title: Current Paradigm for Ischemia in Kidney Surgery.
abstract: Partial nephrectomy is the accepted standard of care for treatment of patients with small renal masses. The primary goal while performing partial nephrectomy is cancer control with a secondary important goal of maximizing renal function preservation with minimal perioperative morbidity. Recent studies have highlighted the importance of renal parenchymal quality and quantity postoperatively rather than duration of ischemia in determining long-term renal function. We review the available data regarding perioperative renal function optimization with special interest in ischemia during partial nephrectomy, highlighting the controversies and establishing future lines of investigation.
  
  
  
  We performed a comprehensive literature review for the years 1970 to 2014 via MEDLINE(®), PubMed(®) and the Cochrane Library. Review was consistent with the PRISMA (Preferred Reporting Items for Systemic Reviews and Meta-Analyses) criteria. We used MeSH (Medical Subject Headings) terms for the search including "acute kidney injury/failure," "carcinoma, renal cell/carcinoma of kidney/neoplasm of kidney," "kidney failure, chronic/end-stage kidney disease," "ischemia-reperfusion" and "warm ischemia/cold ischemia." Relevant review articles were 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.
  
  
  
  Our traditional knowledge of renal ischemia is derived from animal studies, ie kidney transplant and retrospective partial nephrectomy series that indicate the risk of renal function impairment for every minute of ischemia. Careful evaluation of historical studies highlights flaws of the use of ischemia duration as a dichotomous marker (25 or 30 minutes) while predicting renal function outcomes. Recent studies have revealed no effect of duration of ischemia on ultimate kidney function in the short or long term. Quality and quantity of parenchyma preserved postoperatively are key predictors of ultimate renal function after partial nephrectomy. Traditionally partial nephrectomy has been performed with hilar occlusion to provide a 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 avoid the perceived harmful effects of ischemia, although they convert a complex surgery into a more challenging procedure, potentially limiting the widespread use of partial nephrectomy 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 been observed to predict acute kidney injury. Within the partial nephrectomy environment the usefulness of those markers needs to be further investigated. To date, no study has proved their usefulness in the setting of partial nephrectomy.
  
  
  
  Based on the available evidence, use of a single cutoff for duration of ischemia time as a dichotomous value for renal function outcomes in the setting of partial nephrectomy is flawed. Renal ischemia is a controversial topic with a shifted paradigm within the last decade. Current evidence has shown that patients with 2 kidneys undergoing nephron sparing surgery can tolerate ischemia times of more than 30 minutes without a clinically significant decline in renal function. Biomarkers predictive of renal tubular injury fail 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.
authors.affiliation: Department of Urology, University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center, Miami, Florida; Urology Clinic, Department of Medical, Surgical and Health Science, University of Trieste, Trieste, Italy (NP).
authors.forename: Maria C
authors.initials: MC
authors.lastname: Mir
authors.affiliation: Department of Urology, University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center, Miami, Florida; Urology Clinic, Department of Medical, Surgical and Health Science, University of Trieste, Trieste, Italy (NP).
authors.forename: Nicola
authors.initials: N
authors.lastname: Pavan
authors.affiliation: Department of Urology, University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center, Miami, Florida; Urology Clinic, Department of Medical, Surgical and Health Science, University of Trieste, Trieste, Italy (NP). Electronic address: parekhd@miami.edu.
authors.forename: Dipen J
authors.initials: DJ
authors.lastname: Parekh
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000601:surgery; D015415:Biomarkers / Q000097:blood; D006801:Humans; D007511:Ischemia / Q000150:complications* / Q000209:etiology; D007668:Kidney / Q000098:blood supply / Q000503:physiopathology / Q000601:surgery*; D007677:Kidney Function Tests; D007680:Kidney Neoplasms / Q000601:surgery*; D009392:Nephrectomy / Q000009:adverse effects* / Q000379:methods; D011183:Postoperative Complications / Q000209:etiology
chemical_list: D015415:Biomarkers
keywords: acute kidney injury; biomarkers; ischemia; kidney function tests; nephrectomy