Tolerance of the Human Kidney to Isolated Controlled Ischemia

Department of Urology, University of Miami Miller School of Medicine, Dominion Tower, 5th Floor, 1400 NW 10th Avenue, Miami, FL 33136. .
Journal of the American Society of Nephrology (Impact Factor: 9.34). 02/2013; 24(3):506-17. DOI: 10.1681/ASN.2012080786
Source: PubMed


Tolerance of the human kidney to ischemia is controversial. Here, we prospectively studied the renal response to clamp ischemia and reperfusion in humans, including changes in putative biomarkers of AKI. We performed renal biopsies before, during, and after surgically induced renal clamp ischemia in 40 patients undergoing partial nephrectomy. Ischemia duration was >30 minutes in 82.5% of patients. There was a mild, transient increase in serum creatinine, but serum cystatin C remained stable. Renal functional changes did not correlate with ischemia duration. Renal structural changes were much less severe than observed in animal models that used similar durations of ischemia. Other biomarkers were only mildly elevated and did not correlate with renal function or ischemia duration. In summary, these data suggest that human kidneys can safely tolerate 30-60 minutes of controlled clamp ischemia with only mild structural changes and no acute functional loss.

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    • "Nevertheless, the significance of the effect of ischemia type and duration on long-term renal function (RF) has been questioned. In fact, some investigators suggest that the human kidney is extremely tolerant to ischemic insults [3], whereas others report that the amount of preserved healthy renal parenchyma may supersede ischemia as the primary predictor of RF after NSS [4] [5]. "
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    ABSTRACT: Partial nephrectomy (PN) is the current gold standard treatment for small localized renal tumors.; however, the impact of duration and type of intraoperative ischemia on renal function (RF) after PN is a subject of significant debate. To review the current evidence on the relationship of intraoperative ischemia and RF after PN. A review of English-language publications on renal ischemia and RF after PN was performed from 2005 to 2014 using the Medline, Embase, and Web of Science databases. Ninety-one articles were selected with the consensus of all authors and analyzed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. The vast majority of reviewed studies were retrospective, nonrandomized observations. Based on the current literature, RF recovery after PN is strongly associated with preoperative RF and the amount of healthy kidney parenchyma preserved. Warm ischemia time (WIT) is modifiable and prolonged warm ischemia is significantly associated with adverse postoperative RF. Available data suggest a benefit of keeping WIT <25min, although the level of evidence to support this threshold is limited. Cold ischemia safely facilitates longer durations of ischemia. Surgical techniques that minimize or avoid global ischemia may be associated with improved RF outcomes. Although RF recovery after PN is strongly associated with quality and quantity of preserved kidney, efforts should be made to limit prolonged WIT. Cold ischemia should be preferred when longer ischemia is expected, especially in presence of imperative indications for PN. Additional research with higher levels of evidence is needed to clarify the optimal use of renal ischemia during PN. In this review of the literature, we looked at predictors of renal function after surgical resection of renal tumors. There is a strong association between the quality and quantity of renal tissue that is preserved after surgery and long-term renal function. The time of interruption of renal blood flow during surgery is an important, modifiable predictor of postoperative renal function. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
    Full-text · Article · Feb 2015 · European Urology
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    • "Mitochondria of kidney proximal tubules figure prominently in the development of acute kidney injury via their contributions to compromised energetics [1]–[3], by generation of reactive oxygen species that induce both damaging and protective events including sustained upregulation of proinflammatory processes [4], as central mediators of both the intrinsic and extrinsic pathways of apoptosis [5], and as targets of autophagy [6]. Recent observations during controlled clinical ischemia/reperfusion illustrate their involvement in human acute kidney injury [7]. "
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    ABSTRACT: Kidney proximal tubules subjected to hypoxia/reoxygenation develop a nonesterified fatty acid-induced energetic deficit characterized by persistent partial mitochondrial deenergization that can be prevented and reversed by citric acid cycle substrates. To further assess the role of competition between fatty acids and substrates on inner membrane substrate carriers in the deenergization and the contribution to deenergization of fatty acid effects on respiratory function, digitonin-permeabilized rabbit and mouse tubules were studied using either addition of exogenous oleate after control normoxic incubation or increases of endogenous fatty acids produced by hypoxia/reoxygenation. The results demonstrated major effects of matrix oxaloacetate accumulation on succinate-supported energization and respiration and their modification by fatty acids. Improvements of energization in the presence of fatty acids by glutamate were shown to result predominantly from lowering matrix oxaloacetate rather than from amelioration of transmembrane cycling of fatty acids and uncoupling. Mouse tubules had 2.5 fold higher rates of succinate utilization, which resulted in stronger effects of oxaloacetate accumulation than rabbit tubules. Hypoxia/reoxygenation induced respiratory inhibition that was more severe for complex I-dependent substrates. Fatty acids themselves did not acutely contribute to this respiratory inhibition, but lowering them during 60 min. reoxygenation to allow recovery of ATP during that period alleviated it. These data clarify the basis for the nonesterified fatty acid-induced mitochondrial energetic deficit in kidney proximal tubules that impairs structural and functional recovery and provide insight into interactions that need to be considered in the design of substrate-based interventions to improve mitochondrial function.
    Full-text · Article · Apr 2014 · PLoS ONE
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    Preview · Article · Jun 2013 · Journal of the American Society of Nephrology
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