selected for the type of ischemia based on clinical and tu-mor characteristics and on surgeon preferences, whichpotentially introduced selection bias in both groups.Nevertheless, our study demonstrated that ischemic renaldamage was less in the cold ischemia group, particularly inthose individuals with long ischemic times of�25minutes.We could not determine the safe limit of cold ischemic timebecause of an insufficient number of cases with prolongedcold ischemia. Accumulation of cases with longer coldischemic times is required to clarify this point.

CONCLUSIONUsing a 99mTc-MAG3 renal scintigraphy parameter, wecompared renal ischemic damage after open partial ne-phrectomy between warm and cold ischemia groups.Warm ischemic times of 20-25 minutes induced temporaryrenal injury that recovered in 6 months, whereas warmischemia of �25 minutes caused long lasting diffusedamage throughout the operated kidney. Cold ischemiafor up to 58 minutes prevented ischemic injury to the renalremnant. Therefore, renal hypothermia should be appliedwhen the ischemic time is expected to be �25 minutes.

References

1. Sun M, Bianchi M, Hansen J, et al. Chronic kidney disease afternephrectomy in patients with small renal masses: a retrospectiveobservational analysis. Eur Urol. 2012;62:696-703.

2. Kates M, Badalato GM, Pitman M, et al. Increased risk of overalland cardiovascular mortality after radical nephrectomy for renal cellcarcinoma 2 cm or less. J Urol. 2011;186:1247-1253.

3. Tan HJ, Norton EC, Ye Z, et al. Long-term survival following partialvs radical nephrectomy among older patients with early-stage kidneycancer. JAMA. 2012;307:1629-1635.

4. Rizkala ER, Khalifeh A, Autorino R, et al. Zero ischemia roboticpartial nephrectomy: sequential preplaced suture renorrhaphytechnique. Urology. 2013;82:100-104.

5. Harke N, Schoen G, Schiefelbein F, et al. Selective clamping underthe usage of near-infrared fluorescence imaging with indocyaninegreen in robot-assisted partial nephrectomy: a single-surgeonmatched-pair study. World J Urol. 2014;32:1259-1265.

6. Bollens R, Rosenblatt A, Espinoza BP, et al. Laparoscopic partialnephrectomy with “on-demand” clamping reduces warm ischemiatime. Eur Urol. 2007;52:804-809.

7. Southard JH, Senzig KA, Belzer FO. Effects of hypothermia oncanine kidney mitochondria. Cryobiology. 1980;17:148-153.

8. Thompson RH, Frank I, Lohse CM, et al. The impact of ischemiatime during open nephron sparing surgery on solitary kidneys: amulti-institutional study. J Urol. 2007;177:471-476.

9. Gill IS, Kavoussi LR, Lane BR, et al. Comparison of 1,800 lapa-roscopic and open partial nephrectomies for single renal tumors.J Urol. 2007;178:41-46.

10. Lane BR, Gill IS. 5-Year outcomes of laparoscopic partial ne-phrectomy. J Urol. 2007;177:70-74; discussion 74.

11. Becker F, Van Poppel H, Hakenberg OW, et al. Assessing theimpact of ischaemia time during partial nephrectomy. Eur Urol.2009;56:625-634.

12. Iida S, Kondo T, Amano H, et al. Minimal effect of cold ischemiatime on progression to late-stage chronic kidney disease observedlong term after partial nephrectomy. Urology. 2008;72:1083-1088;discussion 1088-9.

13. Tatsugami K, Eto M, Yokomizo A, et al. Impact of cold and warmischemia on postoperative recovery of affected renal function afterpartial nephrectomy. J Endourol. 2011;25:869-873; discussion 873-4.

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14. Marberger M. Renal ischaemia: not a problem in laparoscopicpartial nephrectomy? BJU Int. 2007;99:3-4.

15. Novick AC. Renal hypothermia: in vivo and ex vivo. Urol ClinNorth Am. 1983;10:637-644.

16. McDougal WS. Renal perfusion/reperfusion injuries. J Urol. 1988;140:1325-1330.

17. Funahashi Y, Hattori R, Yamamoto T, et al. Effect of warm ischemiaon renal function during partial nephrectomy: assessment with new99mTc-mercaptoacetyltriglycine scintigraphy parameter. Urology.2012;79:160-164.

18. Kubo A, Hashimoto J, Nakamura K, et al. Can 99mTc-mercap-toacetyltriglycine (99mTc-MAG3) evaluate the renal functionwithout blood sampling?: consensus report from multicenter study.Kaku Igaku. 1997;34:1101-1109.

19. Funahashi Y, KatoM, Yoshino Y, et al. Comparison of renal ischemicdamage during laparoscopic partial nephrectomy with artery-veinand artery-only clamping. J Endourol. 2014;191:1147-1152.

20. Matsuo S, Imai E, Horio M, et al. Revised equations for estimatedGFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53:982-992.

21. Lane BR, Russo P, Uzzo RG, et al. Comparison of cold and warmischemia during partial nephrectomy in 660 solitary kidneys revealspredominant role of nonmodifiable factors in determining ultimaterenal function. J Urol. 2011;185:421-427.

22. Porpiglia F, Fiori C, Bertolo R, et al. Does tumour size really affectthe safety of laparoscopic partial nephrectomy? BJU Int. 2011;108:268-273.

23. Thompson RH, Lane BR, Lohse CM, et al. Comparison of warmischemia versus no ischemia during partial nephrectomy on a soli-tary kidney. Eur Urol. 2010;58:331-336.

24. Lane BR, Gill IS, Fergany AF, et al. Limited warm ischemia duringelective partial nephrectomy has only a marginal impact on renalfunctional outcomes. J Urol. 2011;185:1598-1603.

25. Funahashi Y, Hattori R, Yamamoto T, et al. Ischemic renal damageafter nephron-sparing surgery in patients with normal contralateralkidney. Eur Urol. 2009;55:209-215.

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27. Ward JP. Determination of the optimum temperature for regionalrenal hypothermia during temporary renal ischaemia. Br J Urol.1975;47:17-24.

28. Gill IS, Abreu SC, Desai MM, et al. Laparoscopic ice slush renalhypothermia for partial nephrectomy: the initial experience. J Urol.2003;170:52-56.

29. Orvieto MA, Zorn KC, Lyon MB, et al. Laparoscopic ice slurrycoolant for renal hypothermia. J Urol. 2007;177:382-385.

APPENDIX

SUPPLEMENTARY DATASupplementary data associated with this article can be

found, in the online version, at http://dx.doi.org/10.1016/j.urology.2014.08.040.

EDITORIAL COMMENT

This article focuses on clamped partial nephrectomy and pro-vides a comparison of the impact of warm vs cold ischemia onfunctional recovery. It uses a novel approach to assess ischemicdamage and provides interesting and potentially useful infor-mation about this controversial topic. The most interestingaspect of the report pertains to the use of mercaptoacetyl-triglycine renal scanning to analyze uptake in the surgicallyunaffected portions of the kidney to evaluate for ischemicdamage. For instance, if the tumor was in the upper pole, thisanalysis looked at isotope uptake in a defined region of interestin the lower pole, as shown in Figure 1. If there was no ischemic

UROLOGY 84 (6), 2014

damage or related atrophy, uptake in this region of interestwould not change substantially. The analysis was performed1 week after surgery during the early recovery phase, and thenagain 6 months later corresponding with ultimate functionalrecovery. As illustrated in Figure 2, cold ischemia of any dura-tion and warm ischemia of <20 minutes had little effect onfunctional recovery at either 1 week or 6 months. In contrast,functional recovery after 1 week was deleteriously affected in thewarm ischemia patients whenever the interval was >20 minutes.At 6 months, functional recovery was near complete in patientswith a warm ischemia time of 20-25 minutes, whereas thosewith a warm ischemia time of >25 minutes failed to make acomplete recovery. The latter group was left with an approxi-mate loss of 20% function.

Figure 3 could be misleading and it is important to understandwhat is being analyzed with these data, specifically that it isfocused only on the 1-week time frame, during early recovery.This demonstrates a correlation between warm ischemia timeand mercaptoacetyltriglycine renal scan uptake in the region ofinterest away from the tumor, and the authors have emphasizedthis correlation in some of their conclusions. However, it appliesonly to the 1-week time frame, and when kidneys exposed towarm ischemia were analyzed at 6 months, complete or nearcomplete recovery was documented in all subgroups except theextended warm ischemia group (ischemia time >25 minutes), asdiscussed previously. Again, cold ischemia did not correlate withfunctional recovery at any time point, because functional re-covery tended to be complete and independent of the durationof ischemia in this setting presumably because of the protectiveeffect of hypothermia.

Such data are consistent with a growing body of evidence thatdemonstrates that most nephrons make a complete or nearcomplete recovery from ischemia during partial nephrectomy aslong as limited warm ischemia or hypothermia has beenapplied.1-5 Further studies will be required to substantiate thenovel methodology used in this analysis, such as intraobserverand interobserver reproducibility and sensitivity to choice of theregion of interest.

Steven C. Campbell, M.D., Ph.D., Zhiling Zhang, M.D., andCesar E. Ercole, M.D., Center for Urologic Oncology,Glickman Urological and Kidney Institute, Cleveland Clinic,Cleveland, OH

References

1. Thompson RH, Lane BR, Lohse CM, et al. Renal function afterpartial nephrectomy: impact of warm ischemia relative to thequantity and preoperative quality of preserved kidney. Urology. 2012;79:356-360.

2. Campbell SC. A nonischemic approach to partial nephrectomy isoptimal. Yes. J Urol. 2012;187:387-390.

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3. Simmons MN, Hillyer SP, Lee BH, et al. Functional recovery afterpartial nephrectomy: effects of volume loss and ischemic injury. JUrol. 2012;187:1667-1673.

4. Simmons MN, Lieser SG, Fergany AF, et al. Association betweenwarm ischemia time and renal parenchymal atrophy after partialnephrectomy. J Urol. 2013;189:1638-1642.

5. Mir CM, Campbell RA, Sharma N, et al. Parenchymal volumepreservation and ischemia during partial nephrectomy: functionaland volumetric analysis. Urology. 2013;82:263-268.

http://dx.doi.org/10.1016/j.urology.2014.08.041UROLOGY 84: 1412e1413, 2014. � 2014 Elsevier Inc.

REPLY

The impact of ischemia or reperfusion would be greatestimmediately after partial nephrectomy. This damage decreaseswith time and is compensated for by hyperfunctioning of thecontralateral kidney.1 To assess renal functional damage byischemia and nephron loss separately, we considered regional99mTc-mercaptoacetyltriglycine (99mTc-MAG3) uptake.2 Thiswas correlated with warm ischemic time and was not affected bytumor morphologic features.Importantly, the effect of ischemia or reperfusion was almost

diminished after 6 months when warm ischemia time was within25 minutes; however, it was retained in the prolonged warmischemia group (Fig. 2). We found correlations between 99mTc-MAG3 uptake and warm ischemia time after both 1 week and6 months; however, this was stronger after 1 week (data notshown). Therefore, we demonstrated correlations betweenischemic renal damage and ischemia time during the acutephase. Figure 3 shows that there was no correlation between99mTc-MAG3 uptake and cold ischemia time. Based on theseresults, we recommend renal cooling for cases in which ischemictime is expected to be longer than 25 minutes.

Yasuhito Funahashi, M.D., Ph.D., Department of Urology,Nagoya University Graduate School of Medicine, Nagoya,Japan

References

1. Funahashi Y, Hattori R, Yamamoto T, et al. Ischemic renal damageafter nephron-sparing surgery in patients with normal contralateralkidney. Eur Urol. 2009;55:209-215.

2. Funahashi Y, Hattori R, Yamamoto T, et al. Effect of warm ischemiaon renal function during partial nephrectomy: assessment with new99mTc-mercaptoacetyltriglycine scintigraphy parameter. Urology.2012;79:160-164.

http://dx.doi.org/10.1016/j.urology.2014.08.042UROLOGY 84: 1413, 2014. � 2014 Elsevier Inc.

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