Maria C. Mir, Nicola Pavan, Dipen J. Parekh

Partial nephrectomy is the accepted standard of care for treatment of small renal mass. The primary goal while performing a partial nephrectomy is cancer control with secondary important goals of maximizing renal function preservation with minimal perioperative morbidity. Recent studies have highlighted the importance of renal parenchymal quality and quantity after surgery rather than duration of ischemia in determining the long-term renal function. Our objectives are to review the available data regarding perioperative renal function optimization with special interest on ischemia during partial nephrectomy highlighting the controversies and establishing future lines of investigation. A comprehensive literature review was performed between 1970 and 2014 via MEDLINE, PUBMED and COCHRANE. Review was consistent with the PRISMA (Preferred Reporting Items for Systemic Reviews and Meta-Analysis) criteria. We used MESH terms for search including "acute kidney injury/failure," "carcinoma, renal cell/ carcinoma of kidney/ neoplasm of kidney," "kidney failure, chronic/end-stage kidney disease," "ischemia-reperfusion," "warm ischemia/cold ischemia". Relevant reviews were also included. Abstracts from major urological/surgical conferences were reviewed. All studies included were performed in adults, were written in English and had an abstract available for review. Our traditional knowledge of renal ischemia is derived from animal studies, kidney transplant and retrospective partial nephrectomy studies that indicate the risk of renal function impairment from every single minute of ischemia. Careful evaluation of historical studies highlight the flaws of the use of ischemia duration as a dichotomous marker (25 or 30 min) while predicting renal functional outcomes. Recent studies have demonstrated no effect of duration of ischemia on ultimate kidney function both in the short and long term. Quality and quantity of parenchyma preserved after surgery are the key predictors of ultimate renal function after PN. Traditionally PN has been performed with hilar occlusion to provide relatively bloodless surgical field allowing effective oncologic control during tumor excision with secure management of blood vessels, collecting system and renal reconstruction. Selective clamping and nonclamping techniques have been proposed to obviate the perceived harmful effects of ischemia. Albeit, they convert a complex surgery into a more challenging procedure; potentially limiting the widespread use of PN for management of renal cancers. Promising urine and blood-based biomarkers (NGAL, KIM-1) in the context of critical care settings and global stress have shown to predict acute kidney injury. Within the PN environment, the utility of those markers still needs to be further investigated. None of the studies have proven its usefulness in the setting of PN up to date. The use of a single cut off value for duration of ischemia time as a dichotomous value for renal functional outcomes in the setting of partial nephrectomy is flawed based on available evidence. Renal ischemia is a controversial topic with a shifted paradigm within the last decade. Current evidence has shown that patients with two kidneys undergoing NSS can tolerate ischemia times of more than 30 minutes without a clinically significant decline in renal function. Biomarkers predictive of renal tubular injury failed to predict acute kidney injury in the context of partial nephrectomy. Indications for partial nephrectomy could be significantly expanded, as the safety of limited renal ischemia is now better understood.