Zhiling Zhang1, Juping Zhao2, Joseph Zabell3, Erick Remer4, Jianbo Li5, Jack Campbell3, Wen Dong3, Diego Aguilar Palacios3, Tulsi Patel3, Sevag Demirjian3, Steven C Campbell6. 1. Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA; Department of Urology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. 2. Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA; Department of Urology, Shanghai JiaoTong University School of Medicine, Ruijin Hospital, Shanghai, China. 3. Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA. 4. Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA; Imaging Institute, Cleveland Clinic, Cleveland, OH, USA. 5. Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA; Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA. 6. Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA. Electronic address: campbes3@ccf.org.
Abstract
BACKGROUND: Proteinuria is included in the Kidney Disease: Improving Global Outcomes (KDIGO) risk stratification for chronic kidney disease (CKD) in the general population. However, the importance of proteinuria in patients with renal cancer has not been adequately studied. OBJECTIVE: To evaluate the prognostic impact of preoperative proteinuria on overall survival (OS) and renal function stability (RFS) for patients managed with renal cancer surgery. DESIGN, SETTING, AND PARTICIPANTS: From 1999 to 2008, 977 patients who underwent renal cancer surgery had preoperative data recorded for the glomerular filtration rate (GFR) estimated using the CKD Epidemiology Collaboration equation (G1 ≥90, G2 60-89, G3a 45-59, G3b 30-44, G4 15-29, and G5 <15ml/min/1.73 m2) and proteinuria status according to a dipstick assay (ANEG, negative or trace protein; APOS, ≥30mg/dl). Median follow-up was 8.7 yr (range 7.0-10.7). INTERVENTION: Renal cancer surgery. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: OS and RFS (avoidance of a decline in GFR of ≥50% and of dialysis) were analyzed using the Kaplan-Meier method. We performed multivariable Cox regression to evaluate independent predictors for both outcomes. RESULTS AND LIMITATIONS: The 326 patients (33%) with APOS proteinuria status had compromised 5-yr OS compared with ANEG patients (65% vs 77%; p<0.001). They also had lower RFS at 5 yr (72% vs 86%; p<0.001). However, significant differences in OS according to proteinuria status were only observed in the G1, G2, and G3a groups, and differences in RFS in the G3a group. On multivariable analysis for all patients and for the G1, G2, and G3a groups, proteinuria was an independent prognostic factor for OS (both p<0.05). On multivariable analysis for all patients and for those in the G3a group, proteinuria was an independent prognostic factor for RFS (both p<0.05). Limitations include the retrospective study design and potential ascertainment bias. CONCLUSIONS: Proteinuria appears to be a significant and independent predictor of OS and RFS in patients undergoing renal cancer surgery, particularly for certain cohorts, and should be sensibly incorporated into routine management. Further studies, ideally prospective, are required to evaluate the importance of the degree of proteinuria. The generalizability of our findings will also require further investigation. PATIENT SUMMARY: Protein in the urine (proteinuria) is a sign of kidney damage, and kidney cancer patients with proteinuria have worse outcomes after surgery. Assessment of proteinuria should be routinely included in the preoperative evaluation of patients with kidney cancer.
BACKGROUND: Proteinuria is included in the Kidney Disease: Improving Global Outcomes (KDIGO) risk stratification for chronic kidney disease (CKD) in the general population. However, the importance of proteinuria in patients with renal cancer has not been adequately studied. OBJECTIVE: To evaluate the prognostic impact of preoperative proteinuria on overall survival (OS) and renal function stability (RFS) for patients managed with renal cancer surgery. DESIGN, SETTING, AND PARTICIPANTS: From 1999 to 2008, 977 patients who underwent renal cancer surgery had preoperative data recorded for the glomerular filtration rate (GFR) estimated using the CKD Epidemiology Collaboration equation (G1 ≥90, G2 60-89, G3a 45-59, G3b 30-44, G4 15-29, and G5 <15ml/min/1.73 m2) and proteinuria status according to a dipstick assay (ANEG, negative or trace protein; APOS, ≥30mg/dl). Median follow-up was 8.7 yr (range 7.0-10.7). INTERVENTION: Renal cancer surgery. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: OS and RFS (avoidance of a decline in GFR of ≥50% and of dialysis) were analyzed using the Kaplan-Meier method. We performed multivariable Cox regression to evaluate independent predictors for both outcomes. RESULTS AND LIMITATIONS: The 326 patients (33%) with APOS proteinuria status had compromised 5-yr OS compared with ANEG patients (65% vs 77%; p<0.001). They also had lower RFS at 5 yr (72% vs 86%; p<0.001). However, significant differences in OS according to proteinuria status were only observed in the G1, G2, and G3a groups, and differences in RFS in the G3a group. On multivariable analysis for all patients and for the G1, G2, and G3a groups, proteinuria was an independent prognostic factor for OS (both p<0.05). On multivariable analysis for all patients and for those in the G3a group, proteinuria was an independent prognostic factor for RFS (both p<0.05). Limitations include the retrospective study design and potential ascertainment bias. CONCLUSIONS: Proteinuria appears to be a significant and independent predictor of OS and RFS in patients undergoing renal cancer surgery, particularly for certain cohorts, and should be sensibly incorporated into routine management. Further studies, ideally prospective, are required to evaluate the importance of the degree of proteinuria. The generalizability of our findings will also require further investigation. PATIENT SUMMARY: Protein in the urine (proteinuria) is a sign of kidney damage, and kidney cancer patients with proteinuria have worse outcomes after surgery. Assessment of proteinuria should be routinely included in the preoperative evaluation of patients with kidney cancer.