Sonographic assessment of normal renal parenchymal and medullary pyramid thicknesses among children in Enugu, Southeast, Nigeria

International Nuclear Information System (INIS)

Eze, C.U.; Akpan, V.P.; Nwadike, I.U.

2016-01-01

Background: Renal parenchymal thickness (RPT) and renal medullary pyramid thickness (MPT) are important renal size parameters. This study was aimed at establishing normograms for RPT and MPT with respect to age and somatometric parameters among children. Methods: This was a cross sectional study done in Enugu, Nigeria between May 2013 and April 2014. The subjects were 512 children aged 1–17 years scanned with ultrasound equipment with 3.5 MHz and 5 MHz curvilinear transducers. The RPT was measured perpendicularly to the long axis of the kidney from the medullary papilla to the renal capsule and MPT was measured from the apex to the base of the medullary pyramid on the same plane. The age and somatometric parameters of the subjects were recorded. Results: The mean ± SD of RPT and MPT for the right kidney were 12.62 ± 1.67 mm and 7.10 ± 0.92 mm and the left kidney were 12.81 ± 1.7 and 7.23 ± 0.94 mm respectively. There was a significant difference between the right and left RPT and MPT (p < 0.05). The right and left RPT correlated strongly with age, body surface area (BSA), height, and weight but moderately with body mass index (BMI). A moderate positive correlation was observed between MPT and age, BSA, height, and weight. However, a weak correlation was observed between MPT and BMI. Conclusion: Normograms of RPT and MPT in relation to age could be useful for grading hydronephrosis in children. - Highlights: • Sonography of RPT and MPT at the anterior longitudinal axis of the kidney is simple. • RPT and MPT Measurements are reliable within and between experienced sonographers. • No significant gender differences in RPT and MPT values exist in this study. • Significant differences exist between the right and left RPT and MPT measurements. • Normative values of RPT and MPT in relation to age in children are useful.

Respiratory Syncytial Virus Aggravates Renal Injury through Cytokines and Direct Renal Injury

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Songhui Zhai

2016-09-01

Full Text Available The purpose of this study was to investigate the relationship between renal injury and reinfection that is caused by respiratory syncytial virus (RSV and to analyze the mechanism of renal injury. Rats were repeatedly infected with RSV on days 4, 8, 14, and 28, then sacrificed and examined on day 56 after the primary infection. Renal injury was examined by transmission electron microscopy and histopathology. The F protein of RSV was detected in the renal tissue by indirect immunofluorescence. Proteinuria and urinary glycosaminoglycans (GAGs, serum levels of albumin, urea nitrogen, and creatinine, secretion of cytokines, T lymphocyte population and subsets, and dendritic cell (DC activation state were examined. The results showed that renal injury was more serious in the reinfection group than in the primary infection group. At a higher infection dose, 6×106 PFU, the renal injury was more severe, accompanied by higher levels of proteinuria and urinary GAGs excretion, and lower levels of serum albumin. Podocyte foot effacement was more extensive, and hyperplasia of mesangial cells and proliferation of mesangial matrix were observed. The maturation state of DCs was specific, compared with the primary infection. There was also a decrease in the ratio of CD4+ to CD8+T lymphocytes, due to an increase in the percentage of CD8+T lymphocytes and a decrease in the percentage of CD4+T lymphocytes, and a dramatic increase in the levels of IL-6 and IL-17. In terms of the different reinfection times, the day 14 reinfection group yielded the most serious renal injury and the most significant change in immune function. RSV F protein was still expressed in the glomeruli 56 days after RSV infection. Altogether, these results reveal that RSV infection could aggravate renal injury, which might be due to direct renal injury caused by RSV and the inflammatory lesions caused by the anti-virus response induced by RSV.

Medullary cystic disease of the kidney: report of a case diagnosed by ultrasonography and computed tomography examinations

International Nuclear Information System (INIS)

Carvalho, Tarcisio Nunes; Araujo Junior, Cyrillo Rodrigues de; Fraguas Filho, Sergio Roberto; Costa, Marlos Augusto Bittencourt; Teixeira, Kim-Ir-Sen Santos; Ribeiro, Flavia Aparecida de Souza

2003-01-01

The terms medullary cystic disease, juvenile nephronophthisis or medullary cystic disease complex refer to a group of similar diseases in which the basic pathological abnormality is progressive renal tubular atrophy with secondary glomerular sclerosis and medullary cystic formation. Medullary cystic disease is an important cause of renal failure in adolescent patients. Imaging methods play a primary role in the diagnosis of these diseases. Cysts are characteristically seen in the renal medulla and cortico medullary junction whereas kidneys may be of normal to small size. In this article we present the ultrasonography and computed tomography findings of a female adolescent patient with characteristic clinical picture of medullary cystic disease. (author)

Renal denervation prevents long-term sequelae of ischemic renal injury

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Kim, Jinu; Padanilam, Babu J.

2014-01-01

Signals that drive interstitial fibrogenesis after renal ischemia reperfusion injury remain undefined. Sympathetic activation is manifest even in the early clinical stages of chronic kidney disease and is directly related to disease severity. A role for renal nerves in renal interstitial fibrogenesis in the setting of ischemia reperfusion injury has not been studied. In male 129S1/SvImJ mice, ischemia reperfusion injury induced tubulointerstitial fibrosis as indicated by collagen deposition and profibrotic protein expression 4 to 16 days after the injury.. Leukocyte influx, proinflammatory protein expression, oxidative stress, apoptosis, and cell cycle arrest at G2/M phase were enhanced after ischemia reperfusion injury. Renal denervation at the time of injury or up to 1 day post-injury improved histology, decreased proinflammatory/profibrotic responses and apoptosis, and prevented G2/M cell cycle arrest in the kidney. Treatment with afferent nerve-derived calcitonin gene-related peptide (CGRP) or efferent nerve-derived norepinephrine in denervated and ischemia reperfusion injury-induced kidneys mimicked innervation, restored inflammation and fibrosis, induced G2/M arrest, and enhanced TGF-β1 activation. Blocking norepinephrine or CGRP function using respective receptor blockers prevented these effects. Consistent with the in vivo study, treatment with either norepinephrine or CGRP induced G2/M cell cycle arrest in HK-2 proximal tubule cells, whereas antagonists against their respective receptors prevented G2/M arrest. Thus, renal nerve stimulation is a primary mechanism and renal nerve-derived factors drive epithelial cell cycle arrest and the inflammatory cascade causing interstitial fibrogenesis after ischemia reperfusion injury. PMID:25207878

Fructokinase activity mediates dehydration-induced renal injury.

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Roncal Jimenez, Carlos A; Ishimoto, Takuji; Lanaspa, Miguel A; Rivard, Christopher J; Nakagawa, Takahiko; Ejaz, A Ahsan; Cicerchi, Christina; Inaba, Shinichiro; Le, MyPhuong; Miyazaki, Makoto; Glaser, Jason; Correa-Rotter, Ricardo; González, Marvin A; Aragón, Aurora; Wesseling, Catharina; Sánchez-Lozada, Laura G; Johnson, Richard J

2014-08-01

The epidemic of chronic kidney disease in Nicaragua (Mesoamerican nephropathy) has been linked with recurrent dehydration. Here we tested whether recurrent dehydration may cause renal injury by activation of the polyol pathway, resulting in the generation of endogenous fructose in the kidney that might subsequently induce renal injury via metabolism by fructokinase. Wild-type and fructokinase-deficient mice were subjected to recurrent heat-induced dehydration. One group of each genotype was provided water throughout the day and the other group was hydrated at night, after the dehydration. Both groups received the same total hydration in 24 h. Wild-type mice that received delayed hydration developed renal injury, with elevated serum creatinine, increased urinary NGAL, proximal tubular injury, and renal inflammation and fibrosis. This was associated with activation of the polyol pathway, with increased renal cortical sorbitol and fructose levels. Fructokinase-knockout mice with delayed hydration were protected from renal injury. Thus, recurrent dehydration can induce renal injury via a fructokinase-dependent mechanism, likely from the generation of endogenous fructose via the polyol pathway. Access to sufficient water during the dehydration period can protect mice from developing renal injury. These studies provide a potential mechanism for Mesoamerican nephropathy.

MR imaging of medullary streaks in osteosclerosis: a case report

International Nuclear Information System (INIS)

Lee, Hak Soo; Joo, Kyung Bin; Park, Tae Soo; Song, Ho Taek; Kim, Yong Soo; Park, Dong Woo; Park, Choong Ki

2000-01-01

We present a case of medullary sclerosis of the appendicular skeleton in a patient with chronic renal insufficiency for whom MR imaging findings were characteristic. T1- and T2-weighted MR images showed multiple vertical lines (medullary streaks) of low signal intensity in the metaphyses and diaphyses of the distal femur and proximal tibia

Dynamic autoregulation and renal injury in Dahl rats

DEFF Research Database (Denmark)

Karlsen, F M; Andersen, C B; Leyssac, P P

1997-01-01

of hypertension, a gradual impairment of autoregulatory control of renal blood flow might expose the glomerular circulation to periods of elevated pressure, resulting in renal injuries in Dahl S rats. Dynamic autoregulatory capacity was assessed in Dahl S and Dahl salt-resistant (Dahl R) rats, SHR, and Sprague......-Dawley rats by inducing broad-band fluctuations in the arterial blood pressure and simultaneously measuring renal blood flow. Dynamic autoregulation was estimated by the transfer function using blood pressure as the input and renal blood flow as the output. Renal morphological injuries were evaluated in Dahl......The Dahl salt-sensitive (Dahl S) rat develops hypertension and renal injuries when challenged with a high salt diet and has been considered to be a model of chronic renal failure. Renal injuries appear very early in life compared with the spontaneously hypertensive rat (SHR). During the course...

Renal Medullary Carcinoma with an Aggressive Clinical Course: A Case Report and Review of the Literature

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Madhumati R. Kalavar

2017-01-01

Full Text Available Renal medullary carcinoma (RMC is a rare, yet aggressive malignancy of the kidney that is found predominantly in young patients with African descent and sickle cell hemoglobinopathies and most specifically sickle cell trait. Due to its aggressive nature, most cases have metastasis or local invasion at the time of diagnosis. Prognosis is extremely poor with survival less than 1 year after diagnosis. Here we present a case of metastatic RMC in a 29-year-old African female. Despite chemotherapy with cisplatin, gemcitabine, and paclitaxel, and initial shrinkage of the tumor, the patient died 5 months after diagnosis.

SMARCB1/INI1 inactivation in renal medullary carcinoma.

Science.gov (United States)

Calderaro, Julien; Moroch, Julien; Pierron, Gaelle; Pedeutour, Florence; Grison, Camille; Maillé, Pascale; Soyeux, Pascale; de la Taille, Alexandre; Couturier, Jérome; Vieillefond, Annick; Rousselet, Marie Christine; Delattre, Olivier; Allory, Yves

2012-09-01

Renal medullary carcinoma (RMC), a rare and highly aggressive tumour which occurs in patients with sickle-cell disease, shares many clinicopathological features with collecting duct carcinoma (CDC). The molecular mechanisms underlying RMC and CDC are mainly unknown, and there is ongoing debate about their status as distinct entities. Loss of expression of SMARCB1/INI1, a chromatin remodelling regulator and repressor of cyclin D1 transcription, has been reported recently in RMC. The aim of our study was to investigate if such loss of expression is specific for RMC. SMARCB1/INI1 genetic alterations and cyclin D1 expression were also studied. Using immunochemistry, neoplastic cells showed complete loss of SMARCB1/INI1 expression in all six cases of RMC but in only one of 22 cases of CDC. In two RMC cases investigated, comparative genomic hybridization demonstrated complete loss of one SMARCB1/INI1 allele, with no other genomic imbalances, and no mutations were found on the remaining allele. Cyclin D1 was expressed in all RMCs, suggesting that SMARCB1/INI1 inactivation may result in increased cyclin D1 transcription. The specific SMARCB1/INI1 inactivation observed in RMCs suggests that RMC and CDC are different entities. © 2012 Blackwell Publishing Ltd.

Blunt renal trauma in children: healing of renal injuries and recommendations for imaging follow-up

International Nuclear Information System (INIS)

Abdalati, H.; Bulas, D.I.; Sivit, C.J.; Majd, M.; Rushton, H.G.; Eichelberger, M.R.

1994-01-01

Initial CT grading of renal injury was correlated with the frequency of complications and the time course of healing in 35 children. All renal contusions (grade 1, 8) and small parenchymal lacerations (grade 2, 8) healed without complications. All lacerations extending to the collecting system (grade 3, 9) resulted in mild to severe loss of renal function with progressive healing over 4 months. One of four segmental infarcts (grade 4 A), and five of six vascular pedicle injuries (grade 4 B) resulted in severe loss of renal function. Complications, including urinoma (2), sepsis (1), hydronephrosis (1), and persistent hypertension (2), were limited to grade 3 and 4 injuries. Our results suggest that mild renal injuries do not require follow-up imaging. Major renal lacerations and vascular pedicle injuries, however, often result in loss of renal function and should be followed up closely due to the risk of delayed complications. Follow-up examinations should continue for 3-4 months until healing is documented. (orig.)

Upregulation of Interleukin-33 in obstructive renal injury

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Chen, Wei-Yu, E-mail: wychen624@cgmh.org.tw [Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan (China); Chang, Ya-Jen [Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan (China); Su, Chia-Hao [Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan (China); Tsai, Tzu-Hsien [Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan (China); Chen, Shang-Der [Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan (China); Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung, Taiwan (China); Hsing, Chung-Hsi [Department of Anesthesiology, Chi-Mei Medical Center, Tainan, Taiwan (China); Yang, Jenq-Lin, E-mail: jyang@adm.cgmh.org.tw [Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan (China)

2016-05-13

Interstitial fibrosis and loss of parenchymal tubular cells are the common outcomes of progressive renal diseases. Pro-inflammatory cytokines have been known contributing to the damage of tubular cells and fibrosis responses after renal injury. Interleukin (IL)-33 is a tissue-derived nucleus alarmin that drives inflammatory responses. The regulation and function of IL-33 in renal injury, however, is not well understood. To investigate the involvement of cytokines in the pathogenesis of renal injury and fibrosis, we performed the mouse renal injury model induced by unilateral urinary obstruction (UUO) and analyze the differentially upregulated genes between the obstructed and the contralateral unobstructed kidneys using RNA sequencing (RNAseq). Our RNAseq data identified IL33 and its receptor ST2 were upregulated in the UUO kidney. Quantitative analysis confirmed that transcripts of IL33 and ST2 were upregulated in the obstructed kidneys. Immunofluorescent staining revealed that IL-33 was upregulated in Vimentin- and alpha-SMA-positive interstitial cells. By using genetically knockout mice, deletion of IL33 reduced UUO-induced renal fibrosis. Moreover, in combination with BrdU labeling technique, we observed that the numbers of proliferating tubular epithelial cells were increased in the UUO kidneys from IL33-or ST2-deficient mice compared to wild type mice. Collectively, our study demonstrated the upregulation of IL-33/ST2 signaling in the obstructed kidney may promote tubular cell injury and interstitial fibrosis. IL-33 may serve as a biomarker to detect renal injury and that IL-33/ST2 signaling may represent a novel target for treating renal diseases. -- Highlights: •Interleukin (IL)-33 was upregulated in obstructed kidneys. •Interstitial myofibroblasts expressed IL-33 after UUO-induced renal injury. •Deficiency of IL33 reduced interstitial fibrosis and promoted tubular cell proliferation.

Several issues regarding evaluation of renal injury and renal insufficiency in patients with liver disease

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HAO Kunyan

2016-07-01

Full Text Available In patients with liver disease such as viral hepatitis and liver cirrhosis, renal injury and renal insufficiency can be generally classified as acute kidney injury (AKI, chronic kidney disease, and acute-on-chronic nephropathy. AKI can be classified as stage 1 (risk stage, stage 2 (injury stage, and stage 3 (failure stage. Traditionally hepatorenal syndrome is classified as types Ⅰ and Ⅱ, and in recent years, type Ⅲ hepatorenal syndrome with organic renal injury has been proposed. Hepatorenal disorder(HRD is used to describe any renal disease which occurs in patients with liver cirrhosis. At present, sensitive and accurate biochemical parameters used to evaluate renal function in patients with liver disease in clinical practice include estimated glomerular filtration rate, increase in serum creatinine within unit time, and serum cystatin C level, and urinary microalbumin level also plays an important role in the early diagnosis of nephropathy. Causes of liver disease, severity, complications including infection, nutritional status, therapeutic drugs, and underlying nephropathy may be associated with renal injury and renal insufficiency in patients with liver disease and should be differentiated.

[Heavy metal poisoning and renal injury in children].

Science.gov (United States)

Rong, Li-Ping; Xu, Yuan-Yuan; Jiang, Xiao-Yun

2014-04-01

Along with global environmental pollution resulting from economic development, heavy metal poisoning in children has become an increasingly serious health problem in the world. It can lead to renal injury, which tends to be misdiagnosed due to the lack of obvious or specific early clinical manifestations in children. Early prevention, diagnosis and intervention are valuable for the recovery of renal function and children's good health and growth. This paper reviews the mechanism of renal injury caused by heavy metal poisoning in children, as well as the clinical manifestations, diagnosis, and prevention and treatment of renal injury caused by lead, mercury, cadmium, and chromium.

Sympathetic nerve-derived ATP regulates renal medullary blood flow via vasa recta pericytes

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Scott S Wildman

2013-10-01

Full Text Available Pericyte cells are now known to be a novel locus of blood flow control, being able to regulate capillary diameter via their unique morphology and expression of contractile proteins. We have previously shown that exogenous ATP causes constriction of vasa recta via renal pericytes, acting at a variety of membrane bound P2 receptors on descending vasa recta, and therefore may be able to regulate medullary blood flow (MBF. Regulation of MBF is essential for appropriate urine concentration and providing essential oxygen and nutrients to this region of high, and variable, metabolic demand. Various sources of endogenous ATP have been proposed, including from epithelial, endothelial and red blood cells in response to stimuli such as mechanical stimulation, local acidosis, hypoxia, and exposure to various hormones. Extensive sympathetic innervation of the nephron has previously been shown, however the innervation reported has focused around the proximal and distal tubules, and ascending loop of Henle. We hypothesise that sympathetic nerves are an additional source of ATP acting at renal pericytes and therefore regulate MBF. Using a rat live kidney slice model in combination with video imaging and confocal microscopy techniques we firstly show sympathetic nerves in close proximity to vasa recta pericytes in both the outer and inner medulla. Secondly, we demonstrate pharmacological stimulation of sympathetic nerves in situ (by tyramine evokes pericyte-mediated vasoconstriction of vasa recta capillaries; inhibited by the application of the P2 receptor antagonist suramin. Lastly, tyramine-evoked vasoconstriction of vasa recta by pericytes is significantly less than ATP-evoked vasoconstriction. Sympathetic innervation may provide an additional level of functional regulation in the renal medulla that is highly localized. It now needs to be determined under which physiological/pathophysiological circumstances that sympathetic innervation of renal pericytes is

HV1 acts as a sodium sensor and promotes superoxide production in medullary thick ascending limb of Dahl salt-sensitive rats.

Science.gov (United States)

Jin, Chunhua; Sun, Jingping; Stilphen, Carly A; Smith, Susan M E; Ocasio, Hiram; Bermingham, Brent; Darji, Sandip; Guha, Avirup; Patel, Roshan; Geurts, Aron M; Jacob, Howard J; Lambert, Nevin A; O'Connor, Paul M

2014-09-01

We previously characterized a H(+) transport pathway in medullary thick ascending limb nephron segments that when activated stimulated the production of superoxide by nicotinamide adenine dinucleotide phosphate oxidase. Importantly, the activity of this pathway was greater in Dahl salt-sensitive rats than salt-resistant (SS.13(BN)) rats, and superoxide production was enhanced in low Na(+) media. The goal of this study was to determine the molecular identity of this pathway and its relationship to Na(+). We hypothesized that the voltage-gated proton channel, HV1, was the source of superoxide-stimulating H(+) currents. To test this hypothesis, we developed HV1(-/-) null mutant rats on the Dahl salt-sensitive rat genetic background using zinc-finger nuclease gene targeting. HV1 could be detected in medullary thick limb from wild-type rats. Intracellular acidification using an NH4Cl prepulse in 0 sodium/BaCl2 containing media resulted in superoxide production in thick limb from wild-type but not HV1(-/-) rats (Pthick limb and peritoneal macrophages only when HV1 was present. When fed a high-salt diet, blood pressure, outer medullary renal injury (tubular casts), and oxidative stress (4-hydroxynonenal staining) were significantly reduced in HV1(-/-) rats compared with wild-type Dahl salt-sensitive rats. We conclude that HV1 is expressed in medullary thick ascending limb and promotes superoxide production in this segment when intracellular Na(+) is low. HV1 contributes to the development of hypertension and renal disease in Dahl salt-sensitive rats. © 2014 American Heart Association, Inc.

Renal papillary necrosis

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... asking your provider. Alternative Names Necrosis - renal papillae; Renal medullary necrosis Images Kidney anatomy Kidney - blood and urine flow References Bushinsky DA, Monk RD. Nephrolithiasis and nephrocalcinosis. ...

Renal rescue of dopamine D2 receptor function reverses renal injury and high blood pressure

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Konkalmatt, Prasad R.; Asico, Laureano D.; Zhang, Yanrong; Yang, Yu; Drachenberg, Cinthia; Zheng, Xiaoxu; Han, Fei; Jose, Pedro A.; Armando, Ines

2016-01-01

Dopamine D2 receptor (DRD2) deficiency increases renal inflammation and blood pressure in mice. We show here that long-term renal-selective silencing of Drd2 using siRNA increases renal expression of proinflammatory and profibrotic factors and blood pressure in mice. To determine the effects of renal-selective rescue of Drd2 expression in mice, the renal expression of DRD2 was first silenced using siRNA and 14 days later rescued by retrograde renal infusion of adeno-associated virus (AAV) vector with DRD2. Renal Drd2 siRNA treatment decreased the renal expression of DRD2 protein by 55%, and DRD2 AAV treatment increased the renal expression of DRD2 protein by 7.5- to 10-fold. Renal-selective DRD2 rescue reduced the expression of proinflammatory factors and kidney injury, preserved renal function, and normalized systolic and diastolic blood pressure. These results demonstrate that the deleterious effects of renal-selective Drd2 silencing on renal function and blood pressure were rescued by renal-selective overexpression of DRD2. Moreover, the deleterious effects of 45-minute bilateral ischemia/reperfusion on renal function and blood pressure in mice were ameliorated by a renal-selective increase in DRD2 expression by the retrograde ureteral infusion of DRD2 AAV immediately after the induction of ischemia/reperfusion injury. Thus, 14 days after ischemia/reperfusion injury, the renal expression of profibrotic factors, serum creatinine, and blood pressure were lower in mice infused with DRD2 AAV than in those infused with control AAV. These results indicate an important role of renal DRD2 in limiting renal injury and preserving normal renal function and blood pressure. PMID:27358912

High-grade renal injuries are often isolated in sports-related trauma.

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Patel, Darshan P; Redshaw, Jeffrey D; Breyer, Benjamin N; Smith, Thomas G; Erickson, Bradley A; Majercik, Sarah D; Gaither, Thomas W; Craig, James R; Gardner, Scott; Presson, Angela P; Zhang, Chong; Hotaling, James M; Brant, William O; Myers, Jeremy B

2015-07-01

Most high-grade renal injuries (American Association for Surgery of Trauma (AAST) grades III-V) result from motor vehicle collisions associated with numerous concomitant injuries. Sports-related blunt renal injury tends to have a different mechanism, a solitary blow to the flank. We hypothesized that high-grade renal injury is often isolated in sports-related renal trauma. We identified patients with AAST grades III-V blunt renal injuries from four level 1 trauma centres across the United States between 1/2005 and 1/2014. Patients were divided into "Sport" or "Non-sport" related groups. Outcomes included rates of hypotension (systolic blood pressure 110bpm), concomitant abdominal injury, and procedural/surgical intervention between sports and non-sports related injury. 320 patients met study criteria. 18% (59) were sports-related injuries with the most common mechanisms being skiing, snowboarding and contact sports (25%, 25%, and 24%, respectively). Median age was 24 years for sports and 30 years for non-sports related renal injuries (p=0.049). Males were more commonly involved in sports related injuries (85% vs. 72%, p=0.011). Median injury severity score was lower for sports related injuries (10 vs. 27, pinjury scale scores. Sports related trauma was more likely to be isolated without other significant injury (69% vs. 39% (psports and non-sports renal injuries (p=0.30). Sports injuries had lower transfusion (7% vs. 47%, psports vs. 18% non-sports, p=0.95). High-grade sports-related blunt renal trauma is more likely to occur in isolation without other abdominal or thoracic injuries and clinicians must have a high suspicion of renal injury with significant blows to the flank during sports activities. Copyright © 2015 Elsevier Ltd. All rights reserved.

Update in the classification and treatment of complex renal injuries.

Science.gov (United States)

Reis, Leonardo Oliveira; Kim, Fernando J; Moore, Ernest E; Hirano, Elcio Shiyoiti; Fraga, Gustavo Pereira; Nascimento, Barto; Rizoli, Sandro

2013-01-01

The "Evidence-Based Telemedicine - Trauma and Acute Care Surgery" (EBT-TACS) Journal Club performed a critical review of the literature and selected three up-to-date articles on the management of renal trauma defined as American Association for the Surgery of Trauma (AAST) injury grade III-V. The first paper was the proposal for the AAST grade 4renal injury substratification into grades 4a (Low Risk) and 4b (High Risk). The second paper was a revision of the current AAST renal injury grading system, expanding to include segmental vascular injuries and to establish a more rigorous definition of severe grade IV and V renal injuries.The last article analyses the diagnostic angiography and angioembolization in the acute management of renal trauma using a national data set in the USA. The EBT-TACS Journal Club elaborated conclusions and recommendations for the management of high-grade renal trauma.

Individual renal function study using dynamic computed tomography

International Nuclear Information System (INIS)

Fukuda, Yutaka; Kiya, Keiichi; Suzuki, Yoshiharu

1990-01-01

Dynamic CT scans of individual kindneys were obtained after an intravenous bolus injection of contrast agent. Time-density curves measured from the renal cortex, medulla and pelvis revealed the changes in density produced by the contrast agent reflecting the differential phase of renal function. Renal cortical density increased rapidly after bolus administration and then renal medullary and pelvic density increased continuously. In analyzing time-density curve, the cortico-medullary junction time, which is the time when the cortical and medullary curves cross was 57±8 seconds in patients with normal renal function. The cortico-medullary junction time was delayed in patient with decreased glomerular filtration rate. The cortico-pelvic junction time, which is the time when the cortical and pelvic curves cross was 104±33 seconds in patients with normal renal function. The cortico-pelvic junction time was delayed in patients with declined urinary concentrating capacity. In patients with unilateral renal agenesis and patients who were treated surgically by ureteral sprits, the relationship between individual renal functions and these junction times was examined. As a result of study there were inversely significant correlations between C-M junction time and unilateral GFR and between C-P junction time and urinary concentrating capacity. These studies indicate that dynamic CT scanning is an effective way that individual renal function can be monitored and evaluated. (author)

High-grade renal injuries are often isolated in sports-related trauma

OpenAIRE

Patel, Darshan P.; Redshaw, Jeffrey D.; Breyer, Benjamin N.; Smith, Thomas G.; Erickson, Bradley A.; Majercik, Sarah D.; Gaither, Thomas W.; Craig, James R.; Gardner, Scott; Presson, Angela P.; Zhang, Chong; Hotaling, James M.; Brant, William O.; Myers, Jeremy B.

2015-01-01

© 2015 Elsevier Ltd. All rights reserved. Introduction: Most high-grade renal injuries (American Association for Surgery of Trauma (AAST) grades III-V) result from motor vehicle collisions associated with numerous concomitant injuries. Sports-related blunt renal injury tends to have a different mechanism, a solitary blow to the flank. We hypothesized that high-grade renal injury is often isolated in sports-related renal trauma. Material and methods: We identified patients with AAST grades III...

Emergent endovascular embolization of iatrogenic renal vascular injuries

International Nuclear Information System (INIS)

Liu Fengyong; Wang Maoqiang; Duan Feng; Wang Zhijun; Wang Zhongpu

2007-01-01

Objective: To evaluate the efficacy and safety of the interventional techniques for emergent treatment of iatrogenic renal injuries. Methods: Nine patients with iatrogenic renal vascular injuries were treated with superselective renal arterial embolization. The causes of renal injury included post-renal biopsy in 5 patients, endovascular interventional procedure-related in 2, post-renal surgery in 1, and post-percutaneous nephrostomy in 1 patient. The patients presented clinically with hemodynamical unstability with blood loss shock in 7 patients, severe flank pain in 7, and hematuria in 8 patients. Perirenal hematoma was confirmed in 8 patients by CT and ultrasonography. The embolization materials used were microcoils in 7 and standard stainless steel coils in 2 patients, associated with polyvinyl alcohol particles (PVA) in 5, and gelfoam particles in 2 cases. Results: Renal angiogram revealed intra-renal arteriovenous fistula in 6 cases, intrarenal pseudoaneurysm in 2 cases, and the contrast media extravasation in 1 patient. The technical success of the arterial embolization was achieved in all 9 cases within a single session. All angiographies documented complete obliteration of the abnormal vessels together with all major intrarenal arterial branches maintaining patent. Seven patients with hemodynamically compromise experienced immediate relief of their blood loss related symptoms, and another 7 with severe flank pain got relief progressively.. Hematuria ceased in 8 patients within 2-14 days after the embolization and impairment of renal function occurred after the procedure in 5 cases, including transient aggravation (n=3 )and developed new renal dysfunction (n=2). Two of these patients required hemodialysis. Perirenal hematoma were gradually absorbed on ultrasonography during 2-4 months after the procedures. Follow-up time ranged from 6-78 months (mean, 38 months), 4 patients died of other primary diseases of renal and multi-organ failures. Five patients are

The cellular basis of renal injury by radiation

International Nuclear Information System (INIS)

Williams, M.V.

1986-01-01

This review with substantial bibliography summarises renal assay techniques available and discusses the histological and functional studies leading to differing opinions between the belief that vascular injury provides a general explanation of the late effects of radiotherapy and the opposing view that parenchymal cell damage is more important. It is proposed that the link between glomerular and tubular function obscures the primary site of injury and that radiation injury will result in a reduction of functioning nephron mass by primary damage to the tubules or glomeruli. Compensatory renal vasodilation would close a positive feedback loop. Radiation could also cause direct vascular injury; decreased renal perfusion and hypertension would result. Again sensitisation to hypertensive vascular damage would close a feedback loop. (UK)

Nitric oxide, prostaglandins and angiotensin II in the regulation of renal medullary blood flow during volume expansion.

Science.gov (United States)

Moreno, Carol; Llinás, María T; Rodriguez, Francisca; Moreno, Juan M; Salazar, F Javier

2016-03-01

Regulation of medullary blood flow (MBF) is essential in maintaining renal function and blood pressure. However, it is unknown whether outer MBF (OMBF) and papillary blood flow (PBF) are regulated independently when extracellular volume (ECV) is enhanced. The aim of this study was to determine whether OMBF and PBF are differently regulated and whether there is an interaction between nitric oxide (NO), prostaglandins (PGs) and angiotensin II (Ang II) in regulating OMBF and PBF when ECV is enhanced. To achieve these goals, OMBF and PBF were measured by laser-Doppler in volume-expanded rats treated with a cyclooxygenase inhibitor (meclofenamate, 3 mg/kg) and/or a NO synthesis inhibitor (L-nitro-arginine methyl ester (L-NAME), 3 μg/kg/min) and/or Ang II (10 ng/kg/min). OMBF was unchanged by NO or PGs synthesis inhibition but decreased by 36 % (P blood flows to the outer medulla and renal papilla are differently regulated and showing that there is a complex interaction between NO, PGs and Ang II in regulating OMBF and PBF when ECV is enhanced.

The renin-angiotensin system; development and differentiation of the renal medulla

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Madsen, Kirsten; Robdrup Tinning, Anne; Marcussen, Niels

2013-01-01

on mechanisms of postnatal development the renal medulla and putting medullary developmental lesions into perspective with regard to the programming effect. Moreover, the renin-angiotensin system is critically involved in mammalian kidney development and signaling disorders give rise to developmental renal...... disturbances reaching into adulthood. A review of current knowledge of the role of the renin-angiotensin system for renal medullary development will be given. Acta Physiologica © 2013 Scandinavian Physiological Society....... lesions that has been associated with hypertension later in life. A consistent finding in both experimental animal models and in human case reports is atrophy of the renal medulla with developmental lesions to both medullary nephron segments and vascular development with concomitant functional...

MR measures of renal perfusion, oxygen bioavailability and total renal blood flow in a porcine model: noninvasive regional assessment of renal function.

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Wentland, Andrew L; Artz, Nathan S; Fain, Sean B; Grist, Thomas M; Djamali, Arjang; Sadowski, Elizabeth A

2012-01-01

Magnetic resonance imaging (MRI) may be a useful adjunct to current methods of evaluating renal function. MRI is a noninvasive imaging modality that has the ability to evaluate the kidneys regionally, which is lacking in current clinical methods. Other investigators have evaluated renal function with MRI-based measurements, such as with techniques to measure cortical and medullary perfusion, oxygen bioavailability and total renal blood flow (TRBF). However, use of all three techniques simultaneously, and therefore the relationships between these MRI-derived functional parameters, have not been reported previously. To evaluate the ability of these MRI techniques to track changes in renal function, we scanned 11 swine during a state of hyperperfusion with acetylcholine and a saline bolus and subsequently scanned during a state of hypoperfusion with the prolonged use of isoflurane anesthesia. For each time point, measurements of perfusion, oxygen bioavailability and TRBF were acquired. Measurements of perfusion and oxygen bioavailability were compared with measurements of TRBF for all swine across all time points. Cortical perfusion, cortical oxygen bioavailability, medullary oxygen bioavailability and TRBF significantly increased with the acetylcholine challenge. Cortical perfusion, medullary perfusion, cortical oxygen bioavailability and TRBF significantly decreased during isoflurane anesthesia. Cortical perfusion (Spearman's correlation coefficient = 0.68; P renal function. Maintenance of the medullary oxygen bioavailability in low blood flow states may reflect the autoregulation particular to this region of the kidney. The ability to non-invasively measure all three parameters of kidney function in a single MRI examination and to evaluate the relationships between these functional parameters is potentially useful for evaluating the state of the human kidneys in situ in future studies.

Vascular endothelial growth factor signaling is necessary for expansion of medullary microvessels during postnatal kidney development

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Robdrup Tinning, Anne; Jensen, Boye L; Johnsen, Iben

2016-01-01

Postnatal inhibition or deletion of angiotensin II (ANG II) AT1 receptors impairs renal medullary mircrovascular development through a mechanism that may include vascular endothelial growth factor (VEGF). The present study was designed to test if VEGF/VEGF receptor signaling is necessary....... In human fetal kidney tissue, immature vascular bundles appeared early in the third trimester (GA27-28) and expanded in size until term. Rat pups treated with the VEGF receptor-2 (VEGFR2) inhibitor vandetanib (100 mg·kg(-1)·day(-1)) from P7 to P12 or P10 to P16 displayed growth retardation and proteinuria...... for the development of the renal medullary microcirculation. Endothelial cell-specific immunolabeling of kidney sections from rats showed immature vascular bundles at postnatal day (P) 10 with subsequent expansion of bundles until P21. Medullary VEGF protein abundance coincided with vasa recta bundle formation...

Effect of indomethacin and salt depletion on renal proton MR imaging

International Nuclear Information System (INIS)

Heyman, S.N.; Mammen, M.

1991-01-01

Blockade of the synthesis of vasodilating prostaglandins with non-steroidal anti-inflammatory drugs (NSAID) renders the renal medulla susceptible to hypoxic injury with reduced renal function, especially in clinical conditions characterized by volume depletion. Alterations in renal hemodynamics and urine production may effect renal MR imaging under these circumstances. We injected salt-depleted and control rats undergoing proton MR imaging with indomethacin 10 mg/kg. Indomethacin abolished the cortico-medullary T2-gradient and markedly diminished the overall renal signal in salt-depleted rats only. These changes, which progressed over a period of 40 min after indomethacin was injected, probably result from renal oligemia and decreased urine production, with an associated decrease in T2-values. We suggest that a history of consumption of non-steroidal anti-inflammatory drugs should be obtained and taken into account in the evaluation of renal proton MR imaging, especially in the presence of salt and volume depletion. (orig.)

Endoplasmic Reticulum Chaperon Tauroursodeoxycholic Acid Attenuates Aldosterone-Infused Renal Injury

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Honglei Guo

2016-01-01

Full Text Available Aldosterone (Aldo is critically involved in the development of renal injury via the production of reactive oxygen species and inflammation. Endoplasmic reticulum (ER stress is also evoked in Aldo-induced renal injury. In the present study, we investigated the role of ER stress in inflammation-mediated renal injury in Aldo-infused mice. C57BL/6J mice were randomized to receive treatment for 4 weeks as follows: vehicle infusion, Aldo infusion, vehicle infusion plus tauroursodeoxycholic acid (TUDCA, and Aldo infusion plus TUDCA. The effect of TUDCA on the Aldo-infused inflammatory response and renal injury was investigated using periodic acid-Schiff staining, real-time PCR, Western blot, and ELISA. We demonstrate that Aldo leads to impaired renal function and inhibition of ER stress via TUDCA attenuates renal fibrosis. This was indicated by decreased collagen I, collagen IV, fibronectin, and TGF-β expression, as well as the downregulation of the expression of Nlrp3 inflammasome markers, Nlrp3, ASC, IL-1β, and IL-18. This paper presents an important role for ER stress on the renal inflammatory response to Aldo. Additionally, the inhibition of ER stress by TUDCA negatively regulates the levels of these inflammatory molecules in the context of Aldo.

Retrograde Renal Cooling to Minimize Ischemia

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Janet L. Colli

2013-01-01

Full Text Available Objective: During partial nephrectomy, renal hypothermia has been shown to decrease ischemia induced renal damage which occurs from renal hilar clamping. In this study we investigate the infusion rate required to safely cool the entire renal unit in a porcine model using retrograde irrigation of iced saline via dual-lumen ureteral catheter. Materials and Methods: Renal cortical, renal medullary, bowel and rectal temperatures during retrograde cooling in a laparoscopic porcine model were monitored in six renal units. Iced normal saline was infused at 300 cc/hour, 600 cc/hour, 1000 cc/hour and gravity (800 cc/hour for 600 seconds with and without hilar clamping. Results: Retrograde cooling with hilar clamping provided rapid medullary renal cooling and significant hypothermia of the medulla and cortex at infusion rates ≥ 600 cc/hour. With hilar clamping, cortical temperatures decreased at -0.9° C/min. reaching a threshold temperature of 26.9° C, and medullary temperatures decreased at -0.90 C/min. reaching a temperature of 26.1° C over 600 seconds on average for combined data at infusion rates ≥ 600 cc/hour. The lowest renal temperatures were achieved with gravity infusion. Without renal hilum clamping, retrograde cooling was minimal at all infusion rates. Conclusions: Significant renal cooling by gravity infusion of iced cold saline via a duel lumen catheter with a clamped renal hilum was achieved in a porcine model. Continuous retrograde irrigation with iced saline via a two way ureteral catheter may be an effective method to induce renal hypothermia in patients undergoing robotic assisted and/or laparoscopic partial nephrectomy.

Low-energy shock wave preconditioning reduces renal ischemic reperfusion injury caused by renal artery occlusion.

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Xue, Yuquan; Xu, Zhibin; Chen, Haiwen; Gan, Weimin; Chong, Tie

2017-07-01

To evaluate whether low energy shock wave preconditioning could reduce renal ischemic reperfusion injury caused by renal artery occlusion. The right kidneys of 64 male Sprague Dawley rats were removed to establish an isolated kidney model. The rats were then divided into four treatment groups: Group 1 was the sham treatment group; Group 2, received only low-energy (12 kv, 1 Hz, 200 times) shock wave preconditioning; Group 3 received the same low-energy shock wave preconditioning as Group 2, and then the left renal artery was occluded for 45 minutes; and Group 4 had the left renal artery occluded for 45 minutes. At 24 hours and one-week time points after reperfusion, serum inducible nitric oxide synthase (iNOS), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), creatinine (Cr), and cystatin C (Cys C) levels were measured, malondialdehyde (MDA) in kidney tissue was detected, and changes in nephric morphology were evaluated by light and electron microscopy. Twenty-four hours after reperfusion, serum iNOS, NGAL, Cr, Cys C, and MDA levels in Group 3 were significantly lower than those in Group 4; light and electron microscopy showed that the renal tissue injury in Group 3 was significantly lighter than that in Group 4. One week after reperfusion, serum NGAL, KIM-1, and Cys C levels in Group 3 were significantly lower than those in Group 4. Low-energy shock wave preconditioning can reduce renal ischemic reperfusion injury caused by renal artery occlusion in an isolated kidney rat model.

Protective effect of Urtica dioica L. on renal ischemia/reperfusion injury in rat.

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Sayhan, Mustafa Burak; Kanter, Mehmet; Oguz, Serhat; Erboga, Mustafa

2012-12-01

Renal ischemia-reperfusion (I/R) injury may occur after renal transplantation, thoracoabdominal aortic surgery, and renal artery interventions. This study was designed to investigate the effect of Urtica dioica L. (UD), in I/R induced renal injury. A total of 32 male Sprague-Dawley rats were divided into four groups: control, UD alone, I/R and I/R + UD; each group contain 8 animals. A rat model of renal I/R injury was induced by 45-min occlusion of the bilateral renal pedicles and 24-h reperfusion. In the UD group, 3 days before I/R, UD (2 ml/kg/day intraperitoneal) was administered by gastric gavage. All animals were sacrificed at the end of reperfusion and kidney tissues samples were obtained for histopathological investigation in all groups. To date, no more histopathological changes on intestinal I/R injury in rats by UD treatment have been reported. Renal I/R caused severe histopathological injury including tubular damage, atrophy dilatation, loss of brush border and hydropic epithelial cell degenerations, renal corpuscle atrophy, glomerular shrinkage, markedly focal mononuclear cell infiltrations in the kidney. UD treatment significantly attenuated the severity of intestinal I/R injury and significantly lowered tubulointerstitial damage score than the I/R group. The number of PCNA and TUNEL positive cells in the control and UD alone groups was negligible. When kidney sections were PCNA and TUNEL stained, there was a clear increase in the number of positive cells in the I/R group rats in the renal cortical tissues. However, there is a significant reduction in the activity of PCNA and TUNEL in kidney tissue of renal injury induced by renal I/R with UD therapy. Our results suggest that administration of UD attenuates renal I/R injury. These results suggest that UD treatment has a protective effect against renal damage induced by renal I/R. This protective effect is possibly due to its ability to inhibit I/R induced renal damage, apoptosis and cell proliferation.

Late evaluation of the relationship between morphological and functional renal changes and hypertension after non-operative treatment of high-grade renal injuries

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Pereira Júnior Gerson

2012-08-01

Full Text Available Abstract Objective To evaluate the anatomical and functional renal alterations and the association with post-traumatic arterial hypertension. Methods The studied population included patients who sustained high grades renal injury (grades III to V successfully non-operative management after staging by computed tomography over a 16-year period. Beyond the review of medical records, these patients were invited to the following protocol: clinical and laboratory evaluation, abdominal computed tomography, magnetic resonance angiography, DMSA renal scintigraphy, and ambulatory blood pressure monitoring. The hypertensive patients also were submitted to dynamic renal scintigraphy (99mTc EC, using captopril stimulation to verify renal vascular etiology. Results Of the 31 patients, there were thirteen grade III, sixteen grade IV (nine lacerations, and seven vascular lesions, and two grade V injuries. All the patients were asymptomatic and an average follow up post-injury of 6.4 years. None had abnormal BUN or seric creatinine. The percentage of renal volume reduction correlates with the severity as defined by OIS. There was no evidence of renal artery stenosis in Magnetic Resonance angiography (MRA. DMSA scanning demonstrated a decline in percentage of total renal function corresponding to injury severity (42.2 ± 5.5% for grade III, 35.3 ± 12.8% for grade IV, 13.5 ± 19.1 for grade V. Six patients (19.4% had severe compromised function ( Conclusions Late results of renal function after conservative treatment of high grades renal injuries are favorable, except for patients with grades IV with vascular injuries and grade V renal injuries. Moreover, arterial hypertension does not correlate with the grade of renal injury or reduction of renal function.

Renal autotransplantation--a possibility in the treatment of complex renal vascular diseases and ureteric injuries.

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Hau, Hans Michael; Bartels, Michael; Tautenhahn, Hans-Michael; Morgul, Mehmet Haluk; Fellmer, Peter; Ho-Thi, Phuc; Benckert, Christoph; Uhlmann, Dirk; Moche, Michael; Thelen, Armin; Schmelzle, Moritz; Jonas, Sven

2012-12-31

We report our contemporary experiences with renal autotransplantation in patients with complicated renal vascular diseases and/or complex ureteral injuries. Since its first performance, renal autotransplantation has been steadily improved and become a safe and effective procedure. Between 1998 and 2006, 6 renal autotransplantations in 6 patients were performed at the University Medical Center of Leipzig. After nephrectomy and renal perfusion ex vivo, the kidney was implanted standardized in the fossa iliaca. The vessels were anastomized to the iliac vessels, the ureter was reimplanted in an extravesical tunneled ureteroneocystostomy technique according to Lich-Gregoir. Demographic, clinical, and laboratory data of the patients were collected and analyzed for pre-, intra-, and postoperative period. Indications for renal autotransplantation were complex renovascular diseases in 2 patients (1 with fibromuscular dysplasia and 1 with Takayasu's arteritis) and in 4 patients with complex ureteral injuries. The median duration of follow-up was 9.7 years (range: 5.6-13.3). The laboratory values of our 6 patients showed improvements of creatinine, urea and blood pressure levels in comparison to the preoperative status at the end of follow-up period. The present study reports excellent results of renal autotransplantation in patients with renovascular disease or complex ureteric injuries. After a median follow-up of 9.7 years all 6 patients present with stable renal function as well as normal blood pressure values. Postoperative complications were observed with a rate comparable to other studies.

Urinary calprotectin and posttransplant renal allograft injury

DEFF Research Database (Denmark)

Tepel, Martin; Borst, Christoffer; Bistrup, Claus

2014-01-01

OBJECTIVE: Current methods do not predict the acute renal allograft injury immediately after kidney transplantation. We evaluated the diagnostic performance of urinary calprotectin for predicting immediate posttransplant allograft injury. METHODS: In a multicenter, prospective-cohort study of 144...... incipient renal transplant recipients, we postoperatively measured urinary calprotectin using an enzyme-linked immunosorbent assay and estimated glomerular filtration rate (eGFR) after 4 weeks, 6 months, and 12 months. RESULTS: We observed a significant inverse association of urinary calprotectin...... concentrations and eGFR 4 weeks after transplantation (Spearman r = -0.33; Prelative risk, 4.3; P

Renal Impairment with Sublethal Tubular Cell Injury in a Chronic Liver Disease Mouse Model.

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Tokiko Ishida

Full Text Available The pathogenesis of renal impairment in chronic liver diseases (CLDs has been primarily studied in the advanced stages of hepatic injury. Meanwhile, the pathology of renal impairment in the early phase of CLDs is poorly understood, and animal models to elucidate its mechanisms are needed. Thus, we investigated whether an existing mouse model of CLD induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC shows renal impairment in the early phase. Renal injury markers, renal histology (including immunohistochemistry for tubular injury markers and transmission electron microscopy, autophagy, and oxidative stress were studied longitudinally in DDC- and standard diet-fed BALB/c mice. Slight but significant renal dysfunction was evident in DDC-fed mice from the early phase. Meanwhile, histological examinations of the kidneys with routine light microscopy did not show definitive morphological findings, and electron microscopic analyses were required to detect limited injuries such as loss of brush border microvilli and mitochondrial deformities. Limited injuries have been recently designated as sublethal tubular cell injury. As humans with renal impairment, either with or without CLD, often show almost normal tubules, sublethal injury has been of particular interest. In this study, the injuries were associated with mitochondrial aberrations and oxidative stress, a possible mechanism for sublethal injury. Intriguingly, two defense mechanisms were associated with this injury that prevent it from progressing to apparent cell death: autophagy and single-cell extrusion with regeneration. Furthermore, the renal impairment of this model progressed to chronic kidney disease with interstitial fibrosis after long-term DDC feeding. These findings indicated that DDC induces renal impairment with sublethal tubular cell injury from the early phase, leading to chronic kidney disease. Importantly, this CLD mouse model could be useful for studying the

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

Sonographic findings in primary diseases of renal pyramids

International Nuclear Information System (INIS)

Rao, B.K.

1987-01-01

Primary pathologic processes involving the renal pyramids such as papillary necrosis, drug-induced necrosis or calcinosis, cysts, neoplasms, and medullary nephrocalcinosis are rare. Thirty-four patients with primary renal pyramid diseases underwent US evaluation for altered morphology; a 5-MHz transducer was used. In 20 patients site-specific changes in the pyramid (e.g., papillary necrosis at the apex, small cysts at the base in medullary cystic disease, tubular calcification in MSK, corticomedullary hyperechogenicity in oxalosis) were noted on US. Sonographic delineation of the site and pattern of pathologic changes in the renal pyramid may help to identify specific diseases

The effect of a concomitant renal injury on the outcome of colonic trauma.

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Oosthuizen, G V; Weale, R; Kong, V Y; Bruce, J L; Urry, R J; Laing, G L; Clarke, D L

2017-12-06

The management of colon injuries has steadily evolved over the course of the last half century. So too has the management of renal trauma. It is not clear from the literature as to whether concomitant colon and renal injuries carry increased risk of morbidity and mortality, and whether this combination of injuries necessitates a specifically tailored management approach. A retrospective review was carried out for the period January 2012 to December 2016. All patients over the age of 18 years who were subjected to laparotomy for penetrating trauma (gunshot wounds or stab wounds) and who sustained an intra-operatively proven colonic injury were included in this study. Operative management and outcomes were investigated. A direct comparison was made between patients with a combined colonic and renal injury and those with only a colonic injury. Over the five-year period a total of 268 patients sustained a colonic injury. The 239 patients with a colonic injury (Group A) were compared to the 29 patients with a combined colonic and renal injury (Group B). Regarding the management of the colonic injuries, there were no differences in the rates of primary repair, anastomosis, exteriorization, or damage control surgery between groups A and B. As for the management of the renal injury, 14 were not explored at laparotomy; in 12 a nephrectomy was performed and in 3 the renal injury was repaired. The nephrectomy cohort were more likely to have undergone damage control surgery, to be admitted to ICU, to receive a colostomy, and had higher mortality. While there was no difference in the need for damage control surgery or mortality between groups, Group B had a significantly greater need for ICU admission. Morbidity was similar between the two groups - in particular, there was no difference in the rates of either gastro-intestinal complications or acute kidney injury between the two groups. In patients with combined colon and renal injuries, it seems reasonable to treat each organ

Serum Iron Protects from Renal Postischemic Injury.

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Vaugier, Céline; Amano, Mariane T; Chemouny, Jonathan M; Dussiot, Michael; Berrou, Claire; Matignon, Marie; Ben Mkaddem, Sanae; Wang, Pamella H M; Fricot, Aurélie; Maciel, Thiago T; Grapton, Damien; Mathieu, Jacques R R; Beaumont, Carole; Peraldi, Marie-Noëlle; Peyssonnaux, Carole; Mesnard, Laurent; Daugas, Eric; Vrtovsnik, François; Monteiro, Renato C; Hermine, Olivier; Ginzburg, Yelena Z; Benhamou, Marc; Camara, Niels O S; Flamant, Martin; Moura, Ivan C

2017-12-01

Renal transplants remain a medical challenge, because the parameters governing allograft outcome are incompletely identified. Here, we investigated the role of serum iron in the sterile inflammation that follows kidney ischemia-reperfusion injury. In a retrospective cohort study of renal allograft recipients ( n =169), increased baseline levels of serum ferritin reliably predicted a positive outcome for allografts, particularly in elderly patients. In mice, systemic iron overload protected against renal ischemia-reperfusion injury-associated sterile inflammation. Furthermore, chronic iron injection in mice prevented macrophage recruitment after inflammatory stimuli. Macrophages cultured in high-iron conditions had reduced responses to Toll-like receptor-2, -3, and -4 agonists, which associated with decreased reactive oxygen species production, increased nuclear localization of the NRF2 transcription factor, increased expression of the NRF2-related antioxidant response genes, and limited NF- κ B and proinflammatory signaling. In macrophage-depleted animals, the infusion of macrophages cultured in high-iron conditions did not reconstitute AKI after ischemia-reperfusion, whereas macrophages cultured in physiologic iron conditions did. These findings identify serum iron as a critical protective factor in renal allograft outcome. Increasing serum iron levels in patients may thus improve prognosis of renal transplants. Copyright © 2017 by the American Society of Nephrology.

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

NARCIS (Netherlands)

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

2016-01-01

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

Alteration of renal excretion pathways in gentamicin-induced renal injury in rats.

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Ma, Yan-Rong; Luo, Xuan; Wu, Yan-Fang; Zhang, Tiffany; Zhang, Fan; Zhang, Guo-Qiang; Wu, Xin-An

2018-02-20

The kidney plays a major part in the elimination of many drugs and their metabolites, and drug-induced kidney injury commonly alters either glomerular filtration or tubular transport, or both. However, the renal excretion pathway of drugs has not been fully elucidated at different stages of renal injury. This study aimed to evaluate the alteration of renal excretion pathways in gentamicin (GEN)-induced renal injury in rats. Results showed that serum cystatin C, creatinine and urea nitrogen levels were greatly increased by the exposure of GEN (100 mg kg -1 ), and creatinine concentration was increased by 39.7% by GEN (50 mg kg -1 ). GEN dose-dependently upregulated the protein expression of rOCT1, downregulated rOCT2 and rOAT1, but not affected rOAT2. Efflux transporters, rMRP2, rMRP4 and rBCRP expressions were significantly increased by GEN(100), and the rMATE1 level was markedly increased by GEN(50) but decreased by GEN(100). GEN(50) did not alter the urinary excretion of inulin, but increased metformin and furosemide excretion. However, GEN(100) resulted in a significant decrease of the urinary excretion of inulin, metformin and p-aminohippurate. In addition, urinary metformin excretions in vivo were significantly decreased by GEN(100), but slightly increased by GEN(50). These results suggested that GEN(50) resulted in the induction of rOCTs-rMATE1 and rOAT3-rMRPs pathway, but not changed the glomerular filtration rate, and GEN(100)-induced acute kidney injury caused the downregulated function of glomerular filtration -rOCTs-rMATE1 and -rOAT1-rMRPs pathway. Copyright © 2018 John Wiley & Sons, Ltd.

Medullary sponge kidney and isolated hemihyperplasia

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P S Priyamvada

2014-01-01

Full Text Available The term hemihyperplasia refers to an enlargement of body parts beyond the normal asymmetry. Hemihyperplasia can be isolated or associated with various well-described malformation syndromes. Medullary sponge kidney (MSK has been described with isolated and syndromic hemihyperplasia; the actual prevalence is not known The hemi hypertrophy can be so subtle that it may be easily overlooked. MSK need not be limited to the side of hemihyperplasia - most often it is bilateral. Around 33 cases has been reported from different parts of the world of which 15 cases are isolated hemi hyperplasia (IHH, the remaining occurring in the context of various malformation syndromes So far only one case has been reported from India. We report a case of IHH involving right side of the body, recurrent renal stones, incomplete distal renal tubular acidosis hypercalciuria and imaging showing bilateral MSKs.

Thyroid cancer - medullary carcinoma

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Thyroid - medullary carcinoma; Cancer - thyroid (medullary carcinoma); MTC; Thyroid nodule - medullary ... in children and adults. Unlike other types of thyroid cancer, MTC is less likely to be caused by ...

Novel resveratrol analogues attenuate renal ischemic injury in rats

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Khader, Adam; Yang, Weng-Lang; Kuncewitch, Michael; Prince, Jose M.; Marambaud, Philippe; Nicastro, Jeffrey; Coppa, Gene F.; Wang, Ping

2014-01-01

Background Renal ischemia-reperfusion (I/R) is a severe clinical complication with no specific treatment. Resveratrol has been shown as a promising experimental agent in renal I/R due to its effect on cellular energy metabolism, oxidative stress, and inflammation. Recently, we identified two biologically active resveratrol analogues (RSVAs), RSVA405 and RSVA314. We hypothesized that both RSAVs would attenuate I/R-induced renal injury. Methods Adult male rats were subjected to renal I/R through bilateral renal pedicle clamping for 60 min, followed by reperfusion. RSVA405 (3 mg/kg BW), RSVA314 (3 mg/kg BW), or vehicle (10% DMSO and 33% Solutol in PBS) was administered by intraperitoneal injection 1 h prior to ischemia. Blood and renal tissues were collected 24 h after I/R for evaluation. Results Administration of RSVA405 and RSVA314 significantly reduced the serum levels of renal dysfunction and injury markers, including creatinine, blood urea nitrogen, aspartate aminotransferase, and lactate dehydrogenase, compared to vehicle. The protective effect of RSVA405 and RSVA314 was also reflected on histologic evaluation. Both RSVAs reduced the number of apoptotic cells by more than 60% as determined by TUNEL assay, compared to vehicle. The renal ATP levels of the vehicle group was decreased to 52.4% of control, while those of the RSVA405 and RSVA314 groups were restored to 72.3% and 79.6% of control, respectively. Both RSVAs significantly reduced the protein expression of inducible nitric oxide synthase and nitrotyrosine, and the mRNA levels of TNF-α, IL-6 and IL-1β. Conclusions RSVA405 and RSVA314 attenuate I/R-induced renal injury through the modulation of energy metabolism, oxidative stress, and inflammation. PMID:25214260

Amelioration of renal ischaemia-reperfusion injury by liposomal delivery of curcumin to renal tubular epithelial and antigen-presenting cells.

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Rogers, N M; Stephenson, M D; Kitching, A R; Horowitz, J D; Coates, P T H

2012-05-01

Renal ischaemia-reperfusion (IR) injury is an inevitable consequence of renal transplantation, causing significant graft injury, increasing the risk of rejection and contributing to poor long-term graft outcome. Renal injury is mediated by cytokine and chemokine synthesis, inflammation and oxidative stress resulting from activation of the NF-κB pathway. We utilized liposomal incorporation of a potent inhibitor of the NF-κB pathway, curcumin, to target delivery to renal tubular epithelial and antigen-presenting cells. Liposomes containing curcumin were administered before bilateral renal ischaemia in C57/B6 mice, with subsequent reperfusion. Renal function was assessed from plasma levels of urea and creatinine, 4 and 24 h after reperfusion. Renal tissue was examined for NF-κB activity and oxidative stress (histology, immunostaining) and for apoptosis (TUNEL). Cytokines and chemokines were measured by RT-PCR and Western blotting. Liposomal curcumin significantly improved serum creatinine, reduced histological injury and cellular apoptosis and lowered Toll-like receptor-4, heat shock protein-70 and TNF-α mRNA expression. Liposomal curcumin also reduced neutrophil infiltration and diminished inflammatory chemokine expression. Curcumin liposomes reduced intracellular superoxide generation and increased superoxide dismutase levels, decreased inducible NOS mRNA expression and 3-nitrotyrosine staining consistent with limitations in nitrosative stress and inhibited renal tubular mRNA and protein expression of thioredoxin-interacting protein. These actions of curcumin were mediated by inhibition of NF-κB, MAPK and phospho-S6 ribosomal protein. Liposomal delivery of curcumin promoted effective, targeted delivery of this non-toxic compound that provided cytoprotection via anti-inflammatory and multiple antioxidant mechanisms following renal IR injury. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Blockade of Death Ligand TRAIL Inhibits Renal Ischemia Reperfusion Injury

International Nuclear Information System (INIS)

Adachi, Takaomi; Sugiyama, Noriyuki; Gondai, Tatsuro; Yagita, Hideo; Yokoyama, Takahiko

2013-01-01

Renal ischemia-reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI). Many investigators have reported that cell death via apoptosis significantly contributed to the pathophysiology of renal IRI. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor superfamily, and induces apoptosis and inflammation. However, the role of TRAIL in renal IRI is unclear. Here, we investigated whether TRAIL contributes to renal IRI and whether TRAIL blockade could attenuate renal IRI. AKI was induced by unilateral clamping of the renal pedicle for 60 min in male FVB/N mice. We found that the expression of TRAIL and its receptors were highly upregulated in renal tubular cells in renal IRI. Neutralizing anti-TRAIL antibody or its control IgG was given 24 hr before ischemia and a half-dose booster injection was administered into the peritoneal cavity immediately after reperfusion. We found that TRAIL blockade inhibited tubular apoptosis and reduced the accumulation of neutrophils and macrophages. Furthermore, TRAIL blockade attenuated renal fibrosis and atrophy after IRI. In conclusion, our study suggests that TRAIL is a critical pathogenic factor in renal IRI, and that TRAIL could be a new therapeutic target for the prevention of renal IRI

Assessment of renal fibrosis in chronic kidney disease using diffusion-weighted MRI

International Nuclear Information System (INIS)

Zhao, J.; Wang, Z.J.; Liu, M.; Zhu, J.; Zhang, X.; Zhang, T.; Li, S.; Li, Y.

2014-01-01

Aim: To assess the performance of diffusion-weighted magnetic resonance imaging (MRI) for the assessment of renal fibrosis in chronic kidney disease (CKD), with histopathology as a reference standard. Materials and methods: Forty patients with CKD and 30 healthy volunteers were recruited for the study. All participants underwent diffusion-weighted MRI. Renal biopsy was performed in 25 patients with CKD. Mean renal medullary and cortical apparent diffusion coefficient (ADC) values were compared between CKD patients and the healthy volunteers. Pearson's correlation coefficient was calculated to investigate the relationship between ADC values, serum creatinine (SCr), estimated glomerular filtration rate (eGFR), 24 h urinary protein (24h-UPRO), and renal histopathological scores. Results: Cortical and medullary ADC values in the CKD group were significantly lower compared to those in the healthy controls. In the CKD group, a significant negative correlation was found between cortical ADC values and SCr/24h-UPRO, and significant positive correlation was found between cortical ADC and eGFR. There was also a significant negative correlation between medullary ADC values and SCr. Both cortical and medullary ADC values were significantly correlated with histopathological fibrosis score. Conclusion: Renal ADC values strongly correlate with histological measures of fibrosis, and have the potential to enhance the non-invasive monitoring of chronic kidney disease. - Highlights: • Renal ADC values in the CKD patients were lower than those in controls. • Renal ADC values were strongly correlated with histological fibrosis score. • Renal ADC values have the potential to enhance the noninvasive monitoring of CKD

Protection of Liver as a Remote Organ after Renal Ischemia-Reperfusion Injury by Renal Ischemic Postconditioning

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Behjat Seifi

2014-01-01

Full Text Available This study was designed to investigate the protective effects of local renal ischemic postconditioning (POC on liver damage after renal ischemia-reperfusion (IR injury. Male rats were divided into three groups  (n=8. They underwent a right nephrectomy before induction of 45 minutes of left kidney ischemia or sham operation. POC was performed by four cycles of 10 seconds of ischemia and 10 seconds of reperfusion just at the beginning of 24 hours of reperfusion. Then blood and liver samples were collected to measure serum aspartate aminotransferase (AST, alanine aminotransferase (ALT, and liver oxidative stress parameters including superoxide dismutase (SOD activity and malondialdehyde (MDA level. Renal IR caused a significant increase in liver functional indices as demonstrated by increased serum AST and ALT compared to sham group. These parameters reduced significantly in POC group compared to IR group. Liver MDA levels increased and SOD activity decreased in IR group compared to sham group. Induction of POC reduced the elevated liver MDA levels and increased the reduced liver SOD activity. These results revealed that renal IR injury causes liver damage as a remote organ and POC protects liver from renal IR injury by a modification in the hepatic oxidative stress status.

Application of Color Doppler Ultrasound in Renal Medullary Calcium%彩色多普勒超声在肾髓质钙质沉着症中的应用分析

Institute of Scientific and Technical Information of China (English)

金丽梅

2016-01-01

目的：分析彩色多普勒超声在肾髓质钙沉着症中的应用价值。方法回顾性分析2011—2015年期间在该院行彩色多普勒超声诊断肾髓质钙沉着症的68例患者的临床资料，观察患者的超声诊断特点以及血流动力学改变。结果68例行彩色多普勒超声诊断肾髓质钙沉着症的患者中，诊断阳性共65例，阴性3例，诊断的准确率为95.6%，65例肾髓质钙沉着症患者中包括皮质型30例，髓质型32例，混合型3例，患者的两侧肾脏大小正常，形态对称，包膜光滑，皮质和髓质界限较为清楚，肾脏的皮质厚度和回声均正常，在患者的髓质内，有密集点状的强回声，形态和椎体的形态基本一致，有一侧有弱声影。结论彩色多普勒超声在肾髓质钙沉着症中应用，准确率较高，可以有效的显示内部的形态、血流变化等指标，具有重要的临床诊断价值。%Objective To analyze the value of color Doppler ultrasound in the renal medulla of calcium applications. Methods Convenient selection a retrospective analysis of clinical data by color Doppler ultrasound diagnosis of renal medullary calcinosis disease 68 patients were retrospectively analyzed the period from 2011 to 2015, observed in patients with ultrasonic diagnostic characteristics and hemodynamic change. Results 68 patients with routine color Doppler ultra-sound diagnosis of renal medullary calcinosis disease, the diagnosis of a total of65 positive cases, negative in 3 cases, the diagnostic accuracy was 95.6%, 65 cases of renal medullary calcinosis patients included cortical 30 cases, 32 cases of medullary, mixed three cases, both sides of the patient's normal kidney size, shape symmetry, smooth coated, cortex and medulla boundaries more clearly, renal cortical thickness and echo were normal in patients within the medulla, a strong e-cho dense point-like, form and shape of the vertebral body are basically the same, there is one

Effect of indomethacin and salt depletion on renal proton MR imaging; An experimental study in the rat

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Heyman, S.N.; Mammen, M. (Harvard Medical School, Boston, MA (United States). Charles A Dana Research Inst. Beth Israel Hospital, Boston, MA (United States))

1991-11-01

Blockade of the synthesis of vasodilating prostaglandins with non-steroidal anti-inflammatory drugs (NSAID) renders the renal medulla susceptible to hypoxic injury with reduced renal function, especially in clinical conditions characterized by volume depletion. Alterations in renal hemodynamics and urine production may effect renal MR imaging under these circumstances. We injected salt-depleted and control rats undergoing proton MR imaging with indomethacin 10 mg/kg. Indomethacin abolished the cortico-medullary T2-gradient and markedly diminished the overall renal signal in salt-depleted rats only. These changes, which progressed over a period of 40 min after indomethacin was injected, probably result from renal oligemia and decreased urine production, with an associated decrease in T2-values. We suggest that a history of consumption of non-steroidal anti-inflammatory drugs should be obtained and taken into account in the evaluation of renal proton MR imaging, especially in the presence of salt and volume depletion. (orig.).

DA-1229, a dipeptidyl peptidase IV inhibitor, protects against renal injury by preventing podocyte damage in an animal model of progressive renal injury.

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Eun Lee, Jee; Kim, Jung Eun; Lee, Mi Hwa; Song, Hye Kyoung; Ghee, Jung Yeon; Kang, Young Sun; Min, Hye Sook; Kim, Hyun Wook; Cha, Jin Joo; Han, Jee Young; Han, Sang Youb; Cha, Dae Ryong

2016-05-01

Although dipeptidyl peptidase IV (DPPIV) inhibitors are known to have renoprotective effects, the mechanism underlying these effects has remained elusive. Here we investigated the effects of DA-1229, a novel DPPIV inhibitor, in two animal models of renal injury including db/db mice and the adriamycin nephropathy rodent model of chronic renal disease characterized by podocyte injury. For both models, DA-1229 was administered at 300 mg/kg/day. DPPIV activity in the kidney was significantly higher in diabetic mice compared with their nondiabetic controls. Although DA-1229 did not affect glycemic control or insulin resistance, DA-1229 did improve lipid profiles, albuminuria and renal fibrosis. Moreover, DA-1229 treatment resulted in decreased urinary excretion of nephrin, decreased circulating and kidney DPPIV activity, and decreased macrophage infiltration in the kidney. In adriamycin-treated mice, DPPIV activity in the kidney and urinary nephrin loss were both increased, whereas glucagon-like peptide-1 concentrations were unchanged. Moreover, DA-1229 treatment significantly improved proteinuria, renal fibrosis and inflammation associated with decreased urinary nephrin loss, and kidney DPP4 activity. In cultured podocytes, DA-1229 restored the high glucose/angiotensin II-induced increase of DPPIV activity and preserved the nephrin levels in podocytes. These findings suggest that activation of DPPIV in the kidney has a role in the progression of renal disease, and that DA-1229 may exert its renoprotective effects by preventing podocyte injury.

Normal distribution and medullary-to-cortical shift of Nestin-expressing cells in acute renal ischemia.

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Patschan, D; Michurina, T; Shi, H K; Dolff, S; Brodsky, S V; Vasilieva, T; Cohen-Gould, L; Winaver, J; Chander, P N; Enikolopov, G; Goligorsky, M S

2007-04-01

Nestin, a marker of multi-lineage stem and progenitor cells, is a member of intermediate filament family, which is expressed in neuroepithelial stem cells, several embryonic cell types, including mesonephric mesenchyme, endothelial cells of developing blood vessels, and in the adult kidney. We used Nestin-green fluorescent protein (GFP) transgenic mice to characterize its expression in normal and post-ischemic kidneys. Nestin-GFP-expressing cells were detected in large clusters within the papilla, along the vasa rectae, and, less prominently, in the glomeruli and juxta-glomerular arterioles. In mice subjected to 30 min bilateral renal ischemia, glomerular, endothelial, and perivascular cells showed increased Nestin expression. In the post-ischemic period, there was an increase in fluorescence intensity with no significant changes in the total number of Nestin-GFP-expressing cells. Time-lapse fluorescence microscopy performed before and after ischemia ruled out the possibility of engraftment by the circulating Nestin-expressing cells, at least within the first 3 h post-ischemia. Incubation of non-perfused kidney sections resulted in a medullary-to-cortical migration of Nestin-GFP-positive cells with the rate of expansion of their front averaging 40 microm/30 min during the first 3 h and was detectable already after 30 min of incubation. Explant matrigel cultures of the kidney and aorta exhibited sprouting angiogenesis with cells co-expressing Nestin and endothelial marker, Tie-2. In conclusion, several lines of circumstantial evidence identify a sub-population of Nestin-expressing cells with the mural cells, which are recruited in the post-ischemic period to migrate from the medulla toward the renal cortex. These migrating Nestin-positive cells may be involved in the process of post-ischemic tissue regeneration.

Lacking Ketohexokinase-A Exacerbates Renal Injury in Streptozotocin-induced Diabetic Mice.

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Doke, Tomohito; Ishimoto, Takuji; Hayasaki, Takahiro; Ikeda, Satsuki; Hasebe, Masako; Hirayama, Akiyoshi; Soga, Tomoyoshi; Kato, Noritoshi; Kosugi, Tomoki; Tsuboi, Naotake; Lanaspa, Miguel A; Johnson, Richard J; Kadomatsu, Kenji; Maruyama, Shoichi

2018-03-28

Ketohexokinase (KHK), a primary enzyme in fructose metabolism, has two isoforms, namely, KHK-A and KHK-C. Previously, we reported that renal injury was reduced in streptozotocin-induced diabetic mice which lacked both isoforms. Although both isoforms express in kidney, it has not been elucidated whether each isoform plays distinct roles in the development of diabetic kidney disease (DKD). The aim of the study is to elucidate the role of KHK-A for DKD progression. Diabetes was induced by five consecutive daily intraperitoneal injections of streptozotocin (50 mg/kg) in C57BL/6 J wild-type mice, mice lacking KHK-A alone (KHK-A KO), and mice lacking both KHK-A and KHK-C (KHK-A/C KO). At 35 weeks, renal injury, inflammation, hypoxia, and oxidative stress were examined. Metabolomic analysis including polyol pathway, fructose metabolism, glycolysis, TCA (tricarboxylic acid) cycle, and NAD (nicotinamide adenine dinucleotide) metabolism in kidney and urine was done. Diabetic KHK-A KO mice developed severe renal injury compared to diabetic wild-type mice, and this was associated with further increases of intrarenal fructose, dihydroxyacetone phosphate (DHAP), TCA cycle intermediates levels, and severe inflammation. In contrast, renal injury was prevented in diabetic KHK-A/C KO mice compared to both wild-type and KHK-A KO diabetic mice. Further, diabetic KHK-A KO mice contained decreased renal NAD + level with the increase of renal hypoxia-inducible factor 1-alpha expression despite having increased renal nicotinamide (NAM) level. These results suggest that KHK-C might play a deleterious role in DKD progression through endogenous fructose metabolism, and that KHK-A plays a unique protective role against the development of DKD. Copyright © 2018. Published by Elsevier Inc.

Update on the renal toxicity of iodinated contrast drugs used in clinical medicine

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Andreucci M

2017-05-01

Full Text Available Michele Andreucci,1 Teresa Faga,1 Raffaele Serra,2 Giovambattista De Sarro,3 Ashour Michael1 1Renal Unit, Department of Health Sciences, 2Interuniversity Center of Phlebolymphology (CIFL, International Research and Educational Program in Clinical and Experimental Biotechnology, Department of Medical and Surgical Sciences, 3Pharmacology Unit, Department of Health Sciences, Magna Graecia University, Catanzaro, Italy Abstract: An important side effect of diagnostic contrast drugs is contrast-induced acute kidney injury (CI-AKI; a sudden decrease in renal function occurring 48–72 hours after injection of a contrast drug that cannot be attributed to other causes. Its existence has recently been challenged, because of some retrospective studies in which the incidence of AKI was not different between subjects who received a contrast drug and those who did not, even using propensity score matching to prevent selection bias. For some authors, only patients with estimated glomerular filtration rate <30 mL/min/1.73 m2 are at significant risk of CI-AKI. Most agree that when renal function is normal, there is no CI-AKI risk. Many experimental studies, however, are in favor of the existence of CI-AKI. Contrast drugs have been shown to cause the following changes: renal vasoconstriction, resulting in a rise in intrarenal resistance (decrease in renal blood flow and glomerular filtration rate and medullary hypoxia; epithelial vacuolization and dilatation and necrosis of proximal tubules; potentiation of angiotensin II effects, reducing nitric oxide (NO and causing direct constriction of descending vasa recta, leading to formation of reactive oxygen species in isolated descending vasa recta of rats microperfused with a solution of iodixanol; increasing active sodium reabsorption in the thick ascending limbs of Henle’s loop (increasing O2 demand and consequently medullary hypoxia; direct cytotoxic effects on endothelial and tubular epithelial cells (decrease

The role of Toll-like receptor 2 in inflammation and fibrosis during progressive renal injury.

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Jaklien C Leemans

Full Text Available Tissue fibrosis and chronic inflammation are common causes of progressive organ damage, including progressive renal disease, leading to loss of physiological functions. Recently, it was shown that Toll-like receptor 2 (TLR2 is expressed in the kidney and activated by endogenous danger signals. The expression and function of TLR2 during renal fibrosis and chronic inflammation has however not yet been elucidated. Therefore, we studied TLR2 expression in human and murine progressive renal diseases and explored its role by inducing obstructive nephropathy in TLR2(-/- or TLR2(+/+ mice. We found that TLR2 is markedly upregulated on tubular and tubulointerstitial cells in patients with chronic renal injury. In mice with obstructive nephropathy, renal injury was associated with a marked upregulation and change in distribution of TLR2 and upregulation of murine TLR2 danger ligands Gp96, biglycan, and HMGB1. Notably, TLR2 enhanced inflammation as reflected by a significantly reduced influx of neutrophils and production of chemokines and TGF-beta in kidneys of TLR2(-/- mice compared with TLR2(+/+ animals. Although, the obstructed kidneys of TLR2(-/- mice had less interstitial myofibroblasts in the later phase of obstructive nephropathy, tubular injury and renal matrix accumulation was similar in both mouse strains. Together, these data demonstrate that TLR2 can initiate renal inflammation during progressive renal injury and that the absence of TLR2 does not affect the development of chronic renal injury and fibrosis.

Kidney injury after sodium phosphate solution beyond the acute renal failure.

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Fernández-Juárez, Gema; Parejo, Leticia; Villacorta, Javier; Tato, Ana; Cazar, Ramiro; Guerrero, Carmen; Marin, Isabel Martinez; Ocaña, Javier; Mendez-Abreu, Angel; López, Katia; Gruss, Enrique; Gallego, Eduardo

2016-01-01

Screening colonoscopy with polipectomy reduces colonorectal cancer incidence and mortality. An adequate bowel cleansing is one of the keys to achieving best results with this technique. Oral sodium phosphate solution (OSP) had a widespread use in the 90s decade. Its efficacy was similar to polyethylene glycol (PEG) solution, but with less cost and convenient administration. Series of patients with acute renal failure due to OSP use have been reported. However, large cohorts of patients found no difference in the incidence of renal damage between these two solutions. From 2006 to 2009 we identified twelve cases of phosphate nephropathy after colonoscopy prepared with OSP. All patients were followed up to six months. All patients had received just a single dose. We analyzed 12 cases with phosphate nephropathy; three patients debuted with AKI and nine patients had chronic renal injury. Four cases were confirmed with renal biopsy. One patient with AKI needed hemodialysis at diagnosis without subsequent recovery. Two patients (both with chronic damage) fully recovered their previous renal function. The remaining patients (nine) had an average loss of estimated glomerular filtration rate of 24ml/min/1.73m(2). The use of OSP can lead to both acute and chronic renal damage. However, chronic injury was the most common pattern. Both forms of presentation imply a significant and irreversible loss of renal function. Further studies analyzing renal damage secondary to bowel cleaning should consider these two different patterns of injury. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Adrenal medullary regulation of rat renal cortical adrenergic receptors

International Nuclear Information System (INIS)

Sundaresan, P.R.; Guarnaccia, M.M.; Izzo, J.L. Jr.

1987-01-01

The role of the adrenal medulla in the regulation of renal cortical adrenergic receptors was investigated in renal cortical particular fractions from control rats and rats 6 wk after adrenal demedullation. The specific binding of [ 3 H]prazosin, [ 3 H]rauwolscine, and [ 125 I]iodocyanopindolol were used to quantitate α 1 -, α 2 -, and β-adrenergic receptors, respectively. Adrenal demedullation increased the concentration of all three groups of renal adrenergic receptors; maximal number of binding sites (B max , per milligram membrane protein) for α 1 -, and α 2 -, and β-adrenergic receptors were increased by 22, 18.5, and 25%, respectively. No differences were found in the equilibrium dissociation constants (K D ) for any of the radioligands. Plasma corticosterone and plasma and renal norepinephrine levels were unchanged, whereas plasma epinephrine was decreased 72% by adrenal demedullation, renal cortical epinephrine was not detectable in control or demedullated animals. The results suggest that, in the physiological state, the adrenal medulla modulates the number of renal cortical adrenergic receptors, presumably through the actions of a circulating factor such as epinephrine

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

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

2016-12-20

The effects of blood transfusion on renal microcirculation during sepsis are unknown. This study aimed to investigate the effect of blood transfusion on renal microvascular oxygenation and renal function during sepsis-induced acute kidney injury. Twenty-seven Wistar albino rats were randomized into four groups: a sham group (n = 6), a lipopolysaccharide (LPS) group (n = 7), a LPS group that received fluid resuscitation (n = 7), and a LPS group that received blood transfusion (n = 7). The mean arterial blood pressure, renal blood flow, and renal microvascular oxygenation within the kidney cortex were recorded. Acute kidney injury was assessed using the serum creatinine levels, metabolic cost, and histopathological lesions. Nitrosative stress (expression of endothelial (eNOS) and inducible nitric oxide synthase (iNOS)) within the kidney was assessed by immunohistochemistry. Hemoglobin levels, pH, serum lactate levels, and liver enzymes were measured. Fluid resuscitation and blood transfusion both significantly improved the mean arterial pressure and renal blood flow after LPS infusion. Renal microvascular oxygenation, serum creatinine levels, and tubular damage significantly improved in the LPS group that received blood transfusion compared to the group that received fluids. Moreover, the renal expression of eNOS was markedly suppressed under endotoxin challenge. Blood transfusion, but not fluid resuscitation, was able to restore the renal expression of eNOS. However, there were no significant differences in lactic acidosis or liver function between the two groups. Blood transfusion significantly improved renal function in endotoxemic rats. The specific beneficial effect of blood transfusion on the kidney could have been mediated in part by the improvements in renal microvascular oxygenation and sepsis-induced endothelial dysfunction via the restoration of eNOS expression within the kidney.

Kidney injury molecule-1 in renal disease

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

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

The protective effects of tadalafil on renal damage following ischemia reperfusion injury in rats

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Bulent Erol

2015-09-01

Full Text Available Ischemia-reperfusion injury can cause renal damage, and phosphodiesterase inhibitors are reported to regulate antioxidant activity. We investigated the prevention of renal damage using tadalafil after renal ischemia reperfusion (I/R injury in rats. A total of 21 adult male Wistar albino rats were randomly divided into three groups of seven, including Group 1-control, Group 2-I/R, and Group 3-tadalafil + I/R group (I/R-T group received tadalafil intraperitoneally at 30 minutes before ischemia. Inducible nitric oxide synthase, endothelial nitric oxide synthase, malondialdehyde, and total antioxidant capacity levels were evaluated, and histopathological changes and apoptosis in the groups were examined. Tadalafil decreased malondialdehyde levels in the I/R group and increased the total antioxidant capacity level. Histopathological and immunohistochemical findings revealed that tadalafil decreased renal injury scores and the ratios of injured cells, as measured through apoptotic protease activating factor 1, inducible nitric oxide synthase, and endothelial nitric oxide synthase levels. We suggest that tadalafil has protective effects against I/R-related renal tissue injury.

Frequency and clinical significance of transient hyperechoic renal medulla in neonates

International Nuclear Information System (INIS)

Cho, Sung Shick; Kim, Jung Hoon; Hong, Hyun Sook; Shin, Ji Hoon; Hwang, Jung Hwa; Goo, Dong Erk; Kwon, Kui Hyang; Choi, Deuk Lin

2001-01-01

To evaluate the clinical significance of transient hyperechogenicity of the renal medulla in neonates by comparing the clinical features, urinalysis and follow-up ultrasonographic examination of the control group. One hundred ten neonates were divided into 2 groups, hyperechoic and normal renal medulla groups, and all of them underwent abdominal ultrasound with a 7.5 MHz linear transducer (Sonoace 8800MT, Medicine, Korea) from November 1999 to January 2000. Whether there was any difference in clinical features including birth weight, body surface area, gestational age, sex, date of examination and mode of delivery between two groups was evaluated. In addition, any difference in their urinary osmolarity, albumin, uric acid and calcium in 41 neonates who underwent urinalysis was evaluated. In ten neonates with hyperechoic renal medulla underwent follow-up study, the follow-up ultrasonographic findings were compared with the initial study. In 67 of 110 (61%) neonates, ultrasonography demonstrated hyperechoic renal medulla. There was no difference in clinical features between the hyperechoic renal medullary group and normal group. In 41 neonates, there was no significant difference in urinalysis between two groups. (Osmolarity=146.46 ± 68.4 mOsml/KgH 2 O in the hyperechoic renal medullary group vs. 149.8 ± 77.7 mOsml/KgH 2 O in the normal group; albumin=13.9 ± 10.2 mg/ml vs. 17.6 ± 13.6 mg/dl; uric acid=50.0 ± 23.3 mg/dl vs. 44.9 ± 34.1 mg/dl; calcium=1.38 ± 3.0 mg/ dl vs. 0.44 ± 0.07 mg/dl.) Ten neonates who underwent follow-up ultrasonography within 20 days after the initial study showed the normal medullary echogenicity. There were no significant difference between the hyperechoic renal medullary group and the normal echogenic group in their clinical features and urinalysis. Therefore, the hyperechoic renal medullar in neonate is considered as an usual and transient finding which disappears on follow-up study.

Methods of Blood Oxygen Level-Dependent Magnetic Resonance Imaging Analysis for Evaluating Renal Oxygenation

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Fen Chen

2018-03-01

Full Text Available Blood oxygen level-dependent magnetic resonance imaging (BOLD MRI has recently been utilized as a noninvasive tool for evaluating renal oxygenation. Several methods have been proposed for analyzing BOLD images. Regional ROI selection is the earliest and most widely used method for BOLD analysis. In the last 20 years, many investigators have used this method to evaluate cortical and medullary oxygenation in patients with ischemic nephropathy, hypertensive nephropathy, diabetic nephropathy, chronic kidney disease (CKD, acute kidney injury and renal allograft rejection. However, clinical trials of BOLD MRI using regional ROI selection revealed that it was difficult to distinguish the renal cortico-medullary zones with this method, and that it was susceptible to observer variability. To overcome these deficiencies, several new methods were proposed for analyzing BOLD images, including the compartmental approach, fractional hypoxia method, concentric objects (CO method and twelve-layer concentric objects (TLCO method. The compartmental approach provides an algorithm to judge whether the pixel belongs to the cortex or medulla. Fractional kidney hypoxia, measured by using BOLD MRI, was negatively correlated with renal blood flow, tissue perfusion and glomerular filtration rate (GFR in patients with atherosclerotic renal artery stenosis. The CO method divides the renal parenchyma into six or twelve layers of thickness in each coronal slice of BOLD images and provides a R2* radial profile curve. The slope of the R2* curve associated positively with eGFR in CKD patients. Indeed, each method invariably has advantages and disadvantages, and there is generally no consensus method so far. Undoubtedly, analytic approaches for BOLD MRI with better reproducibility would assist clinicians in monitoring the degree of kidney hypoxia and thus facilitating timely reversal of tissue hypoxia.

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

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Chade, Alejandro R.; Hall, John E.

2016-01-01

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

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.

Reno-Cerebral Reflex Activates the Renin-Angiotensin System, Promoting Oxidative Stress and Renal Damage After Ischemia-Reperfusion Injury.

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Cao, Wei; Li, Aiqing; Li, Jiawen; Wu, Chunyi; Cui, Shuang; Zhou, Zhanmei; Liu, Youhua; Wilcox, Christopher S; Hou, Fan Fan

2017-09-01

A kidney-brain interaction has been described in acute kidney injury, but the mechanisms are uncertain. Since we recently described a reno-cerebral reflex, we tested the hypothesis that renal ischemia-reperfusion injury (IRI) activates a sympathetic reflex that interlinks the renal and cerebral renin-angiotensin axis to promote oxidative stress and progression of the injury. Bilateral ischemia-reperfusion activated the intrarenal and cerebral, but not the circulating, renin-angiotensin system (RAS), increased sympathetic activity in the kidney and the cerebral sympathetic regulatory regions, and induced brain inflammation and kidney injury. Selective renal afferent denervation with capsaicin or renal denervation significantly attenuated IRI-induced activation of central RAS and brain inflammation. Central blockade of RAS or oxidative stress by intracerebroventricular (ICV) losartan or tempol reduced the renal ischemic injury score by 65% or 58%, respectively, and selective renal afferent denervation or reduction of sympathetic tone by ICV clonidine decreased the score by 42% or 52%, respectively (all p renal damage and dysfunction persisted after controlling blood pressure with hydralazine. This study uncovered a novel reflex pathway between ischemic kidney and the brain that sustains renal oxidative stress and local RAS activation to promote ongoing renal damage. These data suggest that the renal and cerebral renin-angiotensin axes are interlinked by a reno-cerebral sympathetic reflex that is activated by ischemia-reperfusion, which contributes to ischemia-reperfusion-induced brain inflammation and worsening of the acute renal injury. Antioxid. Redox Signal. 27, 415-432.

Lower pole renal cut injury due to the iliac wing fracture: A rare case report

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Çaglar Yildirim

2015-07-01

Full Text Available The most frequent causes of blunt genitourinary injuries are falls from heights, motor vehicle accidents and sports injuries. Firearm injuries and penetrating stab wounds are also frequently encountered. Skeletal system traumas in the vicinity of the urogenital system can cause urological organ injuries. Though rarely, renal traumas can be dependent on the kinetic energy of the trauma and the retroperitoneal movement capacity of the kidneys and cannot be explained with the proximity of the kidney to the skeletal system. In cases with high-energy decelerations, renal pedicle and ureteropelvic junction traumas are more frequently observed. Herein, we presented a grade 3 left kidney lower pole injury developed secondary to A2 type pelvic fracture following a high energy deceleration trauma. It should not be forgotten that especially in this type of fractures, injuries of the lower renal pole can occur.

Cordyceps sinensis protects against renal ischemia/reperfusion injury in rats.

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Wang, Hua-Pin; Liu, Ching-Wen; Chang, Hsueh-Wen; Tsai, Jen-Wei; Sung, Ya-Zhu; Chang, Li-Ching

2013-03-01

Cordyceps sinensis (CS) is an entomogenous fungus used as a tonic food and Chinese medicine to replenish health. This study investigated the protective effects of CS in rats post-renal ischemia-reperfusion (I/R) sequence by analyzing the influence on stromal cell-derived factor-1α (SDF-1α and chemokine (C-X-C motif) receptor 4 (CXCR4) expressions and senescence during recovery. Chemokine SDF-1 [now called chemokine C-X-C motif ligand 12 (CXCL12)] and its receptor CXCR4 are crucial in kidney repair after ischemic acute renal failure. CS treatment significantly alleviated I/R-induced renal damage assessed by creatinine levels (p < 0.05) and abated renal tubular damages assessed by periodic acid-Schiff with diastase (PASD) staining. CS induced early SDF-1α expression and increased CXCR4 expression 1-6 h post-reperfusion. Histology studies have revealed that CS induced SDF-1α in squamous cells of Bowman's capsule, mesangial cells, distal convoluted tubules (DCT), and proximal convoluted tubules (PCT). CS also improved renal repair in I/R-induced injury by increasing Ki-67 staining. I/R induced renal senescence after 3 and 6 h of reperfusion. However, CS alleviated I/R-induced senescence at early stage (1 and 3 h). We conclude that CS protects against I/R injury via the SDF-1/CXCR4-signaling axis and alleviates senescence.

Dual Gas Treatment With Hydrogen and Carbon Monoxide Attenuates Oxidative Stress and Protects From Renal Ischemia-Reperfusion Injury.

Science.gov (United States)

Nishida, T; Hayashi, T; Inamoto, T; Kato, R; Ibuki, N; Takahara, K; Takai, T; Yoshikawa, Y; Uchimoto, T; Saito, K; Tanda, N; Kouno, J; Minami, K; Uehara, H; Hirano, H; Nomi, H; Okada, Y; Azuma, H

Hydrogen (H 2 ) and carbon monoxide (CO) gas are both reported to reduce reactive oxygen species and alleviate tissue ischemia-reperfusion (I-R) injury. The present study was conducted to evaluate the effects of a mixture of H 2 gas and CO gas (dual gas) in comparison with hydrogen gas (H 2 : 2%) alone on I-R renal injury (composition of dual gas; N 2 : 77.8%; O 2 : 20.9%; H 2 : 1.30%; CO: 250 parts per million). Adult male Sprague-Dawley rats (body weight 250-280 g) were divided into 5 groups: (1) sham operation control, (2) dual gas inhalation (dual treatment) without I-R treatment, (3) I-R renal injury, (4) H 2 gas alone inhalation (H 2 treatment) with I-R renal injury, and (5) dual treatment with I-R renal injury. I-R renal injury was induced by clamping the left renal artery and vein for 45 minutes followed by reperfusion, and then contralateral nephrectomy was performed 2 weeks later. Renal function was markedly decreased at 24 hours after reperfusion, and thereafter the effects of dual gas were assessed by histologic examination and determination of the superoxide radical, together with functional and molecular analyses. Pathologic examination of the kidney of I-R rats revealed severe renal damage. Importantly, cytoprotective effects of the dual treatment in comparison with H 2 treatment and I-R renal injury were observed in terms of superoxide radical scavenging activity and histochemical features. Rats given dual treatment and I-R renal injury showed significant decreases in blood urea nitrogen. Increased expression of several inflammatory cytokines (tumor necrosis factor-α, interleukin-6, intracellular adhesion molecule-1, nuclear factor-κB, hypoxia inducible factor-1α, and heme oxygenase-1) was attenuated by the dual treatment. Dual gas inhalation decreases oxidative stress and markedly improves I-R-induced renal injury. Copyright © 2017 Elsevier Inc. All rights reserved.

Basolateral P2X receptors mediate inhibition of NaCl transport in mouse medullary thick ascending limb (mTAL)

DEFF Research Database (Denmark)

Marques, Rita D; de Bruijn, Pauline I.A.; Sørensen, Mads Vaarby

2012-01-01

Extracellular nucleotides regulate epithelial transport via luminal and basolateral P2 receptors. Renal epithelia express multiple P2 receptors, which mediate significant inhibition of solute absorption. Recently, we identified several P2 receptors in the medullary thick ascending limb (m...

Effect of tanshinone combined with valsartan therapy on the renal injury and endothelial injury in patients with hypertensive nephropathy

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Wen-Tao Ma1

2017-04-01

Full Text Available Objective: To study the effect of tanshinone combined with valsartan therapy on the renal injury and endothelial injury in patients with hypertensive nephropathy. Methods: A total of 72 patients with hypertensive nephropathy who were treated in our hospital between January 2013 and April 2016 were selected and randomly divided into the control group (n=36 who received conventional treatment + valsartan therapy and the observation group (n=36 who received conventional treatment + tanshinone combined with valsartan therapy, and both therapies lasted for 2 weeks. Before treatment and after 2 weeks of treatment, automatic biochemical analyzer was used to determine the renal function indexes in peripheral blood, enzyme-linked immunosorbent assay (ELISA was used to determine the levels of endothelial injury markers and inflammatory cytokines in peripheral blood, and RIA method was used to determine the serum levels of oxidative stress indexes. Results: Before treatment, the differences in the peripheral blood renal function indexes and endothelial injury markers as well as the serum inflammatory factors and oxidative stress indexes were not statistically significant between two groups of patients. After 2 weeks of treatment, peripheral blood renal function indexes Scr and BUN levels as well as urine mAlb level of observation group were lower than those of control group, and endothelial injury indexes E-selectin and ET levels were lower than those of control group while NOS and CGRP levels were higher than those of control group; serum inflammatory cytokines IL-1, IL-6, CRP and TNF-α levels of observation group were lower than those of control group, and oxidative stress index GSH-Px level was higher than that of control group while MDA and AOPP levels were lower than those of control group. Conclusion: Tanshinone combined with valsartan can reduce the renal injury and endothelial injury in patients with hypertensive nephropathy, and the specific

Comprehensive renal scintillation procedures in spinal cord injury: comparison with excretory urography

International Nuclear Information System (INIS)

Lloyd, L.K.; Dubovsky, E.V.; Bueschen, A.J.; Witten, D.M.; Scott, J.W.; Kuhlemeier, K.; Stover, S.L.

1981-01-01

A 131 iodine orthoiodohippurate comprehensive renal scintillation procedure was performed and compared to results of excretory urography in 200 spinal cord injury patients. No severe urographic abnormalities were undetected by the comprehensive renal scintillation procedure. Only 1.4 per cent of renal units had greater than minimal pyelocaliectasis or ureterectasis in the presence of a normal radionuclide examination. A relatively large number of abnormalities were detected on the renal scintillation procedure when the excretory urogram was normal. Serial followup will be required to determine the significance of these findings but present data suggest that a comprehensive renal scintillation procedure and a plain film of the kidneys, ureters and bladder may be used for screening upper urinary tract abnormalities in lieu of an excretory urogram. This is particularly advantageous for the spinal cord injury population, since there have been no toxic or allergic reactions reported, no bowel preparation or dehydration is required and there is relatively low radiation exposure

Successful renal transplantation from a brain-dead deceased donor with head injury, disseminated intravascular coagulation and deranged renal functions

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P P Ghuge

2013-01-01

Full Text Available Deceased donors (DDs with the brain death due to head injury are the major source of organs for transplantation. The incidence of post-head injury disseminated intravascular coagulation (DIC ranges from 24% to 50%. Many centers do not accept organs from donors with DIC due to increased risk of primary graft non-function and/or high chances of morbidity/mortality. We performed two successful renal transplants from a DD with head injury with DIC and deranged renal function. One of the recipients developed transient thrombocytopenia, but there was no evidence of DIC or delayed graft functions in either of the recipients. Over a follow-up of 1 month, both are doing well with stable graft function and hematological profile. Thus, a carefully selected DD with severe DIC even with deranged renal function is not a contraindication for organ donation if other risk factors for primary non-function are excluded. This approach will also help in overcoming organ shortage.

Detection and Evaluation of Renal Injury in Burst Wave Lithotripsy Using Ultrasound and Magnetic Resonance Imaging.

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May, Philip C; Kreider, Wayne; Maxwell, Adam D; Wang, Yak-Nam; Cunitz, Bryan W; Blomgren, Philip M; Johnson, Cynthia D; Park, Joshua S H; Bailey, Michael R; Lee, Donghoon; Harper, Jonathan D; Sorensen, Mathew D

2017-08-01

Burst wave lithotripsy (BWL) is a transcutaneous technique with potential to safely and effectively fragment renal stones. Preclinical investigations of BWL require the assessment of potential renal injury. This study evaluates the capabilities of real-time ultrasound and MRI to detect and evaluate BWL injury that was induced in porcine kidneys. Ten kidneys from five female farm pigs were treated with either a 170 or 335 kHz BWL transducer using variable treatment parameters and monitored in real-time with ultrasound. Eight kidneys were perfusion fixed and scanned with a 3-Tesla MRI scanner (T1-weighted, T2-weighted, and susceptibility-weighted imaging), followed by processing via an established histomorphometric technique for injury quantification. In addition, two kidneys were separately evaluated for histologic characterization of injury quality. Observed B-mode hyperechoes on ultrasound consistent with cavitation predicted the presence of BWL-induced renal injury with a sensitivity and specificity of 100% in comparison to the histomorphometric technique. Similarly, MRI detected renal injury with a sensitivity of 90% and specificity of 100% and was able to identify the scale of lesion volumes. The injuries purposefully generated with BWL were histologically similar to those formed by shock wave lithotripsy. BWL-induced renal injury can be detected with a high degree of sensitivity and specificity by real-time ultrasound and post-treatment ex vivo MRI. No injury occurred in this study without cavitation detected on ultrasound. Such capabilities for injury detection and lesion volume quantification on MRI can be used for preclinical testing of BWL.

Comparison of the Protective Effects of Erythropoietin and Melatonin on Renal Ischemia-Reperfusion Injury.

Science.gov (United States)

Banaei, Shokofeh; Ahmadiasl, Nasser; Alihemmati, Alireza

2016-07-01

Renal ischemia-reperfusion (IR) contributes to the development of acute renal failure (ARF). Oxygen free radicals are considered to be the principal components involved in the pathophysiological tissue alterations observed during renal IR. In this study, we compared the effects of melatonin (MEL) and erythropoietin (EPO), both known antioxidant and anti-inflammatory agents, on IR-induced renal injury in rats. Wistar albino rats were unilaterally nephrectomized and then subjected to 45 minutes of renal pedicle occlusion followed by 24 hours of reperfusion. MEL (10 mg/kg, i.p) and EPO (5000 U/kg, i.p) were administered prior to the onset of ischemia. After 24 hours of reperfusion and following decapitation, blood samples were collected for the determination of the hemoglobin (Hb) and hematocrit (Hct) levels. Additionally, renal samples were taken for histological evaluation. Ischemia-reperfusion significantly decreased the observed Hb and Hct values. The histopathological findings in the IR group confirmed that there was an increase in the hyaline cast and thickening of the Bowman capsule basement membrane. Treatment with EPO or MEL significantly increased the Hb and Hct values. In the MEL + IR group, the histopathological changes were lower than those found in the EPO + IR group. Treatment with EPO and MEL had a beneficial effect on renal IR injury. The results may also indicate that MEL protects against morphological damage better than EPO in renal IR injury.

VAC Therapy Direct to the Medullary Cavity for Chronic Tibial Osteomyelitis.

Science.gov (United States)

Miyamura, Satoshi; Tsuji, Shigeyoshi; Iwai, Takao; Hamada, Masayuki

2016-06-01

Vacuum-assisted wound closure (VAC) is useful for difficult wound beds, although sites where bleeding or infection is expected are usually regarded as problematic for this therapy. This report outlines the treatment of chronic tibial osteomyelitis (Cierny- Mader type III) due to mixed infection with Nocardia spp and Bacteroi- des fragilis by postoperative VAC therapy direct to the medullary cavity, followed by wound coverage with a gastrocnemius myocutaneous skin flap. A 64-year-old man developed chronic left tibial os- teomyelitis after a work injury. The nonviable tissues were debrided, including a sequestrum. Nocardia spp and B. fragilis were isolated from surgical bone specimens, and chronic tibial osteomyelitis due to mixed infection was diagnosed. Postoperatively, VAC therapy was performed directly to the open medullary cavity of the tibia and sub- sequently covered the residual soft tissue defect with a gastrocnemius myocutaneous flap. The authors could not find any English literature on VAC therapy direct to the medullary cavity combined with transplantation of a myocutaneous flap for osteomyelitis. Nocardia spp can cause a variety of infections, among which osteomyelitis occupies a relatively small percentage. This case raises the possibil- ity of treating chronic tibial osteomyelitis caused by mixed infection with Nocardia spp and B. fragilis by applying postoperative VAC ther- apy directly to the medullary cavity and covering the residual wound with a gastrocnemius myocutaneous flap.

Expression of receptor-type protein tyrosine phosphatase in developing and adult renal vasculature.

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Keiko Takahashi

Full Text Available Renal vascular development is a coordinated process that requires ordered endothelial cell proliferation, migration, intercellular adhesion, and morphogenesis. In recent decades, studies have defined the pivotal role of endothelial receptor tyrosine kinases (RPTKs in the development and maintenance of renal vasculature. However, the expression and the role of receptor tyrosine phosphatases (RPTPs in renal endothelium are poorly understood, though coupled and counterbalancing roles of RPTKs and RPTPs are well defined in other systems. In this study, we evaluated the promoter activity and immunolocalization of two endothelial RPTPs, VE-PTP and PTPμ, in developing and adult renal vasculature using the heterozygous LacZ knock-in mice and specific antibodies. In adult kidneys, both VE-PTP and PTPμ were expressed in the endothelium of arterial, glomerular, and medullary vessels, while their expression was highly limited in peritubular capillaries and venous endothelium. VE-PTP and PTPμ promoter activity was also observed in medullary tubular segments in adult kidneys. In embryonic (E12.5, E13.5, E15.5, E17.5 and postnatal (P0, P3, P7 kidneys, these RPTPs were expressed in ingrowing renal arteries, developing glomerular microvasculature (as early as the S-shaped stage, and medullary vessels. Their expression became more evident as the vasculatures matured. Peritubular capillary expression of VE-PTP was also noted in embryonic and postnatal kidneys. Compared to VE-PTP, PTPμ immunoreactivity was relatively limited in embryonic and neonatal renal vasculature and evident immunoreactivity was observed from the P3 stage. These findings indicate 1 VE-PTP and PTPμ are expressed in endothelium of arterial, glomerular, and medullary renal vasculature, 2 their expression increases as renal vascular development proceeds, suggesting that these RPTPs play a role in maturation and maintenance of these vasculatures, and 3 peritubular capillary VE-PTP expression

Proximal renal tubular injury in rats sub-chronically exposed to low fluoride concentrations

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Cárdenas-González, Mariana C.; Del Razo, Luz M. [Departmento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); Barrera-Chimal, Jonatan [Unidad de Fisiología Molecular, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México, D. F., México (Mexico); Jacobo-Estrada, Tania [Departmento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); López-Bayghen, Esther [Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); and others

2013-11-01

Fluoride is usually found in groundwater at a very wide range of concentration between 0.5 and 25 ppm. At present, few studies have assessed the renal effects of fluoride at environmentally relevant concentrations. Furthermore, most of these studies have used insensitive and nonspecific biomarkers of kidney injury. The aim of this study was to use early and sensitive biomarkers to evaluate kidney injury after fluoride exposure to environmentally relevant concentrations. Recently weaned male Wistar rats were exposed to low (15 ppm) and high (50 ppm) fluoride concentrations in drinking water for a period of 40 days. At the end of the exposure period, kidney injury biomarkers were measured in urine and renal mRNA expression levels were assessed by real time RT-PCR. Our results showed that the urinary kidney injury molecule (Kim-1), clusterin (Clu), osteopontin (OPN) and heat shock protein 72 excretion rate significantly increased in the group exposed to the high fluoride concentration. Accordingly, fluoride exposure increased renal Kim-1, Clu and OPN mRNA expression levels. Moreover, there was a significant dose-dependent increase in urinary β-2-microglobulin and cystatin-C excretion rate. Additionally, a tendency towards a dose dependent increase of tubular damage in the histopathological light microscopy findings confirmed the preferential impact of fluoride on the tubular structure. All of these changes occurred at early stages in which, the renal function was not altered. In conclusion using early and sensitive biomarkers of kidney injury, we were able to found proximal tubular alterations in rats sub-chronically exposed to fluoride. - Highlights: • Exposure to low concentrations of fluoride induced proximal tubular injury • Increase in urinary Kim-1, Clu, OPN and Hsp72 in 50 ppm fluoride-exposed group • Increase in urinary B2M and CysC in 15 and 50 ppm fluoride-exposed groups • Fluoride exposure increased renal Kim, Clu and OPN mRNA expression levels. �

Enamel renal syndrome: A rare case report

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S V Kala Vani

2012-01-01

Full Text Available Enamel renal syndrome is a very rare disorder associating amelogenesis imperfecta with nephrocalcinosis. It is known by various synonyms such as amelogenesis imperfecta nephrocalcinosis syndrome, MacGibbon syndrome, Lubinsky syndrome, and Lubinsky-MacGibbon syndrome. It is characterized by enamel agenesis and medullary nephrocalcinosis. This paper describes enamel renal syndrome in a female patient born in a consanguineous family.

Renal deterioration after spinal cord injury is associated with length of detrusor contractions during cystometry

DEFF Research Database (Denmark)

Elmelund, Marlene; Klarskov, Niels; Bagi, Per

2017-01-01

AIMS: To investigate which urodynamic parameters are associated with renal deterioration over a median of 41 years follow-up after traumatic spinal cord injury. METHODS: Medical records of patients with a traumatic spinal cord injury sustained 1944-1975 were reviewed from time of injury until 2012....... Patients who attended regular renography and/or renal clearance examinations and had minimum one cystometry and pressure-flow study were included. Renal deterioration was diagnosed as split renal function ≤30% in one kidney or relative glomerular filtration rate ≤51% of expected according to age and gender....... Detrusor function, presence of detrusor sphincter dyssynergia, maximum detrusor pressure, post-void residual volume, and cystometric bladder capacity were obtained. In patients with detrusor overactivity, a detrusor overactivity/cystometry ratio was calculated using duration of detrusor contraction...

Prior intake of Brazil nuts attenuates renal injury induced by ischemia and reperfusion

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Natassia Alberici Anselmo

2018-04-01

Full Text Available ABSTRACT Introduction: Ischemia-reperfusion (IR injury results from inflammation and oxidative stress, among other factors. Because of its anti-inflammatory and antioxidant properties, the Brazil nut (BN might attenuate IR renal injury. Objective: The aim of the present study was to investigate whether the intake of BN prevents or reduces IR kidney injury and inflammation, improving renal function and decreasing oxidative stress. Methods: Male Wistar rats were distributed into six groups (N=6/group: SHAM (control, SHAM treated with 75 or 150 mg of BN, IR, and IR treated with 75 or 150 mg of BN. The IR procedure consisted of right nephrectomy and occlusion of the left renal artery with a non-traumatic vascular clamp for 30 min. BN was given daily and individually for 7 days before surgery (SHAM or IR and maintained until animal sacrifice (48h after surgery. We evaluated the following parameters: plasma creatinine, urea, and phosphorus; proteinuria, urinary output, and creatinine clearance; plasmatic TBARS and TEAC; kidney expression of iNOS and nitrotyrosine, and macrophage influx. Results: Pre-treatment with 75 mg of BN attenuated IR-induced renal changes, with elevation of creatinine clearance and urinary output, reducing proteinuria, urea, and plasmatic phosphorus as well as reducing kidney expression of iNOS, nitrotyrosine, and macrophage influx. Conclusion: Low intake of BN prior to IR-induced kidney injury improves renal function by inhibition of macrophage infiltration and oxidative stress.

Renal cystic disease: A practical overview

International Nuclear Information System (INIS)

Hartman, D.S.

1987-01-01

Renal cystic disease includes a group of lesions with extremely diverse clinical, radiographic, and pathologic findings. The recent development of multiple imaging systems to study renal cystic disease has resulted in considerable interest in correlating the images obtained by different modalities with each other and with the underlying gross pathology. A thorough knowledge of the disturbed morphology and natural history of these diseases will lead to a better understanding of their appearance on radiologic imaging. This refresher course correlates disturbed morphology with appearances on diagnostic imaging, urography, US, angiography, CT, and MR imaging. The advantages and limitations of each imaging method are detailed. A practical classification emphasizing differential features is presented. The presentation is divided into two parts. In the first part typical and atypical cystic masses, including acquired cystic disease (from dialysis), Von Hippel-Lindau disease, and the cystic disease of tuberous sclerosis are discussed. In the second part, polycystic kidney disease (dominant and recessive), medullary cystic disease, medullary sponge kidney, multicycle-dysplastic kidney, renal sinus cysts (peripelvic), and pluricystic kidney disease are discussed

Evaluation of Renal Oxygenation Level Changes after Water Loading Using Susceptibility-Weighted Imaging and T2* Mapping.

Science.gov (United States)

Ding, Jiule; Xing, Wei; Wu, Dongmei; Chen, Jie; Pan, Liang; Sun, Jun; Xing, Shijun; Dai, Yongming

2015-01-01

To assess the feasibility of susceptibility-weighted imaging (SWI) while monitoring changes in renal oxygenation level after water loading. Thirty-two volunteers (age, 28.0 ± 2.2 years) were enrolled in this study. SWI and multi-echo gradient echo sequence-based T2(*) mapping were used to cover the kidney before and after water loading. Cortical and medullary parameters were measured using small regions of interest, and their relative changes due to water loading were calculated based on baseline and post-water loading data. An intraclass correlation coefficient analysis was used to assess inter-observer reliability of each parameter. A receiver operating characteristic curve analysis was conducted to compare the performance of the two methods for detecting renal oxygenation changes due to water loading. Both medullary phase and medullary T2(*) values increased after water loading (p T2(*) changes (p > 0.05). Interobserver reliability was excellent for the T2(*) values, good for SWI cortical phase values, and moderate for the SWI medullary phase values. The area under receiver operating characteristic curve of the SWI medullary phase values was 0.85 and was not different from the medullary T2(*) value (0.84). Susceptibility-weighted imaging enabled monitoring changes in the oxygenation level in the medulla after water loading, and may allow comparable feasibility to detect renal oxygenation level changes due to water loading compared with that of T2(*) mapping.

Rosiglitazone Affects Nitric Oxide Synthases and Improves Renal Outcome in a Rat Model of Severe Ischemia/Reperfusion Injury

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Boris Betz

2012-01-01

Full Text Available Background. Nitric oxide (NO-signal transduction plays an important role in renal ischemia/reperfusion (I/R injury. NO produced by endothelial NO-synthase (eNOS has protective functions whereas NO from inducible NO-synthase (iNOS induces impairment. Rosiglitazone (RGZ, a peroxisome proliferator-activated receptor (PPAR-γ agonist exerted beneficial effects after renal I/R injury, so we investigated whether this might be causally linked with NOS imbalance. Methods. RGZ (5 mg/kg was administered i.p. to SD-rats (f subjected to bilateral renal ischemia (60 min. Following 24 h of reperfusion, inulin- and PAH-clearance as well as PAH-net secretion were determined. Morphological alterations were graded by histopathological scoring. Plasma NOx-production was measured. eNOS and iNOS expression was analyzed by qPCR. Cleaved caspase 3 (CC3 was determined as an apoptosis indicator and ED1 as a marker of macrophage infiltration in renal tissue. Results. RGZ improves renal function after renal I/R injury (PAH-/inulin-clearance, PAH-net secretion and reduces histomorphological injury. Additionally, RGZ reduces NOx plasma levels, ED-1 positive cell infiltration and CC3 expression. iNOS-mRNA is reduced whereas eNOS-mRNA is increased by RGZ. Conclusion. RGZ has protective properties after severe renal I/R injury. Alterations of the NO pathway regarding eNOS and iNOS could be an explanation of the underlying mechanism of RGZ protection in renal I/R injury.

Endothelin-A receptor blockade slows the progression of renal injury in experimental renovascular disease.

Science.gov (United States)

Kelsen, Silvia; Hall, John E; Chade, Alejandro R

2011-07-01

Endothelin (ET)-1, a potent renal vasoconstrictor with mitogenic properties, is upregulated by ischemia and has been shown to induce renal injury via the ET-A receptor. The potential role of ET-A blockade in chronic renovascular disease (RVD) has not, to our knowledge, been previously reported. We hypothesized that chronic ET-A receptor blockade would preserve renal hemodynamics and slow the progression of injury of the stenotic kidney in experimental RVD. Renal artery stenosis, a major cause of chronic RVD, was induced in 14 pigs and observed for 6 wk. In half of the pigs, chronic ET-A blockade was initiated (RVD+ET-A, 0.75 mg·kg(-1)·day(-1)) at the onset of RVD. Single-kidney renal blood flow, glomerular filtration rate, and perfusion were quantified in vivo after 6 wk using multidetector computer tomography. Renal microvascular density was quantified ex vivo using three-dimensional microcomputer tomography, and growth factors, inflammation, apoptosis, and fibrosis were determined in renal tissue. The degree of stenosis and increase in blood pressure were similar in RVD and RVD+ET-A pigs. Renal hemodynamics, function, and microvascular density were decreased in the stenotic kidney but preserved by ET-A blockade, accompanied by increased renal expression of vascular endothelial growth factor, hepatocyte growth factor, and downstream mediators such as phosphorilated-Akt, angiopoietins, and endothelial nitric oxide synthase. ET-A blockade also reduced renal apoptosis, inflammation, and glomerulosclerosis. This study shows that ET-A blockade slows the progression of renal injury in experimental RVD and preserves renal hemodynamics, function, and microvascular density in the stenotic kidney. These results support a role for ET-1/ET-A as a potential therapeutic target in chronic RVD.

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

Science.gov (United States)

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

2016-08-01

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

Forty-five-year follow-up on the renal function after spinal cord injury

DEFF Research Database (Denmark)

Elmelund, M; Oturai, P S; Toson, B

2016-01-01

rate (GFR) ⩽75% of expected according to age and gender) was 58%. The cumulative risk of severe renal deterioration (functional distribution outside 30-70% on renography or relative GFR⩽51%) was 29% after 45 years postinjury. Only dilatation of UUT and renal/ureter stone requiring removal significantly...... increased the risk of moderate and severe renal deterioration. CONCLUSION: Renal deterioration occurs at any time after injury, suggesting that lifelong follow-up examinations of the renal function are important, especially in patients with dilatation of UUT and/or renal/ureter stones....

Medullary compression syndrome

International Nuclear Information System (INIS)

Barriga T, L.; Echegaray, A.; Zaharia, M.; Pinillos A, L.; Moscol, A.; Barriga T, O.; Heredia Z, A.

1994-01-01

The authors made a retrospective study in 105 patients treated in the Radiotherapy Department of the National Institute of Neoplasmic Diseases from 1973 to 1992. The objective of this evaluation was to determine the influence of radiotherapy in patients with medullary compression syndrome in aspects concerning pain palliation and improvement of functional impairment. Treatment sheets of patients with medullary compression were revised: 32 out of 39 of patients (82%) came to hospital by their own means and continued walking after treatment, 8 out of 66 patients (12%) who came in a wheelchair or were bedridden, could mobilize by their own after treatment, 41 patients (64%) had partial alleviation of pain after treatment. In those who came by their own means and did not change their characteristics, functional improvement was observed. It is concluded that radiotherapy offers palliative benefit in patients with medullary compression syndrome. (authors). 20 refs., 5 figs., 6 tabs

The normal and pathologic renal medulla: a comprehensive overview.

Science.gov (United States)

López, José I; Larrinaga, Gorka; Kuroda, Naoto; Angulo, Javier C

2015-04-01

The renal medulla comprises an intricate system of tubules, blood vessels and interstitium that is not well understood by most general pathologists. We conducted an extensive review of the literature on the renal medulla, in both normal and pathologic conditions. We set out in detail the points of key interest to pathologists: normal and pathological development, physiology, microscopic anatomy, histology and immunohistochemistry; and the specific and most common other types of disease associated with this part of the kidney: developmental abnormalities, (multicystic dysplastic kidney, autosomal dominant and recessive polycystic kidney diseases, medullary cystic kidney disease), inflammatory conditions (xanthogranulomatous pyelonephritis, malakoplakia), hyperplasia and dysplasia, and neoplastic processes (oncocytoma, atypical oncocytic tumors, chromophobe cell carcinoma, collecting duct carcinoma, urothelial carcinoma, other carcinomas, renal medullary fibroma and metastatic tumors). This condensed overview of the origin, function and pathology of the renal medulla, both in terms of development, inflammation and neoplastic processes, should help focus the interest of clinical pathologists on this widely overlooked part of the kidney. Copyright © 2014 Elsevier GmbH. All rights reserved.

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

Science.gov (United States)

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

2016-01-01

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

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

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

2012-06-01

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

Neural regulation of the kidney function in rats with cisplatin induced renal failure

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Goulding, Niamh E.; Johns, Edward J.

2015-01-01

Aim: Chronic kidney disease (CKD) is often associated with a disturbed cardiovascular homeostasis. This investigation explored the role of the renal innervation in mediating deranged baroreflex control of renal sympathetic nerve activity (RSNA) and renal excretory function in cisplatin-induced renal failure. Methods: Rats were either intact or bilaterally renally denervated 4 days prior to receiving cisplatin (5 mg/kg i.p.) and entered a chronic metabolic study for 8 days. At day 8, other groups of rats were prepared for acute measurement of RSNA or renal function with either intact or denervated kidneys. Results: Following the cisplatin challenge, creatinine clearance was 50% lower while fractional sodium excretion and renal cortical and medullary TGF-β1 concentrations were 3–4 fold higher in both intact and renally denervated rats compared to control rats. In cisplatin-treated rats, the maximal gain of the high-pressure baroreflex curve was only 20% that of control rats, but following renal denervation not different from that of renally denervated control rats. Volume expansion reduced RSNA by 50% in control and in cisplatin-treated rats but only following bilateral renal denervation. The volume expansion mediated natriuresis/diuresis was absent in the cisplatin-treated rats but was normalized following renal denervation. Conclusions: Cisplatin-induced renal injury impaired renal function and caused a sympatho-excitation with blunting of high and low pressure baroreflex regulation of RSNA, which was dependent on the renal innervation. It is suggested that in man with CKD there is a dysregulation of the neural control of the kidney mediated by its sensory innervation. PMID:26175693

The effect of biological sealants and adhesive treatments on matrix metalloproteinase expression during renal injury healing.

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José Miguel Lloris-Carsí

Full Text Available Renal injuries are relatively common in cases of abdominal trauma. Adhesives and sealants can be used to repair and preserve damaged organs. Using a rat model, this study explores the activity of different matrix metalloproteinases (MMP during the healing of renal injuries treated by two biological adhesives (TachoSil and GelitaSpon and a new synthetic elastic cyanoacrylate (Adhflex.Renal traumatic injuries were experimentally induced in 90 male Wistar rats by a Stiefel Biopsy Punch in the anterior aspect of the left kidney. Animals were divided into five groups: 1, sham non-injured (n = 3; 2, non-treated standard punch injury (n = 6; 3, punch injury treated with TachoSil (n = 27; 4, punch injury treated with GelitaSpon (n = 27; and, 5, punch injury treated with Adhflex (n = 27. Wound healing was evaluated 2, 6, and 18 days after injury by determining the expression of MMPs, and the histopathological evolution of lesions.Histologically, the wound size at 6 days post-injury was larger in Adhflex-treated samples than in the other treatments, but the scarring tissue was similar at 18 days post-injury. Only the MMPs subtypes 1, 2, 8, 9, and 13 were sufficiently expressed to be quantifiable. Both time since injury and treatment type had a significant influence on MMPs expression. Two days after injury, the expression of MMP8 and MMP9 was predominant. MMP2 expression was greater 6 days after injury. The Adhflex-treated group had a significantly higher MMPs expression than the other treatment groups at all healing stages.All three sealant treatments induced almost similar expression of MMPs than untreated animals indicating a physiological healing process. Given that all renal trauma injuries must be considered emergencies, both biological and synthetic adhesives, such as Adhflex, should be considered as a treatment options.

Stent revascularization restores cortical blood flow and reverses tissue hypoxia in atherosclerotic renal artery stenosis but fails to reverse inflammatory pathways or glomerular filtration rate.

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Saad, Ahmed; Herrmann, Sandra M S; Crane, John; Glockner, James F; McKusick, Michael A; Misra, Sanjay; Eirin, Alfonso; Ebrahimi, Behzad; Lerman, Lilach O; Textor, Stephen C

2013-08-01

Atherosclerotic renal artery stenosis (ARAS) is known to reduce renal blood flow, glomerular filtration rate (GFR) and amplify kidney hypoxia, but the relationships between these factors and tubulointerstitial injury in the poststenotic kidney are poorly understood. The purpose of this study was to examine the effect of renal revascularization in ARAS on renal tissue hypoxia and renal injury. Inpatient studies were performed in patients with ARAS (n=17; >60% occlusion) before and 3 months after stent revascularization, or in patients with essential hypertension (n=32), during fixed Na(+) intake and angiotensin converting enzyme/angiotensin receptors blockers Rx. Single kidney cortical, medullary perfusion, and renal blood flow were measured using multidetector computed tomography, and GFR by iothalamate clearance. Tissue deoxyhemoglobin levels (R(2)*) were measured by blood oxygen level-dependent MRI at 3T, as was fractional kidney hypoxia (percentage of axial area with R(2)*>30/s). In addition, we measured renal vein levels of neutrophil gelatinase-associated lipocalin, monocyte chemoattractant protein-1, and tumor necrosis factor-α. Pre-stent single kidney renal blood flow, perfusion, and GFR were reduced in the poststenotic kidney. Renal vein neutrophil gelatinase-associated lipocalin, tumor necrosis factor-α, monocyte chemoattractant protein-1, and fractional hypoxia were higher in untreated ARAS than in essential hypertension. After stent revascularization, fractional hypoxia fell (Pblood flow, whereas GFR and neutrophil gelatinase-associated lipocalin, monocyte chemoattractant protein-1, and tumor necrosis factor-α remained unchanged. These data demonstrate that despite reversal of renal hypoxia and partial restoration of renal blood flow after revascularization, inflammatory cytokines and injury biomarkers remained elevated and GFR failed to recover in ARAS. Restoration of vessel patency alone failed to reverse tubulointerstitial damage and partly

Evaluation of renal oxygenation level changes after water loading using susceptibility-weighted imaging and T2{sup *} mapping

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Ding, Jiule; Xing, Wei; Chen, Jie; Pan, Liang; Sun, Jun; Xing, Shi Jun [Dept. of Radiology, Third Affiliated Hospital of Suzhou University, Changzhou (China); Wu, Dong Mei [Shanghai Key Laboratory of Magnetic Resonance Imaging, East China Normal University, Shanghai (China); Dai, Yong Ming [Philips Healthcare, Shanghai (China)

2015-08-15

To assess the feasibility of susceptibility-weighted imaging (SWI) while monitoring changes in renal oxygenation level after water loading. Thirty-two volunteers (age, 28.0 ± 2.2 years) were enrolled in this study. SWI and multi-echo gradient echo sequence-based T2{sup *} mapping were used to cover the kidney before and after water loading. Cortical and medullary parameters were measured using small regions of interest, and their relative changes due to water loading were calculated based on baseline and post-water loading data. An intraclass correlation coefficient analysis was used to assess inter-observer reliability of each parameter. A receiver operating characteristic curve analysis was conducted to compare the performance of the two methods for detecting renal oxygenation changes due to water loading. Both medullary phase and medullary T2{sup *} values increased after water loading (p < 0.001), although poor correlations were found between the phase changes and the T2{sup *} changes (p > 0.05). Interobserver reliability was excellent for the T2{sup *} values, good for SWI cortical phase values, and moderate for the SWI medullary phase values. The area under receiver operating characteristic curve of the SWI medullary phase values was 0.85 and was not different from the medullary T2{sup *} value (0.84). Susceptibility-weighted imaging enabled monitoring changes in the oxygenation level in the medulla after water loading, and may allow comparable feasibility to detect renal oxygenation level changes due to water loading compared with that of T2{sup *} mapping.

Generation of a tenascin-C-CreER2 knockin mouse line for conditional DNA recombination in renal medullary interstitial cells.

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Wenjuan He

Full Text Available Renal medullary interstitial cells (RMIC are specialized fibroblast-like cells that exert important functions in maintaining body fluid homeostasis and systemic blood pressure. Here, we generated a RMIC specific tenascin-C promoter driven inducible CreER2 knockin mouse line with an EGFP reporter. Similar as endogenous tenascin-C expression, the reporter EGFP expression in the tenascin-C-CreER2(+/- mice was observed in the inner medulla of the kidney, and co-localized with COX2 but not with AQP2 or AQP1, suggesting selective expression in RMICs. After recombination (tenascin-C-CreER2(+/-/ROSA26-lacZ(+/- mice + tamoxifen, β-gal activity was restricted to the cells in the inner medulla of the kidney, and didn't co-localize with AQP2, consistent with selective Cre recombinase activity in RMICs. Cre activity was not obvious in other major organs or without tamoxifen treatment. This inducible RMIC specific Cre mouse line should therefore provide a novel tool to manipulate genes of interest in RMICs.

Impact of Mannose-Binding Lectin Deficiency on Radiocontrast-Induced Renal Dysfunction

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Michael Osthoff

2013-01-01

Full Text Available Contrast-induced nephropathy (CIN is the third leading cause of acute renal failure in hospitalized patients. Endothelial dysfunction, renal medullary ischemia, and tubular toxicity are regarded as the most important factors in the pathogenesis of CIN. Mannose-binding lectin (MBL, a pattern recognition protein of the lectin pathway of complement, has been found to aggravate and mediate tissue damage during experimental renal ischemia/reperfusion (I/R injury which was alleviated by inhibition with C1 inhibitor, a potent MBL, and lectin pathway inhibitor. In this paper, we highlight the potential role of MBL in the pathogenesis of human CIN. In experimental I/R models, MBL was previously found to induce tubular cell death independent of the complement system. In addition, after binding to vascular endothelial cells, MBL and its associated serine proteases were able to trigger a proinflammatory reaction and contribute to endothelial dysfunction. In humans, urinary MBL was increased after administration of contrast media and in individuals with CIN. Moreover, individuals with normal/high MBL levels were at increased risk to develop radiocontrast-induced renal dysfunction. Hence, MBL and the lectin pathway seem to be a promising target given that a licensed, powerful, human recombinant inhibitor exits to be added to the scarce armamentarium currently available for prophylaxis of CIN.

βENaC acts as a mechanosensor in renal vascular smooth muscle cells that contributes to renal myogenic blood flow regulation, protection from renal injury and hypertension.

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Drummond, Heather A; Stec, David E

2015-06-01

Pressure-induced constriction (also known as the "myogenic response") is an important mechanodependent response in small renal arteries and arterioles. The response is initiated by vascular smooth muscle cell (VSMC) stretch due to an increase in intraluminal pressure and leads to vasoconstriction. The myogenic response has two important roles as a mechanism of local blood flow autoregulation and protection against systemic blood pressure-induced microvascular damage. However, the molecular mechanisms underlying initiation of myogenic response are unresolved. Although several molecules have been considered initiators of the response, our laboratory has focused on the role of degenerin proteins because of their strong evolutionary link to mechanosensing in the nematode. Our laboratory has addressed the hypothesis that certain degenerin proteins act as mechanosensors in VSMCs. This article discusses the importance of a specific degenerin protein, β Epithelial Na + Channel (βENaC), in pressure-induced vasoconstriction, renal blood flow and susceptibility to renal injury. We propose that loss of the renal myogenic constrictor response delays the correction of renal blood flow that occurs with fluctuations in systemic pressure, which allows pressure swings to be transmitted to the microvasculature, thus increasing the susceptibility to renal injury and hypertension. The role of βENaC in myogenic regulation is independent of tubular βENaC and thus represents a non-tubular role for βENaC in renal-cardiovascular homeostasis.

Anticancer Drug 2-Methoxyestradiol Protects against Renal Ischemia/Reperfusion Injury by Reducing Inflammatory Cytokines Expression

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Ying-Yin Chen

2014-01-01

Full Text Available Background. Ischemia/reperfusion (I/R injury is a major cause of acute renal failure and allograft dysfunction in kidney transplantation. ROS/inflammatory cytokines are involved in I/R injury. 2-Methoxyestradiol (2ME2, an endogenous metabolite of estradiol, inhibits inflammatory cytokine expression and is an antiangiogenic and antitumor agent. We investigated the inhibitory effect of 2ME2 on renal I/R injury and possible molecular actions. Methods. BALB/c mice were intraperitoneally injected with 2ME2 (10 or 20 mg/kg or vehicle 12 h before and immediately after renal I/R experiments. The kidney weight, renal function, tubular damages, and apoptotic response were examined 24 h after I/R injury. The expression of mRNA of interleukin-1β, tumor necrosis factor- (TNF α, caspase-3, hypoxia inducible factor- (HIF 1α, and proapoptotic Bcl-2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3 in kidney tissue was determined using RT-PCR, while the expression of nuclear factor κB (NF-κB, BCL-2, and BCL-xL, activated caspase-9, and HIF-1α was determined using immunoblotting. In vitro, we determined the effect of 2ME2 on reactive oxygen species (ROS production and cell viability in antimycin-A-treated renal mesangial (RMC and tubular (NRK52E cells. Results. Serum creatinine and blood urea nitrogen were significantly higher in mice with renal I/R injury than in sham control and in I/R+2ME2-treated mice. Survival in I/R+2ME2-treated mice was higher than in I/R mice. Histological examination showed that 2ME2 attenuated tubular damage in I/R mice, which was associated with lower expression TNF-α, IL-1β, caspase-9, HIF-1α, and BNIP3 mRNA in kidney tissue. Western blotting showed that 2ME2 treatment substantially decreased the expression of activated caspase-9, NF-κB, and HIF-1α but increased the antiapoptotic proteins BCL-2 and BCL-xL in kidney of I/R injury. In vitro, 2MR2 decreased ROS production and increased cell viability in antimycin

Injúria Renal Aguda no paciente politraumatizado Acute Renal Injury in polytrauma patients

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Thiago Gomes Romano

2013-03-01

Full Text Available A Injúria Renal Aguda (IRA no contexto do paciente politraumatizado ocorre, na maioria das vezes, por uma conjuntura de fatores que passam por eventos correlacionados à ressuscitação volêmica inicial, ao grau de resposta inflamatória sistêmica associada ao trauma, ao uso de contraste iodado para procedimentos diagnósticos, à rabdomiólise e à síndrome compartimental abdominal. Atualmente, passamos por uma fase de uniformização dos critérios diagnósticos da IRA com o Acute Kidney Injury Network (AKIN, sendo a referência mais aceita. Consequentemente, o estudo da IRA no politraumatismo também passa por uma fase de reformulação. Esta revisão da literatura médica visa trazer dados epidemiológicos, fisiológicos e de implicação clínica para o manuseio destes pacientes, bem como expor os riscos do uso indiscriminado de expansores volêmicos e particularidades sobre a instituição de terapia renal substitutiva em indivíduos sob risco de hipertensão intracraniana.Acute Kidney Injury (AKI in trauma is, in most cases, multifactorial. Factors related to the initial ressuscitation protocol, degree of the systemic inflamatory response to trauma, contrast nephropathy in diagnostic procedures, rhabdomyolysis and abdominal compartment syndrome are some of those factors. Nowadays a uniformization in diagnostic criteria for AKI has been proposed by the Acute Kidney Injury Network (AKIN and as a result the incidence of AKI and its impact in outcomes in trauma patients also needs to be reconsider. In this review we aim to approach epidemiologic, physiologic and clinical relevant data in the critical care of patients victims of trauma and also to expose the risks of indiscriminate use of volume expanders and the interaction between renal replacement theraphy and intracranial hypertension.

Mitochondria-Targeted Antioxidant Mito-Tempo Protects Against Aldosterone-Induced Renal Injury In Vivo

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Wei Ding

2017-11-01

Full Text Available Background/Aims: Growing evidence suggests mitochondrial dysfunction (MtD and the Nlrp3 inflammasome play critical roles in chronic kidney disease (CKD progression. We previously reported that Aldosterone (Aldo-induced renal injury in vitro is directly caused by mitochondrial reactive oxygen species (mtROS-mediated activation of the Nlrp3 inflammasome. Here we aimed to determine whether a mitochondria-targeted antioxidant (Mito-Tempo could prevent Aldo-induced kidney damage in vivo. Methods: C57BL/6J mice were treated with Aldo and/or Mito-Tempo (or ethanol as a control for 4 weeks. Renal injury was evaluated by Periodic Acid-Schiff reagent or Masson’s trichrome staining and electron microscopy. ROS were measured by DCFDA fluorescence and ELISA. MtD was determined by real-time PCR and electron microscopy. Activation of the Nlrp3 inflammasome and endoplasmic reticulum stress (ERS was detected via western blot. Results: Compared with control mice, Aldo-infused mice showed impaired renal function, increased mtROS production and MtD, Nlrp3 inflammasome activation, and elevated ERS. We showed administration of Mito-Tempo significantly improved renal function and MtD, and reduced Nlrp3 inflammasome activation and ERS in vivo. Conclusion: Mitochondria-targeted antioxidants may attenuate Aldo-infused renal injury by inhibiting MtD, the Nlrp3 inflammasome, and ERS in vivo. Therefore, targeting mtROS might be an effective strategy for preventing CKD.

Bmi-1 plays a critical role in protection from renal tubulointerstitial injury by maintaining redox balance

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Jin, Jianliang; Lv, Xianhui; Chen, Lulu; Zhang, Wei; Li, Jinbo; Wang, Qian; Wang, Rong; Lu, Xiang; Miao, Dengshun

2014-01-01

To determine whether Bmi-1 deficiency could lead to renal tubulointerstitial injury by mitochondrial dysfunction and increased oxidative stress in the kidney, 3-week-old Bmi-1-/- mice were treated with the antioxidant N-acetylcysteine (NAC, 1 mg mL−1) in their drinking water, or pyrro-quinoline quinone (PQQ, 4 mg kg−1 diet) in their diet for 2 weeks, and their renal phenotypes were compared with vehicle-treated Bmi1-/- and wild-type mice. Bmi-1 was knocked down in human renal proximal tubular epithelial (HK2) cells which were treated with 1 mm NAC for 72 or 96 h, and their phenotypes were compared with control cells. Five-week-old vehicle-treated Bmi-1-/- mice displayed renal interstitial fibrosis, tubular atrophy, and severe renal function impairment with decreased renal cell proliferation, increased renal cell apoptosis and senescence, and inflammatory cell infiltration. Impaired mitochondrial structure, decreased mitochondrial numbers, and increased oxidative stress occurred in Bmi-1-/- mice; subsequently, this caused DNA damage, the activation of TGF-β1/Smad signaling, and the imbalance between extracellular matrix synthesis and degradation. Oxidative stress-induced epithelial-to-mesenchymal transition of renal tubular epithelial cells was enhanced in Bmi-1 knocked down HK2 cells. All phenotypic alterations caused by Bmi-1 deficiency were ameliorated by antioxidant treatment. These findings indicate that Bmi-1 plays a critical role in protection from renal tubulointerstitial injury by maintaining redox balance and will be a novel therapeutic target for preventing renal tubulointerstitial injury. PMID:24915841

Change in iron metabolism in rats after renal ischemia/reperfusion injury.

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Guang-Liang Xie

Full Text Available Previous studies have indicated that hepcidin, which can regulate iron efflux by binding to ferroportin-1 (FPN1 and inducing its internalization and degradation, acts as the critical factor in the regulation of iron metabolism. However, it is unknown whether hepcidin is involved in acute renal ischemia/reperfusion injury (IRI. In this study, an IRI rat model was established via right renal excision and blood interruption for 45 min in the left kidney, and iron metabolism indexes were examined to investigate the change in iron metabolism and to analyze the role of hepcidin during IRI. From 1 to 24 h after renal reperfusion, serum creatinine and blood urea nitrogen were found to be time-dependently increased with different degrees of kidney injury. Regular variations in iron metabolism indexes in the blood and kidneys were observed in renal IRI. Renal iron content, serum iron and serum ferritin increased early after reperfusion and then declined. Hepcidin expression in the liver significantly increased early after reperfusion, and its serum concentration increased beginning at 8 h after reperfusion. The splenic iron content decreased significantly in the early stage after reperfusion and then increased time-dependently with increasing reperfusion time, and the hepatic iron content showed a decrease in the early stage after reperfusion. The early decrease of the splenic iron content and hepatic iron content might indicate their contribution to the increase in serum iron in renal IRI. In addition, the duodenal iron content showed time-dependently decreased since 12 h after reperfusion in the IRI groups compared to the control group. Along with the spleen, the duodenum might contribute to the decrease in serum iron in the later stage after reperfusion. The changes in iron metabolism indexes observed in our study demonstrate an iron metabolism disorder in renal IRI, and hepcidin might be involved in maintaining iron homeostasis in renal IRI. These

Gender difference and sex hormone production in rodent renal ischemia reperfusion injury and repair

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Ghazali Daniel

2011-06-01

Full Text Available Abstract Background Several lines of evidence suggest a protective effect of female sex hormones in several organs subjected to ischemia-reperfusion injury. The aim of the study was to investigate sex hormone production in male rats after a renal ischemia-reperfusion sequence and analyze the influence of gender differences on tissue remodelling during the recovery process. Method Age-matched sexually mature male and female rats were subjected to 60 min of renal unilateral ischemia by pedicle clamping with contralateral nephrectomy and followed for 1 or 5 days after reperfusion. Plasma creatinine, systemic testosterone, progesterone and estradiol levels were determined. Tubular injury, cell proliferation and inflammation, were evaluated as well as proliferating cell nuclear antigen, vimentin and translocator protein (TSPO expressions by immunohistochemistry. Results After 1 and 5 days of reperfusion, plasma creatinine was significantly higher in males than in females, supporting the high mortality in this group. After reperfusion, plasma testosterone levels decreased whereas estradiol significantly increased in male rats. Alterations of renal function, associated with tubular injury and inflammation persisted during the 5 days post-ischemia-reperfusion, and a significant improvement was observed in females at 5 days of reperfusion. Proliferating cell nuclear antigen and vimentin expression were upregulated in kidneys from males and attenuated in females, in parallel to injury development. TSPO expression was transiently increased in proximal tubules in male rats. Conclusions After ischemia, renal function recovery and tissue injury is gender-dependent. These differences are associated with a modulation of sex hormone production and a modification of tissue remodeling and proliferative cell processes.

STUDIES OF THE RENAL CONCENTRATING MECHANISM IN HUMANS. I. THE EFFECT OF HYPERTHYROIDISM,

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Summary: (1) The maximum urinary osmolality after dehydration and exogenous vasopressin was significantly decreased during thyrotoxicosis in... thyrotoxicosis , TcH2O during a moderate mannitol diuresis was unchanged in most patients. The data suggest that the decreased Umax and normal TcH2O...in thyrotoxic individuals is probably caused by an increase in medullary blood flow with a decrease in medullary osmolality. (2) Renal hemodynamics

Dual energy CT monitoring of the renal corticomedullary sodium gradient in swine

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Kumar, Rahi; Wang, Zhen J.; Forsythe, Carlos; Fu Yanjun; Chen, Yunn-Yi; Yeh, Benjamin M.

2012-01-01

Objective: To evaluate the feasibility of dual-energy CT (DECT) for monitoring dynamic changes in the renal corticomedullary sodium gradient in swine. Material and methods: This study was approved by our Institutional Animal Care and Use Committee. Four water-restricted pigs were CT-scanned at 80 and 140 kVp at baseline and at 5 min intervals for 30 min during saline or furosemide diuresis. The renal cortical and medullary CT numbers were recorded. A DECT basis material decomposition method was used to quantify renal cortical and medullary sodium concentrations and medulla-to-cortex sodium ratios at each time point based on the measured CT numbers. The sodium concentrations and medulla-to-cortex sodium ratios were compared between baseline and at 30 min diuresis using paired Student t-tests. The medulla-to-cortex sodium ratios were considered to reflect the corticomedullary sodium gradient. Results: At baseline prior to saline diuresis, the mean medullary and cortical sodium concentrations were 103.8 ± 8.7 and 65.3 ± 1.7 mmol/l, respectively, corresponding to a medulla-to-cortex sodium ratio of 1.59. At 30 min of saline diuresis, the medullary and cortical sodium concentrations decreased to 72.3 ± 1.0 and 56.0 ± 1.4 mmol/l, respectively, corresponding to a significantly reduced medulla-to-cortex sodium ratio of 1.29 (P < 0.05). At baseline prior to furosemide diuresis, the mean medullary and cortical sodium concentrations were 110.5 ± 3.6 and 66.7 ± 4.1 mmol/l, respectively, corresponding to a medulla-to-cortex sodium ratio of 1.66. At 30 min of furosemide diuresis, the medullary and cortical sodium concentrations decreased to 68.5 ± 0.3 and 58.9 ± 4.0 mmol/l, respectively, corresponding to a significantly reduced medulla-to-cortex sodium ratio of 1.16 (P < 0.05). One of the 4 pigs developed acute tubular necrosis likely related to prolonged hypoxia during intubation prior to the furosemide diuresis experiment. The medulla-to-cortex sodium ratio for this

Calpastatin overexpression prevents progression of S-1,2-dichlorovinyl-L-cysteine (DCVC)-initiated acute renal injury and renal failure (ARF) in diabetes

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Dnyanmote, Ankur V.; Sawant, Sharmilee P.; Lock, Edward A.; Latendresse, John R.; Warbritton, Alan A.; Mehendale, Harihara M.

2006-01-01

Previously we have shown that 90% of streptozotocin (STZ)-induced type-1 diabetic (DB) mice survive from acute renal failure (ARF) and death induced by a normally LD 9 dose (75 mg/kg, i.p.) of the nephrotoxicant S-1,2-dichlorovinyl-L-cysteine (DCVC). This remarkable protection is due to a combination of slower progression of DCVC-initiated renal injury and increased compensatory nephrogenic tissue repair in the DB kidneys. BRDU immunohistochemistry revealed that the DB condition led to 4-fold higher number of proximal tubular cells (PTC) entering S-phase of cell cycle. In the present study, we tested the hypothesis that DB-induced augmentation of PTC into S-phase is accompanied by overexpression of the calpain-inhibitor calpastatin, which endogenously prevents the progression of DCVC-initiated renal injury mediated by the calpain escaping out of damaged PTCs. Immunohistochemical detection of renal calpain and its activity in the urine, over a time course after treatment with the LD 9 dose of DCVC, indicated progressive increase in leakage of calpain into the extracellular spaces of the injured PTCs of the non-diabetic (NDB) kidneys as compared to the DB kidneys. Calpastatin expression was minimally detected in the NDB kidneys, using immunohistochemistry, over the time course. On the other hand, consistently higher number of tubules in the DB kidney showed calpastatin expression over the time course. The lower leakage of calpain in the DB kidneys was commensurate with constitutively higher expression of calpastatin in the S-phase-laden PTCs of these mice. To test the protective role of newly divided/dividing PTCs, DB mice were given the anti-mitotic agent colchicine (CLC) (2 mg/kg and 1.5 mg/kg, i.p., on days 8 and 10 after STZ injection) prior to challenge with a LD 9 dose of DCVC, which led to 100% mortality by 48 h. Mortality was due to rapid progression of DCVC-initiated renal injury, suggesting that newly divided/dividing cells are instrumental in mitigating

Ischemic preconditioning provides both acute and delayed protection against renal ischemia and reperfusion injury in mice.

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Joo, Jin Deok; Kim, Mihwa; D'Agati, Vivette D; Lee, H Thomas

2006-11-01

Acute as well as delayed ischemic preconditioning (IPC) provides protection against cardiac and neuronal ischemia reperfusion (IR) injury. This study determined whether delayed preconditioning occurs in the kidney and further elucidated the mechanisms of renal IPC in mice. Mice were subjected to IPC (four cycles of 5 min of ischemia and reperfusion) and then to 30 min of renal ischemia either 15 min (acute IPC) or 24 h (delayed IPC) later. Both acute and delayed renal IPC provided powerful protection against renal IR injury. Inhibition of Akt but not extracellular signal-regulated kinase phosphorylation prevented the protection that was afforded by acute IPC. Neither extracellular signal-regulated kinase nor Akt inhibition prevented protection that was afforded by delayed renal IPC. Pretreatment with an antioxidant, N-(2-mercaptopropionyl)-glycine, to scavenge free radicals prevented the protection that was provided by acute but not delayed renal IPC. Inhibition of protein kinase C or pertussis toxin-sensitive G-proteins attenuated protection from both acute and delayed renal IPC. Delayed renal IPC increased inducible nitric oxide synthase (iNOS) as well as heat-shock protein 27 synthesis, and the renal protective effects of delayed preconditioning were attenuated by a selective inhibitor of iNOS (l-N(6)[1-iminoethyl]lysine). Moreover, delayed IPC was not observed in iNOS knockout mice. Both acute and delayed IPC were independent of A(1) adenosine receptors (AR) as a selective A(1)AR antagonist failed to block preconditioning and acute and delayed preconditioning occurred in mice that lacked A(1)AR. Therefore, this study demonstrated that acute or delayed IPC provides renal protection against IR injury in mice but involves distinct signaling pathways.

The role of hemosorption detoxication in the modification of medullary hemoroisis caused by acute irradiation injury

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Nikolaev, V.G.; Rodionova, N.K.; Petrenko, S.V.; Bychkova, N.P.; Pinchouk, L.B.

2003-01-01

Using the model of a medullar form of acute radiation disease in dogs, we have shown that early detoxification through extracorporal hemosorption in various modifications is of high efficiency. On the basis of results of experimental research, a high efficiency of detoxification therapy of the medullary form of acute radiation diseases is established. It is revealed that the toxicity of liquid media of the body is reduced after the application of various modifications of extracorporal extracorporal hemosorption. The main indicators of the efficiency of these methods are the considerable relief of the medullary syndrome severity, lower level of clinical symptoms, and high survival rate of animals

Involvement of caspase-12-dependent apoptotic pathway in ionic radiocontrast urografin-induced renal tubular cell injury

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Wu, Cheng Tien [Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Weng, Te I. [Department of Forensic Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Chen, Li Ping [Department of Dentistry, Chang Gang Memorial Hospital, Chang Gang University, Taoyuan, Taiwan (China); Chiang, Chih Kang [Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (China); Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (China); Liu, Shing Hwa, E-mail: shinghwaliu@ntu.edu.tw [Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Department of Urology, National Taiwan University Hospital, Taipei, Taiwan (China)

2013-01-01

Contrast medium (CM) induces a direct toxic effect on renal tubular cells. This toxic effect subjects in the disorder of CM-induced nephropathy. Our previous work has demonstrated that CM shows to activate the endoplasmic reticulum (ER)-related adaptive unfolding protein response (UPR) activators. Glucose-regulated protein 78 (GRP78)/eukaryotic initiation factor 2α (eIF2α)-related pathways play a protective role during the urografin (an ionic CM)-induced renal tubular injury. However, the involvement of ER stress-related apoptotic signals in the urografin-induced renal tubular cell injury remains unclear. Here, we examined by the in vivo and in vitro experiments to explore whether ER stress-regulated pro-apoptotic activators participate in urografin-induced renal injury. Urografin induced renal tubular dilation, tubular cells detachment, and necrosis in the kidneys of rats. The tubular apoptosis, ER stress-related pro-apoptotic transcriptional factors, and kidney injury marker-1 (kim-1) were also conspicuously up-regulated in urografin-treated rats. Furthermore, treatment of normal rat kidney (NRK)-52E tubular cells with urografin augmented the expressions of activating transcription factor-6 (ATF-6), C/EBP homologous protein (CHOP), Bax, caspase-12, JNK, and inositol-requiring enzyme (IRE) 1 signals. Urografin-induced renal tubular cell apoptosis was not reversed by the inhibitors of ATF-6, JNK signals or CHOP siRNA transfection, but it could be partially reversed by the inhibitor of caspase-12. Taken together, the present results and our previous findings suggest that exposure of CM/urografin activates the ER stress-regulated survival- and apoptosis-related signaling pathways in renal tubular cells. Caspase-12-dependent apoptotic pathway may be partially involved in the urografin-induced nephropathy. -- Highlights: ► Ionic contrast medium-urografin induces renal tubular cell apoptosis. ► Urografin induces the ER stress-regulated survival and apoptosis

Mechanisms of HO-1 mediated attenuation of renal immune injury: a gene profiling study.

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Duann, Pu; Lianos, Elias A

2011-10-01

Using a mouse model of immune injury directed against the renal glomerular vasculature and resembling human forms of glomerulonephritis (GN), we assessed the effect of targeted expression of the cytoprotective enzyme heme oxygenase (HO)-1. A human (h) HO-1 complementary DNAN (cDNA) sequence was targeted to glomerular epithelial cells (GECs) using a GEC-specific murine nephrin promoter. Injury by administration of antibody against the glomerular basement membrane (anti-GBM) to transgenic (TG) mice with GEC-targeted hHO-1 was attenuated compared with wild-type (WT) controls. To explore changes in the expression of genes that could mediate this salutary effect, we performed gene expression profiling using a microarray analysis of RNA isolated from the renal cortex of WT or TG mice with or without anti-GBM antibody-induced injury. Significant increases in expression were detected in 9 major histocompatibility complex (MHC)-class II genes, 2 interferon-γ (IFN-γ)-inducible guanosine triphosphate (GTP)ases, and 3 genes of the ubiquitin-proteasome system. The increase in MHC-class II and proteasome gene expression in TG mice with injury was validated by real-time polymerase chain reaction (PCR) or Western blot analysis. The observations point to novel mechanisms underlying the cytoprotective effect of HO-1 in renal immune injury. Copyright © 2011. Published by Mosby, Inc.

Magnetization Transfer Magnetic Resonance Imaging Noninvasively Detects Renal Fibrosis in Swine Atherosclerotic Renal Artery Stenosis at 3.0 T.

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Jiang, Kai; Ferguson, Christopher M; Woollard, John R; Zhu, Xiangyang; Lerman, Lilach O

2017-11-01

Renal fibrosis is a useful biomarker for diagnosis and evaluation of therapeutic interventions of renal diseases but often requires invasive testing. Magnetization transfer magnetic resonance imaging (MT-MRI), which evaluates the presence of macromolecules, offers a noninvasive tool to probe renal fibrosis in murine renal artery stenosis (RAS) at 16.4 T. In this study, we aimed to identify appropriate imaging parameters for collagen detection at 3.0 T MRI and to test the utility of MT-MRI in measuring renal fibrosis in a swine model of atherosclerotic RAS (ARAS). To select the appropriate offset frequency, an MT-MRI study was performed on a phantom containing 0% to 40% collagen I and III with offset frequencies from -1600 to +1600 Hz and other MT parameters empirically set as pulse width at 16 milliseconds and flip angle at 800 degrees. Then selected MT parameters were used in vivo on pigs 12 weeks after sham (n = 8) or RAS (n = 10) surgeries. The ARAS pigs were fed with high-cholesterol diet to induce atherosclerosis. The MT ratio (MTR) was compared with ex vivo renal fibrosis measured using Sirius-red staining. Offset frequencies at 600 and 1000 Hz were selected for collagen detection without direct saturation of free water signal, and subsequently applied in vivo. The ARAS kidneys showed mild cortical and medullary fibrosis by Sirius-red staining. The cortical and medullary MTRs at 600 and 1000 Hz were both increased. Renal fibrosis measured ex vivo showed good linear correlations with MTR at 600 (cortex: Pearson correlation coefficient r = 0.87, P 3.0 T. Therefore, MT-MRI may potentially be clinically applicable and useful for detection and monitoring of renal pathology in subjects with RAS.

Adrenal medullary hyperplasia. Hyperplasia-pheochromocytoma sequence.

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Kurihara, K; Mizuseki, K; Kondo, T; Ohoka, H; Mannami, M; Kawai, K

1990-09-01

We present a case of unilateral adrenal medullary hyperplasia in a 63-year-old woman with clinical signs and symptoms of pheochromocytoma unassociated with multiple endocrine neoplasia. The surgically removed adrenal gland revealed diffuse medullary hyperplasia with multiple micronodules measuring up to 2 mm. The micronodules were composed of enlarged chromaffin cells with atypia, histologically similar to those of pheochromocytoma, forming small solid alveolar patterns separated by a fibrovascular stroma. Removal of the hyperplastic adrenal gland resulted in disappearance of paroxysmal nocturnal hypertension and palpitation. These results suggest that diffuse and nodular medullary hyperplasia is the precursor of pheochromocytoma.

Albumin infusion improves renal blood flow autoregulation in patients with acute decompensation of cirrhosis and acute kidney injury.

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Garcia-Martinez, Rita; Noiret, Lorette; Sen, Sambit; Mookerjee, Rajeshwar; Jalan, Rajiv

2015-02-01

In cirrhotic patients with renal failure, renal blood flow autoregulation curve is shifted to the right, which is consequent upon sympathetic nervous system activation and endothelial dysfunction. Albumin infusion improves renal function in cirrhosis by mechanisms that are incompletely understood. We aimed to determine the effect of albumin infusion on systemic haemodynamics, renal blood flow, renal function and endothelial function in patients with acute decompensation of cirrhosis and acute kidney injury. Twelve patients with refractory ascites and 10 patients with acute decompensation of cirrhosis and acute kidney injury were studied. Both groups were treated with intravenous albumin infusion, 40-60 g/days over 3-4 days. Cardiac and renal haemodynamics were measured. Endothelial activation/dysfunction was assessed using von Willebrand factor and serum nitrite levels. F2α Isoprostanes, resting neutrophil burst and noradrenaline levels were quantified as markers of oxidative stress, endotoxemia and sympathetic activation respectively. Albumin infusion leads to a shift in the renal blood flow autoregulation curve towards normalization, which resulted in a significant increase in renal blood flow. Accordingly, improvement of renal function was observed. In parallel, a significant decrease in sympathetic activation, inflammation/oxidative stress and endothelial activation/dysfunction was documented. Improvement of renal blood flow correlated with improvement in endothelial activation (r = 0.741, P renal function in acutely decompensated cirrhotic patients with acute kidney injury by impacting on renal blood flow autoregulation. This is possibly achieved through endothelial stabilization and a reduction in the sympathetic tone, endotoxemia and oxidative stress. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A high-fat diet increases oxidative renal injury and protein glycation in D-galactose-induced aging rats and its prevention by Korea red ginseng.

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Park, Sok; Kim, Chan-Sik; Min, Jinah; Lee, Soo Hwan; Jung, Yi-Sook

2014-01-01

Declining renal function is commonly observed with age. Obesity induced by a high-fat diet (HFD) may reduce renal function. Korean red ginseng (KRG) has been reported to ameliorate oxidative tissue injury and have an anti-aging effect. This study was designed to investigate whether HFD would accelerate the D-galactose-induced aging process in the rat kidney and to examine the preventive effect of KRG on HFD and D-galactose-induced aging-related renal injury. When rats with D-galactose-induced aging were fed an HFD for 9 wk, enhanced oxidative DNA damage, renal cell apoptosis, protein glycation, and extracellular high mobility group box 1 protein (HMGB1), a signal of tissue damage, were observed in renal glomerular cells and tubular epithelial cells. However, treatment of rats with HFD- plus D-galactose-induced aging with KRG restored all of these renal changes. Our data suggested that a long-term HFD may enhance D-galactose-induced oxidative renal injury in rats and that this age-related renal injury could be suppressed by KRG through the repression of oxidative injury.

Cinnabar-Induced Subchronic Renal Injury Is Associated with Increased Apoptosis in Rats

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Ying Wang

2015-01-01

Full Text Available The aim of this study was to explore the role of apoptosis in cinnabar-induced renal injury in rats. To test this role, rats were dosed orally with cinnabar (1 g/kg/day for 8 weeks or 12 weeks, and the control rats were treated with 5% carboxymethylcellulose solution. Levels of urinary mercury (UHg, renal mercury (RHg, serum creatinine (SCr, and urine kidney injury molecule 1 (KIM-1 were assessed, and renal pathology was analyzed. Apoptotic cells were identified and the apoptotic index was calculated. A rat antibody array was used to analyze expression of cytokines associated with apoptosis. Results from these analyses showed that UHg, RHg, and urine KIM-1, but not SCr, levels were significantly increased in cinnabar-treated rats. Renal pathological changes in cinnabar-treated rats included vacuolization of tubular cells, formation of protein casts, infiltration of inflammatory cells, and increase in the number of apoptotic tubular cells. In comparison to the control group, expression of FasL, Fas, TNF-α, TRAIL, activin A, and adiponectin was upregulated in the cinnabar-treated group. Collectively, our results suggest that prolonged use of cinnabar results in kidney damage due to accumulation of mercury and that the underlying mechanism involves apoptosis of tubular cells via a death receptor-mediated pathway.

Glucose supplementation does not interfere with fasting-induced protection against renal ischemia/reperfusion injury in mice.

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Verweij, Mariëlle; van de Ven, Marieke; Mitchell, James R; van den Engel, Sandra; Hoeijmakers, Jan H J; Ijzermans, Jan N M; de Bruin, Ron W F

2011-10-15

Preoperative fasting induces robust protection against renal ischemia/reperfusion (I/R) injury in mice but is considered overcautious and possibly detrimental for postoperative recovery in humans. Furthermore, fasting seems to conflict with reported benefits of preoperative nutritional enhancement with carbohydrate-rich drinks. Here, we investigated whether preoperative ingestion of a glucose solution interferes with fasting-induced protection against renal I/R injury. Mice were randomized into the following groups: fasted for 3 days with access to water (fasted) or a glucose solution (fasted+glc) and fed ad libitum with water (fed) or a glucose solution (fed+glc). After induction of bilateral renal I/R injury, all animals had free access to food and water. Calorie intake, body weight, insulin sensitivity, kidney function, and animal survival were determined. Fed+glc mice had a comparable daily calorie intake as fed mice, but 50% of those calories were obtained from the glucose solution. Fasted+glc mice had a daily calorie intake of approximately 75% of the intake of both fed groups. This largely prevented the substantial body weight loss seen in fasted animals. Preoperative insulin sensitivity was significantly improved in fasted+glc mice versus fed mice. After I/R injury, kidney function and animal survival were superior in both fasted groups. The benefits of fasting and preoperative nutritional enhancement with carbohydrates are not mutually exclusive and may be a clinically feasible regimen to protect against renal I/R injury.

Blood oxygenation level dependent (BOLD). Renal imaging. Concepts and applications

International Nuclear Information System (INIS)

Nissen, Johanna C.; Haneder, Stefan; Schoenberg, Stefan O.; Michaely, Henrik J.

2010-01-01

Many renal diseases as well as several pharmacons cause a change in renal blood flow and/or renal oxygenation. The blood oxygenation level dependent (BOLD) imaging takes advantage of local field inhomogeneities and is based on a T2 * -weighted sequence. BOLD is a non-invasive method allowing an estimation of the renal, particularly the medullary oxygenation, and an indirect measurement of blood flow without administration of contrast agents. Thus, effects of different drugs on the kidney and various renal diseases can be controlled and observed. This work will provide an overview of the studies carried out so far and identify ways how BOLD can be used in clinical studies. (orig.)

Protective effects of Rosmarinic acid against renal ischaemia/reperfusion injury in rats

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Ozturk, H.; Ozturk, H.; Terzi, E.H.

2014-01-01

Objective: To investigate the potential protective effects of Rosmarinic acid (RA) on rats exposed to ischaemia/reperfusion renal injury. Methods: The prospective study was conducted at Abant Izzet Baysal University, Turkey, and comprised 21 male Spraque Dawley rats weighing 250-270g each. They were divided into three equal groups. Unilaterally nephrectomised rats were subjected to 60 minutes of left renal ischaemia followed by 60 minutes of reperfusion. Group 1 had shamoperated animals; group 2 had ischaemia/reperfusion untreated animals; and group 3 had ischaemia/reperfusion animals treated with rosmarinic acid. Serum creatinine, blood urea nitrogen, tissue malondialdehyde, glutathione peroxidase, superoxide dismutase and myeloperoxidase (MPO) activities, and light microscopic findings were evaluated. SPSS 17 was used for statistical analysis. Results: Treatment of rats with rosmarinic acid produced a reduction in the serum levels of creatinine and blood urea nitrogen compared to the other groups. However, no statistically significant difference was found. The levels of malondialdehyde and myeloperoxidase were decreased in the renal tissue of group 3, while glutathione peroxidose and superoxide dismutase levels remained unchanged. The injury score decreased in the treatment group rats compared to the untreated group. Rosmarinic acid significantly decreased focal glomerular necrosis, dilatation of Bowman's capsule, degeneration of tubular epithelium, necrosis in tubular epithelium, and tubular dilatation. Conclusions: Rosmarinic acid prevented ischaemia/reperfusion injury in the kidneys by decreasing oxidative stress. (author)

Effect of Intervention in Mast Cell Function Before Reperfusion on Renal Ischemia-Reperfusion Injury in Rats

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Fei Tong

2016-06-01

Full Text Available Background/Aims: Mast cells are sparsely distributed in the kidneys under normal conditions; however, the number of mast cells increases dramatically during renal ischemia/reperfusion injury (RI/RI. When mast cells are stimulated, numerous mediators are released, and under pathological conditions, they produce a wide range of biological effects. The aim of this study was to investigate the effect of intervention in mast cell function before reperfusion on RI/RI. Methods: Sprague-Dawley (SD rats (n=50 were randomized into five groups: sham group, ischemia/reperfusion (I/R group, cromolyn sodium treatment group (CS+I/R group, ketotifen treatment group (K+I/Rgroup, and compound 48/80 treatment group (C+I/R group. I/R injury was induced by bilateral renal artery and vein occlusion for 45 min followed by 24 h of reperfusion. The agents were intravenously administered 5 min before reperfusion through the tail vein. The serum levels of blood urea nitrogen(BUN, serum creatinine (Scr and histamine and the kidney levels of malondialdehyde (MDA, superoxide dismutase (SOD, tumor necrosis factor α (TNF-α and interleukin-6 (IL-6 were assessed. The expression of intracellular adhesion molecule-1 (ICAM-1 in renal tissue was also measured. Results: I/R injury resulted in severe renal injury, as demonstrated by a large increase in injury scores; serum levels of BUN, Scr and histamine; and kidney levels of MDA, TNF-α, and IL-6; this was accompanied by reduced SOD activity and upregulated ICAM-1 expression. Treatment with cromolyn sodium or ketotifen markedly alleviated I/R-mediated kidney injury, whereas compound 48/80 further aggravated kidney injury. Conclusion: Intervention in mast cell activity prior to reperfusionhas a strong effect on RI/RI.

NMR studies of renal phosphate metabolites in vivo: Effects of hydration and dehydration

International Nuclear Information System (INIS)

Wolff, S.D.; Eng, C.; Balaban, R.S.

1988-01-01

The present study characterizes the 31 P-nuclear magnetic resonance (NMR) spectrum of rabbit kidneys in vivo and evaluates the effect of hydration on phosphorous metabolites including the organic solute glycerophosphorylcholine (GPC). Cortical phosphorylethanolamine is the predominant component of the phosphomonoester region of the 31 P spectrum. The contribution of blood to the spectrum is mainly from 2,3 diphosphoglycerate, which comprises ∼30% of the inorganic phosphate region. Acute infusion of 0.9% saline decreases the sodium content of the inner medulla by >50% in 15 min as shown by 23 Na imaging. Despite this medullary Na dilution, no change in renal GPC content was observed for >1 h even with the addition of furosemide or furosemide and antidiuretic hormone. However, 20 h of chronic dehydration with 0.45% saline did result in a 30% decrease in renal GPC content when compared with dehydrated animals. These findings are consistent with GPC not playing a role in the short-term regulation of the medullary intracellular milieu in response to acute reductions in medullary Na content

Stem cells and their role in renal ischaemia reperfusion injury.

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Bagul, Atul; Frost, Jodie H; Drage, Martin

2013-01-01

Ischaemia-reperfusion injury (IRI) remains one of the leading causes of acute kidney injury (AKI). IRI is an underlying multifactorial pathophysiological process which affects the outcome in both native and transplanted patients. The high morbidity and mortality associated with IRI/AKI and disappointing results from current available clinical therapeutic approaches prompt further research. Stem cells (SC) are undifferentiated cells that can undergo both renewal and differentiation into one or more cell types which can possibly ameliorate IRI. To carry out a detailed literature analysis and construct a comprehensive literature review addressing the role of SC in AKI secondary to IRI. Evidence favouring the role of SC in renal IRI and evidence showing no benefits of SC in renal IRI are the two main aspects to be studied. The search strategy was based on an extensive search addressing MESH terms and free text terms. The majority of studies in the field of renal IRI and stem cell therapy show substantial benefits. Studies were mostly conducted in small animal models, thus underscoring the need for further pre-clinical studies in larger animal models, and results should be taken with caution. SC therapy may be promising though controversy exists in the exact mechanism. Thorough scientific exploration is required to assess mechanism, safety profile, reproducibility and methods to monitor administered SC. Copyright © 2012 S. Karger AG, Basel.

Combination Anti-Apoptotic Effect of Erythropoietin and Melatonin on Ischemia Reperfusion-Induced Renal Injury in Rats

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Shokofeh Banaei

2016-11-01

Full Text Available Renal ischemia-reperfusion (IR contributes to the development of acute renal failure (ARF. Oxygen free radicals are considered to be principal components involved in the pathophysiological tissue alterations observed during renal IR. The purpose of this study was to investigate the combination effect of melatonin (MEL and erythropoietin (EPO, which are a potent antioxidant and anti-apoptotic agents, in IR-induced renal injury in rats. Wistar Albino rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 24 h reperfusion. MEL (10 mg/kg, i.p and EPO (5000 U/kg, i.p were administered prior to ischemia. After 24 h reperfusion, following decapitation, blood samples were collected for the determination of superoxide dismutase (SOD, glutathione peroxidase (GPx, and malondialdehyde (MDA levels. Also, renal samples were taken for histological evaluation and apoptosis assay. Ischemia-reperfusion increased SOD, GPx, MDA levels, and TUNEL positive cells. Histopathological findings of the IR group confirmed that there was renal impairment in the tubular epithelium. Treatment with EPO and MEL decreased SOD, GPx, and MDA levels, histopathological changes, and TUNEL positive cells. These results indicated that the combination of MEL and EPO could not exert more nephroprotective and anti-apoptotic effects than MEL treatment in renal ischemia-reperfusion injury.

Slit2 ameliorates renal inflammation and fibrosis after hypoxia-and lipopolysaccharide-induced epithelial cells injury in vitro

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Zhou, Xiangjun [Department of Urology, Taihe Hospital, Hubei University of Medicine, Hubei (China); Yao, Qisheng, E-mail: yymcyqs@126.com [Department of Urology, Taihe Hospital, Hubei University of Medicine, Hubei (China); Sun, Xinbo; Gong, Xiaoxin; Yang, Yong; Chen, Congbo [Department of Urology, Taihe Hospital, Hubei University of Medicine, Hubei (China); Shan, Guang [Department of Urology, Renmin Hospital of Wuhan University, Hubei (China)

2017-03-01

Hypoxic acute kidney injury (AKI) is often incompletely repaired and leads to chronic kidney disease (CKD), which is characterized by tubulointerstitial inflammation and fibrosis. The Slit2 family of secreted glycoproteins is expressed in the kidney, it has been shown to exert an anti-inflammatory activity and prevent ischemic renal injury in vivo. However, whether Slit2 reduces renal fibrosis and inflammation after hypoxic and inflammatory epithelial cells injury in vitro remains unknown. In this study, we aimed to evaluate whether Slit2 ameliorated fibrosis and inflammation in two renal epithelial cells line challenged with hypoxia and lipopolysaccharide (LPS). Renal epithelial cells were treated with hypoxia and LPS to induce cell injury. Hoechst staining and Western blot analysis was conducted to examine epithelial cells injury. Immunofluorescence staining and Western blot analysis was performed to evaluate tubulointerstitial fibrosis. Real-time polymerase chain reaction (PCR) tested the inflammatory factor interleukin (IL)−1β and tumor necrosis factor (TNF)-α, and Western blot analysis determined the hypoxia-inducible factor (HIF)−1α, Toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB. Results revealed that hypoxia induced epithelial cells apoptosis, inflammatory factor IL-1β and TNF-α release and tubulointerstitial fibrosis. LPS could exacerbate hypoxia -induced epithelial cells apoptosis, IL-1β and TNF-α release and fibrosis. Slit2 reduced the expression of fibronectin, the rate of epithelial cell apoptosis, and the expression of inflammatory factor. Slit2 could also inhibit the expression of TLR4 and NF-κB, but not the expression of HIF-1α. Therefore, Slit2 attenuated inflammation and fibrosis after LPS- and hypoxia-induced epithelial cells injury via the TLR4/NF-κB signaling pathway, but not depending on the HIF-1α signaling pathway. - Highlights: • Slit2 ameliorates inflammation after hypoxia-and LPS-induced epithelial cells injury

Readmission after treatment of Grade 3 and 4 renal injuries at a Level I trauma center: Statewide assessment using the Comprehensive Hospital Abstract Reporting System.

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Winters, Brian; Wessells, Hunter; Voelzke, Bryan B

2016-03-01

One criticism of the existing renal trauma research is the limited outpatient follow-up after index hospitalization. We assessed readmission rates following treatment for American Association for the Surgery of Trauma (AAST) Grade 3 and 4 renal injury using the Comprehensive Hospital Abstract Reporting System (CHARS). We evaluated all patients with AAST Grade 3 and 4 renal injuries admitted to Harborview Medical Center (HMC) between 1998 and 2010, the only Level 1 trauma center in Washington state. Grade 4 renal injuries were stratified by collecting system laceration (CSL) or segmental vascular injury. Data were abstracted from the CHARS database for readmissions to any Washington state hospital within 6 months of renal injury. Clinical variables, diagnoses, and procedures were queried based on DRG International Classification of Diseases-9th Rev. codes. A total of 477 Grade 3 and 159 Grade 4 renal injuries were initially treated at HMC. On admission, 111 patients required intervention: 75 (16%) of 477 Grade 3 and 36 (23%) of 159 Grade 4 injuries. Within 6 months of index hospitalization, 86 (18%) of 477 Grade 3 and 38 (24%) of 159 Grade 4 patients were readmitted to any Washington state hospital. Eighty percent of Grade 3 injuries and 66% of Grade 4 injuries returned to HMC compared with secondary hospitals (p = 0.08). At readmission, 19 (22%) of 86 Grade 3 and 16 (42%) of 38 Grade 4 injuries had a urologic diagnosis. Subsequent procedural intervention was required on readmission in 6 (7%) of 86 Grade 3 and 5 (13%) of 38 Grade 4 renal injuries (all CSL injuries). A subset of patients treated for Grade 3 and 4 renal trauma will be readmitted for further management. While urologic diagnoses and additional procedures may be low overall, readmission to outside hospitals may preclude accurate determination of renal trauma outcomes. Based on these data, patients with Grade 4 CSL injuries seem to be at the highest risk for readmission and to require a subsequent

OCTREOTIDE FOR MEDULLARY-THYROID CARCINOMA ASSOCIATED DIARRHEA

NARCIS (Netherlands)

SMID, WM; DULLAART, RPF

Medullary thyroid carcinoma associated diarrhoea can be disabling. A 75-yr-old man with metastatic medullary thyroid carcinoma and refractory diarrhoea is described. Subcutaneous administration of the somatostatin analogue, octreotide, 100-mu-g thrice daily, resulted in a sustained improvement in

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

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Jeremy S Leventhal

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

Atherosclerotic renal artery stenosis is associated with elevated cell cycle arrest markers related to reduced renal blood flow and postcontrast hypoxia.

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Saad, Ahmed; Wang, Wei; Herrmann, Sandra M S; Glockner, James F; Mckusick, Michael A; Misra, Sanjay; Bjarnason, Haraldur; Lerman, Lilach O; Textor, Stephen C

2016-11-01

Atherosclerotic renal artery stenosis (ARAS) reduces renal blood flow (RBF), ultimately leading to kidney hypoxia and inflammation. Insulin-like growth factor binding protein-7 (IGFBP-7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) are biomarkers of cell cycle arrest, often increased in ischemic conditions and predictive of acute kidney injury (AKI). This study sought to examine the relationships between renal vein levels of IGFBP-7, TIMP-2, reductions in RBF and postcontrast hypoxia as measured by blood oxygen level-dependent (BOLD) magnetic resonance imaging. Renal vein levels of IGFBP-7 and TIMP-2 were obtained in an ARAS cohort (n= 29) scheduled for renal artery stenting and essential hypertensive (EH) healthy controls (n = 32). Cortical and medullary RBFs were measured by multidetector computed tomography (CT) immediately before renal artery stenting and 3 months later. BOLD imaging was performed before and 3 months after stenting in all patients, and a subgroup (N = 12) underwent repeat BOLD imaging 24 h after CT/stenting to examine postcontrast/procedure levels of hypoxia. Preintervention IGFBP-7 and TIMP-2 levels were elevated in ARAS compared with EH (18.5 ± 2.0 versus 15.7 ± 1.5 and 97.4 ± 23.1 versus 62.7 ± 9.2 ng/mL, respectively; Pblood flow (r = -0.59, P= 0.004). These data demonstrate elevated IGFBP-7 and TIMP-2 levels in ARAS as a function of the degree of reduced RBF. Elevated baseline IGFBP-7 levels were associated with protection against postimaging hypoxia, consistent with 'ischemic preconditioning'. Despite contrast injection and stenting, AKI in these high-risk ARAS subjects with elevated IGFBP-7/TIMP-2 was rare and did not affect long-term kidney function. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

MEDULLARY THYROID CARCINOMA

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V. S. Medvedev

2013-01-01

Full Text Available Medullary thyroid carcinoma belongs to orphan diseases affecting a small part of the population. Multicenter trials are required to elaborate a diagnostic algorithm, to define treatment policy, and to predict an outcome.

Dynamic Contrast-Enhanced MR Imaging of Renal Ischemia-Reperfusion Injury

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Baik, Jun Hyun; Ahn, Myeong Im; Park, Young Ha; Chung, Soo Kyo [Catholic University, Seoul (Korea, Republic of)

2010-02-15

To evaluate the usefulness of magnetic resonance imaging (MRI) in a renal ischemia-reperfusion injury. Twenty-four rabbits were randomly divided into four groups, including a sham operated group (n=3). Renal ischemia was induced for 30 minutes (group 1), 60 minutes (group 2) and 120 minutes (group 3). MR imaging was performed before ischemia as well as one hour, 24 hours, and 72 hours after reperfusion. A 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy was performed before ischemia, as well as 24 hours and 72 hours after reperfusion. The signal-to-noise ratio (SNR) on the T2WI, time-relative signal intensity (%RSI) curve on dynamic enhanced images, and relative left renal uptake (%) on DMSA scan were obtained and compared to the histologic findings. The SNR of the cortex on the T2WI changed significantly over the course of the reperfusion time (p<0.001), but was not significantly different among the ischemia groups. The area under the time-%RSI curve gradually decreased from cortex to inner medulla before ischemia, which was reversed and gradually increased after reperfusion. The areas under the time-%RSI curve of outer and inner medulla were significantly different among the ischemia groups (p=0.04, p=0.008). The relative renal uptake (%) of left kidney decreased significantly over the reperfusion time (p=0.03), and was also significantly different among the ischemia groups (p=0.005). Tubular cell necrosis was observed in 16 rabbits (76.2%). The histologic grades of group 3 were higher than those of group 1 and group 2 (p=0.002). Even in rabbits without tubular cell necrosis, the areas under the time-%RSI curves of the cortex, outer, and inner medulla after a 72 hour reperfusion time were significantly lower than those before ischemia (p=0.007, p=0.005, p=0.004). The results of this study suggest that dynamic enhanced MR imaging could be a useful tool for the evaluation of renal ischemia and reperfusion injury.

Aging aggravates long-term renal ischemia-reperfusion injury in a rat model.

Science.gov (United States)

Xu, Xianlin; Fan, Min; He, Xiaozhou; Liu, Jipu; Qin, Jiandi; Ye, Jianan

2014-03-01

Ischemia-reperfusion injury (IRI) has been considered as the major cause of acute kidney injury and can result in poor long-term graft function. Functional recovery after IRI is impaired in the elderly. In the present study, we aimed to compare kidney morphology, function, oxidative stress, inflammation, and development of renal fibrosis in young and aged rats after renal IRI. Rat models of warm renal IRI were established by clamping left pedicles for 45 min after right nephrectomy, then the clamp was removed, and kidneys were reperfused for up to 12 wk. Biochemical and histologic renal damage were assessed at 12 wk after reperfusion. The immunohistochemical staining of monocyte macrophage antigen-1 (ED-1) and transforming growth factor beta 1 (TGF-β1) and messenger RNA level of TGF-β1 in the kidney were analyzed. Renal IRI caused significant increases of malondialdehyde and 8-hydroxydeoxyguanosine levels and a decrease of superoxide dismutase activity in young and aged IRI rats; however, these changes were more obvious in the aged rats. IRI resulted in severe inflammation and tubulointerstitial fibrosis with decreased creatinine (Cr) clearance and increased histologic damage in aged rats compared with young rats. Moreover, we measured the ratio of Cr clearance between young and aged IRI rats. It demonstrated that aged IRI rats did have poor Cr clearance compared with the young IRI rats. ED-1 and TGF-β1 expression levels in the kidney were significantly higher in aged rats than in young rats after IRI. Aged rats are more susceptible to IRI-induced renal failure, which may associate with the increased oxidative stress, increased histologic damage, and increased inflammation and tubulointerstitial fibrosis. Targeting oxidative stress and inflammatory response should improve the kidney recovery after IRI. Copyright © 2014 Elsevier Inc. All rights reserved.

Renal Podocyte Injury in a Rat Model of Type 2 Diabetes Is Prevented by Metformin

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Junghyun Kim

2012-01-01

Full Text Available Hyperglycemia promotes oxidative stress and hence generation of reactive oxygen species (ROS, which is known to play a crucial role in the pathogenesis of diabetic nephropathy. Metformin, an oral hypoglycemic drug, possesses antioxidant effects. The aim of this paper is to investigate the protective effects of metformin on the injury of renal podocytes in spontaneously diabetic Torii (SDT rats, a new model for nonobese type 2 diabetes. Metformin (350 mg/kg/day was given to SDT rats for 17 weeks. Blood glucose, glycated haemoglobin (HbA1c, and albuminuria were examined. Kidney histopathology, renal 8-hydroxydeoxyguanosine (8-OHdG levels and apoptosis were examined. In 43-week-old SDT rats, severe hyperglycemia was developed, and albuminuria was markedly increased. Diabetes induced significant alterations in renal glomerular structure. In addition, urinary and renal 8-OHdG levels were highly increased, and podocyte loss was shown through application of the TUNEL and synaptopodin staining. However, treatment of SDT rats with metformin restored all these renal changes. Our data suggested that diabetes-induced podocyte loss in diabetic nephropathy could be suppressed by the antidiabetes drug, metformin, through the repression of oxidative injury.

Trichloroethylene and trichloroethanol-induced formic aciduria and renal injury in male F-344 rats following 12 weeks exposure.

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Yaqoob, Noreen; Evans, Andrew; Foster, John R; Lock, Edward A

2014-09-02

Trichloroethylene (TCE) is widely used as a cleaning and decreasing agent and has been shown to cause liver tumours in rodents and a small incidence of renal tubule tumours in male rats. The basis for the renal tubule injury is believed to be related to metabolism of TCE via glutathione conjugation to yield the cysteine conjugate that can be activated by the enzyme cysteine conjugate β-lyase in the kidney. More recently TCE and its major metabolite trichloroethanol (TCE-OH) have been shown to cause formic aciduria which can cause renal injury after chronic exposure in rats. In this study we have compared the renal toxicity of TCE and TCE-OH in rats to try and ascertain whether the glutathione pathway or formic aciduria can account for the toxicity. Male rats were given TCE (500mg/kg/day) or TCE-OH at (100mg/kg/day) for 12 weeks and the extent of renal injury measured at several time points using biomarkers of nephrotoxicity and prior to termination assessing renal tubule cell proliferation. The extent of formic aciduria was also determined at several time points, while renal pathology and plasma urea and creatinine were determined at the end of the study. TCE produced a very mild increase in biomarkers of renal injury, total protein, and glucose over the first two weeks of exposure and increased Kim-1 and NAG in urine after 1 and 5 weeks exposure, while TCE-OH did not produce a consistent increase in these biomarkers in urine. However, both chemicals produced a marked and sustained increase in the excretion of formic acid in urine to a very similar extent. The activity of methionine synthase in the liver of TCE and TCE-OH treated rats was inhibited by about 50% indicative of a block in folate synthesis. Both renal pathology and renal tubule cell proliferation were reduced after TCE and TCE-OH treatment compared to controls. Our findings do not clearly identify the pathway which is responsible for the renal toxicity of TCE but do provide some support for metabolism

Trichloroethylene and trichloroethanol-induced formic aciduria and renal injury in male F-344 rats following 12 weeks exposure

International Nuclear Information System (INIS)

Yaqoob, Noreen; Evans, Andrew; Foster, John R.; Lock, Edward A.

2014-01-01

Trichloroethylene (TCE) is widely used as a cleaning and decreasing agent and has been shown to cause liver tumours in rodents and a small incidence of renal tubule tumours in male rats. The basis for the renal tubule injury is believed to be related to metabolism of TCE via glutathione conjugation to yield the cysteine conjugate that can be activated by the enzyme cysteine conjugate β-lyase in the kidney. More recently TCE and its major metabolite trichloroethanol (TCE-OH) have been shown to cause formic aciduria which can cause renal injury after chronic exposure in rats. In this study we have compared the renal toxicity of TCE and TCE-OH in rats to try and ascertain whether the glutathione pathway or formic aciduria can account for the toxicity. Male rats were given TCE (500 mg/kg/day) or TCE-OH at (100 mg/kg/day) for 12 weeks and the extent of renal injury measured at several time points using biomarkers of nephrotoxicity and prior to termination assessing renal tubule cell proliferation. The extent of formic aciduria was also determined at several time points, while renal pathology and plasma urea and creatinine were determined at the end of the study. TCE produced a very mild increase in biomarkers of renal injury, total protein, and glucose over the first two weeks of exposure and increased Kim-1 and NAG in urine after 1 and 5 weeks exposure, while TCE-OH did not produce a consistent increase in these biomarkers in urine. However, both chemicals produced a marked and sustained increase in the excretion of formic acid in urine to a very similar extent. The activity of methionine synthase in the liver of TCE and TCE-OH treated rats was inhibited by about 50% indicative of a block in folate synthesis. Both renal pathology and renal tubule cell proliferation were reduced after TCE and TCE-OH treatment compared to controls. Our findings do not clearly identify the pathway which is responsible for the renal toxicity of TCE but do provide some support for

Dietary nitrate attenuates renal ischemia-reperfusion injuries by modulation of immune responses and reduction of oxidative stress.

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Yang, Ting; Zhang, Xing-Mei; Tarnawski, Laura; Peleli, Maria; Zhuge, Zhengbing; Terrando, Niccolo; Harris, Robert A; Olofsson, Peder S; Larsson, Erik; Persson, A Erik G; Lundberg, Jon O; Weitzberg, Eddie; Carlstrom, Mattias

2017-10-01

Ischemia-reperfusion (IR) injury involves complex pathological processes in which reduction of nitric oxide (NO) bioavailability is suggested as a key factor. Inorganic nitrate can form NO in vivo via NO synthase-independent pathways and may thus provide beneficial effects during IR. Herein we evaluated the effects of dietary nitrate supplementation in a renal IR model. Male mice (C57BL/6J) were fed nitrate-supplemented chow (1.0mmol/kg/day) or standard chow for two weeks prior to 30min ischemia and during the reperfusion period. Unilateral renal IR caused profound tubular and glomerular damage in the ischemic kidney. Renal function, assessed by plasma creatinine levels, glomerular filtration rate and renal plasma flow, was also impaired after IR. All these pathologies were significantly improved by nitrate. Mechanistically, nitrate treatment reduced renal superoxide generation, pro-inflammatory cytokines (IL-1β, IL-6 and IL-12 p70) and macrophage infiltration in the kidney. Moreover, nitrate reduced mRNA expression of pro-inflammatory cytokines and chemo attractors, while increasing anti-inflammatory cytokines in the injured kidney. In another cohort of mice, two weeks of nitrate supplementation lowered superoxide generation and IL-6 expression in bone marrow-derived macrophages. Our study demonstrates protective effect of dietary nitrate in renal IR injury that may be mediated via modulation of oxidative stress and inflammatory responses. These novel findings suggest that nitrate supplementation deserve further exploration as a potential treatment in patients at high risk of renal IR injury. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Renal water molecular diffusion characteristics in healthy native kidneys: assessment with diffusion tensor MR imaging.

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Zhenfeng Zheng

Full Text Available BACKGROUND: To explore the characteristics of diffusion tensor imaging (DTI and magnetic resonance (MR imaging in healthy native kidneys. METHODS: Seventy-three patients without chronic kidney disease underwent DTI-MRI with spin echo-echo planar (SE-EPI sequences accompanied by an array spatial sensitivity encoding technique (ASSET. Cortical and medullary mean, axial and radial diffusivity (MD, AD and RD, fractional anisotropy (FA and primary, secondary and tertiary eigenvalues (λ1, λ2, λ3 were analysed in both kidneys and in different genders. RESULTS: Cortical MD, λ2, λ3, and RD values were higher than corresponding medullary values. The cortical FA value was lower than the medullary FA value. Medullary λ1 and RD values in the left kidney were lower than in the right kidney. Medullary λ2, and λ3 values in women were higher than those in men. Medullary FA values in women were lower than those in men. Medullary FA (r = 0.351, P = 0.002 and λ1 (r = 0.277, P = 0.018 positively correlated with eGFR. Medullary FA (r = -0.25, P = 0.033 negatively correlated with age. CONCLUSIONS: Renal water molecular diffusion differences exist in human kidneys and genders. Age and eGFR correlate with medullary FA and primary eigenvalue.

Medullary bone and humeral breaking strength in laying hens

International Nuclear Information System (INIS)

Fleming, R.H.; McCormack, H.A.; McTeir, L.; Whitehead, C.C.

1998-01-01

To test the hypothesis that large amounts of medullary bone in the humeral diaphysis may increase breaking strength, various parameters of bone quality and quantity were examined in two large flocks of hens near end of lay. We conclude that the amount of medullary bone in the humerus of hens during the laying period influences bone strength. This medullary bone may not have any intrinsic strength, but may act by contributing to the fracture resistance of the surrounding cortical bone. Using a quantitative, low dose, radiographic technique, we can predict, from early in the laying period, those birds which will develop large amounts of medullary bone in their humeri by the end of the laying period. The formation of medullary bone in the humeral diaphysis is not at the expense of the surrounding radiographed cortical bone

MR imaging of renal transplant rejection

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Hanna, S.; Helenon, O.; Legendre, C.; Chichie, J.F.; Di Stefano, D.; Kreis, H.; Moreau, J.F.; Hopital Necker, 75 - Paris

1991-01-01

The results of 62 consecutive MR examinations were correlated with the subsequent clinical course and histologic results. Twenty-six cases of rejection showed a marked diminution of cortico-medullary differentiation (CMD). The renal parenchymal vascular pattern and visibility of renal sinus fat were not markedly altered in rejection and there was no difference between normal and rejected allograft shape. The ability of MR imaging to diagnose renal transplant rejection is only based on CMD, which, however, is non-specific. In 2 cases of severe rejection, T2 weighted images showed an abnormal signal intensity of the cortex due to renal infarction. Our preliminary results in 8 patients with Gd-DOTA injection showed 2 cases with necrosis seen as areas with absent contrast enhancement. This technique seems to be promising in the detection of perfusion defects. (orig.)

Mannan-binding lectin is involved in the protection against renal ischemia/ reperfusion injury by dietary restriction

NARCIS (Netherlands)

Shushimita; P. van der Pol (Pieter); R.W.F. de Bruin (Ron); J.N.M. IJzermans (Jan); C. van Kooten (Cees); F.J.M.F. Dor (Frank)

2015-01-01

textabstractPreoperative fasting and dietary restriction offer robust protection against renal ischemia/ reperfusion injury (I/RI) in mice.We recently showed that Mannan-binding lectin (MBL), the initiator of the lectin pathway of complement activation, plays a pivotal role in renal I/RI. Based on

Molecular Mechanisms of Curcumin Renoprotection in Experimental Acute Renal Injury

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Youling Fan

2017-12-01

Full Text Available As a highly perfused organ, the kidney is especially sensitive to ischemia and reperfusion. Ischemia-reperfusion (IR-induced acute kidney injury (AKI has a high incidence during the perioperative period in the clinic and is an important link in ischemic acute renal failure (IARF. Therefore, IR-induced AKI has important clinical significance and it is necessary to explore to develop drugs to prevent and alleviate IR-induced AKI. Curcumin [diferuloylmethane, 1,7-bis(4-hydroxy-3-methoxiphenyl-1,6-heptadiene-3,5-dione] is a polyphenol compound derived from Curcuma longa (turmeric and was shown to have a renoprotective effect on ischemia-reperfusion injury (IRI in a previous study. However, the specific mechanisms underlying the protective role of curcumin in IR-induced AKI are not completely understood. APPL1 is a protein coding gene that has been shown to be involved in the crosstalk between the adiponectin-signaling and insulin-signaling pathways. In the study, to investigate the molecular mechanisms of curcumin effects in kidney ischemia/reperfusion model, we observed the effect of curcumin in experimental models of IR-induced AKI and we found that curcumin treatment significantly increased the expression of APPL1 and inhibited the activation of Akt after IR treatment in the kidney. Our in vitro results showed that apoptosis of renal tubular epithelial cells was exacerbated with hypoxia-reoxygenation (HR treatment compared to sham control cells. Curcumin significantly decreased the rate of apoptosis in renal tubular epithelial cells with HR treatment. Moreover, knockdown of APPL1 activated Akt and subsequently aggravated apoptosis in HR-treated renal tubular epithelial cells. Conversely, inhibition of Akt directly reversed the effects of APPL1 knockdown. In summary, our study demonstrated that curcumin mediated upregulation of APPL1 protects against ischemia reperfusion induced AKI by inhibiting Akt phosphorylation.

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

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

2011-01-01

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

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.

Constitutive Activation of Smoothened in the Renal Collecting Ducts Leads to Renal Hypoplasia, Hydronephrosis, and Hydroureter.

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Gupta, Deepak Prasad; Hwang, Jae-Won; Cho, Eui-Sic; Kim, Won; Song, Chang Ho; Chai, Ok Hee

2017-01-01

Sonic Hedgehog (Shh) signaling plays a major role in and is essential for regulation, patterning, and proliferation during renal development. Smoothened (Smo) plays a pivot role in transducing the Shh-glioma-associated oncogene Kruppel family member. However, the cellular and molecular mechanism underlying the role of sustained Smo activation in postnatal kidney development is still not clearly understood. Using a conditional knockin mouse model that expresses a constitutively activated form of Smo (SmoM2) upon Homeobox-B7-mediated recombination (Hoxb7-Cre), the effects of Shh signaling were determined in postnatal kidney development. SmoM2;Hoxb7-Cre mutant mice showed growth retardation with a reduction of body weight. Constitutive activation of Smo in the renal collecting ducts caused renal hypoplasia, hydronephrosis, and hydroureter. The parenchymal area and glomerular numbers were reduced, but the glomerular density was increased in SmoM2;Hoxb7-Cre mutant mice. The expression of Patched 1, the receptor of Shh and a downstream target gene of the Shh signaling pathway, was highly restricted and it was upregulated in the inner medullary collecting ducts of the kidney. The proliferative cells in the mesenchyme and collecting ducts were decreased in SmoM2;Hoxb7-Cre mutant mice. This study showed for the first time that sustained Smo inhibits postnatal kidney development by suppressing the proliferation of the mesenchyme and medullary collecting ducts in mice. © 2017 S. Karger AG, Basel.

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

NARCIS (Netherlands)

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

2013-01-01

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

Effects of Human Umbilical Cord Mesenchymal Stem Cells on Renal Ischaemia-reperfusion Injury in Rats

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Zhenyu Qiu

2014-08-01

Full Text Available Objective This study aims to observe the function of umbilical cord-mesenchymal stem cells (UC-MSCs labelled with enhanced green fluorescent protein (eGFP in the repair of renal ischaemia-reperfusion (I/R injury, to determine the effects on inflammatory cascade in an established rat model and to explore possible pathogenesis. Materials and Methods Sixty rats were randomly divided into three groups: the sham-operated, I/R and UC-MSC treatment groups. All rats underwent right nephrectomy. Ischaemia was induced in the left kidney by occlusion of the renal artery and vein for 1hour, followed by reperfusion for 24 hours or 48 hours. Kidney samples were collected to observe morphological changes. Immunohistochemistry was performed to assess the expression of intercellular adhesion molecule 1 (ICAM-1 in the renal tissue sample, as well as the number of infiltrating polymorphonuclear neutrophils (PMNLs and UC-MSCs with positive eGFP. Results Renal histopathological damages and the expression of ICAM-1 and PMNL increased significantly in the I/R group compared with those in the sham-operated group, whereas the damages were less conspicuous in the UC-MSC treatment group. Conclusions Renal ICAM-1, which mediated PMNL infiltration and contributed to renal damage, was significantly up-regulated in the I/R group. UC-MSCs were identified to inhibit these pathological processes and protect the kidney from I/R injury.

Medullary Thyroid Carcinoma Program | Center for Cancer Research

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Medullary Thyroid Carcinoma Program Multiple endocrine neoplasia (MEN) types 2A and 2B are rare genetic diseases, which lead to the development of medullary thyroid cancer, usually in childhood. Surgery is the only standard treatment.

Autophagy activation promotes removal of damaged mitochondria and protects against renal tubular injury induced by albumin overload.

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Tan, Jin; Wang, Miaohong; Song, Shuling; Miao, Yuyang; Zhang, Qiang

2018-01-10

Proteinuria (albuminuria) is an important cause of aggravating tubulointerstitial injury. Previous studies have shown that autophagy activation can alleviate renal tubular epithelial cell injury caused by urinary protein, but the mechanism is not clear. Here, we investigated the role of clearance of damaged mitochondria in this protective effect. We found that albumin overload induces a significant increase in turnover of LC3-II and decrease in p62 protein level in renal proximal tubular (HK-2) cells in vitro. Albumin overload also induces an increase in mitochondrial damage. ALC, a mitochondrial torpent, alleviates mitochondrial damage induced by albumin overload and also decreases autophagy, while mitochondrial damage revulsant CCCP further increases autophagy. Furthermore, pretreatment of HK-2 cells with rapamycin reduced the amount of damaged mitochondria and the level of apoptosis induced by albumin overload. In contrast, blocking autophagy with chloroquine exerted an opposite effect. Taken together, our results indicated autophagy activation promotes removal of damaged mitochondria and protects against renal tubular injury caused by albumin overload. This further confirms previous research that autophagy activation is an adaptive response in renal tubular epithelial cells after urinary protein overload.

Renal blood flow, fractional excretion of sodium and acute kidney injury: time for a new paradigm?

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Prowle, John; Bagshaw, Sean M; Bellomo, Rinaldo

2012-12-01

Global renal blood flow is considered pivotal to renal function. Decreased global renal blood flow (decreased perfusion) is further considered the major mechanism of reduced glomerular filtration rate responsible for the development of acute kidney injury (AKI) in critically ill patients. Additionally, urinary biochemical tests are widely taught to allow the differential diagnosis of prerenal (functional) AKI and intrinsic [structural AKI (so-called acute tubular necrosis)]. In this review we will examine recent evidence regarding these two key clinical paradigms. Recent animal experiments and clinical studies in humans using cine-phase contrast magnetic resonance technology are not consistent with the decreased perfusion paradigm. They suggest instead that changes in the intra-renal circulation including modification in efferent arteriolar function and intra-renal shunting are much more likely to be responsible for AKI, especially in sepsis. Similarly, recent human studies indicate the urinary biochemistry has limited diagnostic or prognostic ability and is dissociated form biomarker and microscopic evidence of tubular injury. Intra-renal microcirculatory changes are likely more important than changes in global blood flow in the development of AKI. Urinary biochemistry is not a clinically useful diagnostic or prognostic tool in critically ill patients at risk of or with AKI.

Attenuated renal and intestinal injury after use of a mini-cardiopulmonary bypass system

NARCIS (Netherlands)

Huybregts, Rien A. J. M.; Morariu, Aurora M.; Rakhorst, Gerhard; Spiegelenberg, Stefan R.; Romijn, Hans W. A.; de Vroege, Roel; van Oeveren, Willem

Background. Transient, subclinical myocardial, renal, intestinal, and hepatic tissue injury and impaired homeostasis is detectable even in low-risk patients undergoing conventional cardiopulmonary bypass (CPB). Small extracorporeal closed circuits with low priming volumes and optimized perfusion

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.

Effect of Regular Exercise on the Histochemical Changes of d-Galactose-Induced Oxidative Renal Injury in High-Fat Diet-Fed Rats

International Nuclear Information System (INIS)

Park, Sok; Kim, Chan-Sik; Lee, Jin; Suk Kim, Jung; Kim, Junghyun

2013-01-01

Renal lipid accumulation exhibits slowly developing chronic kidney disease and is associated with increased oxidative stress. The impact of exercise on the obese- and oxidative stress-related renal disease is not well understood. The purpose of this study was to investigate whether a high-fat diet (HFD) would accelerate d-galactose-induced aging process in rat kidney and to examine the preventive effect of regular exercise on the obese- and oxidative stress-related renal disease. Oxidative stress was induced by an administration of d-galactose (100 mg/kg intraperitoneally injected) for 9 weeks, and d-galactose-treated rats were also fed with a high-fat diet (60% kcal as fat) for 9 weeks to induce obesity. We investigated the efficacy of regular exercise in reducing renal injury by analyzing Nε-carboxymethyllysine (CML), 8-hydroxygluanine (8-OHdG) and apoptosis. When rats were fed with a HFD for 9 weeks in d-galactose-treated rats, an increased CML accumulation, oxidative DNA damage and renal podocyte loss were observed in renal glomerular cells and tubular epithelial cells. However, the regular exercise restored all these renal changes in HFD plus d-galactose-treated rats. Our data suggested that long-term HFD may accelerate the deposition of lipoxidation adducts and oxidative renal injury in d-galactose-treated rats. The regular exercise protects against obese- and oxidative stress-related renal injury by inhibiting this lipoxidation burden

Allopurinol attenuates rhabdomyolysis-associated acute kidney injury: Renal and muscular protection.

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Gois, Pedro H F; Canale, Daniele; Volpini, Rildo A; Ferreira, Daniela; Veras, Mariana M; Andrade-Oliveira, Vinicius; Câmara, Niels O S; Shimizu, Maria H M; Seguro, Antonio C

2016-12-01

Acute kidney injury (AKI) is the most severe complication of rhabdomyolysis. Allopurinol (Allo), a xanthine oxidase inhibitor, has been in the spotlight in the last decade due to new therapeutic applications related to its potent antioxidant effect. The aim of this study was to evaluate the efficacy of Allo in the prevention and treatment of rhabdomyolysis-associated AKI. Male Wistar rats were divided into five groups: saline control group; prophylactic Allo (300mg/L of drinking water, 7 days); glycerol (50%, 5ml/kg, IM); prophylactic Allo + glycerol; and therapeutic Allo (50mg/Kg, IV, 30min after glycerol injection) + glycerol. Glycerol-injected rats showed markedly reduced glomerular filtration rate associated with renal vasoconstriction, renal tubular damage, increased oxidative stress, apoptosis and inflammation. Allo ameliorated all these alterations. We found 8-isoprostane-PGF 2a (F2-IsoP) as a main factor involved in the oxidative stress-mediated renal vasoconstriction following rhabdomyolysis. Allo reduced F2-IsoP renal expression and restored renal blood flow. Allo also reduced oxidative stress in the damaged muscle, attenuated muscle lesion/inflammation and accelerated muscular recovery. Moreover, we showed new insights into the pathogenesis of rhabdomyolysis-associated AKI, whereas Allo treatment reduced renal inflammation by decreasing renal tissue uric acid levels and consequently inhibiting the inflammasome cascade. Allo treatment attenuates renal dysfunction in a model of rhabdomyolysis-associated AKI by reducing oxidative stress (systemic, renal and muscular), apoptosis and inflammation. This may represent a new therapeutic approach for rhabdomyolysis-associated AKI - a new use for an old and widely available medication. Copyright © 2016 Elsevier Inc. All rights reserved.

Sorting the Alphabet Soup of Renal Pathology: A Review.

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Curran-Melendez, Sheilah M; Hartman, Matthew S; Heller, Matthew T; Okechukwu, Nancy

2016-01-28

Diseases of the kidney often have their names shortened, creating an arcane set of acronyms which can be confusing to both radiologists and clinicians. This review of renal pathology aims to explain some of the most commonly used acronyms within the field. For each entity, a summary of the clinical features, pathophysiology, and radiological findings is included to aid in the understanding and differentiation of these entities. Discussed topics include acute cortical necrosis, autosomal dominant polycystic kidney disease, angiomyolipoma, autosomal recessive polycystic kidney disease, acute tubular necrosis, localized cystic renal disease, multicystic dysplastic kidney, multilocular cystic nephroma, multilocular cystic renal cell carcinoma, medullary sponge kidney, paroxysmal nocturnal hemoglobinuria, renal papillary necrosis, transitional cell carcinoma, and xanthogranulomatous pyelonephritis. Copyright © 2016 Mosby, Inc. All rights reserved.

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

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

2013-01-01

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

Curcumin and dexmedetomidine prevents oxidative stress and renal injury in hind limb ischemia/reperfusion injury in a rat model.

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Karahan, M A; Yalcin, S; Aydogan, H; Büyükfirat, E; Kücük, A; Kocarslan, S; Yüce, H H; Taskın, A; Aksoy, N

2016-06-01

Curcumin and dexmedetomidine have been shown to have protective effects in ischemia-reperfusion injury on various organs. However, their protective effects on kidney tissue against ischemia-reperfusion injury remain unclear. We aimed to determine whether curcumin or dexmedetomidine prevents renal tissue from injury that was induced by hind limb ischemia-reperfusion in rats. Fifty rats were divided into five groups: sham, control, curcumin (CUR) group (200 mg/kg curcumin, n = 10), dexmedetomidine (DEX) group (25 μg/kg dexmedetomidine, n = 10), and curcumin-dexmedetomidine (CUR-DEX) group (200 mg/kg curcumin and 25 μg/kg dexmedetomidine). Curcumin and dexmedetomidine were administered intraperitoneally immediately after the end of 4 h ischemia, just 5 min before reperfusion. The extremity re-perfused for 2 h and then blood samples were taken and total antioxidant capacity (TAC), total oxidative status (TOS) levels, and oxidative stress index (OSI) were measured, and renal tissue samples were histopathologically examined. The TAC activity levels in blood samples were significantly lower in the control than the other groups (p OSI were found to be significantly increased in the control group compared to others groups (p model.

Anemia and Long-Term Renal Prognosis in Patients with Post-Renal Acute Kidney Injury of Nonmalignant Cause.

Science.gov (United States)

Sasaki, Sho; Kawarazaki, Hiroo; Hasegawa, Takeshi; Shima, Hideaki; Naganuma, Toshihide; Shibagaki, Yugo

2017-01-01

The renal prognosis of post-renal acute kidney injury (PoR-AKI) has not been verified so far. The objective of this study was to assess the association of baseline anemia with long-term renal prognosis in patients with PoR-AKI. We performed a multicenter retrospective cohort study. Consecutive adult patients from December 2006 to February 2010, who met the requirements as mentioned in the definition of PoR-AKI, were included. Patients without data on baseline renal function and at 6 months after PoR-AKI were excluded. We set baseline hemoglobin (Hb) level (g/dl) as the main exposure to be tested. The main outcome measure was long-term renal prognosis as determined by the difference between proximate estimated glomerular filtration rate (eGFR) at 6 months after diagnosis of PoR-AKI and baseline eGFR prior to the occurrence of the present PoR-AKI (ΔeGFR after 6 months) using the general linear model. We included 136 patients with PoR-AKI. The most frequent cause of PoR-AKI was malignancy, accounting for 39.0% (n = 53) of cases. Multivariate analysis adjusted for possible confounders showed that ΔeGFR after 6 months significantly changed by -4.28 ml/min/1.73 m2 for every 1 g/dl lower Hb at diagnosis (95% CI 1.86-6.69, p < 0.01). An additional multivariate analysis that was stratified by the presence or absence of malignancy as the cause of PoR-AKI yielded the same significant result only in the stratum of the nonmalignant cause of PoR-AKI. Patients with a nonmalignant cause of PoR-AKI who have baseline anemia may have poor long-term renal prognosis. In these cases, close observation of renal function after renal recovery may be required. © 2016 S. Karger AG, Basel.

Medicare Program; End-Stage Renal Disease Prospective Payment System, Payment for Renal Dialysis Services Furnished to Individuals With Acute Kidney Injury, and End-Stage Renal Disease Quality Incentive Program. Final rule.

Science.gov (United States)

2017-11-01

This rule updates and makes revisions to the end-stage renal disease (ESRD) prospective payment system (PPS) for calendar year (CY) 2018. It also updates the payment rate for renal dialysis services furnished by an ESRD facility to individuals with acute kidney injury (AKI). This rule also sets forth requirements for the ESRD Quality Incentive Program (QIP), including for payment years (PYs) 2019 through 2021.

Angiotensin-(1-7 relieved renal injury induced by chronic intermittent hypoxia in rats by reducing inflammation, oxidative stress and fibrosis

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W. Lu

Full Text Available We aimed to study the renal injury and hypertension induced by chronic intermittent hypoxia (CIH and the protective effects mediated by angiotensin 1-7 [Ang(1-7]. We randomly assigned 32 male Sprague-Dawley rats (body weight 180-200 g to normoxia control, CIH, Ang(1-7-treated normoxia, and Ang(1-7-treated CIH groups. Systolic blood pressure (SBP was monitored at the start and end of each week. Renal sympathetic nerve activity (RSNA was recorded. CTGF and TGF-β were detected by immunohistochemistry and western blotting. Tissue parameters of oxidative stress were also determined. In addition, renal levels of interleukin-6, tumor necrosis factor-α, nitrotyrosine, and hypoxia-inducible factor-1α were determined by immunohistochemistry, immunoblotting, and ELISA. TUNEL assay results and cleaved caspase 3 and 12 were also determined. Ang(1-7 induced a reduction in SBP together with a restoration of RSNA in the rat model of CIH. Ang(1-7 treatment also suppressed the production of reactive oxygen species, reduced renal tissue inflammation, ameliorated mesangial expansion, and decreased renal fibrosis. Thus, Ang(1-7 treatment exerted renoprotective effects on CIH-induced renal injury and was associated with a reduction of oxidative stress, inflammation and fibrosis. Ang(1-7 might therefore represent a promising therapy for obstructive sleep apnea-related hypertension and renal injury.

Renal Artery Embolization of Perirenal Hematoma in Hemorrhagic Fever with Renal Syndrome: A Case Report

International Nuclear Information System (INIS)

Choi, Hee Seok; Lee, Yong Seok; Lim, Ji Hyon; Kim, Kyung Soo; Yoon, Yup; Hwang, Jae Cheol

2007-01-01

Hemorrhagic fever with renal syndrome (HFRS) is an acute viral disease characterized by fever, hemorrhage and renal failure. Among the various hemorrhagic complications of HFRS, spontaneous rupture of the kidney and perirenal hematoma are very rare findings. We report here on a case of HFRS complicated by massive perirenal hematoma, and this was treated with transcatheter arterial embolization. Hemorrhagic fever with renal syndrome (HFRS) is an acute infectious disease caused by hantavirus. HFRS is clinically characterized by fever, renal failure and hemorrhage in organs such as lung, kidney, spleen and the pituitary gland. Renal medullary hemorrhage is a well-known complication in the kidney, but spontaneous rupture of the kidney and perirenal hematoma in HFRS is rare, and patients showing continuous bleeding and massive perirenal hematoma have often been surgically treated. We report here on a case of HFRS complicated by massive perirenal hematoma, and the patient was treated with transcatheter arterial embolization. In summary, spontaneous rupture of the kidney and perirenal hematoma is a rare complication of HFRS. We report here on a case of HFRS that caused massive perirenal hematoma, and this was treated with superselective renal artery embolization

Renal Artery Embolization of Perirenal Hematoma in Hemorrhagic Fever with Renal Syndrome: A Case Report

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Choi, Hee Seok; Lee, Yong Seok; Lim, Ji Hyon; Kim, Kyung Soo; Yoon, Yup [Dongguk University College of Medicine, Goyang (Korea, Republic of); Hwang, Jae Cheol [Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan (Korea, Republic of)

2007-08-15

Hemorrhagic fever with renal syndrome (HFRS) is an acute viral disease characterized by fever, hemorrhage and renal failure. Among the various hemorrhagic complications of HFRS, spontaneous rupture of the kidney and perirenal hematoma are very rare findings. We report here on a case of HFRS complicated by massive perirenal hematoma, and this was treated with transcatheter arterial embolization. Hemorrhagic fever with renal syndrome (HFRS) is an acute infectious disease caused by hantavirus. HFRS is clinically characterized by fever, renal failure and hemorrhage in organs such as lung, kidney, spleen and the pituitary gland. Renal medullary hemorrhage is a well-known complication in the kidney, but spontaneous rupture of the kidney and perirenal hematoma in HFRS is rare, and patients showing continuous bleeding and massive perirenal hematoma have often been surgically treated. We report here on a case of HFRS complicated by massive perirenal hematoma, and the patient was treated with transcatheter arterial embolization. In summary, spontaneous rupture of the kidney and perirenal hematoma is a rare complication of HFRS. We report here on a case of HFRS that caused massive perirenal hematoma, and this was treated with superselective renal artery embolization.

The effect of prolonged of warm ischaemic injury on renal function in an experimental ex vivo normothermic perfusion system.

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Hosgood, Sarah A; Shah, K; Patel, M; Nicholson, M L

2015-06-30

Donation after circulatory death (DCD) kidney transplants inevitably sustain a degree of warm ischaemic injury, which is manifested clinically as delayed graft function. The aim of this study was to define the effects of prolonged periods of warm ischaemic injury on renal function in a normothermic haemoperfused kidney model. Porcine kidneys were subjected to 15, 60, 90 (n = 6 per group) and 120 min (n = 4) of in situ warm ischaemia (WI) and then retrieved, flushed with cold preservation fluid and stored in ice for 2 h. Kidneys then underwent 3 h of normothermic reperfusion with a whole blood-based perfusate using an ex vivo circuit developed from clinical grade cardiopulmonary bypass technology. Creatinine clearance, urine output and fractional excretion of sodium deteriorated sequentially with increasing warm time. Renal function was severely compromised after 90 or 120 min of WI but haemodynamic, metabolic and histological parameters demonstrated the viability of kidneys subjected to prolonged warm ischaemia. Isolated kidney perfusion using a warm, oxygenated, red cell-based perfusate allows an accurate ex vivo assessment of the potential for recovery from warm ischaemic injury. Prolonged renal warm ischaemic injury caused a severe decrement in renal function but was not associated with tissue necrosis.

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

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

2017-09-01

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

H+, Water and Urea Transport in the Inner Medullary Collecting Duct and Their Role in the Prevention and Pathogenesis of Renal Stone Disease

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Wall, Susan M.; Klein, Janet D.

2008-09-01

The inner medullary collecting duct (IMCD) is the final site within the kidney for the reabsorption of urea, water and electrolytes and for the secretion of H+ before the luminal fluid becomes the final urine. Transporters expressed in the IMCD contribute to the generation of the large ion gradients that exist between the interstitium and the collecting duct lumen. Thus, the luminal fluid within the human IMCD can reach an osmolality of 1200 mOsm/kg H2O and a pH of 4. This ability of the human nephron to concentrate and acidify the urine might predispose to stone formation. However, under treatment conditions that predispose to stone formation, such as during hypercalciuria, the kidney mitigates stone formation by reducing solute concentration by reducing H2O reabsorption. Moreover, the kidney attenuates stone formation by tightly controlling acid-base balance, which prevents the bone loss, hypocitraturia and hypercalciuria observed during metabolic acidosis by augmenting net H+ excretion by tightly regulating H+ transporter function and through luminal buffering, particularly with NH3. This article will review the ion transporters present in the mammalian IMCD and their role in the prevention and in the pathogenesis of renal stone formation.

Renal Support for Acute Kidney Injury in the Developing World

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Rajeev A. Annigeri

2017-07-01

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

Dynamic computed tomography (CT) in the rat kidney and application to acute renal failure models

International Nuclear Information System (INIS)

Ishikawa, Isao; Saito, Tadashi; Ishii, Hirofumi; Bansho, Junichi; Koyama, Yukinori; Tobita, Akira

1995-01-01

Renal dynamic CT scanning is suitable for determining the excretion of contrast medium in the cortex and medulla of the kidney, which is valuable for understanding the pathogenesis of disease processes in various conditions. This form of scanning would be convenient for use, if a method of application to the rat kidney were available. Therefore, we developed a method of applying renal dynamic CT to rats and evaluated the cortical and medullary curves, e.g., the corticomedullary junction time which is correlated to creatinine clearance, in various rat models of acute renal failure. The rat was placed in a 10deg oblique position and a bilateral hilar slice was obtained before and 5, 10, 15, 20, 25, 30, 40, 50, 60, 80, 100, 120, 140, 160 and 180 sec after administering 0.5 ml of contrast medium using Somatom DR. The width of the slice was 4 mm and the scan time was 3 sec. The corticomedullary junction time in normal rats was 23.0±10.5 sec, the peak value of the cortical curve was 286.3±76.7 Hounsfield Unit (HU) and the peak value of the medullary curve was 390.1±66.2 HU. Corticomedullary junction time after exposure of the kidney was prolonged compared to that of the unexposed kidney. In rats with acute renal failure, the excretion pattern of contrast medium was similar in both the glycerol- and HgCl2-induced acute renal failure models. The peak values of the cortical curve were maintained three hours after a clamp was placed at the hilar region of the kidney for one hour, and the peak values of the medullary curve were maintained during the administration of 10μg/kg/min of angiotensin II. Dynamic CT curves in the acute renal failure models examined were slightly different from those in human acute renal failure. These results suggest that rats do not provide an ideal model for human acute renal failure. However, the application of dynamic CT to the rat kidney models was valuable for estimating the pathogenesis of various human kidney diseases. (author)

Knockout of the interleukin-36 receptor protects against renal ischemia-reperfusion injury by reduction of proinflammatory cytokines.

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Nishikawa, Hirofumi; Taniguchi, Yoshinori; Matsumoto, Tatsuki; Arima, Naoki; Masaki, Mamoru; Shimamura, Yoshiko; Inoue, Kosuke; Horino, Taro; Fujimoto, Shimpei; Ohko, Kentaro; Komatsu, Toshihiro; Udaka, Keiko; Sano, Shigetoshi; Terada, Yoshio

2018-03-01

IL-36, a newly named member of the IL-1 cytokine family, includes 3 isoforms, IL-36α, IL-36β, and IL-36γ, all of which bind to a heterodimer containing the IL-36 receptor (IL-36R). Little is known about the role of the IL-36 axis in acute kidney injury (AKI) pathogenesis. Therefore, we evaluated IL-36 function in the bilateral renal ischemia-reperfusion injury model of AKI using IL-36R knockout and wild-type mice. IL-36R was found to be expressed in the kidney, mainly in proximal tubules. In IL-36R knockout mice, plasma creatinine, blood urea nitrogen, and IL-6 levels after ischemia-reperfusion injury were significantly lower than those in wild-type mice. Immunohistological analysis revealed mild tubular injury. IL-36α/β/γ levels were increased after ischemia-reperfusion injury, and IL-36α was expressed in lymphocytes and proximal tubular cells, but post-ischemia-reperfusion injury mRNA levels of IL-6 and TNF-α were low in IL-36R knockout mice. In primary cultures of renal tubular epithelial cells, IL-36α treatment upregulated NF-κB activity and Erk phosphorylation. Notably, in patients with AKI, urine IL-36α levels were increased, and IL-36α staining in renal biopsy samples was enhanced. Thus, IL-36α/IL-36R blockage could serve as a potential therapeutic target in AKI. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

An analysis of 30 patients with renal trauma

International Nuclear Information System (INIS)

Sakamoto, Eiji; Kuriki, Osamu; Takashi, Munehisa

1989-01-01

Thirty patients with renal trauma were studied by computerized tomography (CT) and angiography. Causes of injuries were traffic accidents in 19 patients (63%), falls in 5 (17%), sports in 2 (7%), and others in 4 (13%). Twenty-nine patients (97%) had hematuria, which was unrelated to the severity of injury. The remaining 3 patients (10%) had shock caused by severe renal injury. Of the 30 patients, 18 (60%) had renal contusions, 7 (23%) had minior laceration, 4 (13%) had major laceration and one had vascular injury. One patient had penetrating trauma and the other 29 had blunt trauma. Two patients (7%) had pre-existing renal anomalies. Sixteen patients (53%) had associated injuries that had no relation to the severity of the renal injury. In detecting subcapsular and perirenal hematoma, CT was more sentitive than excretory pyelography. Findings of renal angiography provided additional anatomical information in both deciding immediate surgical treatment and selecting operative methods for salvage of the kidney. Two patients with major lacerations and one with vascular injury underwent nephrectomy. The remaining 27 patients were managed successfully with conservative therapy. No late complications were seen, except in one case of pseudocyst formation. The persistence of microhematuria after injury was related to the severity of renal injury: a mean of 4.1 days for renal contrusions, 13 days for minor lacerations and 42 days for major lacerations. In conclusion, CT was useful for discriminating the severity of renal injury. When CT suggests major lacerations and vascular injuries, renal angiography should be performed for deciding immediate surgical intervention. (Namekawa, K)

Prospective MR image alignment between breath-holds: Application to renal BOLD MRI.

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Kalis, Inge M; Pilutti, David; Krafft, Axel J; Hennig, Jürgen; Bock, Michael

2017-04-01

To present an image registration method for renal blood oxygen level-dependent (BOLD) measurements that enables semiautomatic assessment of parenchymal and medullary R2* changes under a functional challenge. In a series of breath-hold acquisitions, three-dimensional data were acquired initially for prospective image registration of subsequent BOLD measurements. An algorithm for kidney alignment for BOLD renal imaging (KALIBRI) was implemented to detect the positions of the left and right kidney so that the kidneys were acquired in the subsequent BOLD measurement at consistent anatomical locations. Residual in-plane distortions were corrected retrospectively so that semiautomatic dynamic R2* measurements of the renal cortex and medulla become feasible. KALIBRI was tested in six healthy volunteers during a series of BOLD experiments, which included a 600- to 1000-mL water challenge. Prospective image registration and BOLD imaging of each kidney was achieved within a total measurement time of about 17 s, enabling its execution within a single breath-hold. KALIBRI improved the registration by up to 35% as found with mutual information measures. In four volunteers, a medullary R2* decrease of up to 40% was observed after water ingestion. KALIBRI improves the quality of two-dimensional time-resolved renal BOLD MRI by aligning local renal anatomy, which allows for consistent R2* measurements over many breath-holds. Magn Reson Med 77:1573-1582, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Protective effect of calcium dobesilate combined with benazepril therapy on renal injury in patients with early diabetic nephropathy and the possible molecular mechanisms

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Ling Zhang

2017-06-01

Full Text Available Objective: To explore the protective effect of calcium dobesilate combined with benazepril therapy on renal injury in patients with early diabetic nephropathy and the possible molecular mechanisms. Methods: A total of 50 patients with early diabetic nephropathy treated in our hospital between May 2012 and January 2016 were collected, and according to the random number table, the patients were divided into observation group (n=25 and control group (n=25. On the basis of conventional treatment, control group of patients received benazepril therapy, observation group of patients received calcium dobesilate combined with benazepril therapy, and the treatment lasted for 3 months. Before and after treatment, automatic biochemical analyzer was used to detect the levels of renal injury indexes in peripheral blood, RIA method was used to detect the levels of renal injury indexes in urine, ELISA method was used to detect the levels of renal fibrosis indexes and Western-blot method was used to detect the protein expression of TGF-β1/BMP-7 and Smad signaling pathway molecules in renal tissue. Results: Before treatment, differences in renal injury index levels, renal fibrosis index levels and signaling pathway molecule protein expression were not statistically significant between two groups of patients. After treatment, BUN, SCr and β-TP levels in the peripheral blood as well as KIM-1 level in urine of observation group were lower than those of control group; renal fibrosis indexes TGF-β1, CTGF, TIMP-1, LN and HA levels in serum of observation group were lower than those of control group; TGF-β1 and Smad2/3 protein expression in renal tissue of observation group were lower than those of control group while Smad7 and BMP-7 protein expression were higher than those of control group. Conclusion: Calcium dobesilate combined with benazepril therapy can reduce the renal injury and inhibit the fibrosis process in patients with early diabetic nephropathy, and it

Renal Replacement Therapy Modality in the ICU and Renal Recovery at Hospital Discharge.

Science.gov (United States)

Bonnassieux, Martin; Duclos, Antoine; Schneider, Antoine G; Schmidt, Aurélie; Bénard, Stève; Cancalon, Charlotte; Joannes-Boyau, Olivier; Ichai, Carole; Constantin, Jean-Michel; Lefrant, Jean-Yves; Kellum, John A; Rimmelé, Thomas

2018-02-01

Acute kidney injury requiring renal replacement therapy is a major concern in ICUs. Initial renal replacement therapy modality, continuous renal replacement therapy or intermittent hemodialysis, may impact renal recovery. The aim of this study was to assess the influence of initial renal replacement therapy modality on renal recovery at hospital discharge. Retrospective cohort study of all ICU stays from January 1, 2010, to December 31, 2013, with a "renal replacement therapy for acute kidney injury" code using the French hospital discharge database. Two hundred ninety-one ICUs in France. A total of 1,031,120 stays: 58,635 with renal replacement therapy for acute kidney injury and 25,750 included in the main analysis. None. PPatients alive at hospital discharge were grouped according to initial modality (continuous renal replacement therapy or intermittent hemodialysis) and included in the main analysis to identify predictors of renal recovery. Renal recovery was defined as greater than 3 days without renal replacement therapy before hospital discharge. The main analysis was a hierarchical logistic regression analysis including patient demographics, comorbidities, and severity variables, as well as center characteristics. Three sensitivity analyses were performed. Overall mortality was 56.1%, and overall renal recovery was 86.2%. Intermittent hemodialysis was associated with a lower likelihood of recovery at hospital discharge; odds ratio, 0.910 (95% CI, 0.834-0.992) p value equals to 0.0327. Results were consistent across all sensitivity analyses with odds/hazards ratios ranging from 0.883 to 0.958. In this large retrospective study, intermittent hemodialysis as an initial modality was associated with lower renal recovery at hospital discharge among patients with acute kidney injury, although the difference seems somewhat clinically limited.

Total glucosides of paeony attenuate renal tubulointerstitial injury in STZ-induced diabetic rats: role of Toll-like receptor 2.

Science.gov (United States)

Zhang, Wei; Zhao, Li; Su, Shuang-Quan; Xu, Xing-Xin; Wu, Yong-Gui

2014-01-01

Accumulating evidence suggested that macrophages induce tubulointerstitial injury. Total glucosides of paeony (TGP), extracted from Paeonia lactiflora, has presented anti-inflammatory activities in diabetic kidney disease. This research will investigate the protective effect of TGP on renal tubulointerstitium and its mechanism in streptozotocin-induced diabetic rats. TGP was administered orally at a dose of 50, 100, and 200 mg·kg(-1)·d(-1) for 8 weeks. Tubulointerstitial injury was quantified, followed by immunohistochemistry analysis of renal α-smooth muscle actin (α-SMA), E-cadherin (E-cad) expression, nuclear factor kappa B (NF-κB)-p-p-65(+), Toll-like receptor (TLR)2(+), and ED-1(+) cell infiltration in renal tubulointerstitium. Renal TLR2(+) macrophages were detected by double immunohistochemical staining. Western blotting was used to detect the TLR2 expression. Histologically, there was marked accumulation of TLR2(+), NF-κB-p-p-65(+), ED-1(+) cells, and ED-1(+)TLR2(+) cells (macrophages) in the diabetic kidney and TGP treatment could alleviate it. Accompanying with that, the tubulointerstitial injury was ameliorated, α-SMA expression was lower, and E-cad expression was higher compared with the diabetic rats. Western blot analysis showed that the expression of TLR2 protein was significantly increased in the kidney of the diabetic rats, whereas TGP treatment reduced it. Our study showed that TGP could prevent renal tubulointerstitium injury in diabetic rats through a mechanism that may be at least partly correlated with suppression of increased macrophage infiltration and the expression of TLR2.

Obstructive renal injury: from fluid mechanics to molecular cell biology.

Science.gov (United States)

Ucero, Alvaro C; Gonçalves, Sara; Benito-Martin, Alberto; Santamaría, Beatriz; Ramos, Adrian M; Berzal, Sergio; Ruiz-Ortega, Marta; Egido, Jesus; Ortiz, Alberto

2010-04-22

Urinary tract obstruction is a frequent cause of renal impairment. The physiopathology of obstructive nephropathy has long been viewed as a mere mechanical problem. However, recent advances in cell and systems biology have disclosed a complex physiopathology involving a high number of molecular mediators of injury that lead to cellular processes of apoptotic cell death, cell injury leading to inflammation and resultant fibrosis. Functional studies in animal models of ureteral obstruction using a variety of techniques that include genetically modified animals have disclosed an important role for the renin-angiotensin system, transforming growth factor-β1 (TGF-β1) and other mediators of inflammation in this process. In addition, high throughput techniques such as proteomics and transcriptomics have identified potential biomarkers that may guide clinical decision-making.

Does complete renal denervation translate into superior clinical outcomes? Lessons learned from denervation of accessory renal arteries

OpenAIRE

Mendelsohn, Farrell O.

2014-01-01

Pre-clinical studies of renal denervation would suggest that the extent of renal nerve injury correlates with outcomes. The “completeness” of renal nerve injury following renal denervation correlates with treatment-based variables such as the depth of ablation, the number of ablations along the length of the artery, and the number of renal arteries successfully ablated. Renal denervation techniques targeting only main renal arteries may lead to suboptimal results in patients with accessory re...

MR evaluation of renal function. A preliminary study

Energy Technology Data Exchange (ETDEWEB)

Beomonte Zobel, B; Giammarile, F; Matarese, A; Gallucci, M; Mascicchi, C; Passariello, R; Di Renzi, P; Splendiani, G; Casciani, C U

1988-01-01

The amount of functioning renal parenchyma can be estimated by MRI by considering the ratio between the mean intensities of cortical and medullar zones of the kidney. Fifty-six patients and 5 healthy volunteers were studied by MRI in our department. Scanning was performed with a superconductive magnet system operating at 0.5 Tesla. Pulse sequence was Spin-Echo with TR 300/TE 30 ms. The cortimedullary ratio (CMR) and differentiation (CMD) were standardized and related with creatine blood levels. CMR data ranged from 1.05 to 3.00, while CMD data ranged from 0.04 to 0.50. High values (good cortico-medullary contrast) were observed in subjects with normal renal function. Patients with renal diseases had low CMR and CMD, proportionally to the degree of renal failure, as proved by laboratory findings. Our preliminary study seems to demonstrate that MRI is an useful technique in the follow-up of patients with chronic renal disease. 19 refs.

Análise comparativa da avaliação funcional realizada na lesão medular em animais Comparative analysis of functional evaluation performed in medullary injury in animals

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Alessandra Iague Molina

2004-03-01

Full Text Available A avaliação comportamental após, a contusão da medula espinhal, enfocou por um tempo a locomoção em campo aberto usando uma escala de classificação desenvolvida por Tarlov et al.(18. Tarlov(17 realizou estudos experimentais em cães, produzindo compressão medular com atribuição de zero a cinco para graduação dos movimentos do animal. Contudo, esta escala tem sido modificada por pesquisadores e suas alterações feitas por vários grupos tornaram as comparações das medidas do resultado locomotor difíceis. Um aspecto crítico da pesquisa utilizando lesão medular em animais é a padronização da avaliação da recuperação locomotora. A escala desenvolvida por Tator(19 é simples e de fácil utilização, porém pode não analisar todos os aspectos necessários . Basso, Beattie e Bresnahan(2,3 apresentaram uma escala de classificação com índice de recuperação locomotora em ratos que sofreram lesão medular produzida em laboratório. Os dados indicam que a escala BBB é uma medida válida para a recuperação locomotora capaz de distinguir os resultados comportamentais em função de ferimentos diferentes e para prever alterações anatômicas no centro da lesão. O propósito deste estudo foi analisar e comparar escalas de classificação locomotora sem ambigüidade, eficientes e expandida para se padronizar as medidas resultantes nos laboratórios.The behavior evaluation after a spinal medulla injury focused the locomotion in field during a certain time, using a classification scale developed by Tarlov et al.(18. Tarlov(17 performed experimental studies in dogs, producing medullary compression and assigning a graduation from zero to five to the animal movements. However, this scale has been changed by researchers and its changes, made by several groups, became difficult the comparisons of the measures of the locomotor result. One critical aspect of the research with medullary injury in animals is the standardization of the

Drug-induced renal injury

African Journals Online (AJOL)

The kidney receives a rich blood flow of 25% of resting cardiac output ... Drugs can cause acute renal failure by causing pre-renal, intrinsic or .... tubular epithelial cells causing cell swelling ... the dose as required or prescribe alternative drugs.

Injury - kidney and ureter

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

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.

CD47 regulates renal tubular epithelial cell self-renewal and proliferation following renal ischemia reperfusion.

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Rogers, Natasha M; Zhang, Zheng J; Wang, Jiao-Jing; Thomson, Angus W; Isenberg, Jeffrey S

2016-08-01

Defects in renal tubular epithelial cell repair contribute to renal ischemia reperfusion injury, cause acute kidney damage, and promote chronic renal disease. The matricellular protein thrombospondin-1 and its receptor CD47 are involved in experimental renal ischemia reperfusion injury, although the role of this interaction in renal recovery is unknown. We found upregulation of self-renewal genes (transcription factors Oct4, Sox2, Klf4 and cMyc) in the kidney of CD47(-/-) mice after ischemia reperfusion injury. Wild-type animals had minimal self-renewal gene expression, both before and after injury. Suggestive of cell autonomy, CD47(-/-) renal tubular epithelial cells were found to increase expression of the self-renewal genes. This correlated with enhanced proliferative capacity compared with cells from wild-type mice. Exogenous thrombospondin-1 inhibited self-renewal gene expression in renal tubular epithelial cells from wild-type but not CD47(-/-) mice, and this was associated with decreased proliferation. Treatment of renal tubular epithelial cells with a CD47 blocking antibody or CD47-targeting small interfering RNA increased expression of some self-renewal transcription factors and promoted cell proliferation. In a syngeneic kidney transplant model, treatment with a CD47 blocking antibody increased self-renewal transcription factor expression, decreased tissue damage, and improved renal function compared with that in control mice. Thus, thrombospondin-1 via CD47 inhibits renal tubular epithelial cell recovery after ischemia reperfusion injury through inhibition of proliferation/self-renewal. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Soluble Receptor for Advanced Glycation End Product Ameliorates Chronic Intermittent Hypoxia Induced Renal Injury, Inflammation, and Apoptosis via P38/JNK Signaling Pathways

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Xu Wu

2016-01-01

Full Text Available Obstructive sleep apnea (OSA associated chronic kidney disease is mainly caused by chronic intermittent hypoxia (CIH triggered tissue damage. Receptor for advanced glycation end product (RAGE and its ligand high mobility group box 1 (HMGB1 are expressed on renal cells and mediate inflammatory responses in OSA-related diseases. To determine their roles in CIH-induced renal injury, soluble RAGE (sRAGE, the RAGE neutralizing antibody, was intravenously administered in a CIH model. We also evaluated the effect of sRAGE on inflammation and apoptosis. Rats were divided into four groups: (1 normal air (NA, (2 CIH, (3 CIH+sRAGE, and (4 NA+sRAGE. Our results showed that CIH accelerated renal histological injury and upregulated RAGE-HMGB1 levels involving inflammatory (NF-κB, TNF-α, and IL-6, apoptotic (Bcl-2/Bax, and mitogen-activated protein kinases (phosphorylation of P38, ERK, and JNK signal transduction pathways, which were abolished by sRAGE but p-ERK. Furthermore, sRAGE ameliorated renal dysfunction by attenuating tubular endothelial apoptosis determined by immunofluorescence staining of CD31 and TUNEL. These findings suggested that RAGE-HMGB1 activated chronic inflammatory transduction cascades that contributed to the pathogenesis of the CIH-induced renal injury. Inhibition of RAGE ligand interaction by sRAGE provided a therapeutic potential for CIH-induced renal injury, inflammation, and apoptosis through P38 and JNK pathways.

Role of Calcium Sensing Receptor in Streptozotocin-Induced Diabetic Rats Exposed to Renal Ischemia Reperfusion Injury

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Bo Hu

2018-02-01

Full Text Available Background/Aims: Renal ischemia/reperfusion (I/R injury (RI/RI is a common complication of diabetes, and it may be involved in altering intracellular calcium concentrations at its onset, which can result in inflammation, abnormal lipid metabolism, the production of reactive oxygen species (ROS, and nitroso-redox imbalance. The calcium-sensing receptor (CaSR is a G-protein coupled receptor, however, the functional involvement of CaSR in diabetic RI/ RI remains unclear. The present study was intended to investigate the role of CaSR on RI/RI in diabetes mellitus (DM. Methods: The bilateral renal arteries and veins of streptozotocin (STZ-induced diabetic rats were subjected to 45-min ischemia followed by 2-h reperfusion with or without R-568 (agonist of CaSR and NPS-2143 (antagonist of CaSR at the beginning of I/R procedure. DM without renal I/R rats served as control group. The expressions of CaSR, calmodulin (CaM, and p47phox in the renal tissue were analyzed by qRT-PCR and Western blot. The renal pathomorphology, renal function, oxidative stress, inflammatory response, and calcium disorder were evaluated by detection of a series of indices by hematoxylin-eosin (HE staining, transmission electron microscope (TEM, commercial kits, enzyme-linked immunosorbent assay (ELISA, and spectrophotofluorometry, respectively. Results: Results showed that the expressions of CaSR, CaM, and p47phox in I/R group were significantly up-regulated as compared with those in DM group, which were accompanied by renal tissue injury, increased calcium, oxidative stress, inflammation, and nitroso-redox imbalance. Conclusion: These results suggest that activation of CaSR is involved in the induction of damage of renal tubular epithelial cell during diabetic RI/RI, resulting in lipid peroxidation, inflammatory response, nitroso-redox imbalance, and apoptosis.

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

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Hernán Trimarchi

2009-06-01

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

Recovery of Dysphagia in Lateral Medullary Stroke

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Hitesh Gupta

2014-01-01

Full Text Available Lateral medullary stroke is typically associated with increased likelihood of occurrence of dysphagia and exhibits the most severe and persistent form. Worldwide little research exists on dysphagia in brainstem stroke. An estimated 15% of all patients admitted to stroke rehabilitation units experience a brainstem stroke out of which about 47% suffer from dysphagia. In India, a study showed that 22.3% of posterior circulation stroke patients develop dysphagia. Dearth of literature on dysphagia and its outcome in brainstem stroke particularly lateral medullary stroke motivated the author to present an actual case study of a patient who had dysphagia following a lateral medullary infarct. This paper documents the severity and management approach of dysphagia in brainstem stroke, with traditional dysphagia therapy and VitalStim therapy. Despite being diagnosed with a severe form of dysphagia followed by late treatment intervention, the patient had complete recovery of the swallowing function.

Recovery of Dysphagia in lateral medullary stroke.

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Gupta, Hitesh; Banerjee, Alakananda

2014-01-01

Lateral medullary stroke is typically associated with increased likelihood of occurrence of dysphagia and exhibits the most severe and persistent form. Worldwide little research exists on dysphagia in brainstem stroke. An estimated 15% of all patients admitted to stroke rehabilitation units experience a brainstem stroke out of which about 47% suffer from dysphagia. In India, a study showed that 22.3% of posterior circulation stroke patients develop dysphagia. Dearth of literature on dysphagia and its outcome in brainstem stroke particularly lateral medullary stroke motivated the author to present an actual case study of a patient who had dysphagia following a lateral medullary infarct. This paper documents the severity and management approach of dysphagia in brainstem stroke, with traditional dysphagia therapy and VitalStim therapy. Despite being diagnosed with a severe form of dysphagia followed by late treatment intervention, the patient had complete recovery of the swallowing function.

Recovery of Dysphagia in Lateral Medullary Stroke

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Gupta, Hitesh; Banerjee, Alakananda

2014-01-01

Lateral medullary stroke is typically associated with increased likelihood of occurrence of dysphagia and exhibits the most severe and persistent form. Worldwide little research exists on dysphagia in brainstem stroke. An estimated 15% of all patients admitted to stroke rehabilitation units experience a brainstem stroke out of which about 47% suffer from dysphagia. In India, a study showed that 22.3% of posterior circulation stroke patients develop dysphagia. Dearth of literature on dysphagia and its outcome in brainstem stroke particularly lateral medullary stroke motivated the author to present an actual case study of a patient who had dysphagia following a lateral medullary infarct. This paper documents the severity and management approach of dysphagia in brainstem stroke, with traditional dysphagia therapy and VitalStim therapy. Despite being diagnosed with a severe form of dysphagia followed by late treatment intervention, the patient had complete recovery of the swallowing function. PMID:25045555

Effects of a human recombinant alkaline phosphatase on renal hemodynamics, oxygenation and inflammation in two models of acute kidney injury

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Peters, Esther, E-mail: esther.peters@radboudumc.nl [Department of Intensive Care Medicine, Radboud university medical center, PO Box 9101, Internal Mailbox 710, 6500 HB, Nijmegen (Netherlands); Department of Pharmacology and Toxicology, Radboud university medical center, PO Box 9101, Internal Mailbox 149, 6500 HB, Nijmegen (Netherlands); Ergin, Bülent, E-mail: b.ergin@amc.uva.nl [Department of Translational Physiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam (Netherlands); Kandil, Asli, E-mail: aslikandil@istanbul.edu.tr [Department of Biology, Faculty of Science, Istanbul University, PK 34134, Vezneciler, Istanbul (Turkey); Gurel-Gurevin, Ebru, E-mail: egurelgurevin@gmail.com [Department of Biology, Faculty of Science, Istanbul University, PK 34134, Vezneciler, Istanbul (Turkey); Elsas, Andrea van, E-mail: a.vanelsas@am-pharma.com [AM-Pharma, Rumpsterweg 6, 3981 AK, Bunnik (Netherlands); Masereeuw, Rosalinde, E-mail: r.masereeuw@uu.nl [Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, PO Box 80082, 3508 TB Utrecht (Netherlands); Pickkers, Peter, E-mail: peter.pickkers@radboudumc.nl [Department of Intensive Care Medicine, Radboud university medical center, PO Box 9101, Internal Mailbox 710, 6500 HB, Nijmegen (Netherlands); Ince, Can, E-mail: c.ince@amc.uva.nl [Department of Translational Physiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam (Netherlands)

2016-12-15

Two small clinical trials indicated that administration of bovine intestinal alkaline phosphatase (AP) improves renal function in critically ill patients with sepsis-associated acute kidney injury (AKI), for which the mechanism of action is not completely understood. Here, we investigated the effects of a newly developed human recombinant AP (recAP) on renal oxygenation and hemodynamics and prevention of kidney damage and inflammation in two in vivo AKI models. To induce AKI, male Wistar rats (n = 18) were subjected to renal ischemia (30 min) and reperfusion (I/R), or sham-operated. In a second model, rats (n = 18) received a 30 min infusion of lipopolysaccharide (LPS; 2.5 mg/kg), or saline, and fluid resuscitation. In both models, recAP (1000 U/kg) was administered intravenously (15 min before reperfusion, or 90 min after LPS). Following recAP treatment, I/R-induced changes in renal blood flow, renal vascular resistance and oxygen delivery at early, and cortical microvascular oxygen tension at late reperfusion were no longer significantly affected. RecAP did not influence I/R-induced effects on mean arterial pressure. During endotoxemia, recAP treatment did not modulate the LPS-induced changes in systemic hemodynamics and renal oxygenation. In both models, recAP did exert a clear renal protective anti-inflammatory effect, demonstrated by attenuated immunostaining of inflammatory, tubular injury and pro-apoptosis markers. Whether this renal protective effect is sufficient to improve outcome of patients suffering from sepsis-associated AKI is being investigated in a large clinical trial. - Highlights: • Human recombinant alkaline phosphatase (recAP) is a potential new therapy for sepsis-associated acute kidney injury (AKI). • RecAP can modulate renal oxygenation and hemodynamics immediately following I/R-induced AKI. • RecAP did not modulate endotoxemia-induced changes in systemic hemodynamics and renal oxygenation. • RecAP did exert a clear renal protective

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

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

2017-09-02

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

Health status, renal function, and quality of life after multiorgan failure and acute kidney injury requiring renal replacement therapy

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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

A Modified method for reducing renal injury in zoledronic acid treatment of hypercalcemia and adverse skeletal events

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Jiang Liu

2013-01-01

Full Text Available Aims: In this paper, we have reported a previously undescribed risk factor of deterioration of renal function in zoledronic acid treatment of skeletal metastasis - high serum calcium level. Based on this consideration, a modified method of treatment of hypercalcemia (HCM with zoledronic acid is suggested in this paper. Material and Methods: Bone scan findings of 1090 cancer patients were analyzed, of which 26 had intense renal parenchymal uptake as a result of HCM or bone metastases. Subsequently, a total of 56 bone metastases patients with zoledronic acid treatment were divided into three groups: HCM group who were pre-treated to normal serum calcium level (13 patients, HCM group (19 patients, and normal serum calcium group (24 patients. Results: More patients with intense renal parenchymal uptake were hyperglycemic, statistically significantly (18/26 versus 19/1064, P = 2.1, E-78. No more patients with intense renal parenchymal uptake were associated with bone metastases (14/26 versus 438/1064, P = 0.20. Subsequently, more HCM patients receiving zoledronic acid treatment showed renal injury compared to patients with normal serum calcium level (5/15 versus 2/24, P < 0.05 and HCM patients with pre-treatment to normal serum calcium level (5/15 versus 1/17, P < 0.05. Conclusions: Intense renal parenchymal uptake of bisphosphonates is closely related to HCM rather than to bone metastases in cancer patients. The serum calcium should be measured and reduced to normal level before zoledronic acid is used in managements of adverse skeletal events in order to decrease the risk of renal injury.

Impaired EphA4 signaling leads to congenital hydronephrosis, renal injury, and hypertension

DEFF Research Database (Denmark)

Sällström, Johan; Peuckert, Christiane; Gao, Xiang

2013-01-01

Experimental hydronephrosis induced by partial ureteral obstruction at 3 wk of age causes hypertension and renal impairment in adult rats and mice. Signaling by Ephrin receptors (Eph) and their ligands (ephrins) importantly regulates embryonic development. Genetically modified mice, where...... the cytoplasmic domain of the EphA4 receptor has been substituted by enhanced green fluorescent protein (EphA4(gf/gf)), develop spontaneous hydronephrosis and provide a model for further studies of the disorder. The present study aimed to determine if animals with congenital hydronephrosis develop hypertension...... and renal injuries, similar to that of experimental hydronephrosis. Ultrasound and Doppler techniques were used to visualize renal impairment in the adult mice. Telemetric blood pressure measurements were performed in EphA4(gf/gf) mice and littermate controls (EphA4(+/+)) during normal (0.7% NaCl)- and high...

Effect of complete hilar versus only renal artery clamping on renal histomorphology following ischemia/reperfusion injury in an experimental model.

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Umul, M; Cal, A C; Turna, B; Oktem, G; Aydın, H H

2016-01-01

To evaluate the effect of temporary complete hilar versus only renal artery clamping with different duration of warm ischemia on renal functions, and possibly identify a "safe" clamping type and duration of renal ischemia. Fifty male rabbits have been incorporated to study. Rabbits were subjected to ischemia/reperfusion injury by temporary vascular clamping. Reagents were randomized to 3 experimental groups (only renal artery clamping, complete hilar clamping, sham surgery) and sub-groups were determined according to different clamping times (30 and 60 minutes). Median laparotomy and left renal hilus dissection were performed to sham group. Only artery or complete hilar clamping was performed for 30 or 60 minutes by microvascular bulldog clamps to other reagents. Rabbits were sacrificed 10 days after primary surgery and left nephrectomy performed. Nephrectomy materials were evaluated for the level of nitric-oxide synthase (NOS) immunoreactivity, malondialdehyde (MDA) level and superoxide dismutase (SOD) activity and an electron microscopic examination was performed. NOS immunoreactivity was correlated with the temporary clamping time. We also observed that complete hilar vascular clamping entails an increase on NOS immunoreactivity. MDA levels were similar for all experimental surgery groups (p = 0.42). The SOD activity was decreased among all subgroups compared with sham surgery. But the significant decrease occurred in 30 minutes only artery and 30 minutes complete hilar clamping groups in proportion to sham surgery (p = 0.026 and p = 0.019, respectively). This current study suggested that only renal artery clamping under 30 minutes is more appropriate during renal surgical procedures requiring temporary vascular clamping.

Quantification of deep medullary veins at 7 T brain MRI

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Kuijf, Hugo J.; Viergever, Max A.; Vincken, Koen L. [University Medical Center Utrecht, Image Sciences Institute, Utrecht (Netherlands); Bouvy, Willem H.; Razoux Schultz, Tom B.; Biessels, Geert Jan [University Medical Center Utrecht, Department of Neurology, Brain Center Rudolf Magnus, Utrecht (Netherlands); Zwanenburg, Jaco J.M. [University Medical Center Utrecht, Image Sciences Institute, Utrecht (Netherlands); University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands)

2016-10-15

Deep medullary veins support the venous drainage of the brain and may display abnormalities in the context of different cerebrovascular diseases. We present and evaluate a method to automatically detect and quantify deep medullary veins at 7 T. Five participants were scanned twice, to assess the robustness and reproducibility of manual and automated vein detection. Additionally, the method was evaluated on 24 participants to demonstrate its application. Deep medullary veins were assessed within an automatically created region-of-interest around the lateral ventricles, defined such that all veins must intersect it. A combination of vesselness, tubular tracking, and hysteresis thresholding located individual veins, which were quantified by counting and computing (3-D) density maps. Visual assessment was time-consuming (2 h/scan), with an intra-/inter-observer agreement on absolute vein count of ICC = 0.76 and 0.60, respectively. The automated vein detection showed excellent inter-scan reproducibility before (ICC = 0.79) and after (ICC = 0.88) visually censoring false positives. It had a positive predictive value of 71.6 %. Imaging at 7 T allows visualization and quantification of deep medullary veins. The presented method offers fast and reliable automated assessment of deep medullary veins. (orig.)

Comparison of mammographic and sonographic findings in typical and atypical medullary carcinomas of the breast

International Nuclear Information System (INIS)

Yilmaz, E.; Lebe, B.; Balci, P.; Sal, S.; Canda, T.

2002-01-01

AIM: The aim of this study was to describe the contribution of mammographic and sonographic findings to the discrimination of typical and atypical histopathologic groups of medullary carcinomas of the breast. MATERIALS AND METHODS: Imaging findings were retrospectively assessed in 33 women with medullary carcinomas (15 typical medullary carcinomas and 18 atypical medullary carcinomas) identified during pre-operative mammography. Twenty-nine of these women also had ultrasound and these findings were reviewed. RESULTS: Mammography showed a well circumscribed mass in 10 of the 15 (67%) typical medullary carcinomas and in four of the 17 (24%) atypical medullary carcinomas (P < 0.02). One small tumour in a woman with atypical medullary carcinoma was missed on mammography and was shown only on sonography. Sonographically, an irregular margin surrounding the whole mass or part of it was seen in three out of 14 (21%) patients with typical medullary carcinoma and in nine out of 15 (60%) patients with atypical medullary carcinomas (P < 0.05). Posterior acoustic shadowing was more often observed in the typical medullary carcinoma group than in atypical medullary carcinoma and the difference was found to be statistically significant (P < 0.05). None of the other mammographic and sonographic findings were sufficiently characteristic to allow for a differentiation between two groups. CONCLUSION: When typical medullary carcinomas were compared with atypical medullary carcinomas according to imaging features, they tended to be well circumscribed masses on both mammography and sonography, and a posterior acoustic shadow was not found on sonography. However, the imaging findings in these two subgroups often resembled each other and histopathology will always be required to confirm the diagnosis. Yilmaz, E. et al. (2002)

Comparison of mammographic and sonographic findings in typical and atypical medullary carcinomas of the breast

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Yilmaz, E.; Lebe, B.; Balci, P.; Sal, S.; Canda, T

2002-07-01

AIM: The aim of this study was to describe the contribution of mammographic and sonographic findings to the discrimination of typical and atypical histopathologic groups of medullary carcinomas of the breast. MATERIALS AND METHODS: Imaging findings were retrospectively assessed in 33 women with medullary carcinomas (15 typical medullary carcinomas and 18 atypical medullary carcinomas) identified during pre-operative mammography. Twenty-nine of these women also had ultrasound and these findings were reviewed. RESULTS: Mammography showed a well circumscribed mass in 10 of the 15 (67%) typical medullary carcinomas and in four of the 17 (24%) atypical medullary carcinomas (P < 0.02). One small tumour in a woman with atypical medullary carcinoma was missed on mammography and was shown only on sonography. Sonographically, an irregular margin surrounding the whole mass or part of it was seen in three out of 14 (21%) patients with typical medullary carcinoma and in nine out of 15 (60%) patients with atypical medullary carcinomas (P < 0.05). Posterior acoustic shadowing was more often observed in the typical medullary carcinoma group than in atypical medullary carcinoma and the difference was found to be statistically significant (P < 0.05). None of the other mammographic and sonographic findings were sufficiently characteristic to allow for a differentiation between two groups. CONCLUSION: When typical medullary carcinomas were compared with atypical medullary carcinomas according to imaging features, they tended to be well circumscribed masses on both mammography and sonography, and a posterior acoustic shadow was not found on sonography. However, the imaging findings in these two subgroups often resembled each other and histopathology will always be required to confirm the diagnosis. Yilmaz, E. et al. (2002)

Clinical study of 12 cases of medullary carcinoma of the breast

International Nuclear Information System (INIS)

Shibuya, Hitoshi; Sasaki, Kenichi; Yamamoto, Masaaki; Higaki, Nagato; Nakamura, Yukio

2006-01-01

Medullary carcinoma of the breast is a rare type breast cancer, and shows peculiar clinical features. In a series of 460 cases of breast cancer operated on at the hospital from 1975 to 2004, twelve (2.6%) cases were diagnosed as medullary carcinoma of the breast by postoperative pathological study. When the specimens from the twelve tumors were reevaluated according to the Ridolfi's subtype classification, six tumors were classified into typical medullary carcinoma (TMC) and the remaining six tumors into atypical medullary carcinoma (AMC). On mammography these tumors were visualized as homogeneously enhancing oval masses without calcification and the boundary was comparatively well-defined. US demonstrated well-defied masses with a heterogeneous, hypoechoic texture and with reinforcement of posterior echoes. The rate of lymph node metastasis was 33.3% in medullary carcinomas which was not significantly different from that of infiltrative ductal carcinomas experienced during the same period. The rate of a positivity of a hormone receptor was 8.3% in medullary carcinomas which was low in predominance in comparison with that of infiltrative ductal carcinomas. The positive rate for a HER2/neu (above2+) by the IHC method was 58%. An average observation period is 11 years, and all patients are alive. (author)

Introduction to European comments on "Medullary Thyroid Cancer

DEFF Research Database (Denmark)

Jarzab, Barbara; Feldt-Rasmussen, Ulla

2013-01-01

Guest Editors of Thyroid Research supplement devoted to medullary thyroid cancer present the history on how the discussion about "Medullary Thyroid Cancer: management guidelines of the American Thyroid Association" was initiated and subsequently widely commented before and during European Thyroid...... Association - Cancer Research Network Meeting in Lisbon. It is explained why it has been decided to publish the manuscripts within the supplement - to document voices from the discussion and popularize them....

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

NARCIS (Netherlands)

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

2012-01-01

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

Imaging Renal Urea Handling in Rats at Millimeter Resolution using Hyperpolarized Magnetic Resonance Relaxometry

DEFF Research Database (Denmark)

Reed, Galen D; von Morze, Cornelius; Verkman, Alan S

2016-01-01

of the renal urea handling process: glomerular filtration and the inner-medullary urea transporter (UT)-A1 and UT-A3 mediated urea concentrating process. Simple motion correction and subspace denoising algorithms are presented to aid in the multi exponential data analysis. Furthermore, a T2-edited, ultra long...

The effect of Aqueous Purslane (Portulaca Oleracea Extract on Renal Ischemia/Reperfusion Injury in Rat

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syead Reza Fatemi Tabatabaei

2015-07-01

Full Text Available Background: According to the previous studies Portulaca oleracea (PO has antioxidative effects and several factors such as oxidative stress is involved in the renal injury caused by ischemia - reperfusion (I/R. Therefore, the goal of present study is to evaluate the renal I/R injury in rats received aqueous extracts of PO (AEPO. Material and Methods: First, the right nephrectomy was performed in adult male Wistar rats and after 20 days they were divided into 5 groups (6=n. Sham operated+vehicle (sham, sham operated+ AEPO300mg/kg (AEPO group, I/R, AEPO150+I/R and AEPO300+I/R. Each group was treated orally for 5 consecutive days by 150 or 300 mg/kg of either AEPO or saline. On the fifth day of treatment, I/R (45 min ischemia/24 hours reperfusion or sham operation was performed on the left kidney and amounts of urea and creatinine in serum and malondialdehyde (MDA, superoxide dismutase (SOD, glutathione (GSH and total antioxidant activity (TAA in the kidney tissue were measured. Comparisons between groups were analyzed by ANOVA and LSD test. P values of 0.05 or less were considered statistically significant. Results: Induction of I/R increased urea and creatinine levels. AEPO had no effect on serum urea and creatinine, of non-ischemic animals, but increased the levels of urea and creatinine in I/R and treatment groups. SOD activity was significantly higher in all groups (except AEPO300 group compared to the sham group. However the levels of MDA, GSH and TAA of I/R and treatment groups did not show any significant differences in comparison to sham group. Conclusion: According to the results of this study, the PO aqueous extract did not ameliorate the I/R injury and even possibly some ingredients in the extract aggravate the renal I/R injury.

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.

New non-renal congenital disorders associated with medullary sponge kidney (MSK) support the pathogenic role of GDNF and point to the diagnosis of MSK in recurrent stone formers.

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Ria, Paolo; Fabris, Antonia; Dalla Gassa, Alessandra; Zaza, Gianluigi; Lupo, Antonio; Gambaro, Giovanni

2017-08-01

Medullary sponge kidney (MSK) is a congenital renal disorder. Its association with several developmental abnormalities in other organs hints at the likelihood of some shared step(s) in the embryogenesis of the kidney and other organs. It has been suggested that the REarranged during Transfection (RET) proto-oncogene and the Glial cell line-Derived Neurotrophic Factor (GDNF) gene are defective in patients with MSK, and both RET and GDNF are known to have a role in the development of the central nervous system, heart, and craniofacial skeleton. Among a cohort of 143 MSK patients being followed up for nephrolithiasis and chronic kidney disease at our institution, we found six with one or more associated non-renal anomalies: one patient probably has congenital hemihyperplasia and hypertrophic cardiomyopathy with adipose metaplasia and mitral valve prolapse; one has Marfan syndrome; and the other four have novel associations between MSK and nerve and skeleton abnormalities described here for the first time. The discovery of disorders involving the central nervous system, cardiovascular system and craniofacial skeleton in MSK patients supports the hypothesis of a genetic alteration on the RET-GDNF axis having a pivotal role in the pathogenesis of MSK, in a subset of patients at least. MSK seems more and more to be a systemic disease, and the identification of extrarenal developmental defects could be important in arousing the suspicion of MSK in recurrent stone formers.

Maternal diet during gestation and lactation modifies the severity of salt-induced hypertension and renal injury in Dahl salt-sensitive rats.

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Geurts, Aron M; Mattson, David L; Liu, Pengyuan; Cabacungan, Erwin; Skelton, Meredith M; Kurth, Theresa M; Yang, Chun; Endres, Bradley T; Klotz, Jason; Liang, Mingyu; Cowley, Allen W

2015-02-01

Environmental exposure of parents or early in life may affect disease development in adults. We found that hypertension and renal injury induced by a high-salt diet were substantially attenuated in Dahl SS/JrHsdMcwiCrl (SS/Crl) rats that had been maintained for many generations on the grain-based 5L2F diet compared with SS/JrHsdMcwi rats (SS/Mcw) maintained on the casein-based AIN-76A diet (mean arterial pressure, 116±9 versus 154±25 mm Hg; urinary albumin excretion, 23±12 versus 170±80 mg/d). RNAseq analysis of the renal outer medulla identified 129 and 82 genes responding to a high-salt diet uniquely in SS/Mcw and SS/Crl rats, respectively, along with minor genetic differences between the SS substrains. The 129 genes responding to salt in the SS/Mcw strain included numerous genes with homologs associated with hypertension, cardiovascular disease, or renal disease in human. To narrow the critical window of exposure, we performed embryo-transfer experiments in which single-cell embryos from 1 colony (SS/Mcw or SS/Crl) were transferred to surrogate mothers from the other colony, with parents and surrogate mothers maintained on their respective original diet. All offspring were fed the AIN-76A diet after weaning. Salt-induced hypertension and renal injury were substantially exacerbated in rats developed from SS/Crl embryos transferred to SS/Mcw surrogate mothers. Conversely, salt-induced hypertension and renal injury were significantly attenuated in rats developed from SS/Mcw embryos transferred to SS/Crl surrogate mothers. Together, the data suggest that maternal diet during the gestational-lactational period has substantial effects on the development of salt-induced hypertension and renal injury in adult SS rats. © 2014 American Heart Association, Inc.

14S,21R-dihydroxy-docosahexaenoic acid treatment enhances mesenchymal stem cell amelioration of renal ischemia/reperfusion injury.

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Tian, Haibin; Lu, Yan; Shah, Shraddha P; Wang, Quansheng; Hong, Song

2012-05-01

Bone marrow mesenchymal stem cells (MSCs) have shown potential to improve treatment of renal failure. The prohealing functions of MSCs have been found to be enhanced by treatment with the lipid mediator, 14S,21R-dihydroxy-docosa4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid (14S,21R-diHDHA). In this article, using a murine model of renal ischemia/reperfusion (I/R) injury, we found that treatment with 14S,21R-diHDHA enhanced MSC amelioration of renal I/R injury. Treated MSCs more efficiently inhibited I/R-induced elevation of serum creatinine levels, reduced renal tubular cell death, and inhibited infiltration of neutrophils, macrophages, and dendritic cells in kidneys. Conditioned medium from treated MSCs reduced the generation of tumor necrosis factor-α and reactive oxygen species by macrophages under I/R conditions. Infusion of treated MSCs more efficiently reduced I/R-damage to renal histological structures compared with untreated MSCs (injury score: 7.9±0.4 vs. 10.5±0.5). Treated MSCs were resistant to apoptosis in vivo when transplanted under capsules of I/R-injured kidneys (active caspase-3+ MSCs: 4.2%±2.8% vs. 11.7%±2.4% of control) and in vitro when cultured under I/R conditions. Treatment with 14S,21R-diHDHA promoted viability of MSCs through a mechanism involving activation of the phosphoinositide 3-kinase -Akt signaling pathway. Additionally, treatment of MSCs with 14S,21R-diHDHA promoted secretion of renotrophic hepatocyte growth factor and insulin growth factor-1. Similar results were obtained when 14S,21RdiHDHA was used to inhibit apoptosis of human MSCs (hMSCs) and to increase the generation of renotrophic cytokines from hMSCs. These findings provide a lead for new strategies in the treatment of acute kidney injury with MSCs.

Mining the human urine proteome for monitoring renal transplant injury

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Sigdel, Tara K.; Gao, Yuqian; He, Jintang; Wang, Anyou; Nicora, Carrie D.; Fillmore, Thomas L.; Shi, Tujin; Webb-Robertson, Bobbie-Jo; Smith, Richard D.; Qian, Wei-Jun; Salvatierra, Oscar; Camp, David G.; Sarwal, Minnie M.

2016-06-01

The human urinary proteome reflects systemic and inherent renal injury perturbations and can be analyzed to harness specific biomarkers for different kidney transplant injury states. 396 unique urine samples were collected contemporaneously with an allograft biopsy from 396 unique kidney transplant recipients. Centralized, blinded histology on the graft was used to classify matched urine samples into categories of acute rejection (AR), chronic allograft nephropathy (CAN), BK virus nephritis (BKVN), and stable graft (STA). Liquid chromatography–mass spectrometry (LC-MS) based proteomics using iTRAQ based discovery (n=108) and global label-free LC-MS analyses of individual samples (n=137) for quantitative proteome assessment were used in the discovery step. Selected reaction monitoring (SRM) was applied to identify and validate minimal urine protein/peptide biomarkers to accurately segregate organ injury causation and pathology on unique urine samples (n=151). A total of 958 proteins were initially quantified by iTRAQ, 87% of which were also identified among 1574 urine proteins detected in LC-MS validation. 103 urine proteins were significantly (p<0.05) perturbed in injury and enriched for humoral immunity, complement activation, and lymphocyte trafficking. A set of 131 peptides corresponding to 78 proteins were assessed by SRM for their significance in an independent sample cohort. A minimal set of 35 peptides mapping to 33 proteins, were modeled to segregate different injury groups (AUC =93% for AR, 99% for CAN, 83% for BKVN). Urinary proteome discovery and targeted validation identified urine protein fingerprints for non-invasive differentiation of kidney transplant injuries, thus opening the door for personalized immune risk assessment and therapy.

Lateral medullary infarction with ipsilateral hemiparesis, lemniscal sensation loss and hypoglossal nerve palsy.

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Li, Xiaodi; Wang, Yuzhou

2014-04-01

Here, we present a rare case of a lateral medullary infarction with ipsilateral hemiparesis, lemniscal sensation loss and hypoglossal nerve palsy. In this case, we proved Opalski's hypothesis by diffusion tensor tractography that ipsilateral hemiparesis in a medullary infarction is due to the involvement of the decussated corticospinal tract. We found that the clinical triad of ipsilateral hemiparesis, lemniscal sensation loss and hypoglossal nerve palsy, which had been regarded as a variant of medial medullary syndrome, turned out to be caused by lateral lower medullary infarction. Therefore, this clinical triad does not imply the involvement of the anteromedial part of medulla oblongata, when it is hard to distinguish a massive lateral medullary infarction from a hemimedullary infarction merely from MR images. At last, we suggest that hyperreflexia and Babinski's sign may not be indispensable to the diagnosis of Opalski's syndrome and we propose that "hemimedullary infarction with ipsilateral hemiparesis" is intrinsically a variant of lateral medullary infarction.

Medullary carcinoma of the thyroid - an unusual case of hyalinizing ...

African Journals Online (AJOL)

Medullary thyroid carcinoma is a neoplasm occurring in sporadic and familial patterns. A rare variant of medullary thyroid carcinoma shows microscopic features similar to hyalinizing trabecular adenoma of thyroid. Detection of this variant requires a high index of suspicion and immunohistochemical confirmation by ...

Critical role for complement receptor C5aR2 in the pathogenesis of renal ischemia-reperfusion injury

NARCIS (Netherlands)

Poppelaars, Felix; van Werkhoven, Maaike B; Kotimaa, Juha; Veldhuis, Zwanida J; Ausema, Albertina; Broeren, Stefan G M; Damman, Jeffrey; Hempel, Julia C.; Leuvenink, Henri G D; Daha, Mohamed R; van Son, Willem J; van Kooten, Cees; van Os, Ronald P; Hillebrands, Jan-Luuk; Seelen, Marc A

The complement system, and specifically C5a, is involved in renal ischemia-reperfusion (IR) injury. The 2 receptors for complement anaphylatoxin C5a (C5aR1 and C5aR2) are expressed on leukocytes as well as on renal epithelium. Extensive evidence shows that C5aR1 inhibition protects kidneys from IR

Protective Effect of CXCR3+CD4+CD25+Foxp3+ Regulatory T Cells in Renal Ischemia-Reperfusion Injury

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Cao Jun

2015-01-01

Full Text Available Regulatory T cells (Tregs suppress excessive immune responses and are potential therapeutic targets in autoimmune disease and organ transplantation rejection. However, their role in renal ischemia-reperfusion injury (IRI is unclear. Levels of Tregs and expression of CXCR3 in Tregs were analyzed to investigate their function in the early phase of renal IRI. Mice were randomly divided into Sham, IRI, and anti-CD25 (PC61 + IRI groups. The PC61 + IRI group was established by i.p. injection of PC61 monoclonal antibody (mAb to deplete Tregs before renal ischemia. CD4+CD25+Foxp3+ Tregs and CXCR3 on Tregs were analyzed by flow cytometry. Blood urea nitrogen (BUN, serum creatinine (Scr levels, and tubular necrosis scores, all measures of kidney injury, were greater in the IRI group than in the Sham group. Numbers of Tregs were increased at 72 h after reperfusion in kidney. PC61 mAb preconditioning decreased the numbers of Tregs and aggravated kidney injury. There was no expression of CXCR3 on Tregs in normal kidney, while it expanded at 72 h after reperfusion and inversely correlated with BUN, Scr, and kidney histology score. This indicated that recruitment of Tregs into the kidney was related to the recovery of renal function after IRI and CXCR3 might be involved in the migration of Tregs.

Crosstalk between complement and Toll-like receptor activation in relation to donor brain death and renal ischemia-reperfusion injury.

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Damman, Jeffrey; Daha, Mohamed R; van Son, Willem J; Leuvenink, Henri G; Ploeg, Rutger J; Seelen, Marc A

2011-04-01

Two central pathways of innate immunity, complement and Toll-like receptors (TLRs), play an important role in the pathogenesis of renal injury inherent to kidney transplantation. Recent findings indicate close crosstalk between complement and TLR signaling pathways. It is suggested that mitogen activated protein kinases (MAPKs) might be the key molecules linking both the complement and TLR pathways together. Complement and TLRs are important mediators of renal ischemia-reperfusion injury (IRI). Besides IRI, complement C3 can also be upregulated and activated in the kidney before transplantation as a direct result of brain death (BD) in the donor. This local upregulation and activation of complement in the donor kidney has been proven to be detrimental for renal allograft outcome. Also TLR4 and several of its major ligands are upregulated by donor BD compared to living donors. Important and in line with the observations above, kidney transplant recipients have a benefit when receiving a kidney from a TLR4 Asp299Gly/Thr399Ile genotypic donor. The role of complement and TLRs and crosstalk between these two innate immune systems in relation to renal injury during donor BD and ischemia-reperfusion are focus of this review. Future strategies to target complement and TLR activation in kidney transplantation are considered. ©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

Intraperitoneal curcumin decreased lung, renal and heart injury in abdominal aorta ischemia/reperfusion model in rat.

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Aydin, Mehmet Salih; Caliskan, Ahmet; Kocarslan, Aydemir; Kocarslan, Sezen; Yildiz, Ali; Günay, Samil; Savik, Emin; Hazar, Abdussemet; Yalcin, Funda

2014-01-01

Previous studies have demonstrated that curcumin (CUR) has protective effects against ischemia reperfusion injury to various organs. We aimed to determine whether CUR has favorable effects on tissues and oxidative stress in abdominal aorta ischemia-reperfusion injury. Thirty rats were divided into three groups as sham, control and treatment (CUR) group. Control and CUR groups underwent abdominal aorta ischemia for 60 min followed by a 120 min period of reperfusion. In the CUR group, CUR was given 5 min before reperfusion at a dose of 200 mg/kg via an intraperitoneal route. Total antioxidant capacity (TAC), total oxidative status (TOS), and oxidative stress index (OSI) in blood serum were measured, and lung, renal and heart tissue histopathology were evaluated with light microscopy. TOS and OSI activity in blood samples were statistically decreased in sham and CUR groups compared to the control group (p OSI). Renal, lung, heart injury scores of sham and CUR groups were statistically decreased compared to control group (p model. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Medullary breast carcinoma: anatomo-radiological correlation

International Nuclear Information System (INIS)

Matheus, Valeria Soares; Canella, Ellyete de Oliveira; Djahjah, Maria Celia Resende; Koch, Hilton Augusto; Kestelman, Fabiola Procaci

2008-01-01

To evaluate radiological findings in patients submitted to surgical treatment for medullary breast cancer at Instituto Nacional de Cancer (INCa), Rio de Janeiro, RJ, Brazil, correlating them with histological results. A retrospective descriptive study was developed with patients submitted to surgery at INCa, in the period from January 1997 to December 2006, for identifying the presence of medullary breast carcinoma and analyzing radiological findings. Among 21,287 patients diagnosed with carcinoma, 76 (0.357%) had typical medullary breast carcinoma. The age range of these patients was 32-81 years (mean = 59.1 years). Mammography demonstrated lesions in 19 of these patients, 17 (89.5%) of them with masses, and 2 with focal asymmetry. Among the patients with masses, 15 (88.1%) presented with high density and 2 (11.9%) with isodensity. Twelve patients presented sonographic findings, 11 (91.6%) of them with hypoechoic masses, and one with an anechoic mass with areas of cystic degeneration. Nodular mass was the predominant radiological finding (89.5%), 88.1% of them corresponding to masses with high density and circumscribed margins. Despite the radiological characteristics of benignity, a solid, fast growing, highly dense mass with circumscribed margins should be further investigated to confirm the diagnosis. (author)

Medullary breast carcinoma: anatomo-radiological correlation

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Matheus, Valeria Soares; Canella, Ellyete de Oliveira; Djahjah, Maria Celia Resende; Koch, Hilton Augusto [Instituto Nacional de Cancer (INCa), Rio de Janeiro, RJ (Brazil); Kestelman, Fabiola Procaci [Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil); Instituto Nacional de Cancer (INCa), Rio de Janeiro, RJ (Brazil)]. E-mail: msavaleria@yahoo.com

2008-11-15

To evaluate radiological findings in patients submitted to surgical treatment for medullary breast cancer at Instituto Nacional de Cancer (INCa), Rio de Janeiro, RJ, Brazil, correlating them with histological results. A retrospective descriptive study was developed with patients submitted to surgery at INCa, in the period from January 1997 to December 2006, for identifying the presence of medullary breast carcinoma and analyzing radiological findings. Among 21,287 patients diagnosed with carcinoma, 76 (0.357%) had typical medullary breast carcinoma. The age range of these patients was 32-81 years (mean = 59.1 years). Mammography demonstrated lesions in 19 of these patients, 17 (89.5%) of them with masses, and 2 with focal asymmetry. Among the patients with masses, 15 (88.1%) presented with high density and 2 (11.9%) with isodensity. Twelve patients presented sonographic findings, 11 (91.6%) of them with hypoechoic masses, and one with an anechoic mass with areas of cystic degeneration. Nodular mass was the predominant radiological finding (89.5%), 88.1% of them corresponding to masses with high density and circumscribed margins. Despite the radiological characteristics of benignity, a solid, fast growing, highly dense mass with circumscribed margins should be further investigated to confirm the diagnosis. (author)

Mesenchymal stem cells in renal function recovery after acute kidney injury: use of a differentiating agent in a rat model.

Science.gov (United States)

La Manna, Gaetano; Bianchi, Francesca; Cappuccilli, Maria; Cenacchi, Giovanna; Tarantino, Lucia; Pasquinelli, Gianandrea; Valente, Sabrina; Della Bella, Elena; Cantoni, Silvia; Claudia, Cavallini; Neri, Flavia; Tsivian, Matvey; Nardo, Bruno; Ventura, Carlo; Stefoni, Sergio

2011-01-01

Acute kidney injury (AKI) is a major health care condition with limited current treatment options. Within this context, stem cells may provide a clinical approach for AKI. Moreover, a synthetic compound previously developed, hyaluronan monoesters with butyric acid (HB), able to induce metanephric differentiation, formation of capillary-like structures, and secretion of angiogenic cytokines, was tested in vitro. Thereafter, we investigated the effects of human mesenchymal stem cells from fetal membranes (FMhMSCs), both treated and untreated with HB, after induction of ischemic AKI in a rat model. At reperfusion following 45-min clamping of renal pedicles, each rat was randomly assigned to one of four groups: CTR, PBS, MSC, and MSC-HB. Renal function at 1, 3, 5, and 7 days was assessed. Histological samples were analyzed by light and electron microscopy and renal injury was graded. Cytokine analysis on serum samples was performed. FMhMSCs induced an accelerated renal functional recovery, demonstrated by biochemical parameters and confirmed by histology showing that histopathological alterations associated with ischemic injury were less severe in cell-treated kidneys. HB-treated rats showed a minor degree of inflammation, both at cytokine and TEM analyses. Better functional and morphological recovery were not associated to stem cells' regenerative processes, but possibly suggest paracrine effects on microenvironment that induce retrieval of renal damaged tissues. These results suggest that FMhMSCs could be useful in the treatment of AKI and the utilization of synthetic compounds could enhance the recovery induction ability of cells.

A simple football injury leading to a grade 4 renal trauma.

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Fanning, Deirdre Mary; Forde, James C; Mohan, Ponnusamy

2012-03-08

This case highlights the need for cautious management and serial regular examination of trauma patients. A 22-year-old Caucasian male presented to the emergency department 4 h following an injury sustained during football training. He complained of the immediate onset of severe left upper quadrant and left flank pain. He subsequently developed frank haematuria. On initial review, he was haemodynamically stable. CT of the abdomen and pelvis showed a grade 4 renal trauma. Over the following 36 h, he remained haemodynamically stable. On serial abdominal examinations however, he developed a rigid abdomen and was noted to have a haemoglobin drop. Interval CT scan showed a progression of his injury and the presence of a haemoperitoneum. An emergency laparotomy was performed resulting in a left nephrectomy. He made an uneventful recovery.

A simple football injury leading to a grade 4 renal trauma.

LENUS (Irish Health Repository)

Fanning, Deirdre Mary

2012-01-01

This case highlights the need for cautious management and serial regular examination of trauma patients. A 22-year-old Caucasian male presented to the emergency department 4 h following an injury sustained during football training. He complained of the immediate onset of severe left upper quadrant and left flank pain. He subsequently developed frank haematuria. On initial review, he was haemodynamically stable. CT of the abdomen and pelvis showed a grade 4 renal trauma. Over the following 36 h, he remained haemodynamically stable. On serial abdominal examinations however, he developed a rigid abdomen and was noted to have a haemoglobin drop. Interval CT scan showed a progression of his injury and the presence of a haemoperitoneum. An emergency laparotomy was performed resulting in a left nephrectomy. He made an uneventful recovery.

Renal vasculitis presenting with acute kidney injury.

Science.gov (United States)

Villacorta, Javier; Diaz-Crespo, Francisco; Acevedo, Mercedes; Cavero, Teresa; Guerrero, Carmen; Praga, Manuel; Fernandez-Juarez, Gema

2017-06-01

Renal failure secondary to ANCA-associated vasculitis represents a clinical and therapeutic challenge. In this study, we aimed to assess the treatment response rates and long-term outcomes of vasculitis patients presenting with renal failure. This retrospective study included 151 patients with renal vasculitis from three hospitals who underwent a renal biopsy between 1997 and 2014. Patients with renal failure which required dialysis at the onset were compared to those presenting with more preserved renal function. The primary end point was treatment response and patient surivival. Patients with severe renal involvement had a lower response to treatment compared to those having preserved renal function (26.6 versus 93.4%; p renal recovery (41.6 versus 12.5%; p = 0.05). A higher incidence of severe infections was observed among patients with severe renal involvement (38.4 versus 18.1%, p = 0.01). The mortality rate was significantly higher among vasculitis patients presenting with renal failure (53.8 versus 22.2%, p = 0.001). Global survival at 1 and 5 years was 60 and 47% in patients requiring dialysis compared with 90 and 80% among those with more preserved renal function (p renal dysfunction represents an independent risk factor for patient survival in renal vasculitis. Patients requiring dialysis associate a lower response rate to immunosuppressive therapy and a higher incidence of severe infections.

Antiangiogenic Treatment Diminishes Renal Injury and Dysfunction via Regulation of Local AKT in Early Experimental Diabetes

OpenAIRE

Bai, Xiaoyan; Li, Xiao; Tian, Jianwei; Zhou, Zhanmei

2014-01-01

In view of increased vascular endothelial growth factor-A (VEGF-A) expression and renal dysfunction in early diabetes, we designed a study to test whether VEGF-A inhibition can prevent early renal injury and dysfunction. We investigated the relationship and mechanism between VEGF-A and AKT regulation. In vitro, VEGF-A small interfering RNA (siRNA) and AKT inhibitor MK-2206 were employed to podocytes and NRK-52 cells cultured in high glucose (30 mM). In vivo, the antiangiogenic drug endostatin...

Inhibition of plasma kallikrein-kinin system to alleviate renal injury and arthritis symptoms in rats with adjuvant-induced arthritis.

Science.gov (United States)

Zhu, Jie; Wang, Hui; Chen, Jingyu; Wei, Wei

2018-04-01

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Impairment of kidney functions in RA was observed. However, the mechanism of kidney injury of RA has not been clear. Plasma kallikrein-kinin system (KKS) was involved in inflammatory processes in kidney disease. This study aimed to explore the role of plasma KKS in immune reactions and kidney injury of RA. The paw of AA rats appeared to be swelling and redness, the arthritis index was significantly increased on the 18, 21 and 24 d after injection and secondary inflammation in multi-sites was observed. Kidney dysfunction accompanied with inflammatory cell infiltration, tubular epithelial cell mitochondrial swelling and vacuolar degeneration, renal glomerular foot process fusions and glomerular basement membrane thickening were observed in AA rats. The expressions of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (Kim-1) in kidney of AA rats were increased. In addition, expressions of BK, PK, B1R and B2R in the renal tissue of AA rats were up-regulated. Pro-inflammatory cytokines IL-2, IFN-γ and TNF-α were increased and anti-inflammatory cytokines IL-4 and IL-10 were low in kidney. Plasma kallikrein (PK) inhibitor PKSI-527 attenuated arthritis signs and renal damage, and inhibited BK, PK, B1R and B2R expressions. The protein expressions of P38, p-P38 and p-JNK and IFN-γ and TNF-α were inhibited by PKSI-527. These findings demonstrate that plasma KKS activation contributed to the renal injury of AA rats through MAPK signaling pathway. Plasma KKS might be a potential target for RA therapy.

Effect of olive leaf alcoholic extract on renal ischemia/reperfusion injury in adult male rats

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mohammadreza nasirzade

2014-05-01

Full Text Available Ischemia-reperfusion (I/R is present at various degrees in kidney transplants. Several studies suggest that renal ischemia reperfusion (RIR can induce acute kidney injury.  Liver diseases and neurological disorders related to kidney injury is a common clinical problem. Olive leaf is a significant source of bioactive phenolic compounds. They have better antioxidant capacity, anti-inflammatory and radical scavenging. In this study 50 male rats were allocated randomly into 5 groups: control (intact animals, group-1(I/R 60min+olive leaf extract, group-2 (I/R 60min, group-3(I/R 120min+olive leaf extractand group-4(I/R 120min.The animals  received 100 mg/kg olive leaf extract in0.5 ml drinking water using gavage for 28 days. Other animals received 0.5 ml normal saline by gavages. At the end of the treatment, the level of antioxidant enzymes including TAC, MDA, SOD and GPX were determined in renal tissue. Administration of olive leaf extract can significantly increase activity of TAC, GPX and SOD in group1and 3compared with group2and4. Also, MDA level in renal tissue of treated groups was significantly lower than ischemia-reperfusion groups (p

Measurement of arterial transit time and renal blood flow using pseudocontinuous ASL MRI with multiple post-labeling delays: Feasibility, reproducibility, and variation.

Science.gov (United States)

Kim, Dong Won; Shim, Woo Hyun; Yoon, Seong Kuk; Oh, Jong Yeong; Kim, Jeong Kon; Jung, Hoesu; Matsuda, Tsuyoshi; Kim, Dongeun

2017-09-01

To evaluate the feasibility, reproducibility, and variation of renal perfusion and arterial transit time (ATT) using pseudocontinuous arterial spin labeling magnetic resonance imaging (PCASL MRI) in healthy volunteers. PCASL MRI at 3T was performed in 25 healthy volunteers on two different occasions. The ATT and ATT-corrected renal blood flow (ATT-cRBF) were calculated at four different post-labeling delay points (0.5, 1.0, 1.5, and 2.0 s) and evaluated for each kidney and subject. The intraclass correlation (ICC) and Bland-Altman plot were used to assess the reproducibility of the PCASL MRI technique. The within-subject coefficient of variance was determined. Results were obtained for 46 kidneys of 23 subjects with a mean age of 38.6 ± 9.8 years and estimated glomerular filtration rate (eGFR) of 89.1 ± 21.2 ml/min/1.73 m 2 . Two subjects failed in the ASL MRI examination. The mean cortical and medullary ATT-cRBF for the subjects were 215 ± 65 and 81 ± 21 ml/min/100 g, respectively, and the mean cortical and medullary ATT were 1141 ± 262 and 1123 ± 245 msec, correspondingly. The ICC for the cortical ATT-cRBF was 0.927 and the within-subject coefficient of variance was 14.4%. The ICCs for the medullary ATT-cRBF and the cortical and medullary ATT were poor. The Bland-Altman plot for cortical RBF showed good agreement between the two measurements. PCASL MRI is a feasible and reproducible method for measuring renal cortical perfusion. In contrast, ATT for the renal cortex and medulla has poor reproducibility and high variation. 2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:813-819. © 2017 International Society for Magnetic Resonance in Medicine.

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

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

T-cells contribute to hypertension but not to renal injury in mice with subtotal nephrectomy

NARCIS (Netherlands)

Oosterhuis, Nynke R.; Papazova, Diana A.; Gremmels, Hendrik; Joles, Jaap A.; Verhaar, Marianne C.

2017-01-01

Background: The pathological condition of chronic kidney disease may not be adequately recapitulated in immunocompromised mice due to the lack of T-cells, which are important for the development of hypertension and renal injury. We studied the role of the immune system in relation to salt-sensitive

Mixed organic solvents induce renal injury in rats.

Science.gov (United States)

Qin, Weisong; Xu, Zhongxiu; Lu, Yizhou; Zeng, Caihong; Zheng, Chunxia; Wang, Shengyu; Liu, Zhihong

2012-01-01

To investigate the injury effects of organic solvents on kidney, an animal model of Sprague-Dawley (SD) rats treated with mixed organic solvents via inhalation was generated and characterized. The mixed organic solvents consisted of gasoline, dimethylbenzene and formaldehyde (GDF) in the ratio of 2:2:1, and were used at 12,000 PPM to treat the rats twice a day, each for 3 hours. Proteinuria appeared in the rats after exposure for 5-6 weeks. The incidences of proteinuria in male and female rats after exposure for 12 weeks were 43.8% (7/16) and 25% (4/16), respectively. Urinary N-Acetyl-β-(D)-Glucosaminidase (NAG) activity was increased significantly after exposure for 4 weeks. Histological examination revealed remarkable injuries in the proximal renal tubules, including tubular epithelial cell detachment, cloud swelling and vacuole formation in the proximal tubular cells, as well as proliferation of parietal epithelium and tubular reflux in glomeruli. Ultrastructural examination found that brush border and cytoplasm of tubular epithelial cell were dropped, that tubular epithelial cells were partially disintegrated, and that the mitochondria of tubular epithelial cells were degenerated and lost. In addition to tubular lesions, glomerular damages were also observed, including segmental foot process fusion and loss of foot process covering on glomerular basement membrane (GBM). Immunofluorescence staining indicated that the expression of nephrin and podocin were both decreased after exposure of GDF. In contrast, increased expression of desmin, a marker of podocyte injury, was found in some areas of a glomerulus. TUNEL staining showed that GDF induced apoptosis in tubular cells and glomerular cells. These studies demonstrate that GDF can induce both severe proximal tubular damage and podocyte injury in rats, and the tubular lesions appear earlier than that of glomeruli.

Mixed organic solvents induce renal injury in rats.

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Weisong Qin

Full Text Available To investigate the injury effects of organic solvents on kidney, an animal model of Sprague-Dawley (SD rats treated with mixed organic solvents via inhalation was generated and characterized. The mixed organic solvents consisted of gasoline, dimethylbenzene and formaldehyde (GDF in the ratio of 2:2:1, and were used at 12,000 PPM to treat the rats twice a day, each for 3 hours. Proteinuria appeared in the rats after exposure for 5-6 weeks. The incidences of proteinuria in male and female rats after exposure for 12 weeks were 43.8% (7/16 and 25% (4/16, respectively. Urinary N-Acetyl-β-(D-Glucosaminidase (NAG activity was increased significantly after exposure for 4 weeks. Histological examination revealed remarkable injuries in the proximal renal tubules, including tubular epithelial cell detachment, cloud swelling and vacuole formation in the proximal tubular cells, as well as proliferation of parietal epithelium and tubular reflux in glomeruli. Ultrastructural examination found that brush border and cytoplasm of tubular epithelial cell were dropped, that tubular epithelial cells were partially disintegrated, and that the mitochondria of tubular epithelial cells were degenerated and lost. In addition to tubular lesions, glomerular damages were also observed, including segmental foot process fusion and loss of foot process covering on glomerular basement membrane (GBM. Immunofluorescence staining indicated that the expression of nephrin and podocin were both decreased after exposure of GDF. In contrast, increased expression of desmin, a marker of podocyte injury, was found in some areas of a glomerulus. TUNEL staining showed that GDF induced apoptosis in tubular cells and glomerular cells. These studies demonstrate that GDF can induce both severe proximal tubular damage and podocyte injury in rats, and the tubular lesions appear earlier than that of glomeruli.

Experimental research on local renal injury of dog with microwave ablation guided by DSA

International Nuclear Information System (INIS)

Lin Jianping; Xian Zhengyuan; Shi Rongshu; Zhang Gaofeng; Li Xianlang

2008-01-01

Objective: To explore the efficiency, complications and probability of preserving part renal function by local renal microwave ablation. Methods: The fresh pig renal pelvis full filled with 30% diatrizoate meglumine and the dogs kidney taken arterial pyelography were both ablated with microwave. Dogs were divided into three groups: measuring temperature after ablation group, single point ablation both on the two kidneys group and double points ablation on unilateral kidney group. In measuring temperature after ablation group, DSA and pathology were performed immediately after ablation. In the other groups, DSA with blood and urine samplings were taken for routine tests including renal function right after the ablation and 10 days later. Results: Experiment in vitro showed conspicuous renal pelvic contraction and convolution. The group under power rate of 70, 3 min produced urine leak easily. Preliminary test in vivo with DSA showed the disappearance of local kidney blood supply. The residual renal function was related to areas of necrosis. Acute stage pathology revealed acute renal cortex medulla and pelvic cells injury. DSA of chronic stage showed no change in size of the area of ablation. The blood supply of necrotic areas was not restored. The residual kidney possessed the excretion contrast medium with no urine leaks. Upper pole of right kidney adhered with adjacent tissue, together with thickened covering. Pathology revealed fibrous proliferation around the coagulative necrosis. Conclusion: Microwave ablation can inactivate the local renal tissue, and, effectively preserve the big blood vessels and function of residual kidney. No urine leaks occurred in chronic stage but easily to produce adhesions with adjacent tissue. (authors)

A new electromagnetic shock-wave generator "SLX-F2" with user-selectable dual focus size: ex vivo evaluation of renal injury.

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Leistner, Rasmus; Wendt-Nordahl, Gunnar; Grobholz, Rainer; Michel, Maurice Stephan; Marlinghaus, Ernst; Köhrmann, Kai Uwe; Alken, Peter; Häcker, Axel

2007-08-01

Storz Medical AG (Kreutzlingen/Switzerland) has developed a new electromagnetic shockwave (SW) generator, the "SLX-F2", which allows the user to choose between a small-focus, high-pressure treatment regime or a wide-focus, low-pressure option. The aim of this study was to investigate, under standardized conditions, the impact of these two different treatment regimes on SW-induced renal injury. SW-induced renal injury was investigated by using the standardized model of the perfused ex vivo kidney. SWs were applied under ultrasound control in the parenchyma of a kidney pole. Different SW numbers (20, 50, 125, 250, 500, 1,000) were applied in three groups: group A was treated with a wider focus (80 MPa), groups B (60 MPa) and C (120 MPa) with a smaller focus (each parameter setting was repeated ten-fold). Disintegration capacity (measured by crater volume in cubes of plaster of Paris) was the same in groups A and C. After SW exposure, barium sulphate suspension was perfused through the renal artery. The maximum diameter (mm) of the extravasation in the cortex, representing the extent of vascular injury, was measured on X-ray mammography films. H&E staining was performed. In all three groups (A, B, C) a higher number of SWs caused the diameter of the extravasate to increase, with statistical significance appearing at 1,000 shots versus 20 shots (p generator at the same peak positive pressure and disintegration power. This confirms the in vivo findings that show renal injury caused by SW as being related to the number of SWs administered. Clinical studies are needed to investigate whether there is any advantage to offering both treatment regimes in one SW machine-for example, by using the "wide-focus, low-pressure" option for kidney stones and the "small-focus, high-pressure" regimen for stones in the ureter. The renal injury caused by either regime remains comparable.

Ginger extract diminishes chronic fructose consumption-induced kidney injury through suppression of renal overexpression of proinflammatory cytokines in rats.

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Yang, Ming; Liu, Changjin; Jiang, Jian; Zuo, Guowei; Lin, Xuemei; Yamahara, Johji; Wang, Jianwei; Li, Yuhao

2014-05-27

The metabolic syndrome is associated with an increased risk of development and progression of chronic kidney disease. Renal inflammation is well known to play an important role in the initiation and progression of tubulointerstitial injury of the kidneys. Ginger, one of the most commonly used spices and medicinal plants, has been demonstrated to improve diet-induced metabolic abnormalities. However, the efficacy of ginger on the metabolic syndrome-associated kidney injury remains unknown. This study aimed to investigate the impact of ginger on fructose consumption-induced adverse effects in the kidneys. The fructose control rats were treated with 10% fructose in drinking water over 5 weeks. The fructose consumption in ginger-treated rats was adjusted to match that of fructose control group. The ethanolic extract of ginger was co-administered (once daily by oral gavage). The indexes of lipid and glucose homeostasis were determined enzymatically, by ELISA and/or histologically. Gene expression was analyzed by Real-Time PCR. In addition to improve hyperinsulinemia and hypertriglyceridemia, supplement with ginger extract (50 mg/kg) attenuated liquid fructose-induced kidney injury as characterized by focal cast formation, slough and dilation of tubular epithelial cells in the cortex of the kidneys in rats. Furthermore, ginger also diminished excessive renal interstitial collagen deposit. By Real-Time PCR, renal gene expression profiles revealed that ginger suppressed fructose-stimulated monocyte chemoattractant protein-1 and its receptor chemokine (C-C motif) receptor-2. In accord, overexpression of two important macrophage accumulation markers CD68 and F4/80 was downregulated. Moreover, overexpressed tumor necrosis factor-alpha, interleukin-6, transforming growth factor-beta1 and plasminogen activator inhibitor (PAI)-1 were downregulated. Ginger treatment also restored the downregulated ratio of urokinase-type plasminogen activator to PAI-1. The present results

Renal endothelial function and blood flow predict the individual susceptibility to adriamycin-induced renal damage

NARCIS (Netherlands)

Ochodnicky, Peter; Henning, Robert H.; Buikema, Hendrik; Kluppel, Alex C. A.; van Wattum, Marjolein; de Zeeuw, Dick; van Dokkum, Richard P. E.

2009-01-01

Susceptibility to renal injury varies among individuals. Previously, we found that individual endothelial function of healthy renal arteries in vitro predicted severity of renal damage after 5/6 nephrectomy. Here we hypothesized that individual differences in endothelial function in vitro and renal

Antiangiogenic treatment diminishes renal injury and dysfunction via regulation of local AKT in early experimental diabetes.

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Bai, Xiaoyan; Li, Xiao; Tian, Jianwei; Zhou, Zhanmei

2014-01-01

In view of increased vascular endothelial growth factor-A (VEGF-A) expression and renal dysfunction in early diabetes, we designed a study to test whether VEGF-A inhibition can prevent early renal injury and dysfunction. We investigated the relationship and mechanism between VEGF-A and AKT regulation. In vitro, VEGF-A small interfering RNA (siRNA) and AKT inhibitor MK-2206 were employed to podocytes and NRK-52 cells cultured in high glucose (30 mM). In vivo, the antiangiogenic drug endostatin was administered in 12 week-old streptozotocin-induced male Sprague Dawley rats. The levels of VEGF-A, AKT, phosphorylated Ser⁴⁷³-AKT, phosphorylated Thr³⁰⁸-AKT, nephrin, angiotensin II (Ang II), angiotensin type II receptor 1 (ATR1) were examined using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis and immunohistochemistry. Interactions between phosphorylated Thr³⁰⁸-AKT and either nephrin in podocytes or Ang II in renal tubules were studied, respectively, using confocal immunofluorescence microscopy and immunoprecipitation. Silencing VEGF-A in podocytes upregulated phosphorylated Thr³⁰⁸-AKT and nephrin. Silencing VEGF-A in NRK-52E cells upregulated phosphorylated Thr³⁰⁸-AKT while downregulated Ang II and ATR1. MK-2206 enhanced VEGF-A expression in both podocytes and NRK-52E cells by inhibiting AKT activities. In diabetic rat kidneys, VEGF-A was upregulated and phosphorylated Thr³⁰⁸-AKT colocalized with either nephrin in podocytes or Ang II in renal tubules. With the endostatin treatment, the level of VEGF-A decreased while phosphorylated Thr³⁰⁸-AKT increased in both glomeruli and renal tubules. Treatment with endostatin upregulated nephrin in podocytes while downregulated Ang II and AT1R in renal tubules. Glomerular mesangial expansion was attenuated by the endostatin treatment, however, differences did not reach statistical significance. Endostatin ameliorated the interstitial fibrosis

Antiangiogenic treatment diminishes renal injury and dysfunction via regulation of local AKT in early experimental diabetes.

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Xiaoyan Bai

Full Text Available In view of increased vascular endothelial growth factor-A (VEGF-A expression and renal dysfunction in early diabetes, we designed a study to test whether VEGF-A inhibition can prevent early renal injury and dysfunction. We investigated the relationship and mechanism between VEGF-A and AKT regulation. In vitro, VEGF-A small interfering RNA (siRNA and AKT inhibitor MK-2206 were employed to podocytes and NRK-52 cells cultured in high glucose (30 mM. In vivo, the antiangiogenic drug endostatin was administered in 12 week-old streptozotocin-induced male Sprague Dawley rats. The levels of VEGF-A, AKT, phosphorylated Ser⁴⁷³-AKT, phosphorylated Thr³⁰⁸-AKT, nephrin, angiotensin II (Ang II, angiotensin type II receptor 1 (ATR1 were examined using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR, Western blot analysis and immunohistochemistry. Interactions between phosphorylated Thr³⁰⁸-AKT and either nephrin in podocytes or Ang II in renal tubules were studied, respectively, using confocal immunofluorescence microscopy and immunoprecipitation. Silencing VEGF-A in podocytes upregulated phosphorylated Thr³⁰⁸-AKT and nephrin. Silencing VEGF-A in NRK-52E cells upregulated phosphorylated Thr³⁰⁸-AKT while downregulated Ang II and ATR1. MK-2206 enhanced VEGF-A expression in both podocytes and NRK-52E cells by inhibiting AKT activities. In diabetic rat kidneys, VEGF-A was upregulated and phosphorylated Thr³⁰⁸-AKT colocalized with either nephrin in podocytes or Ang II in renal tubules. With the endostatin treatment, the level of VEGF-A decreased while phosphorylated Thr³⁰⁸-AKT increased in both glomeruli and renal tubules. Treatment with endostatin upregulated nephrin in podocytes while downregulated Ang II and AT1R in renal tubules. Glomerular mesangial expansion was attenuated by the endostatin treatment, however, differences did not reach statistical significance. Endostatin ameliorated the

Renal Tissue Oxygenation in Essential Hypertension and Chronic Kidney Disease

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Menno Pruijm

2013-01-01

Full Text Available Animal studies suggest that renal tissue hypoxia plays an important role in the development of renal damage in hypertension and renal diseases, yet human data were scarce due to the lack of noninvasive methods. Over the last decade, blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI, detecting deoxyhemoglobin in hypoxic renal tissue, has become a powerful tool to assess kidney oxygenation noninvasively in humans. This paper provides an overview of BOLD-MRI studies performed in patients suffering from essential hypertension or chronic kidney disease (CKD. In line with animal studies, acute changes in cortical and medullary oxygenation have been observed after the administration of medication (furosemide, blockers of the renin-angiotensin system or alterations in sodium intake in these patient groups, underlining the important role of renal sodium handling in kidney oxygenation. In contrast, no BOLD-MRI studies have convincingly demonstrated that renal oxygenation is chronically reduced in essential hypertension or in CKD or chronically altered after long-term medication intake. More studies are required to clarify this discrepancy and to further unravel the role of renal oxygenation in the development and progression of essential hypertension and CKD in humans.

Curcumin-carrying nanoparticles prevent ischemia-reperfusion injury in human renal cells.

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Xu, Yong; Hu, Ning; Jiang, Wei; Yuan, Hong-Fang; Zheng, Dong-Hui

2016-12-27

Renal ischemia-reperfusion injury (IRI) is a major complication in clinical practice. However, despite its frequency, effective preventive/treatment strategies for this condition are scarce. Curcumin possesses antioxidant properties and is a promising potential protective agent against renal IRI, but its poor water solubility restricts its application. In this study, we constructed curcumin-carrying distearoylphosphatidylethanolamine-polyethylene glycol nanoparticles (Cur-NPs), and their effect on HK-2 cells exposed to IRI was examined in vitro. Curcumin encapsulated in NPs demonstrated improved water solubility and slowed release. Compared with the IRI and Curcumin groups, Cur-NP groups displayed significantly improved cell viability, downregulated protein expression levels of caspase-3 and Bax, upregulated expression of Bcl-2 protein, increased antioxidant superoxide dismutase level, and reduced apoptotic rate, reactive oxygen species level, and malondialdehyde content. Results clearly showed that Cur-NPs demonstrated good water solubility and slow release, as well as exerted protective effects against oxidative stress in cultured HK-2 cells exposed to IRI.

Mannitol increases renal blood flow and maintains filtration fraction and oxygenation in postoperative acute kidney injury: a prospective interventional study.

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Bragadottir, Gudrun; Redfors, Bengt; Ricksten, Sven-Erik

2012-08-17

Acute kidney injury (AKI), which is a major complication after cardiovascular surgery, is associated with significant morbidity and mortality. Diuretic agents are frequently used to improve urine output and to facilitate fluid management in these patients. Mannitol, an osmotic diuretic, is used in the perioperative setting in the belief that it exerts reno-protective properties. In a recent study on uncomplicated postcardiac-surgery patients with normal renal function, mannitol increased glomerular filtration rate (GFR), possibly by a deswelling effect on tubular cells. Furthermore, experimental studies have previously shown that renal ischemia causes an endothelial cell injury and dysfunction followed by endothelial cell edema. We studied the effects of mannitol on renal blood flow (RBF), glomerular filtration rate (GFR), renal oxygen consumption (RVO2), and extraction (RO2Ex) in early, ischemic AKI after cardiac surgery. Eleven patients with AKI were studied during propofol sedation and mechanical ventilation 2 to 6 days after complicated cardiac surgery. All patients had severe heart failure treated with one (100%) or two (73%) inotropic agents and intraaortic balloon pump (36%). Systemic hemodynamics were measured with a pulmonary artery catheter. RBF and renal filtration fraction (FF) were measured by the renal vein thermo-dilution technique and by renal extraction of chromium-51-ethylenediaminetetraacetic acid (51Cr-EDTA), respectively. GFR was calculated as the product of FF and renal plasma flow RBF × (1-hematocrit). RVO2 and RO2Ex were calculated from arterial and renal vein blood samples according to standard formulae. After control measurements, a bolus dose of mannitol, 225 mg/kg, was given, followed by an infusion at a rate of 75 mg/kg/h for two 30-minute periods. Mannitol did not affect cardiac index or cardiac filling pressures. Mannitol increased urine flow by 61% (P renal vascular resistance (P renal FF. Mannitol treatment of postoperative AKI

The Soluble Epoxide Hydrolase Inhibitor AR9281 Decreases Blood Pressure, Ameliorates Renal Injury and Improves Vascular Function in Hypertension

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Sean Shaw

2009-12-01

Full Text Available Soluble epoxide hydrolase inhibitors (sEHIs are demonstrating promise as potential pharmaceutical agents for the treatment of cardiovascular disease, diabetes, inflammation, and kidney disease. The present study determined the ability of a first-inclass sEHI, AR9281, to decrease blood pressure, improve vascular function, and decrease renal inflammation and injury in angiotensin hypertension. Rats were infused with angiotensin and AR9281 was given orally during the 14-day infusion period. Systolic blood pressure averaged 180 ± 5 mmHg in vehicle treated and AR9281 treatment significantly lowered blood pressure to 142 ± 7 mmHg in angiotensin hypertension. Histological analysis demonstrated decreased injury to the juxtamedullary glomeruli. Renal expression of inflammatory genes was increased in angiotensin hypertension and two weeks of AR9281 treatment decreased this index of renal inflammation. Vascular function in angiotensin hypertension was also improved by AR9281 treatment. Decreased afferent arteriolar and mesenteric resistance endothelial dependent dilator responses were ameliorated by AR9281 treatment of angiotensin hypertensive rats. These data demonstrate that the first-in-class sEHI, AR9281, lowers blood pressure, improves vascular function and reduces renal damage in angiotensin hypertension.

Are diuretics harmful in the management of acute kidney injury?

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Ejaz, A Ahsan; Mohandas, Rajesh

2014-03-01

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

Salubrious effect of C-phycocyanin against oxalate-mediated renal cell injury.

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Farooq, Shukkur Muhammed; Asokan, Devarajan; Sakthivel, Ramasamy; Kalaiselvi, Periandavan; Varalakshmi, Palaninathan

2004-10-01

C-phycocyanin, a biliprotein pigment found in some blue green algae (Spirulina platensis) with nutritional and medicinal properties, was investigated for its efficacy on sodium oxalate-induced nephrotoxicity in experimentally induced urolithic rats. Male Wistar rats were divided into four groups. Hyperoxaluria was induced in two of these groups by intraperitoneal infusion of sodium oxalate (70 mg/kg), and a pretreatment of phycocyanin (100 mg/kg) as a single oral dosage was given to one of these groups by 1 h prior to sodium oxalate infusion challenges. The study also encompasses an untreated control group and a phycocyanin-alone treated drug control group. The extent of lipid peroxidation (LPO) was evaluated in terms of renal concentrations of MDA, conjugated diene and hydroperoxides. The following assay was performed in the renal tissue (a) antioxidant enzymes such as superoxide dismutase (SOD) and catalase, (b) glutathione metabolizing enzymes such as glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST) and glucose 6-phosphate dehydrogenase (G6PD), (c) the low molecular weight antioxidants (GSH, vitamins E and C) and protein carbonyl content. The increased concentrations of MDA, conjugated diene and hydroperoxide (index of the lipid peroxidation) were controlled (P antioxidants were appreciably increased (P antioxidants. It was noticed that the activities of antioxidant enzymes and glutathione metabolizing enzymes were considerably stabilized in rats pretreated with phycocyanin. We suggest that phycocyanin protects the integrity of the renal cell by stabilizing the free radical mediated LPO and protein carbonyl, as well as low molecular weight antioxidants and antioxidant enzymes in renal cells. Thus, the present analysis reveals that the antioxidant nature of C-phycocyanin protects the renal cell against oxalate-induced injury and may be a nephroprotective agent.

Endothelin-like action of Pausinystalia yohimbe aqueous extract on vascular and renal regional hemodynamics in Sprague Dawley rats.

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Ajayi, A A; Newaz, M; Hercule, H; Saleh, M; Bode, C O; Oyekan, A O

2003-12-01

The bark of the African tree Pausinystalia yohimbe has been used as a food additive with aphrodisiac and penile erection enhancing properties. The effect of an aqueous extract of P. yohimbe (CCD-X) on renal circulation was assessed in order to test the hypothesis that it possesses additional effects on nitric oxide production and/or endothelin-1 (ET-1)-like actions. In vivo studies with CCD-X in Sprague Dawley rats demonstrated a dose-dependent (1-1000 ng/kg) increase in mean blood pressure (p < 0.001) and an increase in medullary blood flow (MBF) (p < 0.001). Both the pressor action and renal medullary vasodilation were blocked by endothelinA (ETA) receptor antagonist BMS182874 and endothelinB (ETB) receptor antagonist BQ788 in combination. L-Nomega-nitro-l-arginine methyl ester (L-NAME; 10 mg/kg) also inhibited the increase in MBF induced by CCD-X. In vitro studies in isolated perfused kidney and in pressurized renal microvessels confirmed the dose-dependent vasoconstrictor action of this extract. ETA receptor antagonist BQ610 and ETB receptor antagonist BQ788 separately and significantly attenuated the renal vasoconstrictor actions of the extract (p < 0.001 ANOVA). These preliminary observations indicate that, in addition to the alpha-adrenergic antagonist actions that characterize yohimbine, CCD-X possesses endothelin-like actions and affects nitric oxide (NO) production in renal circulation. These findings suggest a strong possibility of post-receptor cross-talk between alpha2-adrenoceptors and endothelin, as well as a direct effect of alpha2-adrenoceptors on renal NO production. (c) 2003 Prous Science

[Low grade renal trauma (Part II): diagnostic validity of ultrasonography].

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Grill, R; Báca, V; Otcenásek, M; Zátura, F

2010-04-01

The aim of the study was to verify whether ultrasonography can be considered a reliable method for the diagnosis of low-grade renal trauma. The group investigated included patients with grade I or grade II blunt renal trauma, as classified by the AAST grading system, in whom ultrasonography alone or in conjunction with computed tomography was used as a primary diagnostic method. B-mode ultrasound with a transabdominal probe working at frequencies of 2.5 to 5.0 MHz was used. Every finding of post-traumatic changes in the renal tissues, i.e., post-contusion hypotonic infiltration of the renal parenchyma or subcapsular haematoma, was included. The results were statistically evaluated by the Chi-square test with the level of significance set at 5%, using Epi Info Version 6 CZ software. The group comprised 112 patients (43 women, 69 men) aged between 17 and 82 years (average, 38 years). It was possible to diagnose grade I or grade II renal injury by ultrasonography in only 60 (54%) of them. The statistical significance of ultrasonography as the only imaging method for the diagnosis of low-grade renal injury was not confirmed (p=0.543) Low-grade renal trauma is a problem from the diagnostic point of view. It usually does not require revision surgery and, if found during repeat surgery for more serious injury of another organ, it usually does not receive attention. Therefore, the macroscopic presentation of grade I and grade II renal injury is poorly understood, nor are their microscopic findings known, because during revision surgery these the traumatised kidneys are not usually removed and their injuries at autopsy on the patients who died of multiple trauma are not recorded either. The results of this study demonstrated that the validity of ultrasonography for the diagnosis of low-grade renal injury is not significant, because this examination can reveal only some of the renal injuries such as perirenal haematoma. An injury to the renal parenchyma is also indicated by

The optimal timing of continuous renal replacement therapy for patients with sepsis-induced acute kidney injury.

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Tian, Huanhuan; Sun, Ting; Hao, Dong; Wang, Tao; Li, Zhi; Han, Shasha; Qi, Zhijiang; Dong, Zhaoju; Lv, Changjun; Wang, Xiaozhi

2014-10-01

High mortality in the intensive care unit (ICU) is probably associated with sepsis-induced acute kidney injury (AKI). The aim of this study is to explore which stage of AKI may be the optimal timing for continuous renal replacement therapy (CRRT). A retrospective analysis of 160 critically ill patients with septic AKI, treated with or without CRRT was performed in Binzhou medical college affiliated hospital ICU. The parameters including 28-days mortality rate, renal recovery, ventilation time and ICU stay between CRRT group and control group were assessed. Renal recovery, defined as independence from dialysis at discharge, was documented for 64/76 (84.2 %) of the surviving patients (48.1 % of total subjects included in the study). The mortality rate increased proportionally with acute kidney injury Network stages in CRRT subgroups (P = 0.001) and control groups (P = 0.029). CRRT initiation at stage 2 of AKI significantly reduced the 28-day mortality (P = 0.048) and increased the 28-day survival rate (P = 0.036) compared with those in control group. In addition, the ICU stay and ventilation time were shorter in CRRT group than that of control group in stage 2 of AKI. The stage 2 AKI might be the optimal timing for performing CRRT.

Diosmin Attenuates Methotrexate-Induced Hepatic, Renal, and Cardiac Injury: A Biochemical and Histopathological Study in Mice

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Khalifa, Hesham A.; Al-Quraishy, Saleh A.

2017-01-01

The current study was designed to investigate the beneficial role of diosmin, a biologically active flavonoid, against methotrexate- (MTX-) induced hepatic, renal, and cardiac injuries in mice. Male Swiss albino mice received a single intraperitoneal injection of MTX (at 20 mg/kg, body weight) either alone or in combination with oral diosmin (at 50 or 100 mg/kg body weight, for 10 days). Serum was used to evaluate tissue injury markers, while hepatic, renal, and cardiac tissue samples were obtained for determination of antioxidant activity as well as histopathological examination. Diosmin treatment ameliorated the MTX-induced elevation of serum alkaline phosphatase, aminotransferases, urea, creatinine, lactate dehydrogenase, and creatine kinases as well as plasma proinflammatory cytokines (interleukin-1-beta, interleukin-6, and tumor necrosis factor-alpha). Additionally, both diosmin doses significantly reduced tissue levels of malondialdehyde and nitric oxide and increased those of glutathione, glutathione peroxidase, glutathione reductase, glutathione S-transferase, superoxide dismutase, and catalase, compared to the MTX-intoxicated group. Histopathological examination showed that diosmin significantly minimized the MTX-induced histological alterations and nearly restored the normal architecture of hepatic, renal, and cardiac tissues. Based on these findings, diosmin may be a promising agent for protection against MTX-induced cytotoxicity in patients with cancer and autoimmune diseases. PMID:28819543

Perioperative acute renal failure.

LENUS (Irish Health Repository)

Mahon, Padraig

2012-02-03

PURPOSE OF REVIEW: Recent biochemical evidence increasingly implicates inflammatory mechanisms as precipitants of acute renal failure. In this review, we detail some of these pathways together with potential new therapeutic targets. RECENT FINDINGS: Neutrophil gelatinase-associated lipocalin appears to be a sensitive, specific and reliable biomarker of renal injury, which may be predictive of renal outcome in the perioperative setting. For estimation of glomerular filtration rate, cystatin C is superior to creatinine. No drug is definitively effective at preventing postoperative renal failure. Clinical trials of fenoldopam and atrial natriuretic peptide are, at best, equivocal. As with pharmacological preconditioning of the heart, volatile anaesthetic agents appear to offer a protective effect to the subsequently ischaemic kidney. SUMMARY: Although a greatly improved understanding of the pathophysiology of acute renal failure has offered even more therapeutic targets, the maintenance of intravascular euvolaemia and perfusion pressure is most effective at preventing new postoperative acute renal failure. In the future, strategies targeting renal regeneration after injury will use bone marrow-derived stem cells and growth factors such as insulin-like growth factor-1.

High Endogenous Accumulation of ω-3 Polyunsaturated Fatty Acids Protect against Ischemia-Reperfusion Renal Injury through AMPK-Mediated Autophagy in Fat-1 Mice.

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Gwon, Do Hyeong; Hwang, Tae Woong; Ro, Ju-Ye; Kang, Yoon-Joong; Jeong, Jin Young; Kim, Do-Kyung; Lim, Kyu; Kim, Dong Woon; Choi, Dae Eun; Kim, Jwa-Jin

2017-09-30

Regulated autophagy is involved in the repair of renal ischemia-reperfusion injury (IRI). Fat-1 transgenic mice produce ω3-Polyunsaturated fatty acids (ω3-PUFAs) from ω6-Polyunsaturated fatty acids (ω6-PUFAs) without a dietary ω3-PUFAs supplement, leading to a high accumulation of omega-3 in various tissues. ω3-PUFAs show protective effects against various renal injuries and it has recently been reported that ω3-PUFAs regulate autophagy. We assessed whether ω3-PUFAs attenuated IR-induced acute kidney injury (AKI) and evaluated its associated mechanisms. C57Bl/6 background fat-1 mice and wild-type mice (wt) were divided into four groups: wt sham ( n = 10), fat-1 sham ( n = 10), wt IRI (reperfusion 35 min after clamping both the renal artery and vein; n = 15), and fat-1 IRI ( n = 15). Kidneys and blood were harvested 24 h after IRI and renal histological and molecular data were collected. The kidneys of fat-1 mice showed better renal cell survival, renal function, and pathological damage than those of wt mice after IRI. In addition, fat-1 mice showed less oxidative stress and autophagy impairment; greater amounts of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II, Beclin-1, and Atg7; lower amounts of p62; and, higher levels of renal cathepsin D and ATP6E than wt kidneys. They also showed more adenosine monophosphate-activated protein kinase (AMPK) activation, which resulted in the inhibition of phosphorylation of the mammalian target of rapamycin (mTOR). Collectively, ω3-PUFAs in fat-1 mice contributed to AMPK mediated autophagy activation, leading to a renoprotective response.

Effects of sirolimus alone or in combination with cyclosporine A on renal ischemia/reperfusion injury

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B.J. Pereira

2010-08-01

Full Text Available Calcineurin inhibitors exacerbate ischemic injury in transplanted kidneys, but it is not known if sirolimus protects or exacerbates the transplanted kidney from ischemic injury. We determined the effects of sirolimus alone or in combination with cyclosporin A (CsA on oxygenated and hypoxic/reoxygenated rat proximal tubules in the following in vitro groups containing 6-9 rats per group: sirolimus (10, 50, 100, 250, 500, and 1000 ηg/mL; CsA (100 µg/mL; sirolimus (50 and 250 ηg/mL + CsA (100 µg/mL; control; vehicle (20% ethanol. For in vivo studies, 3-week-old Wistar rats (150-250 g were submitted to left nephrectomy and 30-min renal artery clamping. Renal function and histological evaluation were performed 24 h and 7 days after ischemia (I in five groups: sham, I, I + SRL (3 mg·kg-1·day-1, po, I + CsA (3 mg·kg-1·day-1, sc, I + SRL + CsA. Sirolimus did not injure oxygenated or hypoxic/reoxygenated proximal tubules and did not potentiate the tubular toxic effects of CsA. Neither drug affected the glomerular filtration rate (GFR at 24 h. GFR was reduced in CsA-treated rats on day 7 (0.5 ± 0.1 mL/min but not in rats receiving sirolimus + CsA (0.8 ± 0.1 mL/min despite the reduction in renal blood flow (3.9 ± 0.5 mL/min. Acute tubular necrosis regeneration was similar for all groups. Sirolimus alone was not toxic and did not enhance hypoxia/reoxygenation injury or CsA toxicity to proximal tubules. Despite its hemodynamic effects, sirolimus protected post-ischemic kidneys against CsA toxicity.

The 6-hydroxychromanol derivative SUL-109 ameliorates renal injury after deep hypothermia and rewarming in rats.

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Vogelaar, Pieter C; Roorda, Maurits; de Vrij, Edwin L; Houwertjes, Martin C; Goris, Maaike; Bouma, Hjalmar; van der Graaf, Adrianus C; Krenning, Guido; Henning, Robert H

2018-04-11

Mitochondrial dysfunction plays an important role in kidney damage in various pathologies, including acute and chronic kidney injury and diabetic nephropathy. In addition to the well-studied ischaemia/reperfusion (I/R) injury, hypothermia/rewarming (H/R) also inflicts acute kidney injury. Substituted 6-hydroxychromanols are a novel class of mitochondrial medicines that ameliorate mitochondrial oxidative stress and protect the mitochondrial network. To identify a novel 6-hydroxychromanol that protects mitochondrial structure and function in the kidney during H/R, we screened multiple compounds in vitro and subsequently assessed the efficacy of the 6-hydroxychromanol derivatives SUL-109 and SUL-121 in vivo to protect against kidney injury after H/R in rats. Human proximal tubule cell viability was assessed following exposure to H/R for 48/4 h in the presence of various 6-hydroxychromanols. Selected compounds (SUL-109, SUL-121) or vehicle were administered to ketamine-anaesthetized male Wistar rats (IV 135 µg/kg/h) undergoing H/R at 15°C for 3 h followed by rewarming and normothermia for 1 h. Metabolic parameters and body temperature were measured throughout. In addition, renal function, renal injury, histopathology and mitochondrial fitness were assessed. H/R injury in vitro lowered cell viability by 94 ± 1%, which was counteracted dose-dependently by multiple 6-hydroxychomanols derivatives. In vivo, H/R in rats showed kidney injury molecule 1 expression in the kidney and tubular dilation, accompanied by double-strand DNA breaks and protein nitrosylation. SUL-109 and SUL-121 ameliorated tubular kidney damage, preserved mitochondrial mass and maintained cortical adenosine 5'-triphosphate (ATP) levels, although SUL-121 did not reduce protein nitrosylation. The substituted 6-hydroxychromanols SUL-109 and SUL-121 ameliorate kidney injury during in vivo H/R by preserving mitochondrial mass, function and ATP levels. In addition, both 6-hydroxychromanols

Renal myogenic constriction protects the kidney from age-related hypertensive renal damage in the Fawn-Hooded rat

NARCIS (Netherlands)

Vavrinec, Peter; Henning, Robert H.; Goris, Maaike; Landheer, Sjoerd W.; Buikema, Hendrik; van Dokkum, Richard P. E.

Introduction:Intact myogenic constriction plays a role in renal blood flow autoregulation and protection against pressure-related (renal) injury. However, to what extent alterations in renal artery myogenic constriction are involved in development of renal damage during aging is unknown. Therefore,

Dietary docosahexaenoic acid ameliorates, but rapeseed oil and safflower oil accelerate renal injury in stroke-prone spontaneously hypertensive rats as compared with soybean oil, which is associated with expression for renal transforming growth factor-beta, fibronectin and renin.

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Miyazaki, M; Takemura, N; Watanabe, S; Hata, N; Misawa, Y; Okuyama, H

2000-01-03

We have noted that n-3 fatty acid-rich oils, such as fish oil, perilla oil and flaxseed oil as well as ethyl docosahexaenoate (DHA) prolonged the survival time of stroke-prone spontaneously hypertensive rats (SHRSP) rats by approximately 10% as compared with linoleate (n-6)-rich safflower oil. Rapeseed oil with a relatively low n-6/n-3 ratio unusually shortened the survival time by approximately 40%, suggesting the presence of minor components unfavorable to SHRSP rats. This study examined the effects of dietary oils and DHA on renal injury and gene expression related to renal injury in SHRSP rats. Rats fed rapeseed oil- and safflower oil-supplemented diets developed more severe proteinuria than those fed soybean oil-supplemented diet used as a control, but there were no significant differences in blood pressure. In contrast, the DHA-supplemented diet inhibited the development of proteinuria and suppressed hypertension. The mRNA levels for renal TGF-beta, fibronectin and renin were higher in the rapeseed oil and safflower oil groups after 9 weeks of feeding of the experimental diet than in the soybean oil and DHA groups. The fatty acid composition of kidney phospholipids was markedly affected by these diets. These results indicate that the renal injury observed in the groups fed safflower oil with a high n-6/n-3 ratio and rapeseed oil with presumed minor components is accompanied by increased expression of the TGF-beta, renin and fibronectin genes, and that dietary DHA suppresses renal injury and gene expression as compared with soybean oil.

Renal endothelial function and blood flow predict the individual susceptibility to adriamycin-induced renal damage

NARCIS (Netherlands)

Ochodnicky, Peter; Henning, Robert H.; Buikema, Hendrik; Kluppel, Alex C. A.; van Wattum, Marjolein; de Zeeuw, Dick; van Dokkum, Richard P. E.

Background. Susceptibility to renal injury varies among individuals. Previously, we found that individual endothelial function of healthy renal arteries in vitro predicted severity of renal damage after 5/6 nephrectomy. Here we hypothesized that individual differences in endothelial function in

Renal cortical volume measured using automatic contouring software for computed tomography and its relationship with BMI, age and renal function

International Nuclear Information System (INIS)

Muto, Natalia Sayuri; Kamishima, Tamotsu; Harris, Ardene A.; Kato, Fumi; Onodera, Yuya; Terae, Satoshi; Shirato, Hiroki

2011-01-01

Purpose: To evaluate the relationship between renal cortical volume, measured by an automatic contouring software, with body mass index (BMI), age and renal function. Materials and methods: The study was performed in accordance to the institutional guidelines at our hospital. Sixty-four patients (34 men, 30 women), aged 19 to 79 years had their CT scans for diagnosis or follow-up of hepatocellular carcinoma retrospectively examined by a computer workstation using a software that automatically contours the renal cortex and the renal parenchyma. Body mass index and estimated glomerular filtration rate (eGFR) were calculated based on data collected. Statistical analysis was done using the Student t-test, multiple regression analysis, and intraclass correlation coefficient (ICC). Results: The ICC for total renal and renal cortical volumes were 0.98 and 0.99, respectively. Renal volume measurements yielded a mean cortical volume of 105.8 cm 3 ± 28.4 SD, mean total volume of 153 cm 3 ± 39 SD and mean medullary volume of 47.8 cm 3 ± 19.5 SD. The correlation between body weight/height/BMI and both total renal and cortical volumes presented r = 0.6, 0.6 and 0.4, respectively, p < 0.05, while the correlation between renal cortex and age was r = -0.3, p < 0.05. eGFR showed correlation with renal cortical volume r = 0.6, p < 0.05. Conclusion: This study demonstrated that renal cortical volume had a moderate positive relationship with BMI, moderate negative relationship with age, and a strong positive relationship with the renal function, and provided a new method to routinely produce volumetric assessment of the kidney.

Recurrent intramedullary epidermoid cyst of conus medullaris.

LENUS (Irish Health Repository)

Fleming, Christina

2011-01-01

Spinal intramedullary epidermoid cyst is a rare condition. Recurrent epidermoid cyst in the spine cord is known to occur. The authors describe a case of recurrent conus medullaris epidermoid cyst in a 24-year-old female. She initially presented at 7 years of age with bladder disturbance in the form of diurnal enuresis and recurrent urinary tract infection. MRI lumbar spine revealed a 4 cm conus medullaris epidermoid cyst. Since the initial presentation, the cyst had recurred seven times in the same location and she underwent surgical intervention in the form of exploration and debulking. This benign condition, owing to its anatomical location, has posed a surgical and overall management challenge. This occurrence is better managed in a tertiary-care centre requiring multi-disciplinary treatment approach.

Effect of Γ-aminobutyric acid on kidney injury induced by renal ischemia-reperfusion in male and female rats: Gender-related difference.

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Vafapour, Marzieh; Nematbakhsh, Mehdi; Monajemi, Ramesh; Mazaheri, Safoora; Talebi, Ardeshir; Talebi, Nahid; Shirdavani, Soheyla

2015-01-01

The most important cause of kidney injury is renal ischemia/reperfusion injury (IRI), which is gender-related. This study was designed to investigate the protective role of Γ-aminobutyric acid (GABA (against IRI in male and female rats. Thirty-six female and male wistar rats were assigned to six experimental groups. The IRI was induced by clamping renal vessels for 45 min then was performed reperfusion for 24 h. The group sex posed to IRI were pretreated with GABA and were compared with the control groups. Serum levels of creatinine and blood urea nitrogen, kidney weight, and kidney tissue damage score increased in the IRI alone groups, (P GABA decreased these parameters in female significantly (P GABA. Testis weight did not alter in male rats. Serum level of nitrite and kidney level of malondialdehyde (MDA) had no significant change in both female and male rats. Kidney level of nitrite increased significantly in female rats experienced IRI and serum level of MDA increased significantly in males that were exposed to IRI (P GABA could ameliorate kidney injury induced by renal IRI in a gender dependent manner.

Blood oxygenation level dependent (BOLD). Renal imaging. Concepts and applications; Blood Oxygenation Level Dependent (BOLD). Bildgebung der Nieren. Konzepte und Anwendungen

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Nissen, Johanna C.; Haneder, Stefan; Schoenberg, Stefan O.; Michaely, Henrik J. [Heidelberg Univ. Medizinische Fakultaet Mannheim (Germany). Inst. fuer Klinische Radiologie und Nuklearmedizin; Mie, Moritz B.; Zoellner, Frank G. [Heidelberg Univ. Medizinische Fakultaet Mannheim (DE). Inst. fuer Computerunterstuetzte Klinische Medizin (CKM)

2010-07-01

Many renal diseases as well as several pharmacons cause a change in renal blood flow and/or renal oxygenation. The blood oxygenation level dependent (BOLD) imaging takes advantage of local field inhomogeneities and is based on a T2{sup *}-weighted sequence. BOLD is a non-invasive method allowing an estimation of the renal, particularly the medullary oxygenation, and an indirect measurement of blood flow without administration of contrast agents. Thus, effects of different drugs on the kidney and various renal diseases can be controlled and observed. This work will provide an overview of the studies carried out so far and identify ways how BOLD can be used in clinical studies. (orig.)

Juxtarenal Aortic Pseudoaneurysm – Right Renal Vein Fistula with Circumaortic Renal Collar-Delayed Manifestation of a Gunshot Injury – an Uncommon Entity Diagnosed with CT Angiography

International Nuclear Information System (INIS)

Garg, Lalit; Jain, Neeraj; Agrawal, Sachin; Chauhan, Udit; Goel, Vandana; Puri, Sunil Kumar

2016-01-01

Delayed presentation of post-traumatic aortic pseudoaneurysm and its fistulous communication with the right renal vein is a very rare entity. Most of the cases described in literature are due to abdominal aortic aneurysm (AAA) rupture into the left renal vein. To the best of our knowledge, communication with the right renal vein has not been described in published literature. Our patient also had a circumaortic renal collar, which is a rare renal vein anomaly. Aortic pseudoaneurysm, its fistulous communication with the right renal vein and circumaortic renal collar in a single patient is of extremely rare occurrence. A 29-year-old male presented to the cardiology department with complaints of breathlessness, abdominal pain and hematuria for the last 6 months. On clinical examination there was evidence of audible bruit over the abdomen. He had a past history of a gunshot injury around two years back. CT angiography revealed a large partially calcified pseudoaneurysm arising from the right lateral wall of the abdominal aorta with the neck of the pseudoaneurysm at juxtarenal location with a fistula between the anterior wall of the pseudoaneurysm and the posterior wall of the right renal vein. There was an associated incidental finding of circumaortic left renal vein with gross aneurysmal dilatation of both pre- and retro-aortic part of the renal vein. Delayed presentation of aortic pseudoaneurysm with its fistulous communication with the right renal vein is a rare entity. CT angiography is a non-invasive modality for diagnosis of the exact site of communication, length of aneurysm, proximal and distal extent of the affected segment and its relationship with surrounding structures

Neural control of adrenal medullary and cortical blood flow during hemorrhage

International Nuclear Information System (INIS)

Breslow, M.J.; Jordan, D.A.; Thellman, S.T.; Traystman, R.J.

1987-01-01

Hemorrhagic hypotension produces an increase in adrenal medullary blood flow and a decrease in adrenal cortical blood flow. To determine whether changes in adrenal blood flow during hemorrhage are neurally mediated, the authors compared blood flow responses following adrenal denervation (splanchnic nerve section) with changes in the contralateral, neurally intact adrenal. Carbonized microspheres labeled with 153 Gd, 114 In, 113 Sn, 103 Ru, 95 Nb or 46 Se were used. Blood pressure was reduced and maintained at 60 mmHg for 25 min by hemorrhage into a pressurized bottle system. Adrenal cortical blood flow decreased to 50% of control with hemorrhage in both the intact and denervated adrenal. Adrenal medullary blood flow increased to four times control levels at 15 and 25 min posthemorrhage in the intact adrenal, but was reduced to 50% of control at 3, 5, and 10 min posthemorrhage in the denervated adrenal. In a separate group of dogs, the greater splanchnic nerve on one side was electrically stimulated at 2, 5, or 15 Hz for 40 min. Adrenal medullary blood flow increased 5- to 10-fold in the stimulated adrenal but was unchanged in the contralateral, nonstimulated adrenal. Adrenal cortical blood flow was not affected by nerve stimulation. They conclude that activity of the splanchnic nerve profoundly affects adrenal medullary vessels but not adrenal cortical vessels and mediates the observed increase in adrenal medullary blood flow during hemorrhagic hypotension

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

NARCIS (Netherlands)

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

2009-01-01

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

Renal Blood Flow, Glomerular Filtration Rate, and Renal Oxygenation in Early Clinical Septic Shock.

Science.gov (United States)

Skytte Larsson, Jenny; Krumbholz, Vitus; Enskog, Anders; Bragadottir, Gudrun; Redfors, Bengt; Ricksten, Sven-Erik

2018-06-01

Data on renal hemodynamics, function, and oxygenation in early clinical septic shock are lacking. We therefore measured renal blood flow, glomerular filtration rate, renal oxygen consumption, and oxygenation in patients with early septic shock. Prospective comparative study. General and cardiothoracic ICUs. Patients with norepinephrine-dependent early septic shock (n = 8) were studied within 24 hours after arrival in the ICU and compared with postcardiac surgery patients without acute kidney injury (comparator group, n = 58). None. Data on systemic hemodynamics and renal variables were obtained during two 30-minute periods. Renal blood flow was measured by the infusion clearance of para-aminohippuric acid, corrected for renal extraction of para-aminohippuric acid. Renal filtration fraction was measured by renal extraction of chromium-51 labeled EDTA. Renal oxygenation was estimated from renal oxygen extraction. Renal oxygen delivery (-24%; p = 0.037) and the renal blood flow-to-cardiac index ratio (-21%; p = 0.018) were lower, renal vascular resistance was higher (26%; p = 0.027), whereas renal blood flow tended to be lower (-19%; p = 0.068) in the septic group. Glomerular filtration rate (-32%; p = 0.006) and renal sodium reabsorption (-29%; p = 0.014) were both lower in the septic group. Neither renal filtration fraction nor renal oxygen consumption differed significantly between groups. Renal oxygen extraction was significantly higher in the septic group (28%; p = 0.022). In the septic group, markers of tubular injury were elevated. In early clinical septic shock, renal function was lower, which was accompanied by renal vasoconstriction, a lower renal oxygen delivery, impaired renal oxygenation, and tubular sodium reabsorption at a high oxygen cost compared with controls.

High Endogenous Accumulation of ω-3 Polyunsaturated Fatty Acids Protect against Ischemia-Reperfusion Renal Injury through AMPK-Mediated Autophagy in Fat-1 Mice

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Do Hyeong Gwon

2017-09-01

Full Text Available Regulated autophagy is involved in the repair of renal ischemia-reperfusion injury (IRI. Fat-1 transgenic mice produce ω3-Polyunsaturated fatty acids (ω3-PUFAs from ω6-Polyunsaturated fatty acids (ω6-PUFAs without a dietary ω3-PUFAs supplement, leading to a high accumulation of omega-3 in various tissues. ω3-PUFAs show protective effects against various renal injuries and it has recently been reported that ω3-PUFAs regulate autophagy. We assessed whether ω3-PUFAs attenuated IR-induced acute kidney injury (AKI and evaluated its associated mechanisms. C57Bl/6 background fat-1 mice and wild-type mice (wt were divided into four groups: wt sham (n = 10, fat-1 sham (n = 10, wt IRI (reperfusion 35 min after clamping both the renal artery and vein; n = 15, and fat-1 IRI (n = 15. Kidneys and blood were harvested 24 h after IRI and renal histological and molecular data were collected. The kidneys of fat-1 mice showed better renal cell survival, renal function, and pathological damage than those of wt mice after IRI. In addition, fat-1 mice showed less oxidative stress and autophagy impairment; greater amounts of microtubule-associated protein 1A/1B-light chain 3 (LC3-II, Beclin-1, and Atg7; lower amounts of p62; and, higher levels of renal cathepsin D and ATP6E than wt kidneys. They also showed more adenosine monophosphate-activated protein kinase (AMPK activation, which resulted in the inhibition of phosphorylation of the mammalian target of rapamycin (mTOR. Collectively, ω3-PUFAs in fat-1 mice contributed to AMPK mediated autophagy activation, leading to a renoprotective response.

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.

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

Directory of Open Access Journals (Sweden)

Cheng-lu ZHANG

2011-12-01

Full Text Available Objective To investigate the levels of renal injury biomarkers in patients with chronic kidney disease(CKD and evaluate their clinical significances in diagnosis of CKD.Methods A total of 66 subjects(37 patients with CKD and 29 healthy individuals were involved in this study.Serum blood urea nitrogen(SBUN was determined by Glutamate dehydrogenase method;serum creatinine(SCr and urinary creatinine(UCr were detected by sarcosine oxidase method;serum uric acid(SUA was measured by uricase colorimetry;serum cystatin C(Cys C and urinary microalbumin(UmAlbwere analyzed by immunological transmission turbidimetry;urinary protein(U-PROwas measured by Coomassies Brilliant Blue(CBB assay.The UmAlb and U-PRO levels were expressed in units of mg/mmolUCr.Results The results of independent samples t test indicated that significant differences were found in SBUN,SCr,SUA,Cys C,UmAlb and U-PRO(P < 0.05 between patient group and healthy control group.The evaluation of diagnostic effects showed that the areas under the curve at ROC plot for SBUN,SCr,SUA,Cys C,UmAlb and U-PRO were 0.907,0.912,0.742,0.982,0.984 and 0.991,respectively.Conclusions U-PRO,UmAlb and Cys C are ideal biomarkers,SCr and SBUN come next,SUA is the weakest when the above biomarkers are applied to evaluate the renal injury and its severity of the patients with CKD.

PGE2 receptor EP3 inhibits water reabsorption and contributes to polyuria and kidney injury in a streptozotocin-induced mouse model of diabetes.

Science.gov (United States)

Hassouneh, Ramzi; Nasrallah, Rania; Zimpelmann, Joe; Gutsol, Alex; Eckert, David; Ghossein, Jamie; Burns, Kevin D; Hébert, Richard L

2016-06-01

The first clinical manifestation of diabetes is polyuria. The prostaglandin E2 (PGE2) receptor EP3 antagonises arginine vasopressin (AVP)-mediated water reabsorption and its expression is increased in the diabetic kidney. The purpose of this work was to study the contribution of EP3 to diabetic polyuria and renal injury. Male Ep 3 (-/-) (also known as Ptger3 (-/-)) mice were treated with streptozotocin (STZ) to generate a mouse model of diabetes and renal function was evaluated after 12 weeks. Isolated collecting ducts (CDs) were microperfused to study the contribution of EP3 to AVP-mediated fluid reabsorption. Ep 3 (-/-)-STZ mice exhibited attenuated polyuria and increased urine osmolality compared with wild-type STZ (WT-STZ) mice, suggesting enhanced water reabsorption. Compared with WT-STZ mice, Ep 3 (-/-)-STZ mice also had increased protein expression of aquaporin-1, aquaporin-2, and urea transporter A1, and reduced urinary AVP excretion, but increased medullary V2 receptors. In vitro microperfusion studies indicated that Ep 3 (-/-) and WT-STZ CDs responded to AVP stimulation similarly to those of wild-type mice, with a 60% increase in fluid reabsorption. In WT non-injected and WT-STZ mice, EP3 activation with sulprostone (PGE2 analogue) abrogated AVP-mediated water reabsorption; this effect was absent in mice lacking EP3. A major finding of this work is that Ep 3 (-/-)-STZ mice showed blunted renal cyclooxygenase-2 protein expression, reduced renal hypertrophy, reduced hyperfiltration and reduced albuminuria, as well as diminished tubular dilation and nuclear cysts. Taken together, the data suggest that EP3 contributes to diabetic polyuria by inhibiting expression of aquaporins and that it promotes renal injury during diabetes. EP3 may prove to be a promising target for more selective management of diabetic kidney disease.

Renal hemodynamics and oxygenation in transient renal artery occluded rats evaluated with iron-oxide particles and oxygenation-sensitive imaging

International Nuclear Information System (INIS)

Pedersen, Michael; Aarhus Univ.; Univ. Victor Segalen Bordeaux 2; Laustsen, Christoffer; Perot, Vincent; Grenier, Nicolas; Basseau, Fabrice; Moonen, Chrit

2010-01-01

Mild or severe renal arterial occlusion is a phenomenon occasionally observed in daily clinical practice, potentially leading to renal ischemia and a general impairment of renal function. Secondly, closing the blood flow to the kidneys can also occur during kidney transplantation procedures. However, the exact physiological effects of these conditions on renal blood perfusion as well as the renal oxygen handling are poorly understood. The objectives of this study were therefore to measure the lateral changes of renal blood perfusion in rats subjected to transient unilateral arterial occlusion (RAS), and in addition, to measure the consequences on the intrarenal oxygenation. Experimental studies were performed using sixteen adolescent rats. The left renal artery was exposed through a flank incision and acute RAS for 45 min was achieved by placing a ligature around the renal artery. MRI was performed 3 days after the surgical procedure, where a blood oxygenation sensitive sequence (BOLD MRI) was performed, followed by a perfusion-weighted imaging sequence using a single bolus of the iron-oxide nanoparticle Sinerem. The renal oxygenation of blood was indirectly measured by the BOLD-parameter R2 * , and perfusion measures include relative renal blood flow, relative renal blood volume and mean transit time. Histopathologic changes through the outer stripe of the outer medulla showing typical histopathologic findings of ischemia. This study demonstrated that rats with transient renal arterial stenosis (for 45 min) showed a reduction in intrarenal oxygenation and intrarenal blood flow three days after the surgical procedure. A decreased R2 * was measured within the ipsilateral medulla in parallel with a decreased medullary blood flow, is probably related to a lower reabsorption load within the ipsilateral kidney. MRI may therefore be a promising tool in long-term evaluation of RAS. (orig.)

Renal hemodynamics and oxygenation in transient renal artery occluded rats evaluated with iron-oxide particles and oxygenation-sensitive imaging

Energy Technology Data Exchange (ETDEWEB)

Pedersen, Michael [Aarhus Univ. Hospital (Denmark). MR Research Centre; Aarhus Univ. (Denmark). Inst. of Experimental Clinical Medicine; Univ. Victor Segalen Bordeaux 2 (France). Lab. Imagerie Moleculaire et Fonctionnelle: de la physiologie a la therapie CNRS UMR 5231; Laustsen, Christoffer [Aarhus Univ. Hospital (Denmark). MR Research Centre; Perot, Vincent; Grenier, Nicolas [Hopital Pellegrin, CHU Bordeaux (France). Service d' Imagerie Diagnostique et Therapeutique de l' Adulte; Basseau, Fabrice; Moonen, Chrit [Univ. Victor Segalen Bordeaux 2 (France). Lab. Imagerie Moleculaire et Fonctionnelle: de la physiologie a la therapie CNRS UMR 5231

2010-07-01

Mild or severe renal arterial occlusion is a phenomenon occasionally observed in daily clinical practice, potentially leading to renal ischemia and a general impairment of renal function. Secondly, closing the blood flow to the kidneys can also occur during kidney transplantation procedures. However, the exact physiological effects of these conditions on renal blood perfusion as well as the renal oxygen handling are poorly understood. The objectives of this study were therefore to measure the lateral changes of renal blood perfusion in rats subjected to transient unilateral arterial occlusion (RAS), and in addition, to measure the consequences on the intrarenal oxygenation. Experimental studies were performed using sixteen adolescent rats. The left renal artery was exposed through a flank incision and acute RAS for 45 min was achieved by placing a ligature around the renal artery. MRI was performed 3 days after the surgical procedure, where a blood oxygenation sensitive sequence (BOLD MRI) was performed, followed by a perfusion-weighted imaging sequence using a single bolus of the iron-oxide nanoparticle Sinerem. The renal oxygenation of blood was indirectly measured by the BOLD-parameter R2{sup *}, and perfusion measures include relative renal blood flow, relative renal blood volume and mean transit time. Histopathologic changes through the outer stripe of the outer medulla showing typical histopathologic findings of ischemia. This study demonstrated that rats with transient renal arterial stenosis (for 45 min) showed a reduction in intrarenal oxygenation and intrarenal blood flow three days after the surgical procedure. A decreased R2{sup *} was measured within the ipsilateral medulla in parallel with a decreased medullary blood flow, is probably related to a lower reabsorption load within the ipsilateral kidney. MRI may therefore be a promising tool in long-term evaluation of RAS. (orig.)

Traumatic renal infarction

International Nuclear Information System (INIS)

Yashiro, Naobumi; Ohtomo, Kuni; Kokubo, Takashi; Itai, Yuji; Iio, Masahiro

1986-01-01

Four cases of traumatic renal artery occlusion were described and illustrated. In two cases, direct blows to the abdomen compressed the renal artery against the vertebral column. Clinically, they were severely injured with macroscopic hematuria. Aortograms showed abrupt truncation of renal arteries. In the other two, rapid deceleration caused sudden displacement of the kidney producing an intimal tear with resultant thrombosis. Although they showed little injury without macrohematuria, aortograms revealed tapered occlusion of renal arteries. One of them developed hypertension. ''Rim sign'' of post-contrast CT and hypertension resulted from traumatic renal artery occlusion were reviewed. (author)

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

NARCIS (Netherlands)

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

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

Early outcome in renal transplantation from large donors to small and size-matched recipients - a porcine experimental model

DEFF Research Database (Denmark)

Ravlo, Kristian; Chhoden, Tashi; Søndergaard, Peter

2012-01-01

in small recipients within 60 min after reperfusion. Interestingly, this was associated with a significant reduction in medullary RPP, while there was no significant change in the size-matched recipients. No difference was observed in urinary NGAL excretion between the groups. A significant higher level......Kidney transplantation from a large donor to a small recipient, as in pediatric transplantation, is associated with an increased risk of thrombosis and DGF. We established a porcine model for renal transplantation from an adult donor to a small or size-matched recipient with a high risk of DGF...... and studied GFR, RPP using MRI, and markers of kidney injury within 10 h after transplantation. After induction of BD, kidneys were removed from ∼63-kg donors and kept in cold storage for ∼22 h until transplanted into small (∼15 kg, n = 8) or size-matched (n = 8) recipients. A reduction in GFR was observed...

Purinergic Signalling in Inflammatory Renal Disease

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Nishkantha eArulkumaran

2013-07-01

Full Text Available Extracellular purines have a role in renal physiology and adaption to inflammation. However, inflammatory renal disease may be mediated by extracellular purines, resulting in renal injury. The role of purinergic signalling is dependent on the concentrations of extracellular purines. Low basal levels of purines are important in normal homeostasis and growth. Concentrations of extracellular purines are significantly elevated during inflammation and mediate either an adaptive role or propagate local inflammation. Adenosine signalling mediates alterations in regional renal blood flow by regulation of the renal microcirculation, tubulo-glomerular feedback, and tubular transport of sodium and water. Increased extracellular ATP and renal P2 receptor-mediated inflammation are associated with various renal diseases, including hypertension, diabetic nephropathy, and glomerulonephritis. Experimental data suggests P2 receptor deficiency or receptor antagonism is associated with amelioration of antibody-mediated nephritis, suggesting a pathogenic (rather than adaptive role of purinergic signalling. We discuss the role of extracellular nucleotides in adaptation to ischaemic renal injury and in the pathogenesis of inflammatory renal disease.

Relationship between red cell distribution width and early renal injury in patients with gestational diabetes mellitus.

Science.gov (United States)

Cheng, Dong; Zhao, Jiangtao; Jian, Liguo; Ding, Tongbin; Liu, Shichao

2016-09-01

Previous studies found that red cell distribution width was related to adverse cardiovascular events. However, few studies reported the relationship between red cell distribution width and early-stage renal injury in pregnant women with gestational diabetes mellitus. Using a cross-sectional design, 334 pregnant women with gestational diabetes mellitus were enrolled according to the criterion of inclusion and exclusion. Demographic and clinical examination data were collected. Depended on the urine albumin, study population were divided into case group (n = 118) and control group (n = 216). Compared with control group, the case group tend to be higher red cell distribution width level (13.6 ± 0.9 vs.12.5 ± 0.6, p gestational diabetes mellitus patients. The elevated red cell distribution width level might be a predictor of early-stage renal injury in pregnant women with gestational diabetes mellitus. As an easy and routine examination index, red cell distribution width may provide better clinical guidance when combined with other important indices.

[The effect of portal blood stasis on lung and renal injury induced by hepatic ischemia reperfusion in a rabbit model].

Science.gov (United States)

Wang, Ye; Yang, Jia-mei; Hou, Yuan-kai; Li, Dian-qi; Hu, Ming-hua; Liu, Peng

2008-04-15

To investigate the effect and mechanism of portal blood stasis on lung and renal injury induced by hepatic ischemia reperfusion. A rabbit hepatic ischemia reperfusion injury model was established by hepatic portal occlusion and in situ hypothermic irrigation for 30 min. Twenty-four New Zealand white rabbits were employed and randomly divided into 3 groups equally by different dosage of portal blood stasis removal: group A5 (5 ml blood removal), group A10 (10 ml blood removal),and group B (no blood removal). Eight rabbits were served as controls with no hepatic portal occlusion and hypothermic irrigation. After reperfusion 4 h serum endotoxin content, tumor necrosis factor-alpha (TNF-alpha), urea nitrogen (BUN), and creatinine (Cr) were examined respectively, meantime lung and kidney tissues were sampled to determine the content of malondialdehyde (MDA), superoxide dismutase (SOD), the pathology, and wet to dry weight ratio, broncho-alveolar lavage fluid protein content in lung tissues. Removing portal blood stasis ameliorated lung and renal injury as shown by decreasing the level of serum endotoxin, TNF-alpha, BUN, Cr, wet to dry weight ratio, broncho-alveolar lavage fluid protein content, MDA, SOD. TNF-alpha, Cr, broncho-alveolar lavage fluid protein content in lung tissues and MDA in kidney tissue in group A5 were significantly reduced compared with those in group B (P portal blood stasis before the resume of splanchnic circulation may ameliorate the lung and renal injury induced by hepatic ischemia reperfusion. The possible mechanism may be that portal blood stasis removal reduces endotoxin absorption, and further decreases production of serum TNF-alpha.

Dapagliflozin Aggravates Renal Injury via Promoting Gluconeogenesis in db/db Mice.

Science.gov (United States)

Jia, Yingli; He, Jinzhao; Wang, Liang; Su, Limin; Lei, Lei; Huang, Wei; Geng, Xiaoqiang; Zhang, Shun; Meng, Xiaolu; Zhou, Hong; Yang, Baoxue

2018-01-01

A sodium-glucose co-transporter-2 inhibitor dapagliflozin is widely used for lowering blood glucose and its usage is limited in type 2 diabetes mellitus patients with moderate renal impairment. As its effect on kidney function is discrepant and complicated, the aim of this study is to determine the effect of dapagliflozin on the progression of diabetic nephropathy and related mechanisms. Twelve-week-old male C57BL/6 wild-type and db/db mice were treated with vehicle or 1 mg/kg dapagliflozin for 12 weeks. Body weight, blood glucose, insulin tolerance, glucose tolerance, pyruvate tolerance and 24-hour urine were measured every 4 weeks. At 24 weeks of age, renal function was evaluated by blood urea nitrogen level, creatinine clearance, urine output, urinary albumin excretion, Periodic Acid-Schiff staining, Masson's trichrome staining and electron microscopy. Changes in insulin signaling and gluconeogenic key regulatory enzymes were detected using Western blot analysis. Dapagliflozin did not alleviate but instead aggravated diabetic nephropathy manifesting as increased levels of microalbuminuria, blood urea nitrogen, and glomerular and tubular damage in db/db mice. Despite adequate glycemic control by dapagliflozin, urinary glucose excretion increased after administration before 24 weeks of age and was likely associated with renal impairment. Increased urinary glucose excretion was mainly derived from the disturbance of glucose homeostasis with elevated hepatic and renal gluconeogenesis induced by dapagliflozin. Although it had no effect on insulin sensitivity and glucose tolerance, dapagliflozin further induced the expression of gluconeogenic key rate-limiting enzymes through increasing the expression levels of FoxO1 in the kidney and liver. These experimental results indicate that dapagliflozin aggravates diabetes mellitus-induced kidney injury, mostly through increasing gluconeogenesis. © 2018 The Author(s). Published by S. Karger AG, Basel.

The effect of renal denervation on kidney oxygenation as determined by BOLD MRI in patients with hypertension

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Vink, E.E.; Boer, A.; Blankestijn, P.J. [University Medical Center Utrecht, Department of Nephrology, P.O. Box 85500, GA, Utrecht (Netherlands); Verloop, W.L.; Voskuil, M. [University Medical Center Utrecht, Department of Cardiology, Utrecht (Netherlands); Spiering, W.; Leiner, T. [University Medical Center Utrecht, Department of Vascular Medicine, Utrecht (Netherlands); Vonken, E.; Hoogduin, J.M. [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Bots, M.L. [University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Utrecht (Netherlands)

2015-07-15

Renal denervation (RDN) is a promising therapy for resistant hypertension. RDN is assumed to decrease sympathetic activity. Consequently, RDN can potentially increase renal oxygenation. Blood oxygen level-dependent MRI (BOLD-MRI) provides a non-invasive tool to determine renal oxygenation in humans. The aim of the current study was to investigate the effect of RDN on renal oxygenation as determined by BOLD-MRI. Patients with resistant hypertension or the inability to follow a stable drug regimen due to unacceptable side effects were included. BOLD-MRI was performed before and 12 months after RDN. Twenty-seven patients were imaged on 3 T and 19 on 1.5 T clinical MRI systems. Fifty-four patients were included, 46 patients (23 men, mean age 57 years) completed the study. Mean 24-h BP changed from 163(±20)/98(±14) mmHg to 154(±22)/92(±13) mmHg (p = 0.001 and p < 0.001). eGFR did not change after RDN [77(±18) vs. 79(±20) mL/min/1.73 m{sup 2}; p = 0.13]. RDN did not affect renal oxygenation [1.5 T: cortical R2*: 12.5(±0.9) vs. 12.5(±0.9), p = 0.94; medullary R2*: 19.6(±1.7) vs. 19.3(1.4), p = 0.40; 3 T: cortical R2*: 18.1(±0.8) vs. 17.8(±1.2), p = 0.47; medullary R2*: 27.4(±1.9) vs. 26.7(±1.8), p = 0.19]. The current study shows that RDN does not lead to changes in renal oxygenation 1 year after RDN as determined by BOLD-MRI. (orig.)

Two-dimensional Fourier analysis of the spongy medullary keratin of structurally coloured feather barbs

Science.gov (United States)

Prum, R. O.; Torres, R.; Williamson, S.; Dyck, J.

1999-01-01

We conducted two-dimensional (2D) discrete Fourier analyses of the spatial variation in refractive index of the spongy medullary keratin from four different colours of structurally coloured feather barbs from three species of bird: the rose-faced lovebird, Agapornis roseicollis (Psittacidae), the budgerigar, Melopsittacus undulatus (Psittacidae), and the Gouldian finch, Poephila guttata (Estrildidae). These results indicate that the spongy medullary keratin is a nanostructured tissue that functions as an array of coherent scatterers. The nanostructure of the medullary keratin is nearly uniform in all directions. The largest Fourier components of spatial variation in refractive index in the tissue are of the appropriate size to produce the observed colours by constructive interference alone. The peaks of the predicted reflectance spectra calculated from the 2D Fourier power spectra are congruent with the reflectance spectra measured by using microspectrophotometry. The alternative physical models for the production of these colours, the Rayleigh and Mie theories, hypothesize that medullary keratin is an incoherent array and that scattered waves are independent in phase. This assumption is falsified by the ring-like Fourier power spectra of these feathers, and the spacing of the scattering air vacuoles in the medullary keratin. Structural colours of avian feather barbs are produced by constructive interference of coherently scattered light waves from the optically heterogeneous matrix of keratin and air in the spongy medullary layer.

Dynamic magnetic resonance imaging in the assessment of chronic medical nephropathies with impaired renal function

International Nuclear Information System (INIS)

Dalla-Palma, L.; Pozzi-Mucelli, R.S.; Cova, M.; Meduri, S.; Panzetta, G.; Galli, G.

2000-01-01

We examined the value of dynamic magnetic resonance imaging (MRI) in chronic renal disease with renal insufficiency. In 33 consecutive patients (21 vascular nephropathy, 12 glomerular nephropathy) MRI was performed using a 1.5-T unit and a body coil, with SE T1-weighted (TR/TE = 600/19 ms) and dynamic TFFE T1-weighted sequences (TR/TE = 12/5 ms, flip angle = 25 ) after manual bolus injection (via a cubital vein) of 0.1 mmol/kg Gd-DTPA-BMA. Morphological evaluation was performed in unblinded fashion by three radiologists, evaluating renal size, cortical thickness, and corticomedullary differentiation. Functional analysis was performed by one reviewer. Time-signal intensity curves, peak intensity value (P), time to peak intensity (T), and the P/T ratio were obtained at the cortex, medulla, and pyelocaliceal system of each kidney. The relationship of these parameters to serum creatinine and with creatinine clearance was investigated. A good correlation between morphological features of the kidneys and serum creatinine values was found. Morphological findings could not distinguish between vascular and glomerular nephropathies. A statistically significant correlation (P <0.01) between cortical P, cortical P/T, medullary P, and serum creatinine and creatinine clearance was found. A significant correlation (P <0.01) was also found between cortical T, medullary P/T, T of the excretory system, and creatinine clearance. The cortical T value was significantly higher (P <0.01) in vascular nephropathy than in glomerular nephropathy. Thus in patients with chronic renal failure dynamic MRI shows both morphological and functional changes. Morphological changes are correlated with the degree of renal insufficiency and not with the type of nephropathy; the functional changes seem to differ in vascular from glomerular nephropathies. (orig.)

Novel genes in renal aging

OpenAIRE

Noordmans, Gerda Anke

2015-01-01

Renal aging is characterized by structural changes and functional decline. These changes make the elderly more vulnerable to chronic kidney disease, hypertension, and cardiovascular disease. Furthermore, they also make it more difficult to cope with stress factors, such as dehydration, toxicity, and obstruction. These stress factors can lead to acute kidney injury and reduced recovery from acute kidney injury and may result in chronic kidney disease or even end-stage renal disease. The rate o...

A Nitric Oxide-Donor Furoxan Moiety Improves the Efficacy of Edaravone against Early Renal Dysfunction and Injury Evoked by Ischemia/Reperfusion

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Fausto Chiazza

2015-01-01

Full Text Available Edaravone (5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one, EDV is a free-radical scavenger reduces organ ischemic injury. Here we investigated whether the protective effects of EDV in renal ischemia/reperfusion (I/R injury may be enhanced by an EDV derivative bearing a nitric oxide- (NO- donor furoxan moiety (NO-EDV. Male Wistar rats were subjected to renal ischemia (45 minutes, followed by reperfusion (6 hours. Administration of either EDV (1.2–6–30 µmol/kg, i.v. or NO-EDV (0.3–1.2–6 µmol/kg, i.v. dose-dependently attenuated markers of renal dysfunction (serum urea and creatinine, creatinine clearance, urine flow, urinary N-acetyl-β-D-glucosaminidase, and neutrophil gelatinase-associated lipocalin/lipocalin-2. NO-EDV exerted protective effects in the dose-range 1.2–6 µmol/kg, while a higher dose (30 µmol/kg was needed to obtain protection by EDV. Both EDV and NO-EDV modulated tissue markers of oxidative stress and lipid peroxidation. NO-EDV, but not EDV, activated endothelial NO synthase (NOS and blunted I/R-induced upregulation of inducible NOS, secondary to modulation of Akt and NF-κB activation, respectively. Besides NO-EDV administration inhibited I/R-induced IL-1β, IL-18, IL-6, and TNF-α overproduction. Overall, these findings demonstrate that the NO-donor moiety contributes to the protection against early renal I/R injury and suggest that NO-donor EDV codrugs are worthy of additional study as innovative pharmacological tools.

Renal venous thrombosis in an infant with predisposing thrombotic factors: color Doppler ultrasound and MR evaluation

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Argyropoulou, Maria I.; Papadopoulou, Frederica; Nikolopoulos, Pangiotis [Department of Radiology, Medical School, University of Ioannina, 45110, Ioannina (Greece); Giapros, Vassilios I.; Drougia, Aikaterini A.; Andronikou, Styliani [Neonatology Clinic, Medical School, University of Ioannina, 45110, Ioannina (Greece); Vartholomatos, Georgios A. [Department of Haematology, Medical School, University of Ioannina, 45110, Ioannina (Greece)

2003-08-01

We report a case of a neonate with hereditary thrombophilia presenting with renal venous thrombosis (RVT). Early color Doppler findings of RVT were lacking venous flow, and the arterial diastolic flow was reversed. This very high-resistance arterial flow is for the first time described in neonatal RVT. Magnetic resonance imaging showed low signal intensity of the renal pyramids on T1- and T2-weighted images, suggesting acute hemorrhage. After intravenous contrast injection, persistent cortical enhancement was observed along with lack of medullary enhancement. Despite the progressive reestablishment of some venous drainage, the kidney showed atrophy and loss of function. (orig.)

Renal venous thrombosis in an infant with predisposing thrombotic factors: color Doppler ultrasound and MR evaluation

International Nuclear Information System (INIS)

Argyropoulou, Maria I.; Papadopoulou, Frederica; Nikolopoulos, Pangiotis; Giapros, Vassilios I.; Drougia, Aikaterini A.; Andronikou, Styliani; Vartholomatos, Georgios A.

2003-01-01

We report a case of a neonate with hereditary thrombophilia presenting with renal venous thrombosis (RVT). Early color Doppler findings of RVT were lacking venous flow, and the arterial diastolic flow was reversed. This very high-resistance arterial flow is for the first time described in neonatal RVT. Magnetic resonance imaging showed low signal intensity of the renal pyramids on T1- and T2-weighted images, suggesting acute hemorrhage. After intravenous contrast injection, persistent cortical enhancement was observed along with lack of medullary enhancement. Despite the progressive reestablishment of some venous drainage, the kidney showed atrophy and loss of function. (orig.)

CD147/basigin reflects renal dysfunction in patients with acute kidney injury.

Science.gov (United States)

Nagaya, Hiroshi; Kosugi, Tomoki; Maeda-Hori, Mayuko; Maeda, Kayaho; Sato, Yuka; Kojima, Hiroshi; Hayashi, Hiroki; Kato, Noritoshi; Ishimoto, Takuji; Sato, Waichi; Yuzawa, Yukio; Matsuo, Seiichi; Kadomatsu, Kenji; Maruyama, Shoichi

2014-10-01

Acute tubular necrosis (ATN) describes a form of intrinsic acute kidney injury (AKI) that results from persistent hypoperfusion and subsequent activation of the immune system. A glycosylated transmembrane protein, CD147/basigin, is involved in the pathogenesis of renal ischemia and fibrosis. The present study investigated whether CD147 can reflect pathological features and renal dysfunction in patients with AKI. Plasma and spot urine samples were collected from 24 patients (12 controls and 12 with ATN) who underwent renal biopsy between 2008 and 2012. In another study, patients undergoing open surgery to treat abdominal aortic aneurysms (AAAs) were enrolled in 2004. We collected urine and plasma samples from seven patients with AKI and 33 patients without AKI, respectively. In these experiments, plasma and urinary CD147, and urinary L-fatty acid-binding protein (L-FABP) levels were measured, and the former expression in kidneys was examined by immunostaining. In biopsy tissues of ATN with severe histological features, CD147 induction was strikingly present in inflammatory cells such as macrophages and lymphocytes in the injured interstitium, but not in damaged tubules representing atrophy. Both plasma and urinary CD147 levels were strikingly increased in ATN patients; both values showed greater correlations with renal dysfunction compared to urinary L-FABP. In patients who had undergone open AAA surgery, urinary and plasma CD147 values in AKI patients were significantly higher than in non-AKI patients at post-operative day 1, similar to the profile of urinary L-FABP. CD147 was prominent in its ability to detect AKI and may allow the start of preemptive medication.

Renal cortical and medullary blood flow responses to altered NO-availability in humans

DEFF Research Database (Denmark)

Damkjaer, Mads; Vafaee, Manoucher; Møller, Michael Lehd

2010-01-01

The objective was to quantify regional renal blood flow in humans. In nine young volunteers on a controlled diet, the lower abdomen was CT-scanned and regional renal blood flow determined by positron emission tomography (PET) scanning using H(2)(15)O as tracer. Measurements were performed...... of one voxel were eliminated stepwise from the external surface of the VOI ('voxel peeling'), and the blood flow subsequently determined in each new, reduced VOI. Blood flow in the shrinking volumes of interest (VOIs) decreased as the number of cycles of voxel peeling increased. After 4-5 cycles, blood...... flow was not reduced further by additional voxel peeling. This volume-insensitive flow was measured to be 2.30 ±0.17 ml·(g·min)(-1) during the control period; it increased during infusion of glyceryl nitrate to 2.97 ±0.18 ml·(g·min)(-1) (p...

Retrospective Review of Pediatric Blunt Renal Trauma: A Single Institution's Five Year Experience.

Science.gov (United States)

Richards, Carly R; Clark, Margaret E; Sutherland, Ronald S; Woo, Russell K

2017-05-01

Children are at higher risk of renal injury from blunt trauma than adults due to a variety of anatomic factors such as decreased perirenal fat, weaker abdominal muscles, and a less ossified thoracic cage. Non-operative management is gaining in popularity for even major injuries, although there are no universally accepted guidelines. We present a retrospective review of pediatric major blunt renal injuries (grade 3 or higher) at a children's hospital in Hawai'i over a 5-year period. Medical records were examined between January 2009 and September 2014 from Kapi'olani Medical Center for Women and Children in Honolulu, Hawai'i. Inclusion criteria were a diagnosis of renal trauma, or the diagnosis of blunt abdominal trauma with hematuria. Exclusion criteria were grade I or II renal injury or death due to an additional traumatic injury. Mechanism of injury, clinical characteristics on admission, blood product requirements, surgical interventions performed, and hospital length of stay were retrospectively analyzed. Eleven total patient records were examined, nine of which fit inclusion criteria. Uniquely, 33% of patients sustained their renal injury while surfing. No patients required laparotomy or nephrectomy, though 22% of patients received a blood transfusion and 44% of patients underwent ureteral stent placement. Non-operative management of major renal injuries in children is feasible and allows for preservation of renal tissue. A novel mechanism of surfing as a cause of major renal trauma is seen in the state of Hawai'i.

Retrospective Review of Pediatric Blunt Renal Trauma: A Single Institution's Five Year Experience

Science.gov (United States)

Clark, Margaret E; Sutherland, Ronald S; Woo, Russell K

2017-01-01

Children are at higher risk of renal injury from blunt trauma than adults due to a variety of anatomic factors such as decreased perirenal fat, weaker abdominal muscles, and a less ossified thoracic cage. Non-operative management is gaining in popularity for even major injuries, although there are no universally accepted guidelines. We present a retrospective review of pediatric major blunt renal injuries (grade 3 or higher) at a children's hospital in Hawai‘i over a 5-year period. Medical records were examined between January 2009 and September 2014 from Kapi‘olani Medical Center for Women and Children in Honolulu, Hawai‘i. Inclusion criteria were a diagnosis of renal trauma, or the diagnosis of blunt abdominal trauma with hematuria. Exclusion criteria were grade I or II renal injury or death due to an additional traumatic injury. Mechanism of injury, clinical characteristics on admission, blood product requirements, surgical interventions performed, and hospital length of stay were retrospectively analyzed. Eleven total patient records were examined, nine of which fit inclusion criteria. Uniquely, 33% of patients sustained their renal injury while surfing. No patients required laparotomy or nephrectomy, though 22% of patients received a blood transfusion and 44% of patients underwent ureteral stent placement. Non-operative management of major renal injuries in children is feasible and allows for preservation of renal tissue. A novel mechanism of surfing as a cause of major renal trauma is seen in the state of Hawai‘i. PMID:28484665

Intra-Abdominal Cooling System Limits Ischemia-Reperfusion Injury During Robot-Assisted Renal Transplantation.

Science.gov (United States)

Meier, R P H; Piller, V; Hagen, M E; Joliat, C; Buchs, J-B; Nastasi, A; Ruttimann, R; Buchs, N C; Moll, S; Vallée, J-P; Lazeyras, F; Morel, P; Bühler, L

2018-01-01

Robot-assisted kidney transplantation is feasible; however, concerns have been raised about possible increases in warm ischemia times. We describe a novel intra-abdominal cooling system to continuously cool the kidney during the procedure. Porcine kidneys were procured by standard open technique. Groups were as follows: Robotic renal transplantation with (n = 11) and without (n = 6) continuous intra-abdominal cooling and conventional open technique with intermittent 4°C saline cooling (n = 6). Renal cortex temperature, magnetic resonance imaging, and histology were analyzed. Robotic renal transplantation required a longer anastomosis time, either with or without the cooling system, compared to the open approach (70.4 ± 17.7 min and 74.0 ± 21.5 min vs. 48.7 ± 11.2 min, p-values system compared to the open approach group (6.5 ± 3.1°C vs. 22.5 ± 6.5°C; p = 0.001) or compared to the robotic group without the cooling system (28.7 ± 3.3°C; p system that suppresses the noncontrolled rewarming of donor kidneys during the transplant procedure and prevents ischemia-reperfusion injuries. © 2017 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of American Society of Transplant Surgeons.

The diagnostic value of both troponin T and creatinine kinase isoenzyme (CK-MB in detecting combined renal and myocardial injuries in asphyxiated infants.

Directory of Open Access Journals (Sweden)

Wilson E Sadoh

Full Text Available Troponin T (cTnT and Creatinine Kinase Isoenzyme (CK-MB are both markers of myocardial injuries. However, CK-MB is also elevated in acute kidney injury.The diagnostic value of both cTnT and cardiac CK-MB in combined myocardial and acute kidney injuries (AKI in asphyxiated neonates was evaluated.40 asphyxiated infants and 40 non-asphyxiated controls were consecutively recruited. Serum levels of cTnT, CK-MB and creatinine were measured. Myocardial injury and AKI were defined as cTnT >95th percentile of the control and serum creatinine >1.0 mg/dl respectively.Of the 40 subjects, 9 (22.50%, 8 (20.00% and 4 (10.00% had myocardial injury, AKI and combined AKI and myocardial injuries respectively. The mean cTnT and CK-MB values were highest in infants with combined AKI and myocardial injuries. The Mean cTnT in infants with AKI, myocardial injury and combined AKI and myocardial injuries were 0.010±0.0007 ng/ml, 0.067±0.040 ng/ml and 0.084±0.067 ng/ml respectively, p = 0.006. The mean CK-MB in infants with AKI, myocardial injury and combined AKI and myocardial injuries were 2.78±0.22 ng/ml, 1.28±0.11 ng/ml and 4.58±0.52 ng/ml respectively, p = <0.0001.In severe perinatal asphyxia, renal and myocardial injuries could co-exist. Elevated cTnT signifies the presence of myocardial injury. Elevated CK-MB indicates either myocardial injury, AKI or both. Therefore renal injury should be excluded in asphyxiated infants with elevated CK-MB.

Neurobrucellosis presenting as an intra-medullary spinal cord abscess

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Patil Chidanand S

2005-09-01

Full Text Available Abstract Background Of the diverse presentation of neurobrucellosis, intra-medullary spinal cord abscess is extremely rare. Only four other cases have been reported so far. We present a case of spinal cord intra-medullary abscess due to Brucella melitensis. Case presentation A forty-year-old female presented with progressive weakness of both lower limb with urinary incontinence of 6 months duration. She was febrile. Neurological examination revealed flaccid areflexic paraplegia with T10 below sensory impairment including perianal region. An intramedullary mass was diagnosed on Magnetic Resonance Image (MRI scan extending from T12 to L2. At surgery, a large abscess was encountered at the conus medullaris, from which Brucella melitensis was grown on culture. She was started on streptomycin and doxycycline for 1 month, followed by rifampicin and doxycycline for 1 month. At 2-year follow-up, she had recovered only partially and continued to have impaired bladder function. Conclusion Neurobrucellosis, if not treated early, can result in severe neurological morbidity and sequale, which may be irreversible. Hence it is important to consider the possibility of neurobrucellosis in endemic region and treat aggressively.

Resveratrol plays important role in protective mechanisms in renal disease - mini-review

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Guilherme Albertoni

2015-03-01

Full Text Available Resveratrol (RESV is a polyphenolic compound found in various plants, including grapes, berries and peanuts, and its processed foods as red wine. RESV possesses a variety of bioactivities, including antioxidant, anti-inflammatory, cardioprotective, antidiabetic, anticancer, chemopreventive, neuroprotective, renal lipotoxicity preventative, and renal protective effects. Numerous studies have demonstrated that polyphenols promote cardiovascular health. Furthermore, RESV can ameliorate several types of renal injury in animal models, including diabetic nephropathy, hyperuricemic, drug-induced injury, aldosterone-induced injury, ischemia-reperfusion injury, sepsis-related injury, and endothelial dysfunction. In addition, RESV can prevent the increase in vasoconstrictors, such as angiotensin II (AII and endothelin-1 (ET-1, as well as intracellular calcium, in mesangial cells. Together, these findings suggest a potential role for RESV as a supplemental therapy for the prevention of renal injury.

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

Science.gov (United States)

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

2012-02-01

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

Somatostatin Receptor Scintigraphy in Medullary Thyroid Cancer

NARCIS (Netherlands)

van der Horst-Schrivers, Anouk N. A.; Brouwers, Adrienne; Links, Thera; Hubalewska‐Dydejczyk, Alicja; Signore, Alberto; de Jong, Marion; Dierckx, Rudi A.; Buscombe, John; Van de Wiele, Christophe

2015-01-01

Medullary thyroid cancer (MTC) is a neuroendocrine tumor originating from the calcitonin‐secreting C cells. Surgery, consisting of a total thyroidectomy and an extensive lymph node dissection, is the only effective treatment in MTC; however, metastases are frequently found in the regional cervical

A 9 years boy with MEN-2B variant of medullary thyroid carcinoma.

Science.gov (United States)

Sattar, M A; Hadi, H I; Ekramuddoula, F M; Hasanuzzaman, S M

2013-04-01

To highlight a rare disease like multiple endocrine neoplasia (MEN)-2B variant of medullary thyroid carcinoma and to optimize the management option in such cases, we present a nine year old boy with thyroid swelling, cervical lymphadenopathy and thick lips. His calcitonin level was raised. Investigation's results of the boy were as following fine needle aspiration cytology (FNAC) was medullary carcinoma of thyroid, preoperative calcitonin was >2000pg/ml, post operative histopathological report was medullary carcinoma. Total thyroidectomy with aggressive initial neck surgery may reduce the recurrence and increase better prognosis and survival rate. Calcitonin is used as diagnostic and follow-up marker.

Mannan-Binding Lectin Is Involved in the Protection against Renal Ischemia/Reperfusion Injury by Dietary Restriction.

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Shushimita Shushimita

Full Text Available Preoperative fasting and dietary restriction offer robust protection against renal ischemia/reperfusion injury (I/RI in mice. We recently showed that Mannan-binding lectin (MBL, the initiator of the lectin pathway of complement activation, plays a pivotal role in renal I/RI. Based on these findings, we investigated the effect of short-term DR (30% reduction of total food intake or three days of water only fasting on MBL in 10-12 weeks old male C57/Bl6 mice. Both dietary regimens significantly reduce the circulating levels of MBL as well as its mRNA expression in liver, the sole production site of MBL. Reconstitution of MBL abolished the protection afforded by dietary restriction, whereas in the fasting group the protection persisted. These data show that modulation of MBL is involved in the protection against renal I/RI induced by dietary restriction, and suggest that the mechanisms of protection induced by dietary restriction and fasting may be different.

Radionuclide bone scanning of medullary chondrosarcoma

International Nuclear Information System (INIS)

Hudson, T.M.; Chew, F.S.; Manaster, B.J.

1982-01-01

Technetium-99m methylene diphosphonate bone scans of 18 medullary chondrosarcomas of bone were correlated with pathologic macrosections of the resected tumors. There was increased scan intake by all 18 tumors, and the uptake in 15 scans corresponded accurately to the anatomic extent of the tumors. Only three scans displayed increased uptake beyond the true tumor margins; thus, the ''extended pattern of uptake'' beyond the true tumor extent is much less common in medullary chondrosarcomas than in many other primary bone tumors. Therefore, increased uptake beyond the apparent radiographic margin of the tumor suggests possible occult tumor spread. Pathologically, there was intense reactive new bone formation and hyperemia around the periphery of all 18 tumors, and there were foci of enchondral ossification, hyperemia, or calcification within the tumor itself in nearly every tumor. Three scans displayed less uptake in the center of the tumors than around their peripheries. One of these tumors was necrotic in the center, but the other two were pathologically no different from tumors that displayed homogenous uptake on the scan

Radionuclide bone scanning of medullary chondrosarcoma

International Nuclear Information System (INIS)

Hudson, T.M.; Chew, F.S.; Manaster, B.J.

1982-01-01

/sup 99m/Tc methylene diphosphonate bone scans of 18 medullary chondrosarcomas of bone were correlated with pathologic macrosections of the resected tumors. There was increased scan uptake by all 18 tumors, and the uptake in 15 scans corresponded accurately to the anatomic extent of the tumors. Only three scans displayed increased uptake beyond the true tumor margins; thus, the extended pattern of uptake beyond the true tumor extent is much less common in medullary chondrosarcomas than in many other primary bone tumors. Therefore, increased uptake beyond the apparent radiographic margin of the tumor suggests possible occult tumor spread. Pathologically, there was intense reactive new bone formation and hyperemia around the periphery of all 18 tumors, and there were foci of enchondral ossification, hyperemia, or calcification within the tumor itself in nearly every tumor. Three scans displayed less uptake in the center of the tumors than around their peripheries. One of these tumors was necrotic in the center, but the other two were pathologically no different from tumors that displayed homogeneous uptake on the scan

Schwannosis induced medullary compression in VACTERL syndrome.

LENUS (Irish Health Repository)

Treacy, A

2011-10-21

A 7-year-old boy with a history of VACTERL syndrome was found collapsed in bed. MRI had shown basilar invagination of the skull base and narrowing of the foramen magnum. Angulation, swelling and abnormal high signal at the cervicomedullary junction were felt to be secondary to compression of the medulla. Neuropathologic examination showed bilateral replacement of the medullary tegmentum by an irregularly circumscribed cellular lesion which was composed of elongated GFAP\\/S 100-positive cells with spindled nuclei and minimal atypia. The pathologic findings were interpreted as intramedullary schwannosis with mass effect. Schwannosis, is observed in traumatized spinal cords where its presence may represent attempted, albeit aberrant, repair by inwardly migrating Schwann cells ofperipheral origin. In our view the compressive effect of the basilar invagination on this boy\\'s medulla was of sufficient magnitude to have caused tumoral medullary schwannosis with resultant intermittent respiratory compromise leading to reflex anoxic seizures.

Crosstalk between Complement and Toll-like Receptor Activation in Relation to Donor Brain Death and Renal Ischemia-Reperfusion Injury

NARCIS (Netherlands)

Damman, Jeffrey; Daha, Mohamed R.; van Son, Willem J.; Leuvenink, Henri G.; Ploeg, Rutger J.; Seelen, Marc A.

Two central pathways of innate immunity, complement and Toll-like receptors (TLRs), play an important role in the pathogenesis of renal injury inherent to kidney transplantation. Recent findings indicate close crosstalk between complement and TLR signaling pathways. It is suggested that mitogen

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

Science.gov (United States)

2014-01-01

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

Is thyroidectomy necessary in RET mutations carriers of the familial medullary thyroid carcinoma syndrome?

DEFF Research Database (Denmark)

Hansen, H S; Torring, H; Godballe, C

2000-01-01

BACKGROUND: The results and consequences of genetic testing in a family with familial medullary thyroid carcinoma (FMTC) are described. METHODS: In the screening of relatives, serum calcitonin is replaced by RET mutation analysis that was performed in families suspected of hereditary medullary th...

Extracellular vesicles from human-induced pluripotent stem cell-derived mesenchymal stromal cells (hiPSC-MSCs) protect against renal ischemia/reperfusion injury via delivering specificity protein (SP1) and transcriptional activating of sphingosine kinase 1 and inhibiting necroptosis.

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Yuan, Xiaodong; Li, Dawei; Chen, Xiaosong; Han, Conghui; Xu, Longmei; Huang, Tao; Dong, Zhen; Zhang, Ming

2017-12-11

Renal ischemia-reperfusion is a main cause of acute kidney injury (AKI), which is associated with high mortality. Here we show that extracellular vesicles (EVs) secreted from hiPSC-MSCs play a critical role in protection against renal I/R injury. hiPSC-MSCs-EVs can fuse with renal cells and deliver SP1 into target cells, subsequently active SK1 expression and increase S1P formation. Chromatin immunoprecipitation (ChIP) analyses and luciferase assay were used to confirm SP1 binds directly to the SK1 promoter region and promote promoter activity. Moreover, SP1 inhibition (MIT) or SK1 inhibition (SKI-II) completely abolished the renal protective effect of hiPSC-MSCs-EVs in rat I/R injury mode. However, pre-treatment of necroptosis inhibitor Nec-1 showed no difference with the administration of hiPSC-MSCs-EVs only. We then generated an SP1 knockout hiPSC-MSC cell line by CRISPR/Cas9 system and found that SP1 knockout failed to show the protective effect of hiPSC-MSCs-EVs unless restoring the level of SP1 by Ad-SP1 in vitro and in vivo. In conclusion, this study describes an anti-necroptosis effect of hiPSC-MSCs-EVs against renal I/R injury via delivering SP1 into target renal cells and intracellular activating the expression of SK1 and the generation of S1P. These findings suggest a novel mechanism for renal protection against I/R injury, and indicate a potential therapeutic approach for a variety of renal diseases and renal transplantation.

Differential regulation of renal cyclooxygenase mRNA by dietary salt intake

DEFF Research Database (Denmark)

Jensen, B L; Kurtz, A

1997-01-01

RNA correlated directly with salt intake. We conclude that dietary salt intake influences renal cyclooxygenase mRNAs zone-specifically with opposite responses between cortex and medulla. Cortical COX II-mediated prostaglandin formation is probably important in low salt states whereas medullary COX I......Experiments were done to investigate the influence of dietary salt intake on renal cyclooxygenase (COX) I and II mRNA levels. To this end rats were fed either a low NaCl diet (LS; 0.02% NaCl wt/wt) or a high NaCl diet (HS diet; 4% NaCl wt/wt) for 5, 10 and 20 days. After 10 days Na excretion...... differed 760-fold, plasma renin activity and renin mRNA were increased eight- and threefold in LS compared to HS animals. Total renal COX I mRNA decreased 50% following the LS diet and did not change after the HS diet. Conversely, COX II mRNA declined after HS intake and transiently increased after salt...

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

DEFF Research Database (Denmark)

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

2011-01-01

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

Investigations on renal organic and inorganic solutes, in vivo

International Nuclear Information System (INIS)

Wolff, S.D.

1989-01-01

A basic question in renal physiology is how do the cells of the renal medulla survive the high concentrations of sodium chloride and urea which occur with antidiuresis. The problem is two-fold: (1) urea, being highly permeable to cell membranes, should enter the cell and adversely affect protein function; and (2) inorganic ions, being in much higher concentration extracellularly than intracellularly should dehydrate the cell. If these organic solutes exist in response to high concentrations of sodium chloride and urea, then their content should vary with diuretic state. Two protocols were developed to test the validity of this hypothesis. The first protocol used 31 P-NMR in vivo to monitor GPC content before, during, and after acute diuresis in an exteriorized rabbit kidney model. Changes in sodium distribution and tissue structure were monitored dynamically with 23 Na- and 1 H-NMR imaging, respectively. The second protocol used HPLC to quantitate each of the four organic solutes in renal inner medullary homogenates. Here, the effect of diuretic state and acute diuresis on organic solute content was assessed

Nlrp3 prevents early renal interstitial edema and vascular permeability in unilateral ureteral obstruction.

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Wilco P Pulskens

Full Text Available Progressive renal disease is characterized by tubulo-interstitial injury with ongoing inflammation and fibrosis. The Nlrp3 inflammasome contributes to these pathophysiological processes through its canonical effects in cytokine maturation. Nlrp3 may additionally exert inflammasome-independent effects following tissue injury. Hence, in this study we investigated potential non-canonical effects of Nlrp3 following progressive renal injury by subjecting WT and Nlrp3-deficient (-/- mice to unilateral ureter obstruction (UUO. Our results revealed a progressive increase of renal Nlrp3 mRNA in WT mice following UUO. The absence of Nlrp3 resulted in enhanced tubular injury and dilatation and an elevated expression of injury biomarker NGAL after UUO. Moreover, interstitial edema was significantly elevated in Nlrp3-/- mice. This could be explained by increased intratubular pressure and an enhanced tubular and vascular permeability. In accordance, renal vascular leakage was elevated in Nlrp3-/- mice that associated with reduced mRNA expression of intercellular junction components. The decreased epithelial barrier function in Nlrp3-/- mice was not associated with increased apoptosis and/or proliferation of renal epithelial cells. Nlrp3 deficiency did not affect renal fibrosis or inflammation. Together, our data reveal a novel non-canonical effect of Nlrp3 in preserving renal integrity and protection against early tubular injury and interstitial edema following progressive renal injury.

Complement C5a-C5aR interaction enhances MAPK signaling pathway activities to mediate renal injury in trichloroethylene sensitized BALB/c mice.

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Zhang, Jia-xiang; Zha, Wan-sheng; Ye, Liang-ping; Wang, Feng; Wang, Hui; Shen, Tong; Wu, Chang-hao; Zhu, Qi-xing

2016-02-01

We have previously shown complement activation as a possible mechanism for trichloroethylene (TCE) sensitization, leading to multi-organ damage including the kidneys. In particular, excessive deposition of C5 and C5b-9-the membrane attack complex, which can generate significant tissue damage, was observed in the kidney tissue after TCE sensitization. The present study tested the hypothesis that anaphylatoxin C5a binding to its receptor C5aR mediates renal injury in TCE-sensitized BALB/c mice. BALB/c mice were sensitized through skin challenge with TCE, with or without pretreatment by the C5aR antagonist W54011. Kidney histopathology and the renal functional test were performed to assess renal injury, and immunohistochemistry and fluorescent labeling were carried out to assess C5a and C5aR expressions. TCE sensitization up-regulated C5a and C5aR expressions in kidney tissue, generated inflammatory infiltration, renal tubule damage, glomerular hypercellularity and impaired renal function. Antagonist pretreatment blocked C5a binding to C5aR and attenuated TCE-induced tissue damage and renal dysfunction. TCE sensitization also caused the deposition of major pro-inflammatory cytokines IL-2, TNF-α and IFN-γ in the kidney tissue (P < 0.05); this was accompanied by increased expression of P-p38, P-ERK and P-JNK proteins (P < 0.05). Pretreatment with the C5aR antagonist attenuated the increase of expression of P-p38, P-ERK and P-JNK proteins (P < 0.05) and also consistently reduced the TCE sensitization-induced increase of IL-2, TNF-α and IFN-γ (P < 0.05). These data identify C5a binding to C5aR, MAP kinase activation, and inflammatory cytokine release as a novel mechanism for complement-mediated renal injury by sensitization with TCE or other environmental chemicals. Copyright © 2015 John Wiley & Sons, Ltd.

Successful intraosseous infusion in the critically ill patient does not require a medullary cavity.

LENUS (Irish Health Repository)

McCarthy, Gerard

2012-02-03

OBJECTIVES: To demonstrate that successful intraosseous infusion in critically ill patients does not require bone that contains a medullary cavity. DESIGN: Infusion of methyl green dye via standard intraosseous needles into bones without medullary cavity-in this case calcaneus and radial styloid-in cadaveric specimens. SETTING: University department of anatomy. PARTICIPANTS: Two adult cadaveric specimens. MAIN OUTCOME MEASURES: Observation of methyl green dye in peripheral veins of the limb in which the intraosseous infusion was performed. RESULTS: Methyl green dye was observed in peripheral veins of the chosen limb in five out of eight intraosseous infusions into bones without medullary cavity-calcaneus and radial styloid. CONCLUSIONS: Successful intraosseous infusion does not always require injection into a bone with a medullary cavity. Practitioners attempting intraosseous access on critically ill patients in the emergency department or prehospital setting need not restrict themselves to such bones. Calcaneus and radial styloid are both an acceptable alternative to traditional recommended sites.

Thrombin inhibition with melagatran does not attenuate renal ischaemia-reperfusion injury in rats

DEFF Research Database (Denmark)

Nitescu, Nicoletta; Grimberg, Elisabeth; Ricksten, Sven-Erik

2007-01-01

characterized by tubular necrosis and atrophy, tubular cast formation and interstitial inflammation. In addition, there was significant vascular congestion in the inner stripe of the outer medullary zone. Melagatran treatment had no significant effects on any of the abnormalities in kidney morphology...

P2Y2 receptor knock-out mice display normal NaCl absorption in medullary thick ascending limb

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Rita Delgado Marques

2013-10-01

Full Text Available Local purinergic signals modulate renal tubular transport. Acute activation of renal epithelial P2 receptors causes inhibition of epithelial transport and thus, should favor increased water and salt excretion by the kidney. So far only a few studies have addressed the effects of extracellular nucleotides on ion transport in the thick ascending limb. In the medullary thick ascending limb (mTAL, basolateral P2X receptors markedly (~25% inhibit NaCl absorption. Although this segment does express both apical and basolateral P2Y2 receptors, acute activation of the basolateral P2Y2 receptors had no apparent effect on transepithelial ion transport. Here we studied, if the absence of the P2Y2 receptor causes chronic alterations in mTAL NaCl absorption by comparing basal and AVP-stimulated transepithelial transport rates. We used perfused mouse mTALs to electrically measure NaCl absorption in juvenile (35 days male mice. Using microelectrodes, we determined the transepithelial voltage (Vte and the transepithelial resistance (Rte and thus, transepithelial NaCl absorption (equivalent short circuit current, I’sc.We find that mTALs from adult wild type (WT mice have significantly lower NaCl absorption rates when compared to mTALs from juvenile WT mice. This could be attributed to significantly higher Rte values in mTALs from adult WT mice. This pattern was not observed in mTALs from P2Y2 receptor knockout (KO mice. In addition, adult P2Y2 receptor KO mTALs have significantly lower Vte values compared to the juvenile. No difference in absolute I´sc was observed when comparing mTALs from WT and KO mice. AVP stimulated the mTALs to similar increases of NaCl absorption irrespective of the absence of the P2Y2 receptor. No difference was observed in the medullary expression level of NKCC2 in between the genotypes.These data indicate that the lack of P2Y2 receptors does not cause substantial differences in resting and AVP-stimulated NaCl absorption in

Emergency management of renal and genitourinary trauma: best practices update [digest].

Science.gov (United States)

Bryant, Whitney K; Shewakramani, Sanjay; Zaurova, Milana

2017-08-22

In up to 10% of patients who experience abdominal trauma, renal and urogenital systems will be involved. In polytrauma patients with other potentially life-threatening injuries, renal and genitourinary trauma may be overlooked initially, but a delayed or missed diagnosis of these injuries may result in preventable complications. This review provides a best-practice approach to the diagnosis and management of renal and genitourinary injuries, with an emphasis on the systematic approach needed to identify subtle injuries and avoid long-term urinary sequelae such as hypertension, incontinence, erectile dysfunction, chronic kidney disease, and nephrectomy. [Points & Pearls is a digest of Emergency Medicine Practice.].

A Rare Cause of Acute Kidney Injury in a Female Patient with Breast Cancer Presenting as Renal Colic

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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.

Effect of NADPH oxidase inhibitor-apocynin on the expression of Src homology-2 domain-containing phosphatase-1 (SHP-1 exposed renal ischemia/reperfusion injury in rats

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Zhiming Li

2015-01-01

Full Text Available This study was designed to evaluate whether NADPH oxidase inhibitor (apocynin preconditioning induces expression of Src homology-2 domain-containing phosphatase-1 (SHP-1 to protect against renal ischemia/reperfusion (I/R injury (RI/RI in rats. Rats were pretreated with 50 mg/kg apocynin, then subjected to 45 min ischemia and 24 h reperfusion. The results indicated that apocynin preconditioning improved the recovery of renal function and nitroso-redox balance, reduced oxidative stress injury and inflammation damage, and upregulated expression of SHP-1 as compared to RI/RI group. Therefore our study demonstrated that apocynin preconditioning provided a protection to the kidney against I/R injury in rats partially through inducing expression of SHP-1.

The cholinergic pathway alleviates acute oxygen and glucose deprivation induced renal tubular cell injury by reducing the secretion of inflammatory medium of macrophages

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Ming WU

2017-10-01

Full Text Available Objective To investigate the effects of cholinergic pathway on acute renal tubular cell injury induced by acute oxygen and glucose deprivation. Methods Rat kidney macrophages were isolated and cultured for constructing macrophages and renal epithelial cells co-cultivating model of oxygen-glucose deprivation (OGD, and the model cells were divided into three groups: OGD alone group, acetylcholine (ACh 100μmol/L+OGD group and ACh + galantamine (Gal 10μmol/L+OGD group. The cells underwent OGD treatment for 1 hour, and normally cultured for 24 hours. The expressions of TNF alpha, IL-1 beta, and IL-10 in supernatant fluid were detected by ELISA, the renal tubular cell viability was determined by MTT assay, the expression of acetylcholine esterase (AChE mRNA and protein were determined by RT-qPCR and Western blotting. The activity of AChE was determined by colorimetric method. Results The expressions of TNF alpha (pg/ml in OGD, Ach+OGD group, Ach+Gal+OGD groups were 140.2±44.81, 119.46±4.42 and 103.31±1.62 respectively (P0.05; The values of renal tubular cell proliferation were 55.02%±6.28%, 66.65%±6.47%, and 79.75%±4.22% respectively (P0.05; those of AchE protein were 0.66±0.07, 0.74±0.04 and 0.67±0.06 respectively (P>0.05; The activity of AChE (kU/L was 0.51±0.02, 0.35±0.05 and 0.32±0.04 respectively (P=0.001, 0.001 and 0.368. Conclusions ACh and Gal could inhibit the secretion of inflammatory mediators and cholinesterase activity and can reduce the acute hypoxic renal tubular cell injury. The modulation of the cholinergic pathway in macrophages may be the important treatment method for acute renal injury in the future. DOI: 10.11855/j.issn.0577-7402.2017.08.01

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.

[Value of fractional flow reserve measurement in endovascular therapy for patients with Stanford B type aortic dissection complicated with renal blood flow injury].

Science.gov (United States)

Guo, Xi; Li, Peng; Liu, Guangrui; Huang, Xiaoyong; Yong, Qiang; Wang, Guoqin; Huang, Lianjun

2015-10-01

To analyze the value of fractional flow reserve (FFR) measurement on endovascular therapy for patients with renal artery stenosis. Clinical data of 12 patients with Stanford B type aortic dissection complicated with renal blood flow injury in Anzhen hospital hospitalized from May 2013 to February 2014 were retrospectively analyzed. Renal artery angiography was performed and fractional flow reserve (FFR) was measured before Thoracic endovascular aortic repair. After operation, renal artery FFR was measured again, and renal artery stenting was performed in patients with FFR ≤ 0.90 or average pressure difference between proximal and distal of renal artery > 20 mmHg (1 mmHg = 0.133 kPa) and not applied for patients with FFR > 0.90.The patients were then subsequently followed up clinically. Kidney function were measured after 1 month, and contrast-enhanced ultrasonography data were obtained at 1 and 3 months later, respectively. The FFR of 1 patient was 0.90, while the FFR of other patients were less than 0.90 before thoracic endovascular aortic repair. After the procedure,the angiography showed that the blood flow of renal artery in 8 patients were fluency, and the FFR index was over 0.90. There were 4 patients with FFR less than 0.90. After renal artery stenting, the FFR of these 4 patients were all above 0.90. Compared with pre-procedure, blood urea nitrogen ((8.84 ± 3.99) mmol/L vs. (5.18 ± 1.69) mmol/L, P = 0.011) and uric acid ((359.3 ± 77.3) µmol/L vs. (276.9 ± 108.3) µmol/L, P = 0.008) decreased significantly after 1 month, and there was no significant difference in serum creatinine (P = 0.760). Contrast-enhanced ultrasonography results showed that blood flow of renal artery were fluency after 1 month and 3 months. In patients with aortic dissection complicating renal blood flow injury, the FFR measurement is meaningful in evaluating the blood flow status of target organs and guide the endovascular revascularization.

Catalase overexpression prevents nuclear factor erythroid 2-related factor 2 stimulation of renal angiotensinogen gene expression, hypertension, and kidney injury in diabetic mice.

Science.gov (United States)

Abdo, Shaaban; Shi, Yixuan; Otoukesh, Abouzar; Ghosh, Anindya; Lo, Chao-Sheng; Chenier, Isabelle; Filep, Janos G; Ingelfinger, Julie R; Zhang, Shao Ling; Chan, John S D

2014-10-01

This study investigated the impact of catalase (Cat) overexpression in renal proximal tubule cells (RPTCs) on nuclear factor erythroid 2-related factor 2 (Nrf2) stimulation of angiotensinogen (Agt) gene expression and the development of hypertension and renal injury in diabetic Akita transgenic mice. Additionally, adult male mice were treated with the Nrf2 activator oltipraz with or without the inhibitor trigonelline. Rat RPTCs, stably transfected with plasmid containing either rat Agt or Nrf2 gene promoter, were also studied. Cat overexpression normalized systolic BP, attenuated renal injury, and inhibited RPTC Nrf2, Agt, and heme oxygenase-1 (HO-1) gene expression in Akita Cat transgenic mice compared with Akita mice. In vitro, high glucose level, hydrogen peroxide, and oltipraz stimulated Nrf2 and Agt gene expression; these changes were blocked by trigonelline, small interfering RNAs of Nrf2, antioxidants, or pharmacological inhibitors of nuclear factor-κB and p38 mitogen-activated protein kinase. The deletion of Nrf2-responsive elements in the rat Agt gene promoter abolished the stimulatory effect of oltipraz. Oltipraz administration also augmented Agt, HO-1, and Nrf2 gene expression in mouse RPTCs and was reversed by trigonelline. These data identify a novel mechanism, Nrf2-mediated stimulation of intrarenal Agt gene expression and activation of the renin-angiotensin system, by which hyperglycemia induces hypertension and renal injury in diabetic mice. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Accelerated recovery of renal mitochondrial and tubule homeostasis with SIRT1/PGC-1α activation following ischemia–reperfusion injury

Energy Technology Data Exchange (ETDEWEB)

Funk, Jason A., E-mail: funkj@musc.edu [Center for Cell Death, Injury, and Regeneration, Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425 (United States); Schnellmann, Rick G., E-mail: schnell@musc.edu [Center for Cell Death, Injury, and Regeneration, Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425 (United States); Ralph H. Johnson VA Medical Center, Charleston, SC 29401 (United States)

2013-12-01

Kidney ischemia–reperfusion (I/R) injury elicits cellular injury in the proximal tubule, and mitochondrial dysfunction is a pathological consequence of I/R. Promoting mitochondrial biogenesis (MB) as a repair mechanism after injury may offer a unique strategy to restore both mitochondrial and organ function. Rats subjected to bilateral renal pedicle ligation for 22 min were treated once daily with the SIRT1 activator SRT1720 (5 mg/kg) starting 24 h after reperfusion until 72 h–144 h. SIRT1 expression was elevated in the renal cortex of rats after I/R + vehicle treatment (IRV), but was associated with less nuclear localization. SIRT1 expression was even further augmented and nuclear localization was restored in the kidneys of rats after I/R + SRT1720 treatment (IRS). PGC-1α was elevated at 72 h–144 h in IRV and IRS kidneys; however, SRT1720 treatment induced deacetylation of PGC-1α, a marker of activation. Mitochondrial proteins ATP synthase β, COX I, and NDUFB8, as well as mitochondrial respiration, were diminished 24 h–144 h in IRV rats, but were partially or fully restored in IRS rats. Urinary kidney injury molecule-1 (KIM-1) was persistently elevated in both IRV and IRS rats; however, KIM-1 tissue expression was attenuated in IRS rats. Additionally, sustained loss of Na{sup +},K{sup +}–ATPase expression and basolateral localization and elevated vimentin in IRV rats was normalized in IRS rats, suggesting restoration of a differentiated, polarized tubule epithelium. The results suggest that SRT1720 treatment expedited recovery of mitochondrial protein expression and function by enhancing MB, which was associated with faster proximal tubule repair. Targeting MB may offer unique therapeutic strategy following ischemic injury. - Highlights: • We examined recovery of mitochondrial and renal function after ischemia–reperfusion. • SRT1720 treatment after I/R induced mitochondrial biogenesis via SIRT1/PGC-1α. • Recovery of mitochondrial function was

Effect of selective inhibition of renal inducible nitric oxide synthase on renal blood flow and function in experimental hyperdynamic sepsis.

Science.gov (United States)

Ishikawa, Ken; Calzavacca, Paolo; Bellomo, Rinaldo; Bailey, Michael; May, Clive N

2012-08-01

Nitric oxide plays an important role in the control of renal blood flow and renal function. In sepsis, increased levels of inducible nitric oxide synthase produce excessive nitric oxide, which may contribute to the development of acute kidney injury. We, therefore, examined the effects of intrarenal infusion of selective inducible nitric oxide synthase inhibitors in a large animal model of hyperdynamic sepsis in which acute kidney injury occurs in the presence of increased renal blood flow. Prospective crossover randomized controlled interventional studies. University-affiliated research institute. Twelve unilaterally nephrectomized Merino ewes. Infusion of a selective (1400W) and a partially selective inducible nitric oxide synthase inhibitor (aminoguanidine) into the renal artery for 2 hrs after the induction of sepsis, and comparison with a nonselective inhibitor (Nω-nitro-L-arginine methyl ester). In sheep with nonhypotensive hyperdynamic sepsis, creatinine clearance halved (32 to 16 mL/min, ratio [95% confidence interval] 0.51 [0.28-0.92]) despite increased renal blood flow (241 to 343 mL/min, difference [95% confidence interval] 102 [78-126]). Infusion of 1400W did not change renal blood flow, urine output, or creatinine clearance, whereas infusion of Nω-nitro-L-arginine methyl ester and a high dose of aminoguanidine normalized renal blood flow, but did not alter creatinine clearance. In hyperdynamic sepsis, intrarenal infusion of a highly selective inducible nitric oxide synthase inhibitor did not reduce the elevated renal blood flow or improve renal function. In contrast, renal blood flow was reduced by infusion of a nonselective NOS inhibitor or a high dose of a partially selective inducible nitric oxide synthase inhibitor. The renal vasodilatation in septic acute kidney injury may be due to nitric oxide derived from the endothelial and neural isoforms of nitric oxide synthase, but their blockade did not restore renal function.

Interaction of cis-diamminedichloroplatinum and renal irradiation on renal function in the young and adult rat

International Nuclear Information System (INIS)

Jongejan, H.T.M.; Provoost, A.P.; Molenaar, J.C.

1987-01-01

In the present study the age-dependence has been investigated of renal injury following the combined administration of c-DDP and irradiation. Single doses of c-DDP and radiation, causing a limited renal function decline on their own, were applied in combination. Following treatment, renal function and systolic blood pressure (SBP) were measured for 6 months. 25 refs.; 3 figs.; 2 tabs

Citrus bergamia Risso & Poiteau juice protects against renal injury of diet-induced hypercholesterolemia in rats.

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Trovato, Ada; Taviano, Maria F; Pergolizzi, Simona; Campolo, Loredana; De Pasquale, Rita; Miceli, Natalizia

2010-04-01

The present study was designed to evaluate the protective effect of treatment with Citrus bergamia juice (1 mL/day, for 30 days) against hypercholesterolemic diet-induced renal injury in rat.C. bergamia juice provoked a significant reduction in the plasma levels of cholesterol, triglycerides and LDL, and an increase in HDL levels, versus hyperlipidemic controls (p juice administration significantly decreased MDA levels elevations compared with hyperlipidemic controls (4.10 +/- 0.10 nmol/mg protein and 4.78 +/- 0.15 nmol/mg protein, respectively).Histological observations of the kidney supported the biochemical data and indicated a protective effect of C. bergamia juice on the development of renal damage in hypercholesterolemic rats.The antioxidant potential of C. bergamia juice was examined in two in vitro systems: in the DPPH test the juice showed a noticeable effect on scavenging free radicals (IC(50) = 25.01 +/- 0.70 +/-L); in the reducing power assay it showed a strong activity, too (1.44 +/- 0.01 ASE/mL).These findings suggest that C. bergamia juice has a protective role in hypercholesterolemic diet-induced renal damage, which may be attributed to its antioxidant properties. Copyright (c) 2009 John Wiley & Sons, Ltd.

Lesão renal aguda em crianças: incidência e fatores prognósticos em pacientes gravemente enfermos Acute kidney injury in children: incidence and prognostic factors in critical ill patients

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Kenia Machado Souza Freire

2010-06-01

Full Text Available OBJETIVOS: Lesão renal aguda caracteriza-se pela redução súbita e, em geral, reversível da função renal com perda da capacidade de manutenção da homeostase do organismo. Em pediatria, as principais causas de lesão renal aguda são sepse, uso de drogas nefrotóxicas e isquemia renal nos pacientes criticamente enfermos. Nesses pacientes, a incidência de lesão renal aguda varia de 20 a 30%, resultando em aumento da taxa de morbi-mortalidade de 40 a 90%. Este estudo tem como objetivo avaliar a incidência de lesão renal aguda nos pacientes internados em unidade de terapia intensiva, classificar a gravidade da lesão renal aguda de acordo com o Pediatric Risk, Injury, Failure, Loss, End-Stage (pRIFLE, analisar a relação entre lesão renal aguda e a gravidade através do Pediatric Index of Mortality (PIM e estudar os fatores prognósticos associados. MÉTODOS: Realizou-se um estudo prospectivo entre julho de 2008 a janeiro de 2009 dos pacientes internados na unidade de terapia intensiva pediátrica do Hospital Infantil Joana de Gusmão - Florianópolis (SC - Brasil. Todos os pacientes foram analisados diariamente através do débito urinário e creatinina sérica e classificados de acordo com pRIFLE. RESULTADOS: No período de acompanhamento foram internadas 235 crianças. A incidência de lesão renal aguda foi de 30,6%, sendo que o pRIFLE máximo durante a internação foi de 12,1% para R, 12,1% para I e 6,4% para F. A taxa de mortalidade foi de 12,3%. Os pacientes que evoluíram com lesão renal aguda apresentaram risco dez vezes maior de óbito em relação aos não expostos. CONCLUSÃO: Lesão renal aguda é uma entidade comum nos pacientes críticos. O diagnóstico precoce a e instituição imediata de medidas terapêuticas adequadas a cada situação clínica podem alterar o curso e a gravidade do envolvimento renal reduzindo a morbi-mortalidade do paciente.OBJECTIVES: Acute kidney injury is characterized by sudden and generally

Erythropoietin-enhanced endothelial progenitor cell recruitment in peripheral blood and renal vessels during experimental acute kidney injury in rats.

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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. © 2015 International Federation for Cell Biology.

Preclinical Evidence for the Efficacy of Ischemic Postconditioning against Renal Ischemia-Reperfusion Injury, a Systematic Review and Meta-Analysis

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Jonker, Simone J.; Menting, Theo P.; Warlé, Michiel C.; Ritskes-Hoitinga, Merel; Wever, Kimberley E.

2016-01-01

Background Renal ischemia-reperfusion injury (IRI) is a major cause of kidney damage after e.g. renal surgery and transplantation. Ischemic postconditioning (IPoC) is a promising treatment strategy for renal IRI, but early clinical trials have not yet replicated the promising results found in animal studies. Method We present a systematic review, quality assessment and meta-analysis of the preclinical evidence for renal IPoC, and identify factors which modify its efficacy. Results We identified 39 publications studying >250 control animals undergoing renal IRI only and >290 animals undergoing renal IRI and IPoC. Healthy, male rats undergoing warm ischemia were used in the vast majority of studies. Four studies applied remote IPoC, all others used local IPoC. Meta-analysis showed that both local and remote IPoC ameliorated renal damage after IRI for the outcome measures serum creatinine, blood urea nitrogen and renal histology. Subgroup analysis indicated that IPoC efficacy increased with the duration of index ischemia. Measures to reduce bias were insufficiently reported. Conclusion High efficacy of IPoC is observed in animal models, but factors pertaining to the internal and external validity of these studies may hamper the translation of IPoC to the clinical setting. The external validity of future animal studies should be increased by including females, comorbid animals, and transplantation models, in order to better inform clinical trial design. The severity of renal damage should be taken into account in the design and analysis of future clinical trials. PMID:26963819

Evaluation of renal function with dynamic MRI-T2-weighted gradient echo technique

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Kato, Katsuya

1995-01-01

To evaluate the usefulness of dynamic MRI of kidneys in healthy volunteers and patients with different 24-hour creatinine clearance (Ccr) levels, a dynamic study that employed the T2 weighted gradient echo technique (FLASH: TR/TE=34/25 msec, flip angle= 20 degrees) with single images during breathhold was performed on 10 healthy volunteers and 35 patients, all examined for the Ccr and suspected of having renal parenchymal disease after a phantom study. T1-weighted and dynamic MR imagings were obtained with a 1.5T imager. I analyzed the time-intensity curve of renal cortex and medulla, and defined a cortex decreased ratio (CDR) and medulla decreased ratio (MDR) in comparison with the Ccr. The cortico-medullary difference ratio (CMDR) of T1WI was also compared with the Ccr. The parameters of the T2 dynamic MRI study (CDR, MDR) better correlated with the Ccr than CMDR. Renal function can be quantitatively evaluated with the T2 dynamic MRI and there is a possibility that we can qualitatively evaluate the renal dysfunction and estimate its cause. (author)

Effect of a combined treatment with erythropoietin and melatonin on renal ischemia reperfusion injury in male rats.

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Ahmadiasl, Nasser; Banaei, Shokofeh; Alihemati, Alireza; Baradaran, Behzad; Azimian, Ehsan

2014-12-01

Renal ischemia reperfusion (IR) is an important cause of renal dysfunction. It contributes to the development of acute renal failure. Oxidative damage from reactive oxygen species is considered to be the principal component involved in the pathophysiological tissue alterations observed during IR. The purpose of this study was to evaluate the effect of a combined treatment with erythropoietin (EPO) plus melatonin (MEL), which are known anti-inflammatory and antioxidant agents, in IR-induced renal injury in rats. Wistar Albino rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 24 h of reperfusion. MEL (10 mg/kg, i.p) and EPO (5000 U/kg, i.p) were administered prior to ischemia. After 24 h of reperfusion, blood samples were collected for the determination of superoxide dismutase (SOD), glutathione peroxidase (GPx), plasma levels of total antioxidant capacity (TAC), and malondialdehyde (MDA) and serum urea level. Also, renal samples were taken for histological evaluation. Ischemia reperfusion significantly increased urea, blood SOD, and GPx levels. Histological findings of the IR group indicated that there was increase in tubular and glomerular hyaline cast, thickening of Bowman capsule basement membrane, and renal impairment in the glomerular epithelium. Treatment with EPO and MEL significantly decreased blood SOD, GPx, and urea levels and increased TAC level. In the EPO + MEL group, while the histopathological changes were lower than those in EPO group, they were the same as MEL group. EPO and MEL combination treatment exerted more nephroprotective effects than EPO treatment and nearly had protective effects similar to MEL treatment.

Contemporary evaluation and management of renal trauma.

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Chouhan, Jyoti D; Winer, Andrew G; Johnson, Christina; Weiss, Jeffrey P; Hyacinthe, Llewellyn M

2016-04-01

Renal trauma occurs in approximately 1%-5% of all trauma cases. Improvements in imaging and management over the last two decades have caused a shift in the treatment of this clinical condition. A systematic search of PubMed was performed to identify relevant and contemporary articles that referred to the management and evaluation of renal trauma. Computed tomography remains a mainstay of radiological evaluation in hemodynamically stable patients. There is a growing body of literature showing that conservative, non-operative management of renal trauma is safe, even for Grade IV-V renal injuries. If surgical exploration is planned due to other injuries, a conservative approach to the kidney can often be utilized. Follow up imaging may be warranted in certain circumstances. Urinoma, delayed bleeding, and hypertension are complications that require follow up. Appropriate imaging and conservative approaches are a mainstay of current renal trauma management.

Renal morphology of Bradypus torquatus

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Pedro Kastein Faria da Cunha Bianchi

2012-11-01

Full Text Available Among the Xenarthras, sloths present a hydric ingestion restricted to water from leaves, fruits, and vegetables. As a first approach to verify whether these animals have some morphophysiological difference which could justify or compensate this low hydric ingestion, the renal anatomy of these animals was investigated, particularly that of maned sloth (Bradypus torquatus. Kidneys from these animals were macroscopically analyzed, through light microscopy and scanning electron microscopy. The Bradypus torquatus kidneys are bean-shaped paired organs, located dorso-cranially to the pelvic girdle, between the peritoneum and the posterior abdominal wall. The use of histological techniques allowed us to identify, in the cortical region, the renal corpuscles and tubules, and, in the medullary region, a significant amount of interstitial tissue with a collecting duct. The results of this study showed that, although Bradypus torquatus doesn’t drink water directly, its kidneys doesn’t differ from that of most mammals, presenting the same anatomical structure, suggesting that these animals fully reach their hydric needs, basically by consuming leaves, fruits, and sprouts. Nevertheless, in order to confirm this hypothesis, studies on the effectiveness of water reabsorption, such as the renin-angiotensin-aldosterone system, must be carried out.

The role of renal aquaporin 2 in the alleviation of dehydration associated with diabetic polyuria in KKAy mice.

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Satake, Masako; Ikarashi, Nobutomo; Ichikawa, Yuhei; Maniwa, Ayaka; Toda, Takahiro; Ito, Kiyomi; Ochiai, Wataru; Sugiyama, Kiyoshi

2010-10-09

Polyuria is a symptom that appears in association with diabetes mellitus. Because sustained polyuria causes serious dehydration, it is believed that the body has a compensating mechanism to alleviate dehydration. In the present study, the role of renal aquaporin 2 (AQP2) in the compensating mechanism was investigated in KKAy mice, a type 2 diabetes model. The renal AQP2 expression levels in KKAy mice aged between 5 and 24 weeks were determined using Western blotting. The hypothalamic vasopressin mRNA expression levels also were measured by real-time RT-PCR. Insulin was subcutaneously administered to 11-week-old KKAy mice twice a day for 7 days. After insulin treatment, the renal AQP2 protein expression and the hypothalamic vasopressin mRNA expression were measured. The urinary volumes of 5- and 12-week-old KKAy mice were 1.5 ± 0.3 mL and 9.5 ± 1.2 mL, respectively. The inner medullary AQP2 protein expression of 12-week-old KKAy mice was approximately 2.5-fold higher than that of 5-week-old KKAy mice. The hypothalamic vasopressin mRNA expression of 12-week-old KKAy mice was approximately twice that of 5-week-old KKAy mice. Insulin treatment in KKAy mice resulted in a significant reduction in the plasma glucose level, urinary volume, and inner medullary AQP2 protein and hypothalamic vasopressin mRNA expression. The present study demonstrated that AQP2 is a renal functional molecule of vasopressin that controls urinary volume and that AQP2 in the kidney increases to alleviate dehydration due to type 2 diabetes with polyuria. Copyright © 2010 Elsevier Inc. All rights reserved.

Comparison of the Efficacy of Serum Creatinine and Microalbuminuria in Early Diagnosis of Renal Injury in Asphyxiated Infants in Calabar, Southern Nigeria

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Sunny Oteikwu Ochigbo

2017-06-01

Full Text Available Background: Microalbuminuria and serum creatinine are the specific markers of acute renal injury. Perinatal asphyxia is responsible for 50% of all neonatal deaths and nonoliguric acute renal injuryis one of its complications. This study was undertaken to determine the efficacy of serum creatinine and microalbuminuria for early diagnosis of renal injury in severely asphyxiated neonates in Calabar, Nigeria.Methods: This prospective cross-sectional study was performed among severely asphyxiated newborns admitted into the neonatal wards of the University of Calabar Teaching Hospital (UCTH. Standard methods for the determination of blood urea and electrolyte were executed. Micral-test strips have been applied using urine dipstick and the result of the test was negative only for albumin. The developed colors have been compared five minutes after the first test.Results: Fifty full-term newborns were enrolled and their serum electrolytes, creatinine and the creatinine clearance were essentially normal. Six neonates demonstrated positive results in the microalbominuria assessment, while the rest were negative in this regard. The test has 0% sensitivity and 100% specificity, while the positive and negative predictive values were 0% and 88%, respectively.Conclusion: Microalbuminuria is not a useful marker for early diagnosis of acute renal failure in the newborns with severe prenatal asphyxia, but further studies are recommended.

Renal trauma imaging: Diagnosis and management. A pictorial review

International Nuclear Information System (INIS)

Szmigielski, Wojciech; Kumar, Rajendra; Al Hilli, Shatha; Ismail, Mostafa

2013-01-01

The purpose of this review is to illustrate and discuss the spectrum of imaging findings, particularly computed tomography (CT), of blunt and penetrating renal trauma, based on our own materials, according to the American Association for Surgery of Trauma (AAST) renal injury grading scale. The article also indicates the conditions in which interventional radiology procedures can be applied for the management of renal trauma. Cases for this pictorial review were selected from the imaging material collected at the Radiology Department of Hamad Medical Corporation during a 14-year period from 1999 to 2012. The material includes 176 cases (164 males and 12 females) with confirmed blunt or penetrating renal trauma. Following abdominal trauma, all patients had a CT examination performed on admission to the hospital and/or during hospitalization. The most representative and illustrative cases of renal trauma were reviewed according to CT findings and were categorized according to the AAST grading system. The review describes a spectrum of imaging presentations with special emphasis on the 5 grades of renal injury on a CT according to the AAST scale. The most representative cases were illustrated and discussed with indications of possible interventional radiology treatment. Two groups of patients not included in the AAST grading system were presented separately: those with preexisting renal abnormalities and those with sustained iatrogenic renal injury. Proper application of renal trauma grading scale is essential for selecting the patients for conservative treatment, surgery or interventional radiology procedure

Resveratrol, an Nrf2 activator, ameliorates aging-related progressive renal injury.

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Kim, Eun Nim; Lim, Ji Hee; Kim, Min Young; Ban, Tae Hyun; Jang, In-Ae; Yoon, Hye Eun; Park, Cheol Whee; Chang, Yoon Sik; Choi, Bum Soon

2018-01-11

Two important issues in the aging kidney are mitochondrial dysfunction and oxidative stress. An Nrf2 activator, resveratrol, is known to have various effects. Resveratrol may prevent inflammation and oxidative stress by activating Nrf2 and SIRT1 signaling. We examined whether resveratrol could potentially ameliorate the cellular condition, such as renal injury due to cellular oxidative stress and mitochondrial dysfunction caused by aging. Male 18-month-old C57BL/6 mice were used. Resveratrol (40 mg/kg) was administered to aged mice for 6 months. We compared histological changes, oxidative stress, and aging-related protein expression in the kidney between the resveratrol-treated group (RSV) and the control group (cont). We performed experiments using small-interfering RNAs (siRNAs) for Nrf2 and SIRT1 in cultured HK2 cells. Resveratrol improved renal function, proteinuria, histological changes and inflammation in aging mice. Also, expression of Nrf2-HO-1-NOQ-1 signaling and SIRT1-AMPK-PGC-1α signaling was increased in the RSV group. Transfection with Nrf2 and SIRT1 siRNA prevented resveratrol-induced anti-oxidative effect in HK2 cells in media treated with H 2 O 2 . Activation of the Nrf2 and SIRT1 signaling pathways ameliorated oxidative stress and mitochondrial dysfunction. Pharmacological targeting of Nrf2 signaling molecules may reduce the pathologic changes of aging in the kidney.

Quantitative arterial spin labelling perfusion measurements in rat models of renal transplantation and acute kidney injury at 3 T

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Zimmer, Fabian; Schad, Lothar R.; Zoellner, Frank G. [Heidelberg Univ., Mannheim (Germany). Computer Assisted Clinical Medicine; Klotz, Sarah; Hoeger, Simone; Yard, Benito A.; Kraemer, Bernhard K. [Heidelberg Univ., Mannheim (Germany). Dept. of Medicine V

2017-05-01

To employ ASL for the measurement of renal cortical perfusion in particular renal disorders typically associated with graft loss and to investigate its potential to detect and differentiate the related functional deterioration i.e., in a setting of acute kidney injury (AKI) as well as in renal grafts showing acute and chronic transplant rejection. 14 Lewis rats with unilateral ischaemic AKI and 43 Lewis rats with renal grafts showing acute or chronic rejections were used. All ASL measurements in this study were performed on a 3 T MR scanner using a FAIR True-FISP approach to assess renal blood flow (RBF). Perfusion maps were calculated and the cortical blood flow was determined using a region-of-interest based analysis. RBF of healthy and AKI kidneys as well as of both rejection models, were compared. In a subsample of 20 rats, creatinine clearance was measured and correlated with cortical perfusion. RBF differs significantly between healthy and AKI kidneys (P < 0.001) with a mean difference of 213 ± 80 ml/100 g/min. Renal grafts with chronic rejections show a significantly higher (P < 0.001) mean cortical perfusion (346 ± 112 ml/100 g/min) than grafts with acute rejection (240 ± 66 ml/100 g/min). Both transplantation models have a significantly (P < 0.001) lower perfusion than healthy kidneys. Renal creatinine clearance is significantly correlated (R = 0.85, P < 0.001) with cortical blood flow. Perfusion measurements with ASL have the potential to become a valuable diagnostic tool, regarding the detection of renal impairment and the differentiation of disorders that lead to a loss of renal function and that are typically associated with graft loss.

Quantitative arterial spin labelling perfusion measurements in rat models of renal transplantation and acute kidney injury at 3 T

International Nuclear Information System (INIS)

Zimmer, Fabian; Schad, Lothar R.; Zoellner, Frank G.; Klotz, Sarah; Hoeger, Simone; Yard, Benito A.; Kraemer, Bernhard K.

2017-01-01

To employ ASL for the measurement of renal cortical perfusion in particular renal disorders typically associated with graft loss and to investigate its potential to detect and differentiate the related functional deterioration i.e., in a setting of acute kidney injury (AKI) as well as in renal grafts showing acute and chronic transplant rejection. 14 Lewis rats with unilateral ischaemic AKI and 43 Lewis rats with renal grafts showing acute or chronic rejections were used. All ASL measurements in this study were performed on a 3 T MR scanner using a FAIR True-FISP approach to assess renal blood flow (RBF). Perfusion maps were calculated and the cortical blood flow was determined using a region-of-interest based analysis. RBF of healthy and AKI kidneys as well as of both rejection models, were compared. In a subsample of 20 rats, creatinine clearance was measured and correlated with cortical perfusion. RBF differs significantly between healthy and AKI kidneys (P < 0.001) with a mean difference of 213 ± 80 ml/100 g/min. Renal grafts with chronic rejections show a significantly higher (P < 0.001) mean cortical perfusion (346 ± 112 ml/100 g/min) than grafts with acute rejection (240 ± 66 ml/100 g/min). Both transplantation models have a significantly (P < 0.001) lower perfusion than healthy kidneys. Renal creatinine clearance is significantly correlated (R = 0.85, P < 0.001) with cortical blood flow. Perfusion measurements with ASL have the potential to become a valuable diagnostic tool, regarding the detection of renal impairment and the differentiation of disorders that lead to a loss of renal function and that are typically associated with graft loss.

Architecture of interstitial nodal spaces in the rodent renal inner medulla.

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Gilbert, Rebecca L; Pannabecker, Thomas L

2013-09-01

Every collecting duct (CD) of the rat inner medulla is uniformly surrounded by about four abutting ascending vasa recta (AVR) running parallel to it. One or two ascending thin limbs (ATLs) lie between and parallel to each abutting AVR pair, opposite the CD. These structures form boundaries of axially running interstitial compartments. Viewed in transverse sections, these compartments appear as four interstitial nodal spaces (INSs) positioned symmetrically around each CD. The axially running compartments are segmented by interstitial cells spaced at regular intervals. The pairing of ATLs and CDs bounded by an abundant supply of AVR carrying reabsorbed water, NaCl, and urea make a strong argument that the mixing of NaCl and urea within the INSs and countercurrent flows play a critical role in generating the inner medullary osmotic gradient. The results of this study fully support that hypothesis. We quantified interactions of all structures comprising INSs along the corticopapillary axis for two rodent species, the Munich-Wistar rat and the kangaroo rat. The results showed remarkable similarities in the configurations of INSs, suggesting that the structural arrangement of INSs is a highly conserved architecture that plays a fundamental role in renal function. The number density of INSs along the corticopapillary axis directly correlated with a loop population that declines exponentially with distance below the outer medullary-inner medullary boundary. The axial configurations were consistent with discrete association between near-bend loop segments and INSs and with upper loop segments lying distant from INSs.

Venovenous Bypass Is Associated With a Lower Incidence of Acute Kidney Injury After Liver Transplantation in Patients With Compromised Pretransplant Renal Function.

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Sun, Kai; Hong, Fu; Wang, Yun; Agopian, Vatche G; Yan, Min; Busuttil, Ronald W; Steadman, Randolph H; Xia, Victor W

2017-11-01

Although the hemodynamic benefits of venovenous bypass (VVB) during liver transplantation (LT) are well appreciated, the impact of VVB on posttransplant renal function is uncertain. The aim of this study was to determine if VVB was associated with a lower incidence of posttransplant acute kidney injury (AKI). Medical records of adult (≥18 years) patients who underwent primary LT between 2004 and 2014 at a tertiary hospital were reviewed. Patients who required pretransplant renal replacement therapy and intraoperative piggyback technique were excluded. Patients were divided into 2 groups, VVB and non-VVB. AKI, determined by the Acute Kidney Injury Network criteria, was compared between the 2 groups. Propensity match was used to control selection bias that occurred before VVB and multivariable logistic regression was used to control confounding factors during and after VVB. Of 1037 adult patients who met the study inclusion criteria, 247 (23.8%) received VVB. A total of 442 patients (221 patients in each group) were matched. Aftermatch patients were further divided according to a predicted probability AKI model using preoperative creatinine (Cr), VVB, and intraoperative variables into 2 subgroups: normal and compromised pretransplant renal functions. In patients with compromised pretransplant renal function (Cr ≥1.2 mg/dL), the incidence of AKI was significantly lower in the VVB group compared with the non-VVB group (37.2% vs 50.8%; P = .033). VVB was an independent risk factor negatively associated with AKI (odds ratio, 0.1; 95% confidence interval, 0.1-0.4; P = .001). Renal replacement in 30 days and 1-year recipient mortality were not significantly different between the 2 groups. The incidence of posttransplant AKI was not significantly different between the 2 groups in patients with normal pretransplant renal function (Cr the role of intraoperative VVB in posttransplant AKI are warranted.

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

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

2013-01-01

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

Social Determinants of Health Are Associated with Markers of Renal Injury in Adolescents with Type 1 Diabetes.

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Cummings, Laura A M; Clarke, Antoine; Sochett, Etienne; Daneman, Denis; Cherney, David Z; Reich, Heather N; Scholey, James W; Dunger, David B; Mahmud, Farid H

2018-05-08

To examine the relationship between the social determinants of health and markers of early renal injury in adolescent patients with type 1 diabetes (T1D). Renal outcomes included estimated glomerular filtration rate (eGFR) and albumin-creatinine excretion ratio (ACR). Differences in urinary and serum inflammatory markers also were assessed in relation to social determinants of health. Regression analysis was used to evaluate the association between the Ontario Marginalization Index (ON-Marg) as a measure of the social determinants of health, patient characteristics, ACR, eGFR, and renal filtration status (hyperfiltration vs normofiltration). Participants with T1D (n = 199) with a mean age of 14.4 ± 1.7 years and diabetes duration of 7.2 ± 3.1 years were studied. Mean eGFR was 122.0 ± 19.4 mL/min/1.73 m 2 . Increasing marginalization was positively associated with eGFR (P social and biological determinants of health in adolescents with T1D. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

The effect of zinc on healing of renal damage in rats.

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Salehipour, Mehdi; Monabbati, Ahmad; Ensafdaran, Mohammad Reza; Adib, Ali; Babaei, Amir Hossein

2017-07-01

Several studies have previously been performed to promote kidney healing after injuries. Objectives: The aim of this study was to investigate the effect of zinc on renal healing after traumatic injury in rats. Forty healthy female rats were selected and one of their kidneys was incised. Half of the incisions were limited only to the cortex (renal injury type I) and the other ones reached the pelvocalyceal system of the kidney (renal injury type II). All the rats in the zinc treated group (case group) received 36.3 mg zinc sulfate (contained 8.25 mg zinc) orally. After 28 days, the damaged kidneys were removed for histopathological studies. In the rats with type I injury, kidney inflammation of the case group was significantly lower than that of the control group. However, the result was not significant in rats with type II injury. Tissue loss and granulation tissue formation were significantly lower in the case group than the control group in both type I and II kidney injuries. Overall, Zinc can contribute to better healing of the rat's kidneys after a traumatic injury.

An analysis of 99mTc-DTPA renal dynamic imaging in patients with diabetes mellitus

International Nuclear Information System (INIS)

Cao Guoxiang; Zhang Yongxue

2000-01-01

To investigate the regularity of renal dynamic imaging in the various courses of diabetes mellitus, and then to provide the important evidence variety for diagnosis and treatment. The data of renal dynamic imaging was analyzed on 276 kidneys of 40 normal and 98 diabetic patients, and according to course of disease, the diabetic patients was divided into three groups: ≤1 year, 1-5 year and ≥5 year respectively. Based upon was grouped 99m Tc-DTPA renal dynamic imaging and others, the renal functions into normal, approximately normal, I, II and III injury respectively, and the statistics and analysis of these data were carried out. The extent of renal function injury was related to the course of disease significantly, and it showed that the longer the course, the heavier the damage of renal function, and there was a significant difference between them (P 99m Tc-DTPA renal dynamic imaging can effectively evaluate the extent of renal functions injury and was also valuable for the clinical. Also, the study indicated that in diabetic patients susceptible to urinary tract infection could aggravate the injury of renal function

A novel chalcone derivative attenuates the diabetes-induced renal injury via inhibition of high glucose-mediated inflammatory response and macrophage infiltration

International Nuclear Information System (INIS)

Fang, Qilu; Zhao, Leping; Wang, Yi; Zhang, Yali; Li, Zhaoyu; Pan, Yong; Kanchana, Karvannan; Wang, Jingying; Tong, Chao; Li, Dan; Liang, Guang

2015-01-01

Inflammation plays a central role in the development and progression of diabetic nephropathy (DN). Researches on novel anti-inflammatory agents may offer new opportunities for the treatment of DN. We previously found a chalcone derivative L6H21 could inhibit LPS-induced cytokine release from macrophages. The aim of this study was to investigate whether L6H21 could ameliorate the high glucose-mediated inflammation in NRK-52E cells and attenuate the inflammation-mediated renal injury. According to the results, L6H21 showed a great inhibitory effect on the expression of pro-inflammatory cytokines, cell adhesion molecules, chemokines, and macrophage adhesion via down-regulation of NF-κB/MAPKs activity in high glucose-stimulated renal NRK-52E cells. Further, in vivo oral administration with L6H21 at a dosage of 20 mg/kg/2 days showed a decreased expression of pro-inflammatory cytokines, cell adhesion molecules, which subsequently contributed to the inhibition on renal macrophage infiltration, the reduction of serum creatinine and BUN levels, and the improvement on the fibrosis and pathological changes in the renal tissues of diabetic mice. These findings provided that chalcone derived L6H21 may be a promising anti-inflammatory agent and have the potential in the therapy of diabetic nephropathy, and importantly, MAPK/NF-κB signaling system may be a novel therapeutic target for human DN in the future. - Highlights: • Inflammation plays a central role in the development of diabetic nephropathy. • Compound L6H21 reduced the high glucose-mediated inflammation in NRK-52E cells. • Compound L6H21 attenuated the inflammation-mediated renal injury. • L6H21 exhibited anti-inflammatory effects via inactivation of NF-κB/MAPKs. • MAPKs/NF-κB may be a novel therapeutic target in diabetic nephropathy treatment

A novel chalcone derivative attenuates the diabetes-induced renal injury via inhibition of high glucose-mediated inflammatory response and macrophage infiltration

Energy Technology Data Exchange (ETDEWEB)

Fang, Qilu [Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Zhao, Leping [Department of Pharmacy, the Affiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou, Zhejiang (China); Wang, Yi; Zhang, Yali [Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Li, Zhaoyu [Department of International High School, Shanghai Jiaotong University Nanyang Affiliated (Kunshan) School, Minhang District, Shanghai (China); Pan, Yong; Kanchana, Karvannan; Wang, Jingying; Tong, Chao [Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Li, Dan, E-mail: yqyyld@163.com [Department of Nephrology, the Affiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou, Zhejiang (China); Liang, Guang, E-mail: wzmcliangguang@163.com [Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China)

2015-01-15

Inflammation plays a central role in the development and progression of diabetic nephropathy (DN). Researches on novel anti-inflammatory agents may offer new opportunities for the treatment of DN. We previously found a chalcone derivative L6H21 could inhibit LPS-induced cytokine release from macrophages. The aim of this study was to investigate whether L6H21 could ameliorate the high glucose-mediated inflammation in NRK-52E cells and attenuate the inflammation-mediated renal injury. According to the results, L6H21 showed a great inhibitory effect on the expression of pro-inflammatory cytokines, cell adhesion molecules, chemokines, and macrophage adhesion via down-regulation of NF-κB/MAPKs activity in high glucose-stimulated renal NRK-52E cells. Further, in vivo oral administration with L6H21 at a dosage of 20 mg/kg/2 days showed a decreased expression of pro-inflammatory cytokines, cell adhesion molecules, which subsequently contributed to the inhibition on renal macrophage infiltration, the reduction of serum creatinine and BUN levels, and the improvement on the fibrosis and pathological changes in the renal tissues of diabetic mice. These findings provided that chalcone derived L6H21 may be a promising anti-inflammatory agent and have the potential in the therapy of diabetic nephropathy, and importantly, MAPK/NF-κB signaling system may be a novel therapeutic target for human DN in the future. - Highlights: • Inflammation plays a central role in the development of diabetic nephropathy. • Compound L6H21 reduced the high glucose-mediated inflammation in NRK-52E cells. • Compound L6H21 attenuated the inflammation-mediated renal injury. • L6H21 exhibited anti-inflammatory effects via inactivation of NF-κB/MAPKs. • MAPKs/NF-κB may be a novel therapeutic target in diabetic nephropathy treatment.

Renal Vein Reconstruction for Harvesting Injury in Kidney Transplantation

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Birkan Bozkurt

2014-03-01

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

Pre-operative renal volume predicts peak creatinine after congenital heart surgery in neonates.

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Carmody, J Bryan; Seckeler, Michael D; Ballengee, Cortney R; Conaway, Mark; Jayakumar, K Anitha; Charlton, Jennifer R

2014-10-01

Acute kidney injury is common in neonates following surgery for congenital heart disease. We conducted a retrospective analysis to determine whether neonates with smaller pre-operative renal volume were more likely to develop post-operative acute kidney injury. We conducted a retrospective review of 72 neonates who underwent congenital heart surgery for any lesion other than patent ductus arteriosus at our institution from January 2007 to December 2011. Renal volume was calculated by ultrasound using the prolate ellipsoid formula. The presence and severity of post-operative acute kidney injury was determined both by measuring the peak serum creatinine in the first 7 days post-operatively and by using the Acute Kidney Injury Network scoring system. Using a linear change point model, a threshold renal volume of 17 cm³ was identified. Below this threshold, there was an inverse linear relationship between renal volume and peak post-operative creatinine for all patients (p = 0.036) and the subgroup with a single morphologic right ventricle (p = 0.046). There was a non-significant trend towards more acute kidney injury using Acute Kidney Injury Network criteria in all neonates with renal volume ≤17 cm³ (p = 0.11) and in the subgroup with a single morphologic right ventricle (p = 0.17). Pre-operative renal volume ≤17 cm³ is associated with a higher peak post-operative creatinine and potentially greater risk for post-operative acute kidney injury for neonates undergoing congenital heart surgery. Neonates with a single right ventricle may be at higher risk.

Differential expression of T- and L-type voltage-dependent calcium channels in renal resistance vessels

DEFF Research Database (Denmark)

Hansen, Pernille B. Lærkegaard; Jensen, Boye L.; Andreasen, D

2001-01-01

The distribution of voltage-dependent calcium channels in kidney pre- and postglomerular resistance vessels was determined at the molecular and functional levels. Reverse transcription-polymerase chain reaction analysis of microdissected rat preglomerular vessels and cultured smooth muscle cells...... on vascular diameter in the afferent arteriole. We conclude that voltage-dependent L- and T-type calcium channels are expressed and of functional significance in renal cortical preglomerular vessels, in juxtamedullary efferent arterioles, and in outer medullary vasa recta, but not in cortical efferent...

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

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

2016-01-01

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

MRP-1 expression levels determine strain-specific susceptibility to sodium arsenic-induced renal injury between C57BL/6 and BALB/c mice

International Nuclear Information System (INIS)

Kimura, Akihiko; Ishida, Yuko; Wada, Takashi; Yokoyama, Hitoshi; Mukaida, Naofumi; Kondo, Toshikazu

2005-01-01

To clarify the pathophysiological mechanism underlying acute renal injury caused by acute exposure to arsenic, we subcutaneously injected both BALB/c and C57BL/6 mice with sodium arsenite (NaAs; 13.5 mg/kg). BALB/c mice exhibited exaggerated elevation of serum blood urea nitrogen (BUN) and creatinine (CRE) levels, compared with C57BL/6 mice. Moreover, half of BALB/c mice died by 24 h, whereas all C57BL/6 mice survived. Histopathological examination on kidney revealed severe hemorrhages, acute tubular necrosis, neutrophil infiltration, cast formation, and disappearance of PAS-positive brush borders in BALB/c mice, later than 10 h. These pathological changes were remarkably attenuated in C57BL/6 mice, accompanied with lower intrarenal arsenic concentrations, compared with BALB/c mice. Among heavy metal inducible proteins including multidrug resistance-associated protein (MRP)-1, multidrug resistance gene (MDR)-1, metallothionein (MT)-1, and arsenite inducible, cysteine- and histidine-rich RNA-associated protein (AIRAP), intrarenal MDR-1, MT-1, and AIRAP gene expression was enhanced to a similar extent in both strains, whereas NaAs challenge augmented intrarenal MRP-1 mRNA and protein expression levels in C57BL/6 but not BALB/c mice. Moreover, the administration of a specific inhibitor of MRP-1, MK-571, significantly exaggerated acute renal injury in C57BL/6 mice. Thus, MRP-1 is crucially involved in arsenic efflux and eventually prevention of acute renal injury upon acute exposure to NaAs

Roles of Akt and SGK1 in the Regulation of Renal Tubular Transport

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Nobuhiko Satoh

2015-01-01

Full Text Available A serine/threonine kinase Akt is a key mediator in various signaling pathways including regulation of renal tubular transport. In proximal tubules, Akt mediates insulin signaling via insulin receptor substrate 2 (IRS2 and stimulates sodium-bicarbonate cotransporter (NBCe1, resulting in increased sodium reabsorption. In insulin resistance, the IRS2 in kidney cortex is exceptionally preserved and may mediate the stimulatory effect of insulin on NBCe1 to cause hypertension in diabetes via sodium retention. Likewise, in distal convoluted tubules and cortical collecting ducts, insulin-induced Akt phosphorylation mediates several hormonal signals to enhance sodium-chloride cotransporter (NCC and epithelial sodium channel (ENaC activities, resulting in increased sodium reabsorption. Serum- and glucocorticoid-inducible kinase 1 (SGK1 mediates aldosterone signaling. Insulin can stimulate SGK1 to exert various effects on renal transporters. In renal cortical collecting ducts, SGK1 regulates the expression level of ENaC through inhibition of its degradation. In addition, SGK1 and Akt cooperatively regulate potassium secretion by renal outer medullary potassium channel (ROMK. Moreover, sodium-proton exchanger 3 (NHE3 in proximal tubules is possibly activated by SGK1. This review focuses on recent advances in understanding of the roles of Akt and SGK1 in the regulation of renal tubular transport.

Renal complications of anaesthesia.

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McKinlay, J; Tyson, E; Forni, L G

2018-01-01

Peri-operative acute kidney injury is common, accounting for 30-40% of all in-hospital cases of acute kidney injury. It is associated with clinically significant morbidity and mortality even with what was hitherto regarded as relatively trivial increases in serum creatinine, and carries over a 12-fold relative risk of death following major abdominal surgery. Comorbid conditions such as diabetes, hypertension, liver disease and particularly pre-existing chronic kidney disease, as well as the type and urgency of surgery, are major risk factors for the development of postoperative acute kidney injury. As yet, there are no specific treatment options for the injured kidney, although there are several modifiable risk factors of which the anaesthetist should be aware. As well as the avoidance of potential nephrotoxins and appropriate volume balance, optimal anaesthetic management should aim to reduce the risk of postoperative renal complications. This may include careful ventilatory management and blood pressure control, as well as appropriate analgesic strategies. The choice of anaesthetic agent may also influence renal outcomes. Rather than concentrate on the classical management of acute kidney injury, this review focuses on the potential development of acute kidney injury peri-operatively, and the means by which this may be ameliorated. © 2018 The Association of Anaesthetists of Great Britain and Ireland.

Wallenberg's lateral medullary syndrome: diffusion-weighted imaging findings

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Kitis, O.; Calli, C.; Yunten, N.; Kocaman, A.; Sirin, H. [Ege Univ., Izmir (Turkey). Dept. of Radiology

2004-02-01

To investigate the efficacy of diffusion-weighted imaging in patients with Wallenberg's lateral medullary syndrome. Thirteen patients with Wallenberg's lateral medullary syndrome were examined with conventional and echoplanar diffusion-weighted magnetic resonance (MR) imaging in a 1.5 T magnetic resonance unit. MR examinations were obtained in the acute or subacute stage of clinical syndrome, and diffusion-weighted imaging (DWI) was considered to be positive for infarction when an increase in signal was seen on b = 1000 s/mm2 images in the posterolateral medullary localization. DWIs were positive in 12 patients in the acute or subacute stages of this clinical syndrome. A false-negative result was obtained in only one patient examined within the first day, 10 h after onset of the symptoms. In the visual evaluation of the DWI, the contrast between normal and infarcted brainstem area was better in the high b-value images than in the apparent diffusion coefficient map images. DWI is a valuable technique for examining patients presenting with the signs and symptoms of Wallenberg's syndrome and high b-value images can provide complementary data to T2-weighted images. However, because most of our case group were in either the acute or subacute stage, true sensitivity of the method in the hyperacute stage of the syndrome remains unclear.

Medullary thyroid cancer: RET testing of an archival material

DEFF Research Database (Denmark)

Godballe, Christian; Jørgensen, Gita; Gerdes, Anne-Marie Axø

2010-01-01

Medullary thyroid carcinoma (MTC) might be sporadic (75%) or hereditary (25%). Until the mid nineties the diagnosis of hereditary MTC was based on family history, clinical evaluation, histological detection of C-cell hyperplasia and tumor multifocality. Patients and families with hereditary MTC...

Medullary thyroid cancer: RET testing of an archival material

DEFF Research Database (Denmark)

Godballe, Christian; Jørgensen, Gita; Gerdes, Anne-Marie

2009-01-01

Medullary thyroid carcinoma (MTC) might be sporadic (75%) or hereditary (25%). Until the mid nineties the diagnosis of hereditary MTC was based on family history, clinical evaluation, histological detection of C-cell hyperplasia and tumor multifocality. Patients and families with hereditary MTC...

Inhibition of WISE preserves renal allograft function.

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Qian, Xueming; Yuan, Xiaodong; Vonderfecht, Steven; Ge, Xupeng; Lee, Jae; Jurisch, Anke; Zhang, Li; You, Andrew; Fitzpatrick, Vincent D; Williams, Alexia; Valente, Eliane G; Pretorius, Jim; Stevens, Jennitte L; Tipton, Barbara; Winters, Aaron G; Graham, Kevin; Harriss, Lindsey; Baker, Daniel M; Damore, Michael; Salimi-Moosavi, Hossein; Gao, Yongming; Elkhal, Abdallah; Paszty, Chris; Simonet, W Scott; Richards, William G; Tullius, Stefan G

2013-01-01

Wnt-modulator in surface ectoderm (WISE) is a secreted modulator of Wnt signaling expressed in the adult kidney. Activation of Wnt signaling has been observed in renal transplants developing interstitial fibrosis and tubular atrophy; however, whether WISE contributes to chronic changes is not well understood. Here, we found moderate to high expression of WISE mRNA in a rat model of renal transplantation and in kidneys from normal rats. Treatment with a neutralizing antibody against WISE improved proteinuria and graft function, which correlated with higher levels of β-catenin protein in kidney allografts. In addition, treatment with the anti-WISE antibody reduced infiltration of CD68(+) macrophages and CD8(+) T cells, attenuated glomerular and interstitial injury, and decreased biomarkers of renal injury. This treatment reduced expression of genes involved in immune responses and in fibrogenic pathways. In summary, WISE contributes to renal dysfunction by promoting tubular atrophy and interstitial fibrosis.

The Urine Proteome as a Biomarker of Radiation Injury: Submitted to Proteomics- Clinical Applications Special Issue: "Renal and Urinary Proteomics (Thongboonkerd)"

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Sharma, Mukut; Halligan, Brian D; Wakim, Bassam T; Savin, Virginia J; Cohen, Eric P; Moulder, John E

2008-06-18

Terrorist attacks or nuclear accidents could expose large numbers of people to ionizing radiation, and early biomarkers of radiation injury would be critical for triage, treatment and follow-up of such individuals. However, no such biomarkers have yet been proven to exist. We tested the potential of high throughput proteomics to identify protein biomarkers of radiation injury after total body X-ray irradiation in a rat model. Subtle functional changes in the kidney are suggested by an increased glomerular permeability for macromolecules measured within 24 hours after TBI. Ultrastructural changes in glomerular podocytes include partial loss of the interdigitating organization of foot processes. Analysis of urine by LC-MS/MS and 2D-GE showed significant changes in the urine proteome within 24 hours after TBI. Tissue kallikrein 1-related peptidase, cysteine proteinase inhibitor cystatin C and oxidized histidine were found to be increased while a number of proteinase inhibitors including kallikrein-binding protein and albumin were found to be decreased post-irradiation. Thus, TBI causes immediately detectable changes in renal structure and function and in the urinary protein profile. This suggests that both systemic and renal changes are induced by radiation and it may be possible to identify a set of biomarkers unique to radiation injury.

Second messenger production in avian medullary nephron segments in response to peptide hormones.

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Goldstein, D L; Reddy, V; Plaga, K

1999-03-01

We examined the sites of peptide hormone activation within medullary nephron segments of the house sparrow (Passer domesticus) kidney by measuring rates of hormone-induced generation of cyclic nucleotide second messenger. Thin descending limbs, thick ascending limbs, and collecting ducts had baseline activity of adenylyl cyclase that resulted in cAMP accumulation of 207 +/- 56, 147 +/- 31, and 151 +/- 41 fmol. mm-1. 30 min-1, respectively. In all segments, this activity increased 10- to 20-fold in response to forskolin. Activity of adenylyl cyclase in the thin descending limb was stimulated approximately twofold by parathyroid hormone (PTH) but not by any of the other hormones tested [arginine vasotocin (AVT), glucagon, atrial natriuretic peptide (ANP), or isoproterenol, each at 10(-6) M]. Thick ascending limb was stimulated two- to threefold by both AVT and PTH; however, glucagon and isoproterenol had no effect, and ANP stimulated neither cAMP nor cGMP accumulation. Adenylyl cyclase activity in the collecting duct was stimulated fourfold by AVT but not by the other hormones; likewise, ANP did not stimulate cGMP accumulation in this segment. These data support a tubular action of AVT and PTH in the avian renal medulla.

Plasma protein haptoglobin modulates renal iron loading

DEFF Research Database (Denmark)

Fagoonee, Sharmila; Gburek, Jakub; Hirsch, Emilio

2005-01-01

Haptoglobin is the plasma protein with the highest binding affinity for hemoglobin. The strength of hemoglobin binding and the existence of a specific receptor for the haptoglobin-hemoglobin complex in the monocyte/macrophage system clearly suggest that haptoglobin may have a crucial role in heme...... distribution of hemoglobin in haptoglobin-deficient mice resulted in abnormal iron deposits in proximal tubules during aging. Moreover, iron also accumulated in proximal tubules after renal ischemia-reperfusion injury or after an acute plasma heme-protein overload caused by muscle injury, without affecting...... morphological and functional parameters of renal damage. These data demonstrate that haptoglobin crucially prevents glomerular filtration of hemoglobin and, consequently, renal iron loading during aging and following acute plasma heme-protein overload....

Sporotrichosis in Renal Transplant Patients

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Paulo Gewehr

2013-01-01

Full Text Available The current report describes two renal transplant recipients who presented with sporotrichosis. In addition, the authors review the general aspects of sporotrichosis in renal transplant recipients reported in the literature. Sporotrichosis is a rare fungal infection in transplant patients and has been reported primarily in renal transplant recipients not treated with antifungal prophylaxis. Extracutaneous forms of sporotrichosis without skin manifestations and no previous history of traumatic injuries have been described in such patients and are difficult to diagnose. Renal transplant recipients with sporotrichosis described in the present report were successfully treated with antifungal therapy including amphotericin B deoxycholate, lipid amphotericin B formulations, fluconazole and itraconazole.

Clinical and radiological observations in the kidney injury

International Nuclear Information System (INIS)

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

1981-01-01

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

Comparison of the effects of dexmedetomidine administered at two different times on renal ischemia/reperfusion injury in rats

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Edip Gonullu

2014-05-01

Full Text Available Background and objectives: We investigated the effect of dexmedetomidine on ischemic renal failure in rats. Methods: In the present study, 26 male adult Wistar albino rats weighting 230–300 g were randomly separated into four groups: sham-operated (n = 5, ischemia reperfusion (IR (IR group, n = 7, IR/reperfusion treatment with dexmedetomidine (Dex. R group, n = 7 and IR/pre-ischemic treatment with dexmedetomidine (Dex. I group, n = 7. In the first group, sham operation was achieved and renal clamps were not applied. For the IR group, renal ischemia was induced by occlusion of the bilateral renal arteries and veins for 60 min followed by reperfusion for 24 h. For the Dex. R and Dex. I groups, the same surgical procedure as in the IR group was performed, and dexmedetomidine (100 mcg/kg intraperitoneal was administrated at the 5th min after reperfusion and before ischemia. At the end of reperfusion, blood samples were drawn, the rats were sacrificed, and the left kidney was processed for histopathology. Results: The blood urea nitrogen (BUN levels in groups Dex. R and Dex. I were significantly lower than in the IR group (p = 0.015, p = 0.043, although urine flow was significantly higher in group Dex. R (p = 0.003. The renal histopathological score in the IR group was significantly higher than in the other groups. There was no significant difference between the Dex. R and Dex. I groups. Conclusions: The results were shown that administration of dexmedetomidine reduced the renal IR injury histomorphologically. Administration of dexmedetomidine in the reperfusion period was considered as more effective due to increase in urinary output and decrease in BUN levels. Keywords: Kidney, Ischemia/reperfusion, Dexmedetomidine, Acute renal failure

Lateral medullary infarction with cardiovascular autonomic dysfunction: an unusual presentation with review of the literature.

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Huynh, Tridu R; Decker, Barbara; Fries, Timothy J; Tunguturi, Ajay

2018-01-24

We report an unusual case of lateral medullary infarction presenting with orthostatic hypotension with pre-syncope without vertigo or Horner's syndrome. Case report with review of the literature. A 67-year-old man presented with pre-syncope and ataxia without vertigo. Initial brain CT and MRI were normal. Neurological evaluation revealed right-beating nystagmus with left gaze, vertical binocular diplopia, right upper-extremity dysmetria, truncal ataxia with right axial lateropulsion, and right-facial and lower extremity hypoesthesia. Bedside blood pressure measurements disclosed orthostatic hypotension. He had normal sinus rhythm on telemetry and normal ejection fraction on echocardiogram. A repeat brain MRI disclosed an acute right dorsolateral medullary infarct. Autonomic testing showed reduced heart rate variability during paced deep breathing, attenuated late phase II and phase IV overshoot on Valsalva maneuver, and a fall of 25 mmHg of blood pressure at the end of a 10-min head-up tilt with no significant change in heart rate. These results were consistent with impaired sympathetic and parasympathetic cardiovascular reflexes. He was discharged to acute rehabilitation a week later with residual right dysmetria and ataxia. Lateral medullary infarctions are usually reported as partial presentations of classical lateral medullary syndrome with accompanying unusual symptoms ranging from trigeminal neuralgias to hiccups. Pre-syncope from orthostatic hypotension is a rare presentation. In the first 3-4 days, absence of early DWI MRI findings is possible in small, dorsolateral medullary infarcts with sensory disturbances. Physicians should be aware of this presentation, as early diagnosis and optimal therapy are associated with good prognosis.

Protective effects of regular aerobic exercise on renal tissue injury following creatine monohydrate supplementation in rats

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Davoud Rahimi

2017-01-01

Full Text Available Creatine is one of the most common supplements for improvement of athletic performance which is used by athletes. The most important debate about creatine consumption is its adverse effect on kidneys due to increased protein load. This study was performed to evaluate the protective effects of aerobic exercise on renal tissue injury following consumption of creatine monohydrate in the rat. For this purpose, 30 male Wistar rats were randomly divided into 3 groups of 10 animals each. Group 1, as control, received only standard food. Group 2 received 5 g/kg b.w. creatine monohydrate supplement daily for 8 weeks through gavage and group 3 received creatine monohydrate supplementation in the same manner30 minutes before aerobic exercise. Aerobic exercise was performed 5 times per week on treadmill at speed of 10-25m/min for 10-30 minutes with the slope of 5 degrees. At the end of 8 weeks, water intake and urinary excretion of rats were measured and blood samples were collected for measurement of serum renal function biomarkers including urea, uric acid and creatinine. Finally, the rats were euthanized for renal histopathology. In group 3, by doing regular aerobic exercise, water intake and urinary excretion rates were significantly (p

Ascending uretero-pyelography in renal failure.

Science.gov (United States)

Kingston, R D; Shah, K J; Dawson-Edwards, P

1977-09-01

Ascending uretero-pyelography has been carried out over a period of 13 years in 97 consecutive patients with undiagnosed renal failure. Sixty-nine were in a non-obstructive uropathy group while 26 had ureteric obstructions. There were two failures. Over 60% of examinations were performed under local anaesthesia, each examination taking an average of 20 min. There has been no mortality and two anaesthetic complications have been the only significant morbidity. Ureteric injury, urinary infection and renal function have all been investigated and recorded. Five per cent of patients developed urinary infection following AUP but without any major consequences. No significant ureteric injury occurred and no late sequelae were noted. Neither any reaction to contrast medium nor any further deterioration in renal function was observed; AUP was diagnostic in 46% of patients. In the remainder it ruled out obstructive uropathy and gave useful information about the kidneys, ureters and bladder. In experienced hands and with proper facilities AUP is safe and can be helpful in the diagnosis and management of patients in renal failure.

Angiographic Findings and Embolotherapy in Renal Arterial Trauma

International Nuclear Information System (INIS)

Sofocleous, Constantinos T.; Hinrichs, Clay; Hubbi, Basil; Brountzos, Elias; Kaul, Sanjeev; Kannarkat, George; Bahramipour, Philip; Barone, Alison; Contractor, Daniel G.; Shah, Tanmaya

2005-01-01

Purpose To evaluate the angiographic findings and embolotherapy in the management of traumatic renal arterial injury Methods This is a retrospective review of 22 patients with renal trauma who underwent arteriography and percutaneous embolization from December 1995 to January 2002. Medical records, imaging studies and procedural reports were reviewed to assess the type of injury, arteriographic findings and immediate embolization results. Long-term clinical outcome was obtained by communication with the trauma physicians and by clinical chart review.Results Arteriography was performed in 125 patients admitted to a State Trauma Center with suspected internal bleeding. Renal arterial injury was documented in 22 and was the result of a motor-vehicle accident (10), auto-pedestrian accident (1), gunshot (4) or stab wounds (6) and a fall (1). Percutaneous renal arterial embolization was undertaken in 22 of 125 (18%) patients to treat extravasation (11), arterial pedicle rupture (5), abnormal arteriovenous (3) or arteriocalyceal (2) communication and pseudoaneurysm (3). One of the pseudoaneurysms and one of the arteriovenous fistulae were found in addition to extravasation. All 22 patients (16 men, 6 women) were hemodynamically stable, or controlled during arteriography and embolotherapy. Selective and/or superselective embolization of the abnormal vessels was performed using coils in 9 patients, microcoils in 9 patients and Gelfoam pledgets in 3 patients. In one patient Gelfoam pledgets mixed with polyvinyl alcohol (PVA) particles were used for embolization. Immediate angiographic evidence of hemostasis was demonstrated in all cases. Two initial technical failures were treated with repeat arteriography and embolization. There was no procedure-related death. There was no non-target embolization. One episode of renal abscess after embolization was treated by nephrectomy and 3 patients underwent elective post-embolization nephrectomy to prevent infection. Follow-up ranged

Comparison of the effects of dexmedetomidine administered at two different times on renal ischemia/reperfusion injury in rats

Directory of Open Access Journals (Sweden)

Edip Gonullu

2014-06-01

Full Text Available Background and objectives: We investigated the effect of dexmedetomidine on ischemic renal failure in rats. Methods: In the present study, 26 male adult Wistar albino rats weighting 230-300 g were randomly separated into four groups: sham-operated (n = 5, ischemia reperfusion (IR (IR group, n = 7, IR/reperfusion treatment with dexmedetomidine (Dex. R group, n = 7 and IR/pre-ischemic treatment with dexmedetomidine (Dex. I group, n = 7. In the first group, sham operation was achieved and renal clamps were not applied. For the IR group, renal ischemia was induced by occlusion of the bilateral renal arteries and veins for 60 min followed by reperfusion for 24 h. For the Dex. R and Dex. I groups, the same surgical procedure as in the IR group was performed, and dexmedetomidine (100 mcg/kg intraperitoneal was administrated at the 5th min after reperfusion and before ischemia. At the end of reperfusion, blood samples were drawn, the rats were sacrificed, and the left kidney was processed for histopathology. Results: The blood urea nitrogen (BUN levels in groups Dex. R and Dex. I were significantly lower than in the IR group (p = 0.015, p = 0.043, although urine flow was significantly higher in group Dex. R (p = 0.003. The renal histopathological score in the IR group was significantly higher than in the other groups. There was no significant difference between the Dex. R and Dex. I groups. Conclusions: The results were shown that administration of dexmedetomidine reduced the renal IR injury histomorphologically. Administration of dexmedetomidine in the reperfusion period was considered as more effective due to increase in urinary output and decrease in BUN levels.

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

Science.gov (United States)

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

2016-11-01

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

Mathematical Model of Ammonia Handling in the Rat Renal Medulla

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Noiret, Lorette; Baigent, Stephen; Jalan, Rajiv; Thomas, S. Randall

2015-01-01

The kidney is one of the main organs that produces ammonia and release it into the circulation. Under normal conditions, between 30 and 50% of the ammonia produced in the kidney is excreted in the urine, the rest being absorbed into the systemic circulation via the renal vein. In acidosis and in some pathological conditions, the proportion of urinary excretion can increase to 70% of the ammonia produced in the kidney. Mechanisms regulating the balance between urinary excretion and renal vein release are not fully understood. We developed a mathematical model that reflects current thinking about renal ammonia handling in order to investigate the role of each tubular segment and identify some of the components which might control this balance. The model treats the movements of water, sodium chloride, urea, NH3 and NH4+, and non-reabsorbable solute in an idealized renal medulla of the rat at steady state. A parameter study was performed to identify the transport parameters and microenvironmental conditions that most affect the rate of urinary ammonia excretion. Our results suggest that urinary ammonia excretion is mainly determined by those parameters that affect ammonia recycling in the loops of Henle. In particular, our results suggest a critical role for interstitial pH in the outer medulla and for luminal pH along the inner medullary collecting ducts. PMID:26280830

Evaluation of Renal Blood Flow and Oxygenation in CKD Using Magnetic Resonance Imaging.

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Khatir, Dinah S; Pedersen, Michael; Jespersen, Bente; Buus, Niels H

2015-09-01

Animal studies suggest that progression of chronic kidney disease (CKD) is related to renal hypoxia. With renal blood supply determining oxygen delivery and sodium absorption being the main contributor to oxygen consumption, we describe the relationship between renal oxygenation, renal artery blood flow, and sodium absorption in patients with CKD and healthy controls. Cross-sectional study. 62 stable patients with CKD stages 3 to 4 (mean age, 61±13 [SD] years) and 24 age- and sex-matched controls. CKD versus control status. Renal artery blood flow, tissue oxygenation (relative changes in deoxyhemoglobin concentration of the renal medulla [MR2*] and cortex [CR2*]), and sodium absorption. Renal artery blood flow was determined by phase-contrast magnetic resonance imaging (MRI); MR2* and CR2* were determined by blood oxygen level-dependent MRI. Ultrafiltered and reabsorbed sodium were determined from measured glomerular filtration rate (mGFR) and 24-hour urine collections. mGFR in patients was 37% that of controls (36±15 vs 97±23 mL/min/1.73 m(2); P renal artery blood flow was 72% that of controls (319 vs 443 mL/min; P renal artery blood flow or sodium absorption. Increasing arterial blood oxygen tension by breathing 100% oxygen had very small effects on CR2*, but reduced MR2* in both groups. Only renal artery blood flow was determined and thus regional perfusion could not be related to CR2* or MR2*. In CKD, reductions of mGFR and reabsorbed sodium are more than double that of renal artery blood flow, whereas cortical and medullary oxygenation are within the range of healthy persons. Reduction in glomerular filtration fraction may prevent renal hypoxia in CKD. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Renal injury in neonates: use of "omics" for developing precision medicine in neonatology.

Science.gov (United States)

Joshi, Mandar S; Montgomery, Kelsey A; Giannone, Peter J; Bauer, John A; Hanna, Mina H

2017-01-01

Preterm birth is associated with increased risks of morbidity and mortality along with increased healthcare costs. Advances in medicine have enhanced survival for preterm infants but the overall incidence of major morbidities has changed very little. Abnormal renal development is an important consequence of premature birth. Acute kidney injury (AKI) in the neonatal period is multifactorial and may increase lifetime risk of chronic kidney disease.Traditional biomarkers in newborns suffer from considerable confounders, limiting their use for early identification of AKI. There is a need to develop novel biomarkers that can identify, in real time, the evolution of renal dysfunction in an early diagnostic, monitoring and prognostic fashion. Use of "omics", particularly metabolomics, may provide valuable information regarding functional pathways underlying AKI and prediction of clinical outcomes.The emerging knowledge generated by the application of "omics" (genomics, proteomics, metabolomics) in neonatology provides new insights that can help to identify markers of early diagnosis, disease progression, and identify new therapeutic targets. Additionally, omics will have major implications in the field of personalized healthcare in the future. Here, we will review the current knowledge of different omics technologies in neonatal-perinatal medicine including biomarker discovery, defining as yet unrecognized biologic therapeutic targets, and linking of omics to relevant standard indices and long-term outcomes.

Frequency of Cushing's syndrome due to ACTH-secreting adrenal medullary lesions: a retrospective study over 10 years from a single center.

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Falhammar, Henrik; Calissendorff, Jan; Höybye, Charlotte

2017-01-01

Cushing's syndrome due to ectopic adrenocorticotropic hormone production from adrenal medullary lesions has occasionally been described. We retrospectively reviewed all 164 cases of Cushing's syndrome and 77 cases of pheochromocytomas during 10 years. Of all cases with Cushing's syndrome, only two cases (1.2 %) were due to ectopic adrenocorticotropic hormone production from adrenal medullary lesions (one case of pheochromocytoma and one case of adrenal medullary hyperplasia). Of all pheochromocytomas only the above-mentioned case (1.3 %) also gave rise to an ectopic adrenocorticotropic hormone syndrome. The clinical presentation of adrenocorticotropic hormone-secreting pheochromocytoma and adrenal medullary hyperplasia can be anything from mild to dramatic. These are rare conditions important to bear in mind in the workup of a patient with Cushing's syndrome or with pheochromocytoma. The identification of ectopic adrenocorticotropic hormone secretion from adrenal medullary lesions can be life-saving.

Recovery of Dysphagia in Lateral Medullary Stroke

OpenAIRE

Gupta, Hitesh; Banerjee, Alakananda

2014-01-01

Lateral medullary stroke is typically associated with increased likelihood of occurrence of dysphagia and exhibits the most severe and persistent form. Worldwide little research exists on dysphagia in brainstem stroke. An estimated 15% of all patients admitted to stroke rehabilitation units experience a brainstem stroke out of which about 47% suffer from dysphagia. In India, a study showed that 22.3% of posterior circulation stroke patients develop dysphagia. Dearth of literature on dysphagia...

The potential value of somatostatin receptor scintigraphy in medullary thyroid carcinoma

Energy Technology Data Exchange (ETDEWEB)

Doerr, U.; Bihl, H. (Katharinenhospital, Stuttgart (Germany). Dept. of Nuclear Medicine); Frank-Raue, K.; Raue, F. (Heidelberg Univ. (Germany). Dept. of Internal Medicine); Sautter-Bihl, M.L.; Buhr, H.J. (Staedt. Klinikum, Karlsruhe (Germany). Dept. of Radiooncology and Nuclear Medicine); Guzman, G. (Katherinenhospital, Stuttgart (Germany). Dept. of Nuclear Medicine Inst. de Neurocirugia, Investigationes Cerebrales ' Dr Asenjo' Santiago (Chile). Dept. de Medicina Nuclear)

1993-06-01

In a prospective study, ten patients with recurrent medullary thyroid carcinoma (markedly elevated calcitonin levels) were investigated by means of somatostatin receptor scintigraphy (SRS) with [sup 111]In-pentetreotide. Scintigraphically, 30 sites of pathological uptake were found, mostly located in the neck and upper mediastinum. So far, 18 suspected tumour sites underwent histological examination and 14 of them could be verified as metastases of medullary thyroid carcinoma (MTC). The remaining four putative tumour lesions turned out to be false positive scintigraphic findings caused by chronic inflammation and somatostatin receptor positive tumours other than MTC. We conclude that SRS is a promising imaging modality for localization of MTC recurrence and may thus make a contribution to better management of this patient group. (Author).

The potential value of somatostatin receptor scintigraphy in medullary thyroid carcinoma

International Nuclear Information System (INIS)

Doerr, U.; Bihl, H.; Frank-Raue, K.; Raue, F.; Sautter-Bihl, M.L.; Buhr, H.J.; Guzman, G.; Inst. de Neurocirugia, Investigationes Cerebrales 'Dr Asenjo' Santiago

1993-01-01

In a prospective study, ten patients with recurrent medullary thyroid carcinoma (markedly elevated calcitonin levels) were investigated by means of somatostatin receptor scintigraphy (SRS) with 111 In-pentetreotide. Scintigraphically, 30 sites of pathological uptake were found, mostly located in the neck and upper mediastinum. So far, 18 suspected tumour sites underwent histological examination and 14 of them could be verified as metastases of medullary thyroid carcinoma (MTC). The remaining four putative tumour lesions turned out to be false positive scintigraphic findings caused by chronic inflammation and somatostatin receptor positive tumours other than MTC. We conclude that SRS is a promising imaging modality for localization of MTC recurrence and may thus make a contribution to better management of this patient group. (Author)

Urinary acidification and urinary excretion of calcium and citrate in women with bilateral medullary sponge kidney

DEFF Research Database (Denmark)

Osther, P J; Mathiasen, Helle; Hansen, A B

1994-01-01

Urinary acidification ability, acid-base status and urinary excretion of calcium and citrate were evaluated in 10 women with bilateral medullary sponge kidney (MSK) and in 10 healthy women. Patients with MSK had higher fasting urine pH compared to normal controls (p ... in the mechanism of hypercalciuria and hypocitraturia in patients with medullary sponge kidney.(ABSTRACT TRUNCATED AT 250 WORDS)...

ADAMTS-7 Expression Increases in the Early Stage of Angiotensin II-Induced Renal Injury in Elderly Mice

Directory of Open Access Journals (Sweden)

Yan-Xiang Gao

2014-03-01

Full Text Available Background/Aims: We investigated the recently described family of proteinases, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTs, and matrix metalloproteinases (MMPs as inflammatory mediators in inflammatory kidney damage by studying ADAMTS-1, -4, and -7 and MMP-9 expression in elderly mouse kidneys after angiotensin II (Ang II administration. Methods: Ang II (2.5 µg/kg/min or norepinephrine (8.3 µg/kg/min was subcutaneously infused in old mice. Renal injury was assessed by hematoxylin-eosin staining, 24-h albuminuria, and immunohistochemistry to evaluate inflammatory cell markers. The mRNA and protein expression of ADAMTS-1, -4, and -7 and MMP-9 were determined using real-time PCR, Western blot, and immunohistochemistry 3 days after Ang II or norepinephrine administration. Results: Elderly mice in the Ang II group developed hypertension and pathological kidney damage. The mRNA and protein levels of ADAMTS-7 in the Ang II group were 3.3 ± 1.1 (P = 0.019 and 1.6 ± 0.1 (P = 0.047 vs. 1.0 ± 0.1 and 1.0 ± 0.1 in the control group on day 3. In contrast, treatment with the hypertensive agent norepinephrine did not lead to obvious renal damage or an increase in renal ADAMTS-7 expression. Conclusions: Renal ADAMTS-7 expression was induced by Ang II in elderly mice. The overexpression of ADATMTS-7 might contribute to early inflammatory kidney damage associated with aging.

Biochemical markers in the follow-up of medullary thyroid cancer

NARCIS (Netherlands)

de Groot, Jan Willem B.; Kema, Ido P.; Breukelman, Henk; van der Veer, Eveline; Wiggers, Theo; Plukker, John T. M.; Wolffenbuttel, Bruce H. R.; Links, Thera P.

2006-01-01

Medullary thyroid cancer (MTC) shares biochemical features with other neuroendocrine tumors but the particular characteristics are largely unexplored. We investigated the biochemical neuroendocrine profile of MTC and whether specific markers could be useful in follow-up. In addition to the standard

Effects of compound Shenhua tablet on renal tubular Na+-K+-ATPase in rats with acute ischemic reperfusion injury.

Science.gov (United States)

Yang, Yue; Wei, Ri-bao; Zheng, Xiao-yong; Qiu, Qiang; Cui, Shao-yuan; Yin, Zhong; Shi, Suo-zhu; Chen, Xiang-mei

2014-03-01

To observe the effect of Compound Shenhua Tablet (, SHT) on the sodium-potassium- exchanging adenosinetriphosphatase (Na(+)-K(+)-ATPase) in the renal tubular epithelial cells of rats with acute ischemic reperfusion and to investigate the mechanisms underlying the effects of SHT on renal ischemic reperfusion injury (RIRI). Fifty male Wistar rats were randomly divided into the sham surgery group, model group, astragaloside group [150 mg/(kg·d)], SHT low-dose group [1.5 g/(kg·d)] and SHT high-dose group [3.0 g/(kg·d)], with 10 rats in each group. After 1 week of continuous intragastric drug administration, surgery was performed to establish the model. At either 24 or 72 h after the surgery, 5 rats in each group were sacrificed, blood biochemistry, renal pathology, immunoblot and immunohistochemical examinations were performed, and double immunofluorescence staining was observed under a laser confocal microscope. Compared with the sham surgery group, the serum creatinine (SCr) and blood urea nitrogen (BUN) levels were significantly increased, Na(+)-K(+)-ATPase protein level was decreased, and kidney injury molecule-1 (KIM-1) protein level was increased in the model group after the surgery (P<0.01 or P<0.05). Compared with the model group, the SCr, BUN, pathological scores, Na(+)-K(+)-ATPase, and the KIM-1 protein level of the three treatment groups were significantly improved at 72 h after the surgery (P<0.05 or P<0.01). And the SCr, BUN of the SHT low- and high-dose groups, and the pathological scores of the SHT high-dose group were significantly lower than those of the astragaloside group (P<0.05). The localizations of Na(+)-K(+)-ATPase and megalin of the model group were disrupted, with the distribution areas overlapping with each other and alternately arranged. The severity of the disruption was slightly milder in three treatment groups compared with that of the model group. The results of immunofluorescence staining showed that the SHT high-dose group had a

βENaC is a molecular component of a VSMC mechanotransducer that contributes to renal blood flow regulation, protection from renal injury, and hypertension.

Science.gov (United States)

Drummond, Heather A

2012-01-01

Pressure-induced constriction (also known as the "myogenic response") is an important mechano-dependent response in certain blood vessels. The response is mediated by vascular smooth muscle cells (VSMCs) and characterized by a pressure-induced vasoconstriction in small arteries and arterioles in the cerebral, mesenteric, cardiac, and renal beds. The myogenic response has two important roles; it is a mechanism of blood flow autoregulation and provides protection against systemic blood pressure-induced damage to delicate microvessels. However, the molecular mechanism(s) underlying initiation of myogenic response is unclear. Degenerin proteins have a strong evolutionary link to mechanotransduction in the nematode. Our laboratory has addressed the hypothesis that these proteins may also act as mechanosensors in certain mammalian tissues such as VSMCs and arterial baroreceptor neurons. This article discusses the importance of a specific degenerin protein, β Epithelial Na(+) Channel (βENaC) in pressure-induced vasoconstriction in renal vessels and arterial baroreflex function as determined in a mouse model of reduced βENaC (βENaC m/m). We propose that loss of baroreflex sensitivity (due to loss of baroreceptor βENaC) increases blood pressure variability, increasing the likelihood and magnitude of upward swings in systemic pressure. Furthermore, loss of the myogenic constrictor response (due to loss of VSMC βENaC) will permit those pressure swings to be transmitted to the microvasculature in βENaC m/m mice, thus increasing the susceptibility to renal injury and hypertension.

Thoracoscopic repair of renal ectopia associated with congenital ...

African Journals Online (AJOL)

R.S. Kamble

2015-12-04

Dec 4, 2015 ... During plication of the diaphragm, care must be taken to avoid renal injury. Following, we present two rare variants of CDH with concomitant renal ectopia managed thoracoscopically. Post- operative recovery was uneventful. Doppler ultrasound study performed one month after surgery confirmed.

Microsatellite instability in medullary carcinoma of the colon