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Query: UMLS:C0035078 (renal failure)
 31,970 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tubular cell apoptosis is involved in ischemic renal failure, but the underlying mechanism is unclear. Bid, a proapoptotic Bcl-2 family protein, may regulate the intrinsic as well as the extrinsic pathway of apoptosis. In vivo, Bid is most abundantly expressed in the kidneys. However, the role played by Bid in renal pathophysiology is unknown. Our recent work demonstrated Bid activation during renal ischemia-reperfusion. The current study has determined the role of Bid in ischemic renal injury and renal failure using Bid-deficient mice. In wild-type C57BL/6 mice, Bid was proteolytically processed into active forms during renal ischemia-reperfusion, which subsequently targeted mitochondria. This was accompanied by the development of tissue damage and severe renal failure, showing serum creatinine of 3.0 mg/dl after 48 h of reperfusion. The same ischemic insult induced acute renal failure in Bid-deficient mice, which was nonetheless less severe than the wild-type, showing 1.3 mg/dl serum creatinine. In addition, Bid deficiency attenuated tubular disruption, tubular cell apoptosis, and caspase-3 activation during 48 h of reperfusion. Compared with wild-type, animal death following renal ischemia was delayed in Bid-deficient mice. Collectively, the results suggest a role for Bid in ischemic renal injury and renal failure.
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PMID:Bid deficiency ameliorates ischemic renal failure and delays animal death in C57BL/6 mice. 1610 37

The small GTPase p21 Ras and its downstream effectors play a central role in the control of cell survival and apoptosis. We studied the effects of Ras/ERK1/2 signaling inhibition on oxidative damage in cultured renal and endothelial cells and on renal ischemia-reperfusion injury in the rat. Primary human renal tubular and human endothelial ECV304 cells underwent significant cell death when subjected to oxidative stress. This type of stress induced robustly ERK1/2 and phosphoinositide 3-kinase (PI3-kinase) signaling. Inhibition of Ras/ERK1/2 with a farnesyl transferase inhibitor, chaetomellic acid A (S-FTI), or with PD-98059, an inhibitor of MEK, a kinase upstream ERK1/2, significantly reduced the fraction of dead cells. The inhibitor of the PI3-kinase/Akt pathway, LY-294002, failed to exert a protective effect. We have translated these data in a rat model of renal ischemic injury in vivo. In uninephrectomized animals, anesthetized with pentobarbital sodium (Nembutal, 50 mg/kg i.p.), 24 h after an acute ischemic renal insult (45-min occlusion of left renal artery) a significant fraction of kidney cells succumbed to cell death resulting in renal failure [glomerular filtration rate (GFR) 0.17 +/- 0.1 vs. 0.90 +/- 0.4 ml x min(-1) x 100 g body wt(-1) in normal rats]. Rats treated with S-FTI maintained the renal function (GFR 0.50 +/- 0.1 ml x min(-1) x 100 g body wt(-1)), and the kidneys showed a significant reduction of tubular necrosis. Reduction of ischemic damage in kidney and tubular cells paralleled Ha-Ras inhibition, assayed by cytosolic translocation of the protein. These data demonstrate that inhibition of farnesylation and consequently of Ras/ERK1/2 signaling significantly reduces acute postischemic renal injury.
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PMID:Inhibition of Ras/ERK1/2 signaling protects against postischemic renal injury. 1643 73

Renal ischemia as a course of renal transplantation is a common cause of renal dysfunction as renal failure. The purpose of this study was to investigate the influence of ascorbic acid on blood urea nitrogen (BUN), creatinine (Cr) and resistive index (RI) for dog models with renal ischemia-reperfusion (I/R) injury. Renal ischemia was induced on 6 Beagle dogs. The left kidney was exposed to normothermic ischemia for a short period at 30 min followed by reperfusion. On the blood Cr level and RI, there was no significant difference comparing both groups. 14 days after I/R injury a significant reduction on the blood BUN level was observed in the vehicle group (34.06 mg/dl) compared to that of ischemia induced treated group (10.3 mg/dl) (p < 0.05). In conclusion, administration of ascorbic acid for renal ischemic-reperfusion injury had influence on blood BUN level, but it was not revealed the influence on blood Cr and RI.
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PMID:Influence of ascorbic acid on BUN, creatinine, resistive index in canine renal ischemia-reperfusion injury. 1643 55

Diverse functions have been reported for lipocalin 2. To investigate these functions in vivo, we generated gene-targeted lipocalin 2-deficient mice (Lcn2-/- mice). In vitro studies have suggested that lipocalin 2 is important for cellular apoptosis induced by IL-3 withdrawal, and for the induction of kidney differentiation during embryogenesis. Analysis of Lcn2-/- mice showed normal cell death upon IL-3 withdrawal and normal kidney development. However, we found that Lcn2-/- mice exhibited an increased susceptibility to bacterial infections, in keeping with the proposed function of lipocalin 2 in iron sequestration. Neutrophils isolated from Lcn2-/- mice showed significantly less bacteriostatic activity compared with WT controls. The bacteriostatic property of the WT neutrophils was abolished by the addition of exogenous iron, indicating that the main function of lipocalin 2 in the antibacterial innate immune response is to limit this essential element. Another important function ascribed to lipocalin 2 has been its protective role against kidney ischemia-reperfusion injury. We analyzed Lcn2-/- mice using a mouse model for severe renal failure and could not detect any significant differences compared with their WT littermates.
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PMID:Lipocalin 2-deficient mice exhibit increased sensitivity to Escherichia coli infection but not to ischemia-reperfusion injury. 1644 25

Acute renal failure is a frequent clinical problem with an increasing incidence, an unacceptably high mortality rate that has not improved in more than 40 years, and no specific treatment, yet renal failure is not the usual cause of death. The role of inflammation has been documented in both acute renal injury and cardiac dysfunction. Several investigators have shown that congestive heart failure is associated with increased mortality in patients with acute renal failure. This article reviews some of the cardiac and other distant organ effects of acute renal injury that may be important in the morbidity and mortality observed clinically. Cardiac changes after experimental renal ischemia include cytokine induction, leukocyte infiltration, cell death by apoptosis, and impaired function. I propose that the extrarenal effects of kidney injury must be considered in designing therapies. Acute renal failure has systemic consequences and must be thought of as more than a kidney disease.
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PMID:Acute renal failure: much more than a kidney disease. 1653 Jun 3

Neutrophil gelatinase associated lipocalin belongs to a family of small proteins, lipocalins, engaged in the transmembrane transportation of lipophylic substances. Originally isolated from specific granules of neutrophils, it was later located in bone marrow cells as well as lung, bronchial and colon epithelial cells. The expression of neutrophil lipocalin in epithelial cells and in body fluids considerably augments during the occurrence of inflammations and some cancers. A modulation of immunity response was thus suggested to be the main function of neutrophil lipocalin as well as the bacteriostatic effect originating from competition between neutrophil lipocalin and bacteria for siderophoric iron. Forming protective complexes with gelatinase B, the neutrophil lipocalin is implicated in regulatory processes of physiological and pathological rebuilding of tissues, mainly in the angiogenesis. The determination of neutrophil lipocalin levels in body fluids able to discriminate between bacterial and viral infections provides a powerful diagnostic tool. The examination of neutrophil lipocalin in the sera and urine of patients at risk of renal failure offers a very early marker of this acute state. Neutrophil lipocalin represents a sensitive non-invasive marker of renal ischemia and in patients with cystic fibrosis the marker of acute pulmonary exacerbation. Discussions have been conducted regarding the role of neutrophil lipocalin as an early marker of pancreatic cancer or of neutrophilic activation in severe cases of bowel diseases.
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PMID:[NGAL--neutrophil gelatinase associated lipocalin in biochemistry, physiology and clinical praxis]. 1675 74

Renal failure from ischemia contributes to morbidity and mortality. Ischemic preconditioning (IP) represents a powerful strategy for kidney protection, and recent advances in transgenic mice may help elucidate its molecular mechanisms. However, murine IP is technically challenging and experimental details significantly influence results. Thus we developed a novel model for renal IP using a hanging-weight system for isolated renal artery occlusion. In contrast to previous models, this technique eliminates the need for clamping the vascular pedicle (artery/vein). In fact, assessment of renal injury after different time periods of ischemia (10-60 min) revealed highly reproducible increases in plasma creatinine and potassium levels, while creatinine clearance, urinary flow and potassium/sodium excretion were significantly attenuated. Using different numbers of IP cycles, we found maximal protection with four cycles of 4 min of ischemia-reperfusion. In contrast, no significant renal protection was observed with IP of the vascular pedicle. To assess transcriptional responses in this model, we isolated RNA from preconditioned kidneys and found time-dependent induction of erythropoietin mRNA and plasma levels with IP. Taken together, this model provides highly reproducible renal injury and protection by IP, thus minimizing variability associated with previous techniques based on clamping of the renal pedicle. Further studies on renal ischemia/IP in mice may consider this technique.
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PMID:Use of a hanging-weight system for isolated renal artery occlusion during ischemic preconditioning in mice. 1691 63

Ischemia/reperfusion (IR) injury is a leading cause of acute renal failure and an important contributor to allograft damage. Tissue factor (TF) is up-regulated during IR, and TF inhibition reduces renal injury. However, the underlying mechanisms by which TF contributes to injury have not been elucidated. We postulated that TF contributes to IR injury by production of coagulation proteases and subsequent signaling by protease activated receptor (PARs). We compared renal injury after 25 minutes of bilateral renal ischemia and varying periods of reperfusion in C57BL/6 mice, those expressing low levels of TF (low-TF), hirudin-treated C57BL/6, and mice lacking either PAR-1 or PAR-2. C57BL/6 mice developed severe renal failure and died within 48 hours of reperfusion. In contrast, low-TF, hirudin-treated C57BL/6, and PAR-1-/- mice were protected from renal failure and had reduced mortality, tubular injury, neutrophil accumulation, and lower levels of the chemokines KC and MIP-2. Importantly, PAR-1-/- mice had lower chemokine levels despite up-regulation of TF and fibrin deposition. In addition, treating PAR-1-/- mice with hirudin conferred no additional benefit. Somewhat surprisingly, PAR-2 deficiency did not protect from renal failure. These experiments indicate that increased TF activity after renal IR leads to increased CXC chemokine expression and subsequent neutrophil-mediated injury predominantly by thrombin-dependent PAR-1 signaling.
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PMID:Tissue factor deficiency and PAR-1 deficiency are protective against renal ischemia reperfusion injury. 1699 Jun 8

The purpose of this study was to determine the effects of hiatal and thoracic clamping on postoperative outcome and morbidity and factors affecting mortality and morbidity. The records of 102 patients who had undergone ruptured abdominal aortic aneurysm repair between 1993 and 2005 were evaluated retrospectively. Hiatal clamping and thoracic clamping were performed in 72 patients and 30 patients, respectively. Postoperative complications and survival were evaluated comparatively between the two groups by univariate and multivariate statistical analyses. Overall mortality and hospital mortality rates were 63 (61.8%) and 24 (23.5%) patients, respectively; and there was no difference between the two groups. Postoperative respiratory complications, gastrointestinal complications, and blood requirement were higher in the thoracic clamping group. Preoperative shock and renal ischemia time (>30 min) were found to be significant predictors of hospital mortality. Postoperative renal failure was the only independent postoperative predictor of mortality. In the follow-up period, cardiac event was an independent predictor of late mortality. If hospital mortalities were excluded, 5-year and 10-year cumulative survivals were 57.82 +/- 5.85% and 38.16 +/- 6.97%, respectively. Cross-clamp level did not have a significant effect on long-term survival. Although both thoracic and hiatal clamping had no effect on mortality, postoperative respiratory complications, blood requirement, and intestinal ischemia were more pronounced in patients operated with thoracic clamping. Hiatal clamping is preferable for a safe postoperative period.
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PMID:Effects of thoracic and hiatal clamping in repair of ruptured abdominal aortic aneurysms. 1751 62

The present study evaluated the effects of heme oxygenase-1 (HO-1) induction on the changes in renal outer medullary nitric oxide (NO) and peroxynitrite levels during 45-min renal ischemia and 30-min reperfusion in anesthetized rats. Glomerular filtration rate (GFR), outer medullary blood flow (OMBF), HO and nitric oxide synthase (NOS) isoform expression, and renal low-molecular-weight thiols (-SH) were also determined. During ischemia significant increases in NO levels and peroxynitrite signal were observed (from 832.1 +/- 129.3 to 2,928.6 +/- 502.0 nM and from 3.8 +/- 0.7 to 9.0 +/- 1.6 nA before and during ischemia, respectively) that dropped to preischemic levels during reperfusion. OMBF and -SH significantly decreased after 30 min of reperfusion. Twenty-four hours later, an acute renal failure was observed (GFR 923.0 +/- 66.0 and 253.6 +/- 55.3 microl.min(-1).g kidney wt(-1) in sham-operated and ischemic kidneys, respectively; P < 0.05). The induction of HO-1 (CoCl(2) 60 mg/kg sc, 24 h before ischemia) decreased basal NO concentration (99.7 +/- 41.0 nM), although endothelial and neuronal NOS expression were slightly increased. CoCl(2) administration also blunted the ischemic increase in NO and peroxynitrite (maximum values of 1,315.6 +/- 445.6 nM and 6.3 +/- 0.5 nA, respectively; P < 0.05), preserving postischemic OMBF and GFR (686.4 +/- 45.2 microl.min(-1).g kidney wt(-1)). These beneficial effects of CoCl(2) on ischemic acute renal failure seem to be due to HO-1 induction, because they were abolished by stannous mesoporphyrin, a HO inhibitor. In conclusion, HO-1 induction has a protective effect on ischemic renal failure that seems to be partially mediated by decreasing the excessive production of NO with the subsequent reduction in peroxynitrite formation observed during ischemia.
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PMID:Heme oxygenase-1 induction improves ischemic renal failure: role of nitric oxide and peroxynitrite. 1789 Apr 22


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