Preservation of Renal Function Following Partial or Radical Nephrectomy Using 24-Hour Creatinine Clearance

european urology 54 (2008) 143 152 available at www.sciencedirect.com journal homepage: www.europeanurology.com Kidney Cancer Preservation of Renal Function Following Partial or Radical Nephrectomy Using 24-Hour Creatinine Clearance Aaron T.D. Clark a, Rodney H. Breau a, Chris Morash a, Dean Fergusson b, Steve Doucette b, Ilias Cagiannos a, * a Division of Urology, Department of Surgery, University of Ottawa, Ontario, Canada b Ottawa Health Research Institute, University of Ottawa, Ontario, Canada Article info Article history: Accepted March 16, 2008 Published online ahead of print on March 27, 2008 Keywords: Creatinine Creatinine clearance Partial nephrectomy Nephrectomy Nephron sparing Renal function Renal function tests Abstract Objective: To compare the effect on renal function of partial and radical nephrectomy using creatinine clearance measurements from 24-hr urine collection. Methods: All patients with a solid enhancing renal mass suspicious for renal cell carcinoma, a normal contralateral kidney, and not dialysis dependent were enrolled in this prospective cohort study. Patients were treated with partial or radical nephrectomy by one urologist. Creatinine clearance (CrCl) measurements were prospectively obtained by 24-hr urine collection preoperatively, and at 3, 6, and 12 mo postoperatively. Mean change in creatinine clearance from baseline was compared at 3, 6, and 12 mo. Serum creatinine and Cockcroft-Gault calculations were also performed for comparison. Mixed model analysis incorporating patient and tumor characteristics and the procedure type was performed in SAS Version 9.1. Results: Sixty-three consecutive patients were enrolled in this study. The partial nephrectomy (n = 26) and radical nephrectomy (n = 37) groups were similar with respect to age, sex, presence of hypertension, vascular disease, diabetes mellitus, and angiotensin converting enzyme inhibitor or receptor blocker use. The postoperative change in creatinine clearance was significantly less ( p-value < 0.0001) in the partial nephrectomy group ( 0.09 ml/s, 6.1%) compared to the radical nephrectomy group ( 0.56 ml/s, 31.6%). Linear regression analysis showed intervention type (partial vs. radical nephrectomy) was the most significant predictor of change in creatinine clearance ( p-value < 0.0001). Conclusions: There is significantly less deterioration in the overall renal function of patients who are treated with partial nephrectomy compared to radical nephrectomy. This highlights the importance of performing nephron-sparing surgery on appropriate patients. # 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved. Abbreviations: CrCl, Creatinine Clearance; egfr, estimated Glomerular Filtration Rate; Cr, Serum Creatinine; NSS, Nephron Sparing Surgery; PN, Partial Nephrectomy; RN, Radical Nephrectomy; NSAID, Non-Steroidal Anti-Inflammatory Drugs; ACEI, Angiotensin Converting Enzyme Inhibitor; ARB, Angiotensin Receptor Blocker; CT, Computed Tomography; GFR, Glomerular Filtration Rate. * Corresponding author. Division of Urology, Department of Surgery, The Ottawa Hospital Civic Campus, B3 Urology, 1053 Carling Avenue, Ottawa, Ontario K1Y 4E9, Canada. Tel. +1 613 761 4500; Fax: +1 613 761 5305. E-mail address: icagiannos@ottawahospital.on.ca (I. Cagiannos). 0302-2838/$ see back matter # 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.eururo.2008.03.037

144 european urology 54 (2008) 143 152 1. Introduction Surgical extirpation with radical or partial nephrectomy remains the preferred management for solid or complex cystic renal masses. In appropriate patients, it has been found that oncologic outcome is equivalent between radical and partial nephrectomy, and the incidence of adverse surgical events is similar [1 4]. As favorable outcome and safety data mature, urologists have become more aggressive in sparing kidneys which contain large tumors in patients who have a normal contralateral kidney. Furthermore, ubiquitous use of, and improvement in, abdominal imaging modalities such as computed tomography has resulted in an increase in the detection of incidental small renal masses that now account for 60% 70% of all diagnosed renal masses [5]. These small renal masses are thought to be ideal candidates for nephron-sparing surgery. However, recent population-based studies have revealed, somewhat surprisingly, that radical nephrectomies were being performed on the great majority of patients (92% to 96%), and up to 80% of those tumors that may be amenable to partial nephrectomy [6 8]. These findings are concerning, as several studies have shown that patients who undergo partial nephrectomy have better renal function and are less likely to require renal replacement therapy [9 12]. These studies evaluated renal function using serum creatinine or calculated glomerular filtration rates (GFR), which have been shown to underestimate true kidney function and are less accurate when compared to measured creatinine clearance by 24-hr urine collection [13,14]. In this study, we compare renal function in patients who have undergone a partial or radical nephrectomy using 24-hr urine creatinine clearance, considered a superior measure for renal function estimation over the use of serum creatinine alone or GFR estimate equations. 2. Methods Between November 2003 and November 2006, 81 consecutive patients with solid enhancing renal masses suspicious for renal cell carcinoma (RCC) were treated by a single urologic oncologist at our institution. Patients presenting with a solitary renal mass and a normal contralateral kidney were enrolled in a prospective internal review board (IRB) approved study. Patients were excluded if they had a solitary kidney, bilateral renal tumors, were on dialysis preoperatively, or had a diagnosis of renal artery stenosis. Other exclusion criteria were noncompliance with 24-hr urine collection or follow-up, postoperative NSAID use for greater than 1 wk, postoperative use of gentamicin, intravenous contrast within the first 3 mo, or postoperative shock. Treatment with radical (RN) or partial nephrectomy (PN) was selected at the discretion of the treating surgeon. Laparoscopic or open radical nephrectomy was deemed necessary or preferred in patients with large or extensive tumors and in those with suspected lymph node involvement. Patients with tumors less than 4 cm and those with impaired renal function were predominantly treated with open partial nephrectomy. Partial nephrectomy was performed using an open retroperitoneal approach. Cold ischemia was employed in all partial nephrectomy cases by clamping the renal vessels and packing the kidney with ice for 10 min prior to tumor excision. Radical nephrectomy was performed by either an open retroperitoneal approach or laparoscopic transperitoneal approach. Patients baseline demographic information was collected, including age; sex; presence of hypertension, vascular disease, and diabetes; use of angiotensin converting enzyme inhibitors (ACEI) or receptor blockers (ARB); and tumor size, histology, and stage. Renal function evaluations were performed preoperatively and at 3, 6, and 12 mo postoperatively. Creatinine clearance (CrCl) measurements were obtained in all patients who met the inclusion criteria by 24-hr urine collection (CrCl = (24-hr urine creatinine 24-hr urine volume)/(serum creatinine 86400 s/day)). Routine blood work, including serum creatinine (Cr), was also collected at the same intervals for comparison. Cockcroft-Gault calculations of estimated glomerular filtration rate (egfr) were also performed. The mean change in 24-hr urine CrCl and egfr was calculated for each procedure type and compared using a standard t-test. Linear regression multivariate analysis using average postoperative CrCl as the dependent variable and incorporating the recorded patient and tumor characteristics as well as procedure type was performed in SAS Version 9.1 (SAS Institute Inc., Cary, NC) to show the effect of individual risk factors on renal function. To account for correlation in responses within each patient, the spatial power covariance structure in SAS proc mixed was used. 3. Results Of the 81 patients who underwent a radical or partial nephrectomy during the study period (Fig. 1), 18 patients were excluded. Eight patients in the RN group and 10 patients in the PN group were excluded. Sixty-three consecutive patients who had two kidneys, had unilateral tumor involvement, and were not dialysis dependent had preoperative CrCl measured by 24-hr urine collection available for analysis. Of 26 patients in the PN group, 24 patients had 3-mo follow-up, 19 had 6-mo follow-up, and 21 had 12-mo follow-up. Of 37 patients in the RN group, 35 patients had 3-mo follow-up, 29 had 6-mo follow-up, and 33 had 12-mo follow-up. Preoperative risk factors were similar between the two groups (Table 1); however, the PN group had worse preoperative creatinine clearance measured

european urology 54 (2008) 143 152 145 Fig. 1 Selection of patients during the study. Table 1 Demographics and distribution of preoperative risk factors for renal insufficiency Radical nephrectomy Partial nephrectomy p-value No. pts. 37 26 Baseline CrCl 1.77 0.59 ml/s 1.48 0.57 ml/s 0.06 Baseline serum Cr 90 29 mmol/l 109 52 mmol/l 0.11 Age (mean) 63.7 12.5 60.0 13.9 0.27 Male sex 21 (56.8%) 21 (80.8%) 0.05 Hypertension 23 (62.2%) 16 (61.5%) 0.96 Vascular disease 11 (29.7%) 10 (38.5%) 0.47 Diabetes 5 (13.5%) 2 (7.8%) 0.47 ACEI/ARB use 12 (32.4%) 9 (34.6%) 0.87 Tumor size (mean) 5.2 2.9 cm 2.7 1.5 cm <0.0001 by 24-hr urine (1.48 ml/min. vs. 1.77 ml/min, p-value = 0.06) and higher preoperative serum Cr (109 mmol/l vs. 90 mmol/l, p-value = 0.11). Tumor size was smaller in patients undergoing PN as compared to RN (2.7 cm vs 5.2 cm, p-value < 0.0001). The mean decrease in measured CrCl was 0.09 ml/s ( 6.1%) in the PN group and 0.56 ml/ min ( 31.6%) in the RN group ( p-value < 0.0001) (Table 2). Mean decrease in egfr was 0.05 ml/s ( 5.3%) in the PN group and 0.21 ml/s ( 21.2%) in the RN group ( p-value = 0.0002) (Table 3). The change in CrCl at 3-, 6-, and 12-mo follow-up periods is shown in Fig. 2. One patient in the RN group and no patients in the PN group went on permanent dialysis. The linear regression analysis using average postoperative CrCl as the dependent variable and controlling for tumor size, patient age, sex, comorbidity, angiotensin active medication, baseline measured CrCl, and procedure type showed that Table 2 Preoperative CrCl, average of postoperative CrCl, and change (D) in CrCl Preop CrCl (ml/s) Postop CrCl (ml/s) D CrCl 95% CI PN 1.48 0.57 1.39 0.59 0.09 (6.1%) 0.02 0.16 RN 1.77 0.59 1.21 0.41 0.56 (31.6%) 0.45 0.67 p-value (D CrCl) 0.06 0.13 < 0.0001

146 european urology 54 (2008) 143 152 Table 3 Preoperative egfr, average of postoperative egfr, and change (D) in egfr Preop egfr (ml/s) Postop egfr (ml/s) D egfr 95% CI PN 0.95 0.33 0.90 0.33 0.06 (5.3%) 0.03 0.08 RN 0.99 0.33 0.78 0.25 0.21 (21.2%) 0.14 0.28 p-value (D CrCl) 0.71 0.11 0.0002 Fig. 2 Change in creatinine clearance over 12 mo of followup after a partial or radical nephrectomy. Table 4 Results of the regression analysis of factors affecting kidney function Variable Model coefficient p-value Baseline creatinine clearance 0.69 <0.0001 Partial procedure 0.39 <0.0001 Hypertension 0.06 0.45 Vascular disease 0.05 0.52 ACEI/ARB 0.09 0.26 Diabetes 0.10 0.36 Tumor size 0.02 0.16 Age 0.006 0.02 only type of procedure (PN vs RN), age, and preoperative CrCl were predictive of postoperative change in kidney function measured by 24-hr urine creatinine clearance ( p-value < 0.0001) (Table 4). 4. Discussion Radical nephrectomy has been the standard of care for the management of solid or complex cystic masses for many years [15]. It has been traditional thinking among urologists that removal of the entire kidney provides excellent cancer control without compromise of overall renal function. This rationale stems from transplant literature where renal donors have not been found to have a higher long-term risk of renal insufficiency or dialysis compared to agematched controls [16 21]. For this reason, partial nephrectomy was originally reserved for patients with compromised renal function and for those with a solitary kidney or bilateral tumors. As indications and experience with partial nephrectomy have expanded, more recent studies have suggested that there is a significant decline in renal function after radical nephrectomy as compared to partial nephrectomy [9 12]. In the present study, we have shown radical nephrectomy results in a 31.6% reduction in overall renal function, as measured by 24-hr urine CrCl, compared to only a 6.1% reduction with partial nephrectomy ( p-value < 0.0001). Patients undergoing RN therefore had a 25.5% greater decline in their renal function compared to those having PN. This is the first study to use 24-hr urine CrCl measurements and, therefore, provides the most compelling evidence to date of the superiority of partial nephrectomy regarding renal function preservation. The changes in renal function as a result of PN and RN were seen at the 3-, 6-, and 12-mo follow-up assessments and were consistent throughout (Fig. 2). The immediate and then persistent change in CrCl measurement suggests that the choice of operation will have long-term impact on renal function. Indeed, in our multivariate analysis controlling for preoperative factors that may impact renal function, the operation performed, RN or PN, strongly predicted postoperative change, with patients undergoing PN having significantly less deterioration in their renal function. Over the past 10 yr, nephron-sparing surgery has become the standard of care for patients with tumors 4 cm as studies have demonstrated equivalent cancer control compared to radical nephrectomy [1 4,22]. The boundary for NSS surgery is constantly being challenged, with recent evidence suggesting that expanding the indications to tumors up to 7 cm in appropriately selected patients is safe and efficacious [23 26]. Recent advances in technology, patient demands, and widespread acceptance of laparoscopic techniques have, however, produced a resurgence in radical nephrectomy for small, solitary tumors. A recent paper revealed that 58% of patients with tumors < 2 cm and 80% of patients with tumors 2 4 cm were managed with radical nephrectomy in the United States in 2001 [6]. The Nationwide Inpatient Sample also showed that only 7.5% of all kidney cancer was surgically managed

european urology 54 (2008) 143 152 147 with partial nephrectomy [7]. This trend also applied to England, where only 4% of kidney cancer surgeries were partial nephrectomies in 2002 [8]. The authors of that study concluded that partial nephrectomy is underutilized in the ideal candidates for nephron-sparing surgery and suggested this is due to urologists unfamiliarity with this procedure. Furthermore, due to emphasis on outcomes such as reduced hospital stay, reduced analgesic usage, and earlier return to work, some are concerned that patients are preferentially being offered laparoscopic nephrectomy when an open partial nephrectomy may provide the best outcome [27]. Overemphasis on the short-term benefits of laparoscopy may drive surgeons unable to perform the more technically advanced procedure of laparoscopic partial nephrectomy away from nephronsparing surgery altogether. In other cases in which attempted laparoscopic partial nephrectomies are abandoned for technical reasons, surgeons are preferentially performing laparoscopic total nephrectomies instead of converting to an open partial nephrectomy. Our study indicates that the underutilization of PN comes with significant renal function consequences. Previous studies have also suggested that there is a significant decline in renal function after radical nephrectomy as compared to partial nephrectomy. Matin et al compared the outcomes of open partial nephrectomy and laparoscopic radical nephrectomy for patients with tumors less than 4 cm [1]. This group found that there was a 25% (0.97 to 1.38 mg/dl) increase in mean serum creatinine from preop to postop in the laparoscopic radical nephrectomy group as compared to 0% (0.91 to 0.96 mg/dl) in the open partial nephrectomy group ( p < 0.001). McKiernan et al found an increase in mean serum creatinine from 1.0 mg/dl to 1.5 mg/ dl for the RN group compared to 0.98 to 1.0 mg/dl for the partial nephrectomy group ( p-value < 0.001) [2]. Lau et al retrospectively compared the two procedures and found a lower 10-yr cumulative incidence of chronic renal insufficiency, as defined by a serum creatinine level greater than 2 mg/dl, in patients who underwent partial nephrectomy compared to radical nephrectomy (11.6% vs 22.4%, RR = 3.7, p = 0.01) [3]. A recent paper by Huang et al estimated glomerular filtration rate (GFR) from serum creatinine using the abbreviated Modification in Diet and Renal Disease (MDRD) study equation; they found that patients undergoing a radical nephrectomy were at significant risk (65% 3-yr probability) compared to partial nephrectomy (20% 3-yr probability) for the development of chronic kidney disease, defined as GFR less than 60 ml/min per 1.73 m 2 and less than 45 ml/min per 1.73 m 2 [12]. All of these studies evaluated renal function using serum creatinine or calculated glomerular filtration rates. Serum creatinine or calculations using only serum Cr are inaccurate in patients with mild renal insufficiency, in patients who are older, and in patients who are not in a steady state of creatinine production and distribution [28]. GFR estimate equations, including the MDRD and Cockcroft-Gault equations, were designed using populations with chronic kidney disease and are therefore less accurate in populations with mild renal insufficiency or normal renal function [28]. All of these variables are represented in this patient population. For this reason, in our study, we used creatinine clearance based on direct measurement of 24-hr urine collection. Although still a surrogate marker of GFR, this is considered a far more accurate estimation [12,13]. A recent paper looking at different calculations to estimate GFR in patients with advanced bladder cancer concluded that these calculations underestimate GFR when compared to CrCl measurements by 24-hr urine [13]. In our analysis, the percentage decline in postoperative renal function comparing RN to PN was, 21.2% vs 5.3% for the Cockroft-Gault equation and 31.6% vs 6.1% with 24-hr urine CrCl measurements. This highlights that egfr based on serum Cr underestimates the true impact of radical nephrectomy on postoperative renal function. Using the more accurate measure of 24-hr urine CrCl shows the true detriment that loss of an entire kidney causes. Conversely, partial nephrectomy is excellent at preserving renal function. There was only a minimal 6.1% decline in CrCl, which, although statistically significant, may not be clinically relevant. Only one of the patients in our study met criteria for renal failure and went onto dialysis over the 12-mo follow-up. However, the changes in kidney function estimated by 24-hr urine creatinine clearance seen in our patient population puts them at an increased risk of developing chronic renal failure with longer-term follow-up. Patients with chronic renal failure have reduced quality of life and are at increased risk of comorbid events such as hypertension, anemia, malnutrition, neuropathy, cardiovascular disease, and mortality [29,30]. This study has several limitations. We designed this study to prospectively collect data on all patients surgically treated for a renal mass for 3 yr total as opposed to performing power calculations for sample size. This could be viewed as a limitation with our sample size; however, the 95% confidence interval calculations for change in CrCl

148 european urology 54 (2008) 143 152 are significantly different for the PN and RN groups, therefore limiting the possibility of a Type II error (Table 2). Additionally, this study represents a single-surgeon experience performed in a nonrandomized fashion. We should also point out that creatinine clearance measured by 24-hr urine collection can have inherent difficulties with respect to patient compliance when applied to the general population outside the study setting. The results of a 24-hr urine collection must be interpreted with caution if applied outside the study setting because of errors in collection of timed urine. Despite these limitations, we feel the results of this study contribute to our knowledge of the natural history of renal function following surgical management for renal cell carcinoma. This data set is the first to our knowledge to use CrCl measured by 24-hr urine collection and provides compelling evidence for the benefits of PN. 5. Conclusion Partial nephrectomy has minimal impact on postoperative renal function measured by 24-hr urine CrCl, whereas radical nephrectomy is associated with significantly greater renal function decline. Our study highlights the importance of using more accurate measurements of renal function in assessing the true impact on renal function in patients undergoing surgical management of kidney cancer. Partial nephrectomy is currently an underutilized procedure, and our data highlight the importance of performing nephron-sparing surgery in all eligible patients. Author contributions: Ilias Cagiannos had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Clark, Cagiannos, Morash Acquisition of data: Clark, Breau Analysis and interpretation of data: Clark, Cagiannos, Breau, Fergusson, Doucette Drafting of the manuscript: Clark, Cagiannos, Breau Critical revision of the manuscript for important intellectual content: Cagiannos, Morash, Fergusson Statistical analysis: Doucette, Fergusson, Clark Obtaining funding: none Administrative, technical, or material support: none Supervision: Cagiannos, Morash Other (specify): none Financial disclosures: I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/ affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: none Funding/Support and role of the sponsor: none References [1] Belledegrun A, Tsui KH, dekernion JB, Smith RB. Efficacy of nephron-sparing surgery for renal cell carcinoma: analysis based on the new 1997 tumor-node-metastasis staging system. J Clin Oncol 1999;17:2868 75. [2] Lerner SE, Hawkins CA, Blute ML, et al. Disease outcome in patients with low stage renal cell carcinoma treated with nephron sparing or radical surgery. J Urol 1996;155:1868 73. [3] Hafez KS, Fergany AF, Novick AC. Nephron sparing surgery for localized renal cell carcinoma: impact of tumor size on patient survival, tumor recurrence and TNM staging. J Urol 1999;162:1930 3. [4] Herr H. Partial nephrectomy for unilateral renal carcinoma and a normal contralateral kidney: 10 year followup. J Urol 1999;161:33 4. [5] Russo P. Renal cell carcinoma: presentation, staging, and surgical treatment. Semin Oncol 2000;27:160 76. [6] Hollenbeck BK, Taub DA, Miller DC, et al. National utilization trends of partial nephrectomy for renal cell carcinoma: a case of underutilization. Urol 2006;67:254 9. [7] Miller DC, Hollingsworth JM, Hafez KS, et al. Partial nephrectomy for small renal masses: an emerging quality of care concern? J Urol 2006;175:853 7. [8] Nuttall M, Cathcart P, van der Meulen J, et al. A description of radical nephrectomy practice and outcomes in England: 1995 2002. BJU Int 2005;96:58 61. [9] Matin SF, Gill IS, Worley S, Novick AC. Outcome of laparoscopic radical and open partial nephrectomy for the sporadic 4 cm or less renal tumor with a normal contralateral kidney. J Urol 2002;168:1356 60. [10] McKiernan J, Simmons R, Katz J, Russo P. Natural history of chronic renal insufficiency after partial and radical nephrectomy. Urology 2002;59:816 20. [11] Lau WK, Blute ML, Weaver AL, Zincke H. 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 42. [12] Huang WC, Levey AS, Serio AM, et al. Chronic kidney disease after nephrectomy in patients with renal cortical tumors: a retrospective cohort study. Lancet Oncol 2006;7:735 40. [13] Raj GV, Iasonos A, Herr H, Donat SM. Formulas calculating creatinine clearance are inadequate for determining eligibility for cisplatin based chemotherapy in bladder cancer. J Clin Oncol 2006;24:3095 100. [14] Toussaint ND, Agar JWM, D Intini V. Calculating glomerular filtration rate in a young man with a large muscle mass. Med J Aust 2006;4:221 2.

european urology 54 (2008) 143 152 149 [15] Robson CJ, Churchill BM, Anderson W. The results of radical nephrectomy for renal cell carcinoma. J Urol 1969;101:297 301. [16] Talseth T, Fauchald P, Skrede S, et al. Long-term blood pressure and renal function in kidney donors. Kidney Int 1986;29:1072 6. [17] Vincenti F, Amend WJC, Kaysen G, et al. Long-term renal function in kidney donors. Transplantation 1983;36: 626 9. [18] Williams SL, Oler J, Jorkansky DK, et al. Long-term renal function in kidney donors: a comparison of donors and their siblings. Ann Intern Med 1986;105:1 8. [19] Najarian JS, Chavers BM, McHugh LE, et al. 20 years and more follow-up of living related kidney donors. Lancet 1992;340:807 10. [20] Miller IJ, Suthanthiran M, Riggio RR, et al. Impact of renal donation: long-term clinical and biochemical follow-up of living related donors in a single center. Am J Med 1985;79:201 8. [21] Fehrman-Ekholm I, Norden G, Lennerling A, et al. Incidence of end-stage renal disease among live kidney donors. Transplantation 2006;82:1646 8. [22] Ljungberg B, Hanbury DC, Kuczyk MA, et al. Renal cell carcinoma guideline. Eur Urol 2007;51:1502 10. [23] Becker F, Siemer S, Hack M, et al. Excellent long-term cancer control with elective nephron-sparing surgery for selected renal cell carcinomas measuring more than 4 cm. Eur Urol 2006;49:1058 64. [24] Leibovich BC, Blute ML, Cheville JC, et al. Nephron sparing surgery for appropriately selected renal cell carcinoma between 4 and 7 cm results in outcome similar to radical nephrectomy. J Urol 2004;171:1066 70. [25] Patard JJ, Shvarts O, Lam JS, et al. Safety and efficacy of partial nephrectomy for all T1 tumors based on an international multicenter experience. J Urol 2004;171: 2181 5. [26] Russo P, Goetzl M, Simmons R, et al. Partial nephrectomy: the rationale for expanding the indications. Ann Surg Oncol 2002;9:680 7. [27] Kirkali Z. The motion: open partial nephrectomy is the standard of care for small respectable solid renal masses. Eur Urol 2007;51:561 4. [28] Stevens LA, Coresh J, Greene T, Levey AS. Assessing kidney function measured and estimated glomerular filtration rate. N Engl J Med 2006;354:2473 83. [29] Levey AS, Coresh J, Balk E, et al. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med 2003;139:137 47. [30] Go A, Chertow G, Fan D, et al. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004;351:1296 305. Editorial Comment on: Preservation of Renal Function Following Partial or Radical Nephrectomy Using 24-Hour Creatinine Clearance Paul Russo Cornell Weill Medical College, Department of Surgery, Urology Service, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York, USA russop@mskcc.org The authors evaluated 63 consecutive patients with renal tumors, 37 of whom underwent a radical nephrectomy (mean tumor size 5.2 cm) and 26 of whom underwent a partial nephrectomy (mean tumor size 2.7 cm). Patients were otherwise similar relative to age, sex, and presence of medical comorbidities [1]. A 24-h creatinine clearance (CrCl) was obtained preoperatively and at 3, 6, and 12 mo postoperatively. Radical nephrectomy was associated with a significantly greater decline in CrCl versus partial nephrectomy (31.6% vs 6.1%). A similar result was obtained when glomerular filtration rate was estimated (egfr) using the Cockcroft Gault equation (21.2% vs 5.3%). Although the impact on baseline renal function of larger renal tumors ultimately treated by radical nephrectomy is not known, particularly those that are endophytic and clearly replace normal kidney, and setting aside differences in accuracy between CrCl and egfr and patient compliance issues with 24-h urinary collections, the results obtained in this study confirm the deleterious impact on kidney function of radical nephrectomy previously reported. It is now abundantly clear that for small renal tumors (< 7 cm), oncologic control is equivalent whether radical or partial nephrectomy is performed [2,3]. In addition, approximately 20% of patients will have a benign tumor (including oncocytoma, lipid poor angiomyolipoma), and an additional 25% will have an indolent tumor (papillary or chromophobe carcinoma) with limited metastatic potential [4,5]. Iatrogenic creation or worsening of preexisting chronic kidney disease is now a serious concern following radical nephrectomy, and evidence is emerging that overall survival (not cancer-specific survival) is worse for radical nephrectomy patients when compared to a similar cohort of patients treated with partial nephrectomy [6]. In western societies where medical comorbidities related to obesity, diabetes, hypertension, and cardiovascular disease are on the rise, chronic kidney disease is considered an independent risk factor for hospitalization, cardiovascular events, and death [7]. In a recent study from our center, 26%

150 european urology 54 (2008) 143 152 of patients with small renal tumors (< 4 cm), a serum creatinine within normal limits, and a normal-appearing contra lateral kidney had a preoperative egfr of less than 60 ml/min/1.73 m 2, consistent with stage 3 chronic kidney disease [8]. The casual radical nephrectomy for these small renal tumors, whether done by open or minimally invasive techniques, serves only to overtreat the renal tumor and create or worsen preexisting chronic kidney disease. Although radical nephrectomy is still required for massive renal tumors that are locally advanced with or without regional adenopathy, that involve the renal vein and vena cava, or as part of a cytoreductive strategy prior to systemic treatment, it should be discouraged for patients with small renal tumors amenable to partial nephrectomy. Urologists must now carefully consider chronic kidney disease and its serious consequences as they consult with patients and plan operations, particularly for T1 tumors. An easyto-do preoperative determination of egfr using web-based formulas (ie, http://www.nephron.com/ MDRD_GFR.cgi) may change surgical plans toward partial nephrectomy or careful observation in elderly patients with significant comorbidities. References [1] Clark ATD, Breau RH, Morash C, et al. Preservation of renal function following partial or radical nephrectomy using 24-hour creatinine clearance. Eur Urol 2008;54: 143 52. [2] Lee CT, Katz J, Shi WW, Thaler HT, Reuter VE, Russo P. Surgical management of renal tumors of 4 cm or less in a contemporary cohort. J Urol 2000;163:730 6. [3] Dash A, Vickers AJ, Schachter LR, et al. Comparison of outcomes in elective partial vs. radical nephrectomy for clear cell renal cell carcinoma of 4 7 cm. BJU International 2006;97:939 45. [4] McKiernan JM, Yossepowitch O, Kattan M, Simmons R, Motzer RJ, Reuter VE, et al. Partial nephrectomy for renal cortical tumors: pathological findings and impact on outcome. Urology 2002;60:1003 9. [5] Snyder ME, Bach A, Kattan MW, Raj GV, Reuter VE, Russo P. Incidence of benign lesions for clinically localized renal masses < 7 cm in radiological diameter: influence of gender. J Urol 2006;176:239 46. [6] Thompson HR, Boorjian SA, Lohse CM, et al. Radical nephrectomy for pt1a renal masses may be associated with decreased overall survival compared to partial nephrectomy. J Urol 2008;179:468 73. [7] Go AS, Chertow GM, Fan D, McCulloch CE, et al. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Eng J Med 2004;351:1296 305. [8] Huang WC, Levey AS, Serio AM, et al. Chronic kidney disease after nephrectomy in patients with renal cortical tumors: a retrospective cohort study. Lancet Oncology 2006;7:735 40. DOI: 10.1016/j.eururo.2008.03.059 DOI of original article: 10.1016/j.eururo.2008.03.037 Editorial Comment on: Preservation of Renal Function Following Partial or Radical Nephrectomy Using 24-Hour Creatinine Clearance Francesco Porpiglia University of Turin, Department of Clinical and Biological Sciences, San Luigi Hospital Orbassano (Turin), Italy porpiglia@libero.it In the past 10 years, partial nephrectomy (PN) has become the standard of care for patients with tumour 4 cm. It has been widely demonstrated that oncological control after PN is equivalent to that following radical nephrectomy (RN) and that renal function preserved for quality of life is better after nephron-sparing surgery [1 3]. Renal function after RN decreases significantly over time related to the development of a focal glomeruloscerosis because of hyperfiltration by the remaining nephrons. The severity of the glomerulosclerosis correlates with the number of removed nephrons. To prevent or avoid hyperfiltration when treating a small renal mass, it is essential to preserve the highest number of nephrons. This goal can be achieved by performing PN in eligible patients and by resecting few millimetres of healthy parenchyma during PN. The assessment of renal function should be estimated with the glomerular filtration rate (GFR). The best methods for estimating GFR are the plasmatic clearance of inuline and the 51Crethylenediaminetetraacetic acid (EDTA) scientigraphy [4]. Urinary creatinine clearance or GFR estimate equations (Cockcroft-Gauldt) can be considered as surrogates. Clark et al s well-designed, prospective study [5] compares the GFR obtained with the two abovementioned surrogates to assess renal function after PN and RN. The authors demonstrate in a

european urology 54 (2008) 143 152 151 small series that patients undergoing RN had a 25.5% greater decline in their renal function compared to those who underwent PN. They state that the best method for evaluating global renal function is the 24-h creatinine clearance. These authors should be congratulated, first, for using a scientific method to evaluate overall renal function that can be considered in the design of other urological trials and, second, especially for stressing the functional benefits of an underutilized procedure such as PN. References [1] Ljungberg B, Hanbury DC, Kuczyk MA, et al. Renal cell carcinoma guideline. Eur Urol 2007;51:1502 10. [2] Lesage K, Joniau S, Fransis K, Van Poppel H. Comparison between open partial and radical nephrectomy for renal tumours: perioperative outcome and health-related quality of life. Eur Urol 2007;51:614 20. [3] Becker F, Siemer S, Humke U, Hack M, Ziegler M, Stöckle M. Elective nephron-sparing surgery should become standard treatment for small unilateral renal cell carcinoma: long-term survival data of 216 patients. Eur Urol 2006;49:308 13. [4] Porpiglia F, Renard J, Billia M, et al. Is renal warm ischemia over 30 minutes during laparoscopic partial nephrectomy possible? One-year results of a prospective study. Eur Urol 2007;52:1170 8. [5] Clark ATD, Breau RH, Morash C, Fergusson D, Doucette S, Cagiannos I. Preservation of renal function following partial or radical nephrectomy using 24-hours creatinine clearance. Eur Urol 2008;54:143 52. DOI: 10.1016/j.eururo.2008.03.039 DOI of original article: 10.1016/j.eururo.2008.03.037 Editorial Comment on: Preservation of Renal Function Following Partial or Radical Nephrectomy Using 24-Hour Creatinine Clearance Ziya Kirkali Dokuz Eylul University School of Medicine, Department of Urology, Izmir, Turkey ziya.kirkali@gmail.com Chronic kidney disease (CKD) is an important health problem for the community. Not only do patients with renal insufficiency require renal replacement therapy, which adds a major burden to healthcare costs. Patients with various stages of CKD also have reduced quality of life and are more prone to develop cardiovascular disease and hypertension. They have increased hospitalization and mortality [1]. Contrary to our beliefs that renal insufficiency rates in patients with congenital unilateral renal agenesis, renal transplant donors, and those undergoing nephrectomy for benign disease do not differ from renal insufficiency rates in the general population, there is increasing evidence that radical nephrectomy for renal cell carcinoma (RCC) causes significantly more risk of deteriorated renal function [2]. Despite its small sample size and some minor drawbacks, the study by Clark et al [3] is important and shows us that it is time to change our paradigm and attitude. These authors have prospectively assessed preoperative and postoperative renal function by 24-hr creatinine clearance in all new patients coming to their institution with suspected RCC and a normal contralateral kidney. They found that the postoperative renal function decline is significantly higher in those undergoing radical nephrectomy compared with partial nephrectomy. This decline was persistent throughout 12 mo. The most important aspect of this study is that the authors have used 24-h creatinine clearance for the first time in this setting. While serum creatinine levels, measurement of glomerular filtration rate (GFR) by Cockroft-Gault formula, or the Modification of Diet in Renal Disease study (MDRD) equation are reasonable estimations of renal function, they may not be as accurate as the 24- h creatinine clearance in those populations with normal or minimal loss of renal function. Although we have no level 1 evidence that partial nephrectomy is oncologically equal or superior to radical nephrectomy for RCC, it has been the standard practice based on accumulated data that show equal if not better survival rates. As stated in the paper, partial nephrectomy and other nephronsparing approaches are underutilized in different parts of the world. It is not uncommon even today to see that a patient with a T1 renal mass is treated by laparosocopic radical nephrectomy. The time has come to change our paradigm and consider nephron-sparing surgery for RCC whenever feasible and possible. We must train our colleagues on the proper management of patients

152 european urology 54 (2008) 143 152 with small renal masses. It is also our endeavor to teach our colleagues the techniques of partial nephrectomy and reduce the complications with an attempt to preserve renal function as much as possible while obtaining the best oncologic outcome. [2] Lucas SM, Stern JM, Adibi M, Zeltser IS, Cadeddu JA, Raj GV. Renal function outcomes in patients treated for renal masses smaller than 4 cm by ablative and extirpative techniques. J Urol 2008;179:75 80. [3] Clark ATD, Breau RH, Morash C, Fergusson D, Doucette S, Cagiannos I. Preservation of renal function following partial or radical nephrectomy using 24-hour creatinine clearance. Eur Urol 2008;54:143 52. References [1] Go A, Chertow G, Fan D, et al. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004;351:1296 305. DOI: 10.1016/j.eururo.2008.03.058 DOI of original article: 10.1016/j.eururo.2008.03.037