Puri Dhruv, Meagher Margaret F, Wu Zhenjie, Franco Antonio, Wang Linhui, Margulis Vitaly, Bhanvadia Raj, Abdollah Firas, Finati Marco, Antonelli Alessandro, Ditonno Francesco, Singla Nirmish, Broenimann Stephan, Simone Giuseppe, Tuderti Gabriele, Rais-Bahrami Soroush, Moon Sol C, Ferro Matteo, Tozzi Marco, Porpiglia Francesco, Amparore Daniele, Correa Andreas, Helstrom Emma, Gonzalgo Mark L, Mendiola Dinno F, Perdonà Sisto, Tufano Antonio, Eilender Benjamine M, Mehrazin Reza, Yong Courtney, Ghoreifi Alireza, Sundaram Chandru P, Djaladat Hooman, Autorino Riccardo, Derweesh Ithaar H
Department of Urology, UC San Diego School of Medicine, La Jolla, California, USA.
Department of Urology, Changhai Hospital, Naval Medical University, Shanghai, China.
BJU Int. 2025 Mar;135(3):481-488. doi: 10.1111/bju.16569. Epub 2024 Dec 11.
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).
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) and CKD-S3b (eGFR <45 mL/min/1.73 m) 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]; CKD-S3a [eGFR 59-45 mL/min/1.73 m] and CKD-S3b [eGFR <45 mL/min/1.73 m]). 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.
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).
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.
探讨手术诱发的慢性肾脏病（CKD-S）在上尿路尿路上皮癌（UTUC）患者根治性肾输尿管切除术（RNU）后对生存结局的患病率、预测因素及影响。
利用ROBUUST 2.0登记册，对2006年至2022年间接受RNU且基线时无慢性肾脏病（CKD）3-5期的UTUC患者进行多中心回顾性分析。我们根据慢性肾脏病流行病学协作组2021年的公式计算术后CKD-S3a（估计肾小球滤过率[eGFR]59-45 mL/min/1.73 m²）和CKD-S3b（eGFR<45 mL/min/1.73 m²）的患病率。分析队列根据术后CKD分期进行分层[无CKD-S（eGFR≥60 mL/min/1.73 m²）；CKD-S3a（eGFR 59-45 mL/min/1.73 m²）和CKD-S3b（eGFR<45 mL/min/1.73 m²）]。主要结局是全因死亡率（ACM）。分别使用逻辑回归和Cox回归分析CKD-S3a/3b发生的预测因素以及ACM/癌症特异性死亡率（CSM）。采用Kaplan-Meier分析来分析术后CKD组之间的总生存期（OS）和癌症特异性生存期（CSS）。
我们分析了1862例患者；分别有34.7%（646例）和39.6%（738例）发生了CKD-S3a和CKD-S3b。CKD-S3b的预测因素包括年龄增加（比值比[OR]为1.03，P=0.029）、术前eGFR降低（OR为1.06，P<0.001）以及接受新辅助化疗（OR为2.07，P=0.006）和辅助化疗（OR为1.41，P=0.012）。ACM恶化与CKD-S3b相关（风险比为1.42，P=0.032），但与CKD-S3a无关（P=0.766）。CKD-S3a（P=0.812）和CKD-S3b（P=0.316）的发生与CSM无关。CKD-S3b组的5年OS率明显更差（无CKD组为71%，CKD-S3a组为70%，CKD-S3b组为59%；P=0.017）。CKD-S组之间的5年CSS无差异（无CKD组为78%，CKD-S3a组为77%，CKD-S3b组为82%；P=0.44）。
接受RNU的UTUC患者中有很大一部分发生了CKD-S。CKD-S3b的发生与更差的ACM相关。年龄增加、术前eGFR以及化疗与CKD-S3b的发生相关。我们的研究结果呼吁进一步探索和完善保留肾单位的手术策略以及非肾毒性全身治疗，以改善UTUC患者的生存结局。
