Editorial Comment
2
14. Saggi SJ, Allon M, Bernardini J, et al. Considerations in the optimal preparation of patients for dialysis. Nat Rev Nephrol. 2012;8: 381-389. 15. Najarian JS, Chavers BM, McHugh LE, et al. 20 years or more of follow-up of living kidney donors. Lancet. 1992;340:807-810. 16. Goldfarb DA, Matin SF, Braun WE, et al. Renal outcome 25 years after donor nephrectomy. J Urol. 2001;166:2043-2047. 17. Fehrman-Ekholm I, Duner F, Brink B, et al. No evidence of accelerated loss of kidney function in living kidney donors: results from a cross-sectional follow-up. Transplantation. 2001;72: 444-449. 18. Ibrahim HN, Foley R, Tan L, et al. Long-term consequences of kidney donation. New Engl J Med. 2009;360:459-469. 19. Klarenbach S, Moore RB, Chapman DW, et al. Adverse renal outcomes in subjects undergoing nephrectomy for renal tumors: a population-based analysis. Eur Urol. 2011;59:333-339. 20. Chung JS, Son NH, Byun SS, et al. Trends in renal function after radical nephrectomy: a multicentre analysis. BJU Int. 2014;113: 408-415. 21. Malcolm JB, Bagrodia A, Derweesh IH, et al. Comparison of rates and risk factors for developing chronic renal insufficiency, pro- teinuria and metabolic acidosis after radical or partial nephrectomy. BJU Int. 2009;104:476-481. 22. Sun M, Bianchi M, Hansen J, et al. Chronic kidney disease after nephrectomy in patients with small renal masses: a retrospective observational analysis. Eur Urol. 2012;62:696-703. 23. Lau WK, Blute ML, Weaver AL, et al. Matched comparison of radical nephrectomy vs nephron-sparing surgery in patients with unilateral renal cell carcinoma and a normal contralateral kidney. Mayo Clin Proc. 2000;75:1236-1242. 24. Lane BR, Campbell SC, Demirjian S, et al. Surgically induced chronic kidney disease may be associated with a lower risk of pro- gression and mortality than medical chronic kidney disease. J Urol. 2013;189:1649-1655. 25. Takagi T, Kondo T, Iizuka J, et al. Postoperative renal function after partial nephrectomy for renal cell carcinoma in patients with pre-existing chronic kidney disease: a comparison with radical nephrectomy. Int J Urol. 2011;18:472-476. 26. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratifica- tion. Am J Kidney Dis. 2002;39:S1-266. APPENDIX SUPPLEMENTARY DATA Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.urology. 2014.05.061. EDITORIAL COMMENT This is a complex study that evaluates a series of 1306 patients with localized renal masses managed with either nephron- sparing surgery (NSS) or radical nephrectomy (RN). The objective is implied by the title, namely, to determine which subgroups of patients benefit most from NSS. This is an important issue in the field as we now recognize that all chronic kidney disease (CKD) is not created equal, and in particular that patients with CKD primarily due to surgical removal of neph- rons may be more stable than those with pre-existing CKD due to medical comorbidities. 1-3 NSS is still strongly preferred for small renal masses because RN is therapeutic overkill in this setting and for patients with pre-existing CKD or whenever preservation of renal function is at a premium. 4 However, when the contralateral kidney is normal anatomically and function- ally, and the oncologic stakes are higher, decisions about NSS vs RN can be very challenging. 5 Studies such as this are greatly needed to provide further guidance in this space. What can we learn from this analysis? The authors stratified the population into 3 groups based on preoperative level of renal function: CKD I (GFR >90 mL/min/ 1.73 m 2 ), CKD II (60-89 mL/min/1.73 m 2 ), and CKD III (30-59 mL/min/1.73 m 2 ), and then they looked at potential correlates between surgical extent (NSS vs RN) and renal outcomes, either annual decline in renal function or threshold events such as development of CKD IV (GFR <30 mL/min/ 1.73 m 2 ) or CKD IIIB (GFR <45 mL/min/1.73 m 2 ). The first major finding was that the annual decline in renal function was significantly lower for NSS when compared with RN for patients with CKD I and CKD II, but not for CKD III. The second major finding relates to threshold events mentioned previously, and in this analysis NSS correlated with better outcomes than RN for the CKD-II group, but not for CKD I or CKD III. It is notable that benefits for NSS were not observed in the CKD III group, where we would prioritize NSS in our daily clinical practice. How can we account for the negative findings in this group? One potential explanation is that patients with pre- existing CKD are “driven” by their medical comorbidities, and surgical approach may not make as much of a difference in this setting. But this is a nihilistic stance that we cannot accept as renal surgeons. A better explanation lies in the data itself, namely the limitations of only modest numbers of patients in the CKD- III group and short follow-up for the study as a whole. Median follow-up was only 12 months in this study; so, many patients did not contribute meaningful data about long-term renal functional outcomes, and the CKD-III group comprised only 262 patients, with only 188 in the CKD-IIIA subgroup that was used for some of the threshold analyses. These limitations are likely contrib- uting to the negative findings in the CKD-III group, and it would be inappropriate to derive policy from this part of the analysis. At the other end of the spectrum are the CKD-I patients where threshold events related to decline of function were rarely observed, and where the functional benefit of NSS is likely not nearly as impactful, given strong functional reserve and a normal contralateral kidney in most instances. In between lies the CKD-II population where the data appear to suggest a benefit for NSS, yet even this is debatable. Mean annual decline of renal function in this population was relatively low (<2%) after both NSS and RN, and although threshold events were less common after NSS than RN (16% vs 26% after 5 years), it is not clear what impact such events will have on long- term outcomes. Indeed, the data mentioned previously about CKD due to surgical removal of nephrons are highly relevant here, in that it shows that patients with CKD primarily due to surgical removal of nephrons experienced much better overall survival than those with CKD due to medical comorbidities and approximated the survival of patients with no CKD at all. 1,3 Despite these limitations, this study promises to advance the debate about the relative merits of NSS in various settings, and will hopefully stimulate more research in this field. The authors have in general avoided overinterpretation of the data, and the readers are encouraged to follow their example. Steven C. Campbell, M.D., Ph.D., Department of Urology, Center for Urologic Oncology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH Sevag Demirjian, M.D., Department of Nephrology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OHand UROLOGY 84 (4), 2014 867
Transcript of Editorial Comment
14. Saggi SJ, Allon M, Bernardini J, et al. Considerations in the optimalpreparation of patients for dialysis. Nat Rev Nephrol. 2012;8:381-389.
15. Najarian JS, Chavers BM, McHugh LE, et al. 20 years or more offollow-up of living kidney donors. Lancet. 1992;340:807-810.
16. Goldfarb DA, Matin SF, Braun WE, et al. Renal outcome 25 yearsafter donor nephrectomy. J Urol. 2001;166:2043-2047.
17. Fehrman-Ekholm I, Duner F, Brink B, et al. No evidence ofaccelerated loss of kidney function in living kidney donors:results from a cross-sectional follow-up. Transplantation. 2001;72:444-449.
18. Ibrahim HN, Foley R, Tan L, et al. Long-term consequences ofkidney donation. New Engl J Med. 2009;360:459-469.
19. Klarenbach S, Moore RB, Chapman DW, et al. Adverse renaloutcomes in subjects undergoing nephrectomy for renal tumors: apopulation-based analysis. Eur Urol. 2011;59:333-339.
20. Chung JS, Son NH, Byun SS, et al. Trends in renal function afterradical nephrectomy: a multicentre analysis. BJU Int. 2014;113:408-415.
21. Malcolm JB, Bagrodia A, Derweesh IH, et al. Comparison of ratesand risk factors for developing chronic renal insufficiency, pro-teinuria and metabolic acidosis after radical or partial nephrectomy.BJU Int. 2009;104:476-481.
22. 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.
23. Lau WK, Blute ML, Weaver AL, et al. Matched comparison ofradical nephrectomy vs nephron-sparing surgery in patients withunilateral renal cell carcinoma and a normal contralateral kidney.Mayo Clin Proc. 2000;75:1236-1242.
24. Lane BR, Campbell SC, Demirjian S, et al. Surgically inducedchronic kidney disease may be associated with a lower risk of pro-gression and mortality than medical chronic kidney disease. J Urol.2013;189:1649-1655.
25. Takagi T, Kondo T, Iizuka J, et al. Postoperative renal function afterpartial nephrectomy for renal cell carcinoma in patients withpre-existing chronic kidney disease: a comparison with radicalnephrectomy. Int J Urol. 2011;18:472-476.
26. National Kidney Foundation. K/DOQI clinical practice guidelinesfor chronic kidney disease: evaluation, classification, and stratifica-tion. Am J Kidney Dis. 2002;39:S1-266.
APPENDIX
SUPPLEMENTARY DATASupplementary data associated with this article can be found,
in the online version, at http://dx.doi.org/10.1016/j.urology.2014.05.061.
EDITORIAL COMMENT
This is a complex study that evaluates a series of 1306 patientswith localized renal masses managed with either nephron-sparing surgery (NSS) or radical nephrectomy (RN). Theobjective is implied by the title, namely, to determine whichsubgroups of patients benefit most from NSS. This is animportant issue in the field as we now recognize that all chronickidney disease (CKD) is not created equal, and in particular thatpatients with CKD primarily due to surgical removal of neph-rons may be more stable than those with pre-existing CKD dueto medical comorbidities.1-3 NSS is still strongly preferred forsmall renal masses because RN is therapeutic overkill in thissetting and for patients with pre-existing CKD or wheneverpreservation of renal function is at a premium.4 However, whenthe contralateral kidney is normal anatomically and function-ally, and the oncologic stakes are higher, decisions about NSS vsRN can be very challenging.5 Studies such as this are greatly
UROLOGY 84 (4), 2014
needed to provide further guidance in this space. What can welearn from this analysis?The authors stratified the population into 3 groups based on
preoperative level of renal function: CKD I (GFR >90 mL/min/1.73 m2), CKD II (60-89 mL/min/1.73 m2), and CKD III(30-59 mL/min/1.73 m2), and then they looked at potentialcorrelates between surgical extent (NSS vs RN) and renaloutcomes, either annual decline in renal function or thresholdevents such as development of CKD IV (GFR <30 mL/min/1.73 m2) or CKD IIIB (GFR <45 mL/min/1.73 m2). The firstmajor finding was that the annual decline in renal function wassignificantly lower for NSS when compared with RN forpatients withCKD I andCKD II, but not for CKD III. The secondmajor finding relates to threshold events mentioned previously,and in this analysis NSS correlated with better outcomes thanRNfor the CKD-II group, but not for CKD I or CKD III.It is notable that benefits for NSS were not observed in the
CKD III group, where we would prioritize NSS in our dailyclinical practice. How can we account for the negative findings inthis group? One potential explanation is that patients with pre-existing CKD are “driven” by their medical comorbidities, andsurgical approach may not make as much of a difference in thissetting. But this is a nihilistic stance that we cannot accept asrenal surgeons. A better explanation lies in the data itself, namelythe limitations of only modest numbers of patients in the CKD-III group and short follow-up for the study as a whole. Medianfollow-up was only 12 months in this study; so, many patients didnot contribute meaningful data about long-term renal functionaloutcomes, and the CKD-III group comprised only 262 patients,with only 188 in the CKD-IIIA subgroup that was used for someof the threshold analyses. These limitations are likely contrib-uting to the negative findings in the CKD-III group, and it wouldbe inappropriate to derive policy from this part of the analysis.At the other end of the spectrum are the CKD-I patients
where threshold events related to decline of function were rarelyobserved, and where the functional benefit of NSS is likely notnearly as impactful, given strong functional reserve and a normalcontralateral kidney in most instances.In between lies the CKD-II population where the data appear
to suggest a benefit for NSS, yet even this is debatable. Meanannual decline of renal function in this population was relativelylow (<2%) after both NSS and RN, and although thresholdevents were less common after NSS than RN (16% vs 26% after5 years), it is not clear what impact such events will have on long-term outcomes. Indeed, the data mentioned previously aboutCKD due to surgical removal of nephrons are highly relevanthere, in that it shows that patients with CKD primarily due tosurgical removal of nephrons experienced much better overallsurvival than those with CKD due to medical comorbidities andapproximated the survival of patients with no CKD at all.1,3
Despite these limitations, this study promises to advance thedebate about the relative merits of NSS in various settings, andwill hopefully stimulate more research in this field. The authorshave in general avoided overinterpretation of the data, and thereaders are encouraged to follow their example.
Steven C. Campbell, M.D., Ph.D., Department of Urology,Center for Urologic Oncology, Glickman Urological andKidney Institute, Cleveland Clinic, Cleveland, OH
Sevag Demirjian, M.D., Department of Nephrology,Glickman Urological and Kidney Institute, Cleveland Clinic,Cleveland, OHand
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Cesar E. Ercole, M.D., Center for Urologic Oncology,Glickman Urological and Kidney Institute, Cleveland Clinic,Cleveland, OH
References
1. Lane BR, Campbell SC, Demirjian S, Fergany AF. Surgically-induced chronic kidney disease may be associated with a lower risk ofprogression and mortality than medical chronic kidney disease.J Urol. 2013;189:1649-1655.
2. Demirjian S, Lane BR, Derweesh I, et al. Chronic kidney disease dueto surgical removal of nephrons: relative rates of progression andsurvival [e-pub ahead of print]. J Urol. doi: 10.1016/j.juro.2014.04.016, accessed April 2014.
3. Lane BR, Demirjian S, Derweesh IH, et al: Is all chronic kidneydisease created equal? minimally invasive oncology, Edited by IS Gill,Current Opinion in Urology, 24:127-134, 2014.
4. Campbell SC, Novick AC, Belldegrun A, et al. Guideline formanagement of the clinical T1 renal mass. J Urol. 2009;182:1271-1279.
5. Campbell SC, Derweesh IH, Lane BR, Messing EM. The manage-ment of a clinical T1b renal tumor in the presence of a normalcontralateral kidney. J Urol. 2013;289:1198-1202.
http://dx.doi.org/10.1016/j.urology.2014.05.062UROLOGY 84: 867e868, 2014. � 2014 Elsevier Inc.
REPLY
Our study represents a retrospective review of nephrectomycases for localized renal masses over a 20-year time period, inwhich we compare the effects of surgical extent (nephronsparing surgery [NSS] vs radical nephrectomy [RN]) and pre-operative renal function on postoperative renal outcomes.Although many methodologically sound studies purport thebenefits of NSS compared with RN on postoperative renalfunction, the results of our study should lead to a more nuancedappreciation of the merits of NSS. Namely, when stratifyingpatients by preoperative CKD stage (I, II, or III), the annualrate of GFR decline was significantly lower for NSS vs RN inCKD stage-I and -II patients, but not in patients with stage-IIIkidney disease. The finding that those with diminished pre-operative renal function fail to demonstrate a difference in therate of postoperative GFR decline is novel in and of itself;
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however, GFR represents a numerical estimate of kidneyfunction and should be placed into clinically meaningful pa-rameters. Therefore, we also analyzed the risk of developingsignificant renal impairment (new-onset GFR <30 or <45 mL/min/1.73 m2). In terms of these more meaningful outcomes, wefind that the risk of developing significant renal impairment doesnot differ between patients who underwent NSS vs RN withpreoperative CKD stage I (as the risk is very low to begin with) orin patients with preoperative CKD stage-III disease. Only pa-tients with preoperative CKD stage-II disease demonstrated alower risk of developing significant renal impairment with NSSvs RN, a finding that held true both on univariate and multi-variate analysis. We consider this finding to be worthy ofconsideration, as it represents a seemingly counterintuitiveconclusion: the “benefits” of NSS may be lost on those withsignificant pre-existing renal impairment. As the editorscorrectly suggest, it is possible that postoperative renal functionis being “driven” by the various comorbidities that lead to thepreoperative renal impairment.The editors are correct to point out some very important
limitations of the study and caution about over interpretation ofthe results. The purpose of our study was not to question theutility of NSS, either in general or in those patients withsignificant preoperative renal impairment; but rather to providean honest accounting of the renal functional outcomes afterNSS or RN at our institution. With improved surgical tech-niques and a relatively low perioperative complication rate forNSS, performing RN is certainly therapeutic overkill in tumorsamenable for NSS. Furthermore, as urologic surgeons, we shouldalways strive to give our patients the best opportunity to livewithout developing renal impairment. But we feel the results ofour study should lead to a re-examination of the benefits of NSSat other institutions and more realistic discussion about post-operative function in patients with pre-existing renal impair-ment, regardless of renal surgery extent.
Solomon L. Woldu, M.D., andJames M. McKiernan, M.D., Department of Urology,Columbia University Medical Center, New York, NY
http://dx.doi.org/10.1016/j.urology.2014.05.063UROLOGY 84: 868, 2014. � 2014 Elsevier Inc.
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