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 m²) and CKD-S3b (eGFR <45 mL/min/1.73 m²) 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 m²]; CKD-S3a [eGFR 59-45 mL/min/1.73 m²] and CKD-S3b [eGFR <45 mL/min/1.73 m²]). 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.