EURURO-6105; No. of Pages 2 EUROPEAN UROLOGY XXX (2015) XXX–XXX

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Platinum Priority – Editorial Referring to the article published on pp. x–y of this issue

Renal Ischemia During Partial Nephrectomy: Does Every Minute Still Count? James Porter * Department of Urology, Swedish Medical Center, Seattle, WA, USA

The current state of research on the impact of renal ischemia on renal function (RF) after partial nephrectomy (PN) is presented by Volpe et al [1] in this month’s issue of European Urology. The authors, including many of the thought leaders on PN, have presented a thorough overview of this topic including the early research on ischemic injury of the kidney. This background provides an important historical context for the current concepts of the role of warm ischemic injury during nephron-sparing surgery (NSS). They remind us that normothermic renal ischemia creates a spectrum of injury based on histologic alterations beginning approximately 20 min after clamping and extending >60 min. This indicates that the traditional 30-min limit of warm ischemia time (WIT) is a somewhat arbitrary time point and was not based on clinical outcomes. They present more recent work on renal ischemia focusing on solitary kidneys, and one well-known study in particular revealed a 5% increase in risk for acute renal failure for every additional minute of WIT, leading to the conclusion that ‘‘every minute counts’’ when the renal hilum is clamped during PN [2]. This study, more than any other, focused attention on the impact of renal ischemia on RF and set the stage for much of the debate on what is an acceptable WIT. The most recent research on RF after PN has shifted focus toward the contribution of preserved functional renal parenchyma after NSS. Interestingly, in many of the reports, when the amount of preserved renal parenchyma was evaluated on multivariate analysis, renal ischemia was found not to be a significant factor affecting RF. The authors of this review correctly point out that ischemia time and preserved renal parenchyma may be linked based on the fact that larger, more complex tumors require longer ischemia times and removal of more normal tissue with complex reconstruction

[1]. They reach the overall conclusion that RF after PN is most dependent on preoperative RF and the amount of preserved vascularized renal parenchyma. WIT correlates with the amount of renal tissue preserved, and prolonged warm ischemia periods (>25 min) should be avoided. What does this review [1] add to the current understanding of ischemic injury during PN? Simply stated, factors other than renal ischemia must be considered to maintain optimal RF after NSS. These factors can be divided into modifiable and nonmodifiable categories, with the latter being patient age, preoperative RF, and nephrometry score, which takes into account tumor size and location. The modifiable factors are WIT and preserved functional renal parenchyma and are the subject of current debate as to which is most important in maintaining RF after PN. Given the characterization by Lane et al [3] of preserved renal parenchyma as a nonmodifiable factor, it may be reasonable to consider that for a given tumor location and size, there are multiple methods of tumor excision and renorrhaphy, and each technique will result in more or less preserved renal parenchyma. Many surgeons perform tumor enucleation exclusively, whereas others will aim for a 5-mm rim of normal tissue to ensure an adequate surgical margin. Renorrhaphy technique can vary widely as well, from deep sutures running the base of the defect to precise vessel suture ligation to no renorrhaphy at all [4]. Given these variations in surgical approach, the amount of preserved renal parenchyma is dependent on the surgeon, not unlike how long a surgeon may choose to leave a kidney clamped. If the amount of preserved functional parenchyma is potentially more important than renal ischemia in determining RF after PN, then how this measure is determined is vitally important to the stated results and the conclusions

DOI of original article: http://dx.doi.org/10.1016/j.eururo.2015.01.025. * Department of Urology, Swedish Medical Center, 1101 Madison, Suite 1400, Seattle, WA 98104, USA. Tel. +1 206 386 6266; Fax: +1 206 622 1052. E-mail address: [email protected]. http://dx.doi.org/10.1016/j.eururo.2015.02.037 0302-2838/# 2015 Published by Elsevier B.V. on behalf of European Association of Urology.

Please cite this article in press as: Porter J. Renal Ischemia During Partial Nephrectomy: Does Every Minute Still Count? Eur Urol (2015), http://dx.doi.org/10.1016/j.eururo.2015.02.037

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reached. Surgeons’ intraoperative estimates of preserved renal volume were used in several studies cited in this review, and these studies have been influential in changing our view of the role of ischemia during PN [3,5,6]. However, intraoperative estimates of tissue preservation are subjective and tend to be inaccurate [7]. In the study by Lane et al [3] of 660 open PNs in solitary kidneys, preserved parenchyma was estimated by multiple surgeons (21 surgeons in the study) and 35% of the cases had no data on estimated preserved renal parenchyma. Because surgeon estimates of preserved parenchyma are subjective, computed tomography–based volumetric measurements of renal parenchyma before and after PN have provided an objective method for determining percentage of renal volume preserved and may provide a reproducible way to compare results across institutions [8,9]. Until consensus can be reached on the best way to determine preserved functional renal parenchyma after PN and external validation can be performed outside of a few institutions, the conclusions reached regarding the role of preserved tissue on RF need to be viewed carefully. The evidence of the impact of preserved functional renal tissue after PN does not mean we can now ignore renal ischemia; rather, the surgeon attempting NSS must broaden the focus beyond WIT alone and consider factors that improve the quantity and quality of renal tissue. Determining which factor is more important for maintaining RF may be hindered by the nature of retrospective data. A prospective randomized trial using a reproducible, objective method of measuring preserved functional renal tissue and warm ischemia ranges may be a step toward gaining more clarity on this issue. Until that time, renal ischemia should be limited, if at all possible, during NSS. So, the debate continues: Is renal ischemia more important than preserved renal tissue or vice versa? At this time, it appears that both are vital to preserving RF after

PN, and this review has illuminated this point very well [1]. Whether ischemia and preserved tissue represent two sides of the same coin may not be as important as the recognition that both factors are under surgeon control and must be balanced with the other goal of NSS: cancer control. Conflicts of interest: Dr. Porter is a speaker and proctor for Intuitive Surgical and a speaker for B-K Medical.

References [1] Volpe A, Blute ML, Ficarra V, et al. Renal ischemia and function after partial nephrectomy: a collaborative review of the literature. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2015.01.025 [2] Thompson RH, Lane BR, Lohse CM, et al. Every minute counts when the renal hilum is clamped during partial nephrectomy. Eur Urol 2010;58:340–5. [3] Lane BR, Russo P, Uzzo RG, et al. Comparison of cold and warm ischemia during partial nephrectomy in 660 solitary kidneys reveals predominant role of nonmodifiable factors in determining ultimate renal function. J Urol 2011;185:421–7. [4] Baumert H, Ballaro A, Shah N, et al. Reducing warm ischaemia time during laparoscopic partial nephrectomy: a prospective comparison of two renal closure techniques. Eur Urol 2007;52:1164–9. [5] Thompson RH, Lane BR, Lohse CM, et al. Renal function after partial nephrectomy: effect of warm ischemia relative to quantity and quality of preserved kidney. Urology 2012;79:356–60. [6] Chan AA, Wood CG, Caicedo J, Munsell MF, Matin SF. Predictors of unilateral renal function after open and laparoscopic partial nephrectomy. Urology 2010;75:295–302. [7] Simmons MN, Fergany AF, Campbell SC. Effect of parenchymal volume preservation on kidney function after partial nephrectomy. J Urol 2011;186:405–10. [8] Simmons MN, Hillyer SP, Lee BA, et al. Functional recovery after partial nephrectomy:effects of volume loss and ischemic injury. J Urol 2012;187:1667–73. [9] Mir MC, Campbell RA, Sharma N, et al. Parenchymal volume preservation and ischemia during partial nephrectomy: functional and volumetric analysis. Urology 2013;82:263–8.

Please cite this article in press as: Porter J. Renal Ischemia During Partial Nephrectomy: Does Every Minute Still Count? Eur Urol (2015), http://dx.doi.org/10.1016/j.eururo.2015.02.037

Renal Ischemia During Partial Nephrectomy: Does Every Minute Still Count?

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