Introduction. Original Article: Clinical Investigation

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1 International Journal of Urology (2019) 26, doi: /iju Original Article: Clinical Investigation Hypertension and diabetes mellitus are not associated with worse renal functional outcome after partial nephrectomy in patients with normal baseline kidney function Alp Tuna Beksac, 1 Balaji N Reddy, 1 Alberto Martini, 1 David J Paulucci, 1 Erin Moshier, 2 Ronney Abaza, 3 Daniel D Eun, 4 Ashok K Hemal 5 and Ketan K Badani 1 1 Department of Urology, 2 The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York City, New York, 3 Robotic Urologic Surgery, Ohio Health Dublin Methodist Hospital, Dublin, Ohio, 4 Department of Urology, Temple University School of Medicine, Philadelphia, Pennsylvania, and 5 Department of Urology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA Abbreviations & Acronyms BMI = body mass index CCI = Charlson Comorbidity Index CKD = chronic kidney disease DM = diabetes mellitus egfr = estimated glomerular filtration rate HTN = hypertension PN = partial nephrectomy RCC = renal cell carcinoma RN = radical nephrectomy RPN = robotic partial nephrectomy Correspondence: Ketan K Badani M.D., Department of Urology, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, 6th Floor, New York City, NY 10029, USA. ketan.badani@mountsinai.org Received 3 May 2018; accepted 5 September Online publication 7 October 2018 Objective: To analyze the association of hypertension and/or diabetes mellitus on renal function after partial nephrectomy in patients with normal baseline kidney function. Methods: We identified 453 patients with baseline estimated glomerular filtration rate 60 that underwent robotic partial nephrectomy for a ct1 renal mass from 2008 to 2014 using a multi-institutional database. The association between estimated glomerular filtration rate and time (pre-partial nephrectomy to 24 months post-partial nephrectomy) was compared between 269 (59.4%) patients with preoperative hypertension and/or diabetes mellitus and 184 (40.6%) patients with neither hypertension nor diabetes mellitus using a multivariable model adjusting for confounders. Results: The estimated glomerular filtration rate significantly decreased over time for both groups compared with baseline (average units/month: hypertension/diabetes mellitus, no hypertension/diabetes mellitus; P < ), and the estimated glomerular filtration rate decrease per month reduced over time (P < ). The estimated glomerular filtration rate began to increase at approximately 12 months for the hypertension/diabetes mellitus group, and at approximately 18 months for the no hypertension/diabetes mellitus group. Although a greater initial decline in the estimated glomerular filtration rate after partial nephrectomy was observed for the hypertension/ diabetes mellitus group (0.68 units/month), this was not statistically significant (P = ); and while the rate of recovery from this decline was faster for the hypertension/diabetes mellitus group, this also was not statistically significant (P = ). The predicted estimated glomerular filtration rate was similar (83 ml/min/ 1.73 m 2 ) for both groups 24 months after partial nephrectomy. Conclusions: There seems to be no significant association between hypertension, diabetes mellitus and renal functional outcome after partial nephrectomy in patients with normal baseline glomerular filtration rate. Renal function declines after partial nephrectomy, but then it recovers, irrespective of the presence of hypertension or diabetes mellitus. Key words: chronic kidney disease, diabetes mellitus, functional outcome, hypertension, partial nephrectomy. Introduction PN is the preferred method to treat small renal masses. 1 The primary benefit of PN over RN is improved functional outcome. 2 However, there is a risk of ischemic damage and de novo CKD that can occur after PN. 3 Renal damage can be minimized by surgical factors, such as decreased ischemia time and decreased parenchymal volume loss. 4 HTN and DM are the most common non-surgical factors that affect renal function. Between the years , the prevalence of age-adjusted HTN among adults aged 20 years has increased to 30.4%, and a similar increase was seen for diabetes, with an age The Japanese Urological Association

2 PN in patients with DM or HTN adjusted prevalence of 11.9%. 5 Type 2 DM has been associated with decreased overall survival in patients with RCC. 6 Furthermore, HTN is second to DM in leading causes of CKD, 7 hence, the effect of HTN and DM on renal function has mostly been shown through their association with CKD. There are limited data regarding the effects of HTN and DM in patients with normal baseline kidney function undergoing PN. 8 We sought to analyze the association of these comorbidities with renal functional outcome in patients undergoing PN with normal baseline kidney function. Methods Data source and patient population The present study used a multi-institutional database of patients who underwent RPN from four surgeons in the USA from 2008 to Institutional review board approval for participation in this multi-institutional consortium was obtained by each institution. An initial sample of 715 patients undergoing RPN was identified from this database. Patients were excluded if they had surgery after 2014 (n = 120), baseline egfr <60 (n = 115), a tumor size >7 cm or no data available on baseline egfr, hypertensive and diabetic status (n = 27). There were 453 patients meeting eligibility criteria with egfr 60 and a tumor size 7 cm who underwent RPN from 2008 to 2014 who were included in the present study. Patients were classified depending on their hypertensive and diabetic status before PN. Specifically, patients in the HTN/DM group had HTN and or DM before PN. Patients in the non-htn/dm group did not have HTN or DM before PN. The HTN and DM groups were not analyzed separately because of the uneven sample size, which made the hypothesis testing invalid. Overall, there were 269 (59.4%) patients in the HTN/DM group and 184 (40.6%) patients in the no HTN/DM group. Study variables The primary outcome in the present analysis was the difference in the association between time and egfr from pre- to 24 months post-pn between the HTN/DM group and the no HTN/DM group. egfr (ml/min/1.73 m 2 ) was calculated using the Modification of Diet in Renal Disease equation. 9 HTN was defined according to the American College of Cardiology/American Heart Association Task Force guidelines. 10 Patients with HTN stage 1 were included in the analysis. DM was defined according to the American Diabetes Association criteria. 11 All patients with type 2 DM have been included in the analysis. Demographic and tumor-specific covariates compared between the groups included age, sex, race, history of tobacco use, BMI, CCI, preoperative egfr, preoperative creatinine, tumor size, RENAL nephrometry score, pathological tumor volume and kidney volume removed, pathological T stage, and tumor histology. Volume calculation was carried out using the ellipsoid formula (length 9 width 9 height 9 p / 6). 12 Perioperative characteristics including ischemia time, blood loss and postoperative complications were also compared between groups. Statistical analysis Categorical demographic, tumor-specific and operative characteristics were compared between groups using v 2 -tests of independence or Fisher s exact tests, whereas continuous variables were compared between groups using independent samples t-tests or Mann Whitney U-tests. The method of generalized estimating equations was used to estimate the curvilinear association between egfr and time from PN ( time ) in patients with and without a history of diabetes and/or HTN ( group ). A compound symmetric covariance structure was assumed to account for the correlation among repeated measurements made over time within a patient. The association between egfr and time was hypothesized and confirmed to be curvilinear, we therefore included both linear and quadratic time terms in our generalized estimating equations model. To test whether the relationship between egfr and time differed between patient groups, we included interaction terms between linear/quadratic time effects and patient group. Multivariable models were run adjusting for age, sex, BMI, preoperative egfr, CCI, ischemia time, estimated blood loss and tumor size. Variables used in the multivariate model were chosen based on clinical association with egfr recovery. Statistical analyses were carried out with the SAS version 9.4 (SAS Institute, Cary, NC, USA) software package. Results Demographic, tumor-specific and operative characteristics Characteristics of the 453 patients overall and for each group are shown in Table 1. Compared with those with neither HTN nor diabetes, patients with a history of either or both were older (61.0 vs 52.5, P < ), more likely to be male (63.2% vs 51.1%, P = ), with higher median BMI (30.77 vs 28.59, P = ) and higher CCI (3 vs 2, P < ). There was a trend for the HTN/DM group to have a larger median tumor size (3.0 cm vs 2.6 cm, P = ), with the HTN/DM group having a significantly higher pathological tumor volume (7.65 cm 3 vs 3.91 cm 3, P = ) and higher median kidney volume removed (13.49 vs 8.15, P = ). Renal function post-pn Overall, the median time for egfr follow up was 9 months for both groups, with an interquartile range (Q1 Q3) of 6 18 months. Figure 1 shows the egfr over time after PN separately for the HTN/DM and no HTN/DM groups. Results from the unadjusted analysis predicting egfr within 24 months of PN are presented in Table 2. Results from the multivariable model (Table 3) predicting egfr over time showed a significant decrease in egfr over time for both the HTN/DM group (P < ) and the no HTN/DM group (P < ). Specifically, the average decrease in egfr after PN was units per month for the HTN/DM group and units per month for the no HTN/DM group The Japanese Urological Association 121

3 AT BEKSAC ET AL. Table 1 Demographic, tumor-specific and operative characteristics of patients undergoing RPN with and without HTN or DM Overall Patients without HTN or DM Patients with HTN or DM n (40.6%) 269 (59.4%) Demographic characteristics Sex * Male 264 (58.28%) 94 (51.09%) 170 (63.20%) Female 189 (41.72%) 90 (48.91%) 99 (36.80%) Mean age, years (SD) (12.80) (13.90) (10.74) <0.0001* Race White 271 (59.82%) 104 (56.52%) 167 (62.08%) Black 29 (6.40%) 12 (6.52%) 17 (6.32%) Hispanic 8 (1.77%) 1 (0.54%) 7 (2.60%) Asian/Pacific Islander 2 (0.44%) 1 (0.54%) 1 (0.37%) Unknown 143 (31.57%) 6 (35.87%) 77 (28.62%) History of tobacco use No 114 (25.17%) 51 (27.72%) 63 (23.42%) Yes 126 (27.81%) 44 (23.91%) 82 (30.48%) Unknown 213 (47.02%) 89 (48.37%) 124 (46.10%) Median BMI (range) (17.00, 55.60) (17.00, 54.00) (17.80, 55.60) * Median CCI (range) 3 (0, 9) 2 (0, 9) 3 (0, 9) <0.0001* Median preoperative egfr (range) (60.11, ) (60.79, ) (60.11, ) Median preoperative creatinine (range) 0.87 (0.40, 1.52) 0.81 (0.45, 1.50) 0.90 (0.40, 1.52) Tumor-specific characteristics Median tumor size (range) 2.90 (0.60, 6.60) 2.60 (0.90, 6.60) 3.00 (0.60, 6.30) Tumor size (82.78%) 154 (83.70%) 221 (82.16%) (17.22%) 30 (16.30%) 48 (17.84%) Mean total renal score (SD) 6.77 (1.88) 6.68 (1.86) 6.83 (1.90) Median kidney volume removed (range) 9.65 ( 4.29, ) 8.15 ( 4.29, ) (0.75, ) * Median tumor volume (range) 5.60 (0.02, 86.70) 3.91 (0.02, 86.70) 7.65 (0.56, 76.05) * Stage pt1a 285 (62.91%) 121 (65.76%) 164 (60.97%) pt1b 43 (9.49%) 13 (7.07%) 30 (11.15%) pt2a 1 (0.22%) 1 (0.54%) 0 (0%) pt3a 19 (4.19%) 5 (2.72%) 14 (5.20%) Unknown 105 (23.18%) 44 (23.91%) 61 (22.68%) Malignant disease No 69 (15.23%) 32 (17.39%) 37 (13.75%) Yes 288 (63.58%) 117 (63.59%) 171 (63.57%) Unknown 96 (21.19%) 35 (19.02%) 61 (22.68%) Perioperative outcome Postoperative complications * No 39 (86.98%) 168 (91.30%) 226 (84.01%) Yes 58 (12.80%) 16 (8.70%) 42 (15.61%) Unknown 1 (0.22%) 0 (0%) 1 (0.37%) Median estimated blood loss (range) 100 (0, 1500) 75 (0, 800) 100 (5, 1500) Median ıschemia time (range) 15 (0 52) (0 52) 15 (0 49) *P < P-value Notably, statistical significance of the quadratic term for egfr over time (P < for both groups) provided evidence that for both groups, the rate change in egfr over time was not constant or purely linear, but was curvilinear/ convex. That is, egfr at first decreased over time for both groups, but the decrease became smaller over time until egfr began to actually improve over time for both groups (Fig. 1). Specifically for the HTN/DM group, egfr was at first decreasing, but this decrease in egfr per month became smaller by units per month (P < ), until egfr began to increase at approximately 12 months. For the no HTN/DM group, egfr was also at first decreasing, but this decrease in egfr per month became smaller by units per month (P < ) until egfr began to increase at approximately 18 months. Ultimately, the multivariable model for prediction of egfr showed no differential effect of egfr over time by HTN and diabetic status. Although a greater initial decline in egfr after PN was observed for the HTN/DM group (egfr decrease of 0.68 units more per month), this difference in the decline in egfr over time was not statistically significant (P = for the linear interaction term; Table 3) The Japanese Urological Association

4 PN in patients with DM or HTN No HTN or DM HTN and/or DM egfr Fig. 1 Comparison of egfr over time between patients with HTN and/or DM and patients Postoperative time (months) without HTN and/or DM. Table 2 Mixed model regression estimates for egfr within 24 months of PN No HTN/DM HTN/DM Unadjusted P-value Multivariable P-value Preoperative egfr (ml/min/1.73 m 2 ) Average decline in egfr per month (ml/min/1.73 m 2 ) Multivariable model adjusted for age, sex, BMI, CCI, ischemia time, estimated blood loss, tumor size and baseline egfr. b SE (standard error of b estimate) shown. Additionally, although the rate of recovery (i.e. extent to which the decline in egfr became less negative over the 2- year follow-up period after the initial decline) was faster for the HTN/DM group, this greater rate of recovery was not statistically significant (P = for the quadratic interaction term; Table 3). By 24 months after PN, the predicted egfr was 83 ml/ min/1.73 m 2 for both the HTN/DM and non-htn/dm patients, respectively. Before 24 months, HTN/DM patients in this series maintained a lower-to-slightly lower egfr after PN. Specifically, the predicted egfr for a typical patient at 6 months after PN was 77 and 85 ml/min/1.73 m 2 among hypertensive/diabetic and non-hypertensive/diabetic patients, respectively. At 12 months after PN, the egfr was 74 and 81 ml/min/1.73 m 2 among hypertensive/diabetic and nonhypertensive/diabetic patients, respectively. Discussion HTN and DM are significant risk factors for CKD. 7 The present analysis, however, shows that the presence of HTN and/ or DM is not associated with worse renal functional outcome of patients with normal baseline renal function after PN. Initially, HTN/DM was associated with a slightly more detrimental effect on the egfr, but was also associated with faster recovery, ultimately leading to a predicted egfr that was the same (83 ml/min/1.73 m 2 ) for both groups 24 months after PN. egfr outcome was similar despite the higher age, tumor size, BMI, CCI and lower baseline egfr in the HTN/DM group, all of which are associated with worse functional outcome. 13,14 Because all patients had normal baseline kidney function (i.e. egfr 60), it is likely that sufficient nephron reserve negated the detrimental effect of DM and HTN on functional outcome in 2 years. Normal baseline kidney function is beneficial in counteracting the ischemic damage of PN and functional recovery after PN. 15 This is most likely due to the compensatory function of the healthy contralateral kidney. Thus, in patients without CKD, it is often difficult to show the detrimental effect of ischemia time and clamping techniques on global kidney function after PN, unless the effect is large. 16,17 Based on the present results that show no association between HTN/ DM and functional outcome, we hypothesized that the effects of HTN and DM on functional outcome were also likely mediated by the high global kidney function of this cohort. Indeed, our multivariate analysis showed that higher preoperative GFR was associated with higher egfr at postoperative 24 months, which correlates well with other studies in the literature. 16,18 Future studies are necessary to evaluate whether HTN and DM are associated with worse renal function outcome after PN in patients with baseline CKD or with a solitary kidney. The clinical significance of the present results is twofold. One is the prediction of functional outcome and counseling 2018 The Japanese Urological Association 123

5 AT BEKSAC ET AL. Table 3 Adjusted multivariable model for prediction of egfr within 24 months of PN Variable Estimate Standard error of estimate P-value Intercept < Age (years) Female BMI CCI Ischemia time Estimated blood loss Tumor size Preoperative egfr < No HTN or DM Months postoperative < Months postoperative < No HTN or DM 9 months postoperative No HTN or DM 9 months postoperative Preoperative egfr for the HTN/DM group adjusting for all other factors. The difference in preoperative egfr for the no HTN/DM group versus HTN/DM group adjusting for all other factors. The average decline in egfr per month for the HTN/DM group adjusting for all other factors. The average change in the decline in egfr per month for the HTN/DM group adjusting for all other factors. The difference in the average decline in egfr per month for the no HTN/DM group versus HTN/DM group adjusting for all other factors. The difference in the average decline in egfr per month for the no HTN/DM group versus HTN/DM group adjusting for all other factors. of patients accordingly. The second benefit is in the clinical decision-making. Evidence suggests that comorbidities do affect the decision-making of urologists. In a case control study of 835 patients who underwent surgery for kidney cancer, Filson et al. reported that patients with both DM and HTN were twice as likely to receive PN over RN. However, patients with either DM or HTN were not more likely to receive PN. 19 The present results show that the decision to carry out surgery should not be affected by the presence of DM and/or HTN, as long as the baseline kidney function is normal. The present results are supported by Isharwal et al., who reported that comorbidities did not impact renal functional recovery in a multi-institutional analysis of 405 patients. Functional renal mass preservation was the major factor in predicting functional outcome. 20 It is likely that in the present PN series, functional volume loss was not significant enough to cause detrimental effects. Although our results do not have a sufficient level of evidence to suggest anything regarding the surgical treatment methods, the presence of HTN and DM should not influence the follow up of functional outcome. The functional outcome was similar between the two groups, despite the unfavorable characteristics in the DM/ HTN group. BMI was higher in the HTN/DM group, which is to be expected, as the association of weight and type 2 DM is well known. 21 The mean age was higher by 9 years and the median CCI was higher, which was also unsurprising, as we compared two groups based on their comorbidities. These differences seem to have resulted in an increased rate of complications in the HTN/DM group. 22 Furthermore, the median tumor volume was slightly higher in the HTN/DM group, which likely resulted in the increased resected volume, which has detrimental effects on functional outcome. Furthermore, the present multivariate analysis showed that PN had a curvilinear effect on functional outcome. Patients with HTN/DM had lower egfr in the short-term outcome. However, this effect diminished at 24 months. Furthermore, warm ischemia time was associated with postoperative egfr decline up to 24 months. Specifically, for every minute increase in ischemia time, egfr at 24 months decreased by 4.08 ml/min/1.73 m 2. The present results contradict the literature. Thompson et al. previously reported that ischemia time resulted in worse egfr only if ischemia was >25 min. 23 The present results differed from the previous studies, in that we found an association between ischemia time and egfr despite our low mean ischemia time of 15 min, which was much lower than the threshold of 25 min in the aforementioned studies. 3,23 However, we did not analyze or control for resected or remaining parenchymal volume in our study. The present study was limited by its retrospective design and the inherently associated selection bias. Our database did not include the presence or absence of proteinuria, which is shown to predict CKD after PN. 24 We also did not assess the duration and severity of HTN or DM due to the lack of such data, which is a significant contributor to kidney function. Additionally, the Modification of Diet in Renal Disease formula was originally validated for patients with CKD, and does not include adjustment for BMI. The strengths of the present study include the multi-institutional design and relative data granularity in our standardized, prospectively collected database. Overall, HTN and DM were not associated with worse renal functional outcome in patients with normal baseline GFR after PN. These comorbidities should not influence surgical approach or functional follow up of localized renal tumors. Future studies with prospective design are required to validate the present results. Conflict of interest None declared. References 1 Motzer RJ, Jonasch E, Agarwal N et al. Kidney cancer, version , NCCN clinical practice guidelines in oncology. J. Natl. Compr. Canc. Netw. 2017; 15: Campbell S, Uzzo RG, Allaf ME et al. Renal mass and localized renal cancer: AUA guideline. J. Urol. 2017; 198: Volpe A, Blute ML, Ficarra V et al. Renal ıschemia and function after partial nephrectomy: a collaborative review of the literature. Eur. Urol. 2015; 68: Dagenais J, Maurice MJ, Mouracade P, Kara O, Malkoc E, Kaouk JH. Excisional precision matters: understanding the ınfluence of excisional volume loss on renal function after partial nephrectomy. Eur. Urol. 2017; 72: National Center for Health Statistics. Health, United States, 2015: With Special Feature on Racial and Ethnic Health Disparities. National Center for Health Statistics, Hyattsville, MD, The Japanese Urological Association

6 PN in patients with DM or HTN 6 Vavallo A, Simone S, Lucarelli G et al. Pre-existing type 2 diabetes mellitus is an independent risk factor for mortality and progression in patients with renal cell carcinoma. Medicine 2014; 93: e Hart PD, Bakris GL. Hypertensive nephropathy: prevention and treatment recommendations. Expert Opin. Pharmacother. 2010; 11: Abouassaly R, Finelli A, Tomlinson GA, Urbach DR, Alibhai SM. How often are patients with diabetes or hypertension being treated with partial nephrectomy for renal cell carcinoma? A population-based analysis BJU Int. 2011; 108: Levey AS, Stevens LA, Schmid CH et al. A new equation to estimate glomerular filtration rate. Ann. Intern. Med. 2009; 150: Whelton PK, Carey RM, Aronow WS et al ACC/AHA/AAPA/ABC/ ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the american college of cardiology/american heart association task force on clinical practice guidelines. J. Am. Coll. Cardiol. 2018; 71: e American Diabetes Association. 2. Classification and diagnosis of diabetes. Diabetes Care 2017; 40: S Jorns J, Thiel DD, Lohse CM et al. Three-dimensional tumour volume and cancer-specific survival for patients undergoing nephrectomy to treat pt1 clear-cell renal cell carcinoma. BJU Int. 2012; 110: Chapman D, Moore R, Klarenbach S, Braam B. Residual renal function after partial or radical nephrectomy for renal cell carcinoma. Can. Urol. Assoc. J. 2010; 4: Reinstatler L, Klaassen Z, Barrett B, Terris MK, Moses KA. Body mass index and comorbidity are associated with postoperative renal function after nephrectomy. Int. Braz. J. Urol. 2015; 41: Lane BR, Demirjian S, Derweesh IH et al. Survival and functional stability in chronic kidney disease due to surgical removal of nephrons: ımportance of the new baseline glomerular filtration rate. Eur. Urol. 2015; 68: 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: Lee JW, Kim H, Choo M et al. Different methods of hilar clamping during partial nephrectomy: ımpact on renal function. Int. J. Urol. 2014; 21: Hakimi AA, Ghavamian R, Williams SK et al. Factors that affect proportional glomerular filtration rate after minimally invasive partial nephrectomy. J. Endourol. 2013; 27: Filson CP, Schwartz K, Colt JS et al. Use of nephron-sparing surgery among renal cell carcinoma patients with diabetes and hypertension. Urol. Oncol. 2014; 32: e Isharwal S, Ye W, Wang A et al. Impact of comorbidities on functional recovery from partial nephrectomy. J. Urol. 2017; 199: Gallagher EJ, LeRoith D. Obesity and diabetes: the ıncreased risk of cancer and cancer-related mortality. Physiol. Rev. 2015; 95: Tomaszewski JJ, Uzzo RG, Kutikov A et al. Assessing the burden of complications after surgery for clinically localized kidney cancer by age and comorbidity status. Urology 2014; 83: 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: O Donnell K, Tourojman M, Tobert CM et al. Proteinuria is a predictor of renal functional decline in patients with kidney cancer. J. Urol. 2016; 196: Editorial Comment Editorial Comment to Hypertension and diabetes mellitus are not associated with worse renal functional outcome after partial nephrectomy in patients with normal baseline kidney function There are abundant data in the literature showing that in patients with underlying chronic kidney disease due to medical causes, there are worse long-term renal functional outcomes and less renal recovery after partial nephrectomy (PN). 1 However, studies thus far have failed to show the impact of patient comorbidities on postoperative renal function. 2,3 The authors of the present study sought to clarify what role, if any, the presence of chronic kidney disease risk factors should play in clinical decision-making. 4 They investigated 453 patients who had normal renal function before undergoing robotic PN, and analyzed renal functional outcomes based on a patient history of diabetes mellitus (DM) and/or hypertension (HTN). Using a multivariable model for prediction of the estimated glomerular filtration rate (egfr), they found that although there was an initial steeper decline in renal function after robot-assisted PN among patients with these comorbidities, this effect was negated by a greater recovery of function at 2 years, when no difference in the predicted egfr between patients with DM and/or HTN and healthy individuals was recorded. This lack of difference in egfr at 24 months is even more striking in light of the statistically significant difference in tumor volume and median kidney volume removed, with a substantially larger number of nephrons excised in the HTN/DM group. Previous literature showed that preoperative GFR and the quantity of spared nephrons are the most important factors in renal functional preservation after PN. 5 Interestingly, the DM and/or HTN cohort in the present study had a larger average presurgical tumor size, as well as significantly larger pathological tumor size and median kidney volume removed. This might suggest that the surgeons treating this cohort attempted more aggressive PN in patients who might otherwise simply have undergone radical nephrectomy. Also worth noting is that the study sample size prohibited separate analysis of DM and HTN. As such, it is unclear if any of the study findings are more heavily attributable to either comorbidity. This is important given that DM has been suggested to play a larger role in the development of chronic kidney disease than HTN. 6 Furthermore, all stages of diabetic and hypertensive disease were analyzed together, ignoring the potential impact of disease severity on susceptibility to both renal injury and recovery. Finally, the findings regarding the effect of warm ischemia time on egfr decline are particularly interesting, as they suggest that warm ischemia time might still be important in the min window. Clearly, the jury is still out and more evidence is required The Japanese Urological Association 125