The impact of post‐nephroureterectomy surgically induced chronic kidney disease on survival outcomes

Objective To investigate the prevalence, predictors and impact of surgically induced chronic kidney disease (CKD‐S) on survival outcomes in patients with upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU). Methods Utilising the ROBUUST 2.0 registry, a multicentre retrospective analysis was conducted in patients with UTUC undergoing RNU between 2006 and 2022 who did not have baseline chronic kidney disease (CKD) stages 3–5. We calculated the prevalence of postoperative CKD‐S3a (estimated glomerular filtration rate [eGFR] 59–45 mL/min/1.73 m 2 ) and CKD‐S3b (eGFR <45 mL/min/1.73 m 2 ) as measured by the Chronic Kidney Disease Epidemiology Collaboration 2021 equation. The analytical cohort was stratified by postoperative CKD stage [no CKD‐S [eGFR ≥60 mL/min/1.73 m 2 ]; CKD‐S3a [eGFR 59–45 mL/min/1.73 m 2 ] and CKD‐S3b [eGFR <45 mL/min/1.73 m 2 ]). The primary outcome was all‐cause mortality (ACM). Predictors for development of CKD‐S3a/3b and ACM/cancer‐specific mortality (CSM) were analysed using logistic and Cox regression, respectively. Kaplan–Meier analysis was used to analyse overall survival (OS) and cancer‐specific survival (CSS) among postoperative CKD groups. Results We analysed 1862 patients; 34.7% (646) and 39.6% (738), respectively, developed CKD‐S3a and CKD‐S3b. Predictors of CKD‐S3b included increasing age (odds ratio [OR] 1.03, P = 0.029), decreasing preoperative eGFR (OR 1.06, P < 0.001) and receipt of neoadjuvant (OR 2.07, P = 0.006) and adjuvant chemotherapy (OR 1.41, P = 0.012). Worsened ACM was associated with CKD‐S3b (hazard ratio 1.42, P = 0.032), but not CKD‐S3a ( P = 0.766). Development of CKD‐S3a ( P = 0.812) and CKD‐S3b ( P = 0.316) were not associated with CSM. The 5‐year OS rate was significantly worse in CKD‐S3b (no‐CKD 71%, CKD‐S3a 70%, CKD‐S3b 59%; P = 0.017). No differences between CKD‐S groups were noted for 5‐year CSS (no‐CKD 78%, CKD‐S3a 77%, CKD‐S3b 82%; P = 0.44). Conclusions A significant proportion of UTUC patients undergoing RNU developed CKD‐S. Development of CKD‐S3b was associated with worse ACM. Increasing age, preoperative eGFR, and chemotherapy were associated with developing CKD‐S3b. Our findings call for further exploration and refinement of nephron‐preserving surgical strategies and non‐nephrotoxic systemic therapy to improve survival outcomes in UTUC.