP2] in Apparently Healthy Subjects and Chronic Comorbid Subjects without AKI” [1]. In order to determine the specificity of [IGFBP7]·[TIMP-2] for identifying patients at risk of developing AKI we studied a cohort with nine broad classification of disease who did not have AKI. Details regarding the population that was targeted for inclusion in the study are also described. Finally, we present data on the inclusion criteria for the healthy subjects used in this investigation to determine the reference range.

  18. A Rare Cause of Acute Kidney Injury in a Female Patient with Breast Cancer Presenting as Renal Colic

    Directory of Open Access Journals (Sweden)

    Roxana Jurubita

    2016-01-01

    Full Text Available Renal infarction is a rare cause of acute kidney injury which could lead to permanent loss of renal function. A prompt diagnosis is necessary in order to achieve a successful revascularization of the occluded artery. Given the rarity of the disease and the paucity of the reported cases in the previous literature a high index of suspicion must be maintained not only in the classical cardiac sources of systemic emboli (atrial fibrillation, dilated cardiomyopathy, or endocarditis, but also in the situations when a hypercoagulable state is presumed. The unspecific presenting symptoms often mask the true etiology of the patient’s complaints. We present here a rare case of renal infarction that occurred in the setting of a hypercoagulable state, in a female patient with a history of breast cancer and documented hepatic metastases.

  19. Kidney Dysplasia

    Science.gov (United States)

    ... Disease Ectopic Kidney Medullary Sponge Kidney Kidney Dysplasia Kidney Dysplasia What is kidney dysplasia? Kidney dysplasia is a condition in which ... Kidney dysplasia in one kidney What are the kidneys and what do they do? The kidneys are ...

  20. Indoxyl Sulfate as a Mediator Involved in Dysregulation of Pulmonary Aquaporin-5 in Acute Lung Injury Caused by Acute Kidney Injury

    Directory of Open Access Journals (Sweden)

    Nozomi Yabuuchi

    2016-12-01

    Full Text Available High mortality of acute kidney injury (AKI is associated with acute lung injury (ALI, which is a typical complication of AKI. Although it is suggested that dysregulation of lung salt and water channels following AKI plays a pivotal role in ALI, the mechanism of its dysregulation has not been elucidated. Here, we examined the involvement of a typical oxidative stress-inducing uremic toxin, indoxyl sulfate (IS, in the dysregulation of the pulmonary predominant water channel, aquaporin 5 (AQP-5, in bilateral nephrectomy (BNx-induced AKI model rats. BNx evoked AKI with the increases in serum creatinine (SCr, blood urea nitrogen (BUN and serum IS levels and exhibited thickening of interstitial tissue in the lung. Administration of AST-120, clinically-used oral spherical adsorptive carbon beads, resulted in a significant decrease in serum IS level and thickening of interstitial tissue, which was accompanied with the decreases in IS accumulation in various tissues, especially lung. Interestingly, a significant decrease in AQP-5 expression of lung was observed in BNx rats. Moreover, the BNx-induced decrease in pulmonary AQP-5 protein expression was markedly restored by oral administration of AST-120. These results suggest that BNx-induced AKI causes dysregulation of pulmonary AQP-5 expression, in which IS could play a toxico-physiological role as a mediator involved in renopulmonary crosstalk.

  1. A unified theory of sepsis-induced acute kidney injury: inflammation, microcirculatory dysfunction, bioenergetics, and the tubular cell adaptation to injury.

    Science.gov (United States)

    Gomez, Hernando; Ince, Can; De Backer, Daniel; Pickkers, Peter; Payen, Didier; Hotchkiss, John; Kellum, John A

    2014-01-01

    Given that the leading clinical conditions associated with acute kidney injury (AKI), namely, sepsis, major surgery, heart failure, and hypovolemia, are all associated with shock, it is tempting to attribute all AKI to ischemia on the basis of macrohemodynamic changes. However, an increasing body of evidence has suggested that in many patients, AKI can occur in the absence of overt signs of global renal hypoperfusion. Indeed, sepsis-induced AKI can occur in the setting of normal or even increased renal blood flow. Accordingly, renal injury may not be entirely explained solely on the basis of the classic paradigm of hypoperfusion, and thus other mechanisms must come into play. Herein, we put forward a "unifying theory" to explain the interplay between inflammation and oxidative stress, microvascular dysfunction, and the adaptive response of the tubular epithelial cell to the septic insult. We propose that this response is mostly adaptive in origin, that it is driven by mitochondria, and that it ultimately results in and explains the clinical phenotype of sepsis-induced AKI.

  2. Urat1-Uox double knockout mice are experimental animal models of renal hypouricemia and exercise-induced acute kidney injury.

    Science.gov (United States)

    Hosoyamada, Makoto; Tsurumi, Yu; Hirano, Hidenori; Tomioka, Naoko H; Sekine, Yuko; Morisaki, Takayuki; Uchida, Shunya

    2016-12-01

    Renal hypouricemia (RHUC) is a hereditary disease characterized by a low level of plasma urate but with normal urinary urate excretion. RHUC type 1 is caused by mutations of the urate transporter URAT1 gene (SLC22A12). However, the plasma urate levels of URAT1 knockout mice are no different from those of wild-type mice. In the present study, a double knockout mouse, in which the URAT1 and uricase (Uox) genes were deleted (Urat1-Uox-DKO), were used as an experimental animal model of RHUC type 1 to investigate RHUC and excise-induced acute kidney injury (EIAKI). Mice were given a variable content of allopurinol for one week followed by HPLC measurement of urate and creatinine concentrations in spot urine and blood from the tail. The urinary excretion of urate in Urat1-Uox-DKO mice was approximately 25 times higher than those of humans. With allopurinol, the plasma urate levels of Urat1-Uox-DKO mice were lower than those of Uox-KO mice. There were no differences in the urinary urate excretions between Urat1-Uox-DKO and Uox-KO mice administered with 9 mg allopurinol /100 g feed. In the absence of allopurinol, plasma creatinine levels of some Urat1-Uox-DKO mice were higher than those of Uox-KO mice. Consequently, hypouricemia and normouricosuria may indicate that the Urat1-Uox-DKO mouse administered with allopurinol may represent a suitable animal model of RHUC type 1. Urat1-Uox-DKO mice without allopurinol exhibited acute kidney injury, thus providing additional benefit as a potential animal model for EIAKI. Finally, our data indicate that allopurinol appears to provide prophylactic effects for EIAKI.

  3. Fish Oil-Based Fat Emulsion Reduces Acute Kidney Injury and Inflammatory Response in Antibiotic-Treated Polymicrobial Septic Mice

    Directory of Open Access Journals (Sweden)

    Juey-Ming Shih

    2016-03-01

    Full Text Available Acute kidney injury (AKI is a common complication in sepsis. This study compared the effects of a fish oil-based with a mixed oil fat emulsion on remote renal injury in an antibiotic-treated septic murine model. Mice were randomly assigned to a normal control (NC group and three septic groups. Sepsis was induced by cecal ligation and puncture (CLP. The antibiotic was injected intraperitoneally (IP after CLP and then daily till the time of sacrifice. Three hours after antibiotic treatment, one of the septic groups was injected IP with a fish oil-based emulsion (FO, while the other two groups were given either a mixed oil emulsion (MO or saline (SC. The septic groups were further divided into two separate time groups, with blood and kidneys samples collected at 24 h or 72 h post-CLP. The results showed that sepsis leads to the activation of neutrophils, T helper (Th1/Th-2/Th-17 and Treg cells (p < 0.05. Plasma NGAL and mRNA expressions of renal MyD88 and TLR4 were also enhanced (p < 0.05. Compared to the SC group, the group given the fish oil-based emulsion had decreased plasma NGAL by 22% and Treg by 33%. Furthermore, renal gene expressions of MyD88 and TLR4 reduced by 46% and 62%, respectively, whereas heat shock protein 70 and peroxisome proliferator-activated receptor-γ increased by 158% and 69%, respectively (p < 0.05, at Day 3 after CLP. These results suggest that administration of a fish oil-based emulsion has favorable effects, maintaining blood T cell percentage, downregulating Treg expression, attenuating systemic and local inflammation and offering renal protection under conditions of antibiotic-treated polymicrobial sepsis.

  4. An association of losartan-hydrochlorothiazide, but not losartan-furosemide, completely arrests progressive injury in the remnant kidney.

    Science.gov (United States)

    Arias, Simone Costa Alarcon; Souza, Renata Alves; Malheiros, Denise Maria Avancini Costa; Fanelli, Camilla; Fujihara, Clarice Kazue; Zatz, Roberto

    2016-01-15

    We have previously shown that an association of losartan and hydrochlorothiazide, initiated 1 mo after 5/6 nephrectomy (Nx), reversed hypertension and albuminuria and promoted lasting renoprotection. In this new study, we investigated whether equal or even better protection could be obtained by combining losartan and furosemide. Nx was performed in 58 Munich-Wistar rats. One month later, tail-cuff pressure and albuminuria were markedly elevated. At this time, Nx rats were distributed among the following four groups: untreated Nx rats, Nx rats that received losartan, Nx rats that received losartan + hydrochlorothiazide, and Nx rats that received losartan + furosemide. Seven months later, Nx rats exhibited high mortality, severe hypertension, albuminuria, glomerulosclerosis, and interstitial fibrosis. Losartan treatment limited mortality and attenuated the renal and hemodynamic abnormalities associated with Nx. As previously shown, the losartan + hydrochlorothiazide association normalized tail-cuff pressure and albumin, prevented renal injury, and reduced mortality to zero. The losartan + furosemide treatment failed to reduce tail-cuff pressure or albumin to normal and prevented renal injury less efficiently than the losartan and hydrochlorothiazide regimen. The reasons for the differing efficacies of the losartan + furosemide and losartan + hydrochlorothiazide schemes are unclear and may include beneficial nondiuretic actions of thiazides, such as vasorelaxation and antiproliferative activity. These results refute the established concept that thiazides and thiazide-like diuretics are ineffective at advanced chronic kidney disease stages. Rather, they suggest that, in view of their renoprotective action, these compounds may even be preferable to loop diuretics in the management of hypertension in advanced chronic kidney disease.

  5. The restrained expression of NF-kB in renal tissue ameliorates folic acid induced acute kidney injury in mice.

    Directory of Open Access Journals (Sweden)

    Dev Kumar

    Full Text Available The Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB represent family of structurally-related eukaryotic transcription factors which regulate diverse array of cellular processes including immunological responses, inflammation, apoptosis, growth & development. Increased expression of NF-kB has often been seen in many diverse diseases, suggesting the importance of genomic deregulation to disease pathophysiology. In the present study we focused on acute kidney injury (AKI, which remains one of the major risk factor showing a high rate of mortality and morbidity. The pathology associated with it, however, remains incompletely known though inflammation has been reported to be one of the major risk factor in the disease pathophysiology. The role of NF-kB thus seemed pertinent. In the present study we show that high dose of folic acid (FA induced acute kidney injury (AKI characterized by elevation in levels of blood urea nitrogen & serum creatinine together with extensive tubular necrosis, loss of brush border and marked reduction in mitochondria. One of the salient observations of this study was a coupled increase in the expression of renal, relA, NF-kB2, and p53 genes and proteins during folic acid induced AKI (FA AKI. Treatment of mice with NF-kB inhibitor, pyrrolidine dithio-carbamate ammonium (PDTC lowered the expression of these transcription factors and ameliorated the aberrant renal function by decreasing serum creatinine levels. In conclusion, our results suggested that NF-kB plays a pivotal role in maintaining renal function that also involved regulating p53 levels during FA AKI.

  6. Acute kidney injury in patients with systemic sclerosis participating in hematopoietic cell transplantation trials in the United States.

    Science.gov (United States)

    Hosing, Chitra; Nash, Richard; McSweeney, Peter; Mineishi, Shin; Seibold, James; Griffith, Linda M; Shulman, Howard; Goldmuntz, Ellen; Mayes, Maureen; Parikh, Chirag R; Crofford, Leslie; Keyes-Elstein, Lynette; Furst, Daniel; Steen, Virginia; Sullivan, Keith M

    2011-05-01

    Recipients of hematopoietic cell transplantation may be at risk for developing acute kidney injury (AKI), and this risk may be increased in patients who undergo transplantation for severe systemic sclerosis (SSc) due to underlying scleroderma renal disease. AKI after transplantation can increase treatment-related mortality. To better define these risks, we analyzed 91 patients with SSc who were enrolled in 3 clinical trials in the United States of autologous or allogeneic hematopoietic cell transplantation (HCT). Eleven (12%) of the 91 patients with SSc in these studies (8 undergoing autologous HCT, 1 undergoing allogeneic HCT, 1 pretransplantation, 1 given i.v. cyclophosphamide on a transplantation trial) experienced AKI, of whom 8 required dialysis and/or therapeutic plasma exchange. AKI injury in the 9 HCT recipients developed a median of 35 days (range, 0-90 days) after transplantation. Ten of 11 patients with AKI received angiotensin-converting enzyme inhibitor (ACE-I) therapy. The etiology of AKI was attributed to scleroderma renal crisis in 6 patients (including 2 with normotensive renal crisis), to AKI of uncertain etiology in 2 patients, and to AKI superimposed on scleroderma kidney disease in 3 patients. Eight of the 11 patients died, one each because of progression of SSc, multiorgan failure, gastrointestinal and pulmonary bleeding, pericardial tamponade and pulmonary complications, diffuse alveolar hemorrhage, pulmonary embolism, graft-versus-host disease, and malignancy. Limiting nephrotoxins, cautious use of corticosteroids, renal shielding during total body irradiation, strict control of blood pressure, and aggressive use of ACE-Is may be of importance in preventing renal complications after HCT for SSc.

  7. PROSPECTIVE STUDY OF ETIOLOGY, CLINICAL PROFILE AND OUTCOME IN PATIENTS WITH FEVER, JAUNDICE AND ACUTE KIDNEY INJURY

    Directory of Open Access Journals (Sweden)

    Pradeep

    2015-09-01

    Full Text Available OBJECTIVE: To study etiology, risk factors, various clinical and lab parameters and outcome of patients presenting with fever, jaundice and acute kidney injury. MATERIALS AND METHODS : An open prospective study was done on 100 patients presented with triad of fever, jaundice and acute kidney injury (AKI in the Depar tment of Medicine of G R Medical College and JA Group of Hospitals, Gwalior, MP from September 2011 to November 2012. Patients having temperature more than >100 0 F, serum creatinine ≥1.3 mg/dL or a 50 % increase from baseline or a reduction in urine output (documented oliguria of 6 hours, serum bilirubin >1.8 mg/dL were included in the study. A detailed history, clinical examination and investigations were done to find the cause of these derangements and all the patients were managed acc ordingly. RESULTS: A total 100 patients were included in study out of which 70% were males. Out of 100 patients, 50% were of septicemia, 34% were having malaria, 12% had acute pancreatitis and 4% patients were of dengue. Out of 50 septicemia patients, 35(7 0% were male, out of which 11(31.42% were of 56 - 65 years of age. Out of 17 deaths, 13(76% were males. Among total death, 11(22% were in septicemia followed by 5(14.70% in malaria patients. CONCLUSION: Many infectious and non - infectious diseases like malaria, septicemia, acute pancreatitis, dengue fever etc. can present with fever, jaundice and deranged renal functions. This triad of presentation is associated wi th high morbidity and mortality and the advanced age, male gender presences of anemia were the risk factors for high mortality. AKI occurs most commonly in association with P. falciparum malaria. Early diagnosis and prompt management including dialysis can reduce mortality and expedite recovery of renal function

  8. Incidence and Progression of Cardiac Surgery-associated Acute Kidney Injury and its Relationship with Bypass and Cross Clamp Time

    Science.gov (United States)

    Karim, Habib Md Reazaul; Yunus, Mohd; Saikia, Manuj Kumar; Kalita, Jyoti Prasad; Mandal, Mrinal

    2017-01-01

    Introduction: Cardiac surgery-associated kidney injury (CSA-AKI) is common but relatively less is known about its progression. The present study is aimed at evaluating the incidence and course of CSA-AKI and its relationship with the different durations of cardiopulmonary bypass (CPB) and cross clamp times. Materials and Methods: Occurrences of CSA-AKI are evaluated as per the Akin Kidney Injury Network (AKIN) criteria over the course of 5 postoperative day (POD) in 100 patients. The relationship of different durations of CPB and aortic cross clamp time with CSA-AKI is analyzed by Chi-squared test for trend and other appropriate tests using INSTAT software. Results: One hundred (43 male, 57 female; mean age of 37.01 ± 12.28 years, and baseline mean serum creatinine 0.99 ± 0.20 mg %) patients undergone mostly valve replacement, and congenital heart disease correction was evaluated. Nearly 49% suffered CSA-AKI (81.63% AKIN Class I) with maximum numbers on 2nd POD. Serum creatinine followed a falling trend 3rd POD onward except in 8.16% cases of CSA-AKI. Oliguria was absent even in AKIN Class II. The CPB time >70 min and cross clamp time >60 min increase CSA-AKI risk by an OR of 4.76 and 2.84, respectively (P < 0.05). Conclusion: CSA-AKI is very prevalent; mostly of AKIN Class I and increases with increasing CPB and cross clamp time. Urine output is not a reliable indicator of CSA-AKI. The AKIN Class II on the very 1st POD or increasing trend of serum creatinine beyond 3rd POD should alert for early intervention. PMID:28074790

  9. Acute Kidney Injury in Severe Sepsis and Septic Shock in Patients with and without Diabetes Mellitus: A Multicenter Study.

    Directory of Open Access Journals (Sweden)

    Marion Venot

    Full Text Available Whether diabetes mellitus increases the risk of acute kidney injury (AKI during sepsis is controversial.We used a case-control design to compare the frequency of AKI, use of renal replacement therapy (RRT, and renal recovery in patients who had severe sepsis or septic shock with or without diabetes. The data were from the Outcomerea prospective multicenter database, in which 12 French ICUs enrolled patients admitted between January 1997 and June 2009.First, we compared 451 patients with severe sepsis or septic shock and diabetes to 3,277 controls with severe sepsis or septic shock and without diabetes. Then, we compared 318 cases (with diabetes to 746 matched controls (without diabetes. Diabetic patients did not have a higher frequency of AKI (hazard ratio [HR], 1.18; P = 0.05] or RRT (HR, 1.09; P = 0.6. However, at discharge, diabetic patients with severe sepsis or septic shock who experienced acute kidney injury during the ICU stay and were discharged alive more often required RRT (9.5% vs. 4.8%; P = 0.02, had higher serum creatinine values (134 vs. 103 µmoL/L; P<0.001 and had less often recovered a creatinine level less than 1.25 fold the basal creatinine (41.1% vs. 60.5%; P<0.001.In patients with severe sepsis or septic shock, diabetes is not associated with occurrence of AKI or need for RRT but is an independent risk factor for persistent renal dysfunction in patients who experience AKI during their ICU stay.

  10. Erythropoietin-enhanced endothelial progenitor cell recruitment in peripheral blood and renal vessels during experimental acute kidney injury in rats.

    Science.gov (United States)

    Cakiroglu, Figen; Enders-Comberg, Sora Maria; Pagel, Horst; Rohwedel, Jürgen; Lehnert, Hendrik; Kramer, Jan

    2016-03-01

    Beneficial effects of erythropoietin (EPO) have been reported in acute kidney injury (AKI) when administered prior to induction of AKI. We studied the effects of EPO administration on renal function shortly after ischemic AKI. For this purpose, rats were subjected to renal ischemia for 30 min and EPO was administered at a concentration of 500 U/kg either i.v. as a single shot directly after ischemia or with an additional i.p. dose until 3 days after surgery. The results were compared with AKI rats without EPO application and a sham-operated group. Renal function was assessed by measurement of serum biochemical markers, histological grading, and using an isolated perfused kidney (IPK) model. Furthermore, we performed flow cytometry to analyze the concentration of endothelial progenitor cells (EPCs) in the peripheral blood and renal vessels. Following EPO application, there was only a statistically non-significant tendency of serum creatinine and urea to improve, particularly after daily EPO application. Renal vascular resistance and the renal perfusion rate were not significantly altered. In the histological analysis, acute tubular necrosis was only marginally ameliorated following EPO administration. In summary, we could not demonstrate a significant improvement in renal function when EPO was applied after AKI. Interestingly, however, EPO treatment resulted in a highly significant increase in CD133- and CD34-positive EPC both in the peripheral blood and renal vessels.

  11. Treatment of Metformin Intoxication Complicated by Lactic Acidosis and Acute Kidney Injury: The Role of Prolonged Intermittent Hemodialysis.

    Science.gov (United States)

    Regolisti, Giuseppe; Antoniotti, Riccardo; Fani, Filippo; Greco, Paolo; Fiaccadori, Enrico

    2017-02-17

    Metformin intoxication with lactic acidosis, a potentially lethal condition, may develop in diabetic patients when the drug dose is inappropriate and/or its clearance is reduced. Diagnosis and therapy may be delayed due to nonspecific symptoms at presentation, with severe anion gap metabolic acidosis and elevated serum creatinine values being the most prominent laboratory findings. Confirmation requires measurement of serum metformin by high-performance liquid chromatography-tandem mass spectrometry, but this technique is available only at specialized institutions and cannot be relied on as a guide to immediate treatment. Thus, based on strong clinical suspicion, renal replacement therapy must be started promptly to achieve efficient drug clearance and correct the metabolic acidosis. However, because metformin accumulates in the intracellular compartment with prolonged treatment, a rebound in serum concentrations due to redistribution is expected at the end of dialysis. We report a case of metformin intoxication, severe lactic acidosis, and acute kidney injury in a diabetic patient with pre-existing chronic kidney disease stage 3, treated effectively with sustained low-efficiency dialysis. We discuss the pathophysiology, differential diagnosis, and treatment options and highlight specific pharmacokinetic issues that should be considered in selecting the appropriate modality of renal replacement therapy