Advanced Chronic Kidney Disease; a Comparison Between Nephroureterectomy and Nephron-Sparing Surgery for Upper Tract Urothelial Carcinoma - Beyond the Abstract

With increased utilization of nephron-sparing surgical (NSS) approaches for upper tract urothelial carcinoma, we sought to compare longitudinal renal function outcomes of patients managed with NSS versus radical nephroureterectomy (RNU).


Our outcome of interest was the cumulative incidence of advanced chronic kidney disease (CKD), defined as a glomerular filtration rate (GFR) < 30 mL/min, which was selected as it represented a clinically relevant renal function endpoint. Competing-risks analyses were utilized to account for competing mortality. We additionally stratified our analysis by pre-operative GFR, comparing renal function outcomes between the surgical modalities among patients with pre-operative eGFR ≥ 60 mL/min and eGFR < 60 mL/min.

Our analysis included 426 patients treated at Duke University Medical Center between 1992-2022, 293 with RNU and 133 with NSS. Median pre-operative renal function was not significantly different between the two groups (NSS: 68 mL/min/1.73 m2, RNU: 65 mL/min/1.73 m2, P = 0.220). When comparing the overall cohort, there was a significantly higher cumulative incidence of advanced CKD among patients receiving RNU (p=0.009). We found no difference in the cumulative incidence of all-cause mortality (p=0.2). After stratification by pre-operative GFR, we found NSS to have a lower incidence of advanced CKD in the GFR ≥ 60 mL/min group (p=0.035), however, saw no significant difference in the cumulative incidence of advanced CKD in the GFR < 60 mL/min group (p=0.25). On Fine-Gray analysis, we found multiple comorbidities to be associated with incidence of advanced CKD in the pre-operative eGFR <60 mL/min cohort, including age (HR 1.1), diabetes (HR 2.8), and recurrent acute kidney injury events (HR 3.6). In patients with excellent pre-operative renal function (GFR ≥60 mL/min),  RNU (HR 2.3) and recurrent AKI (HR 2.9) were found to be associated with incidence of advanced CKD. These findings led us to consider that pre-operative medical factors which cause renal function decline may have greater influence on longitudinal renal function outcomes in patients with pre-operative CKD, as medically induced CKD has been shown to have different clinical impact than surgically induced CKD.1

Additionally, we compared the incidence of acute kidney injuries (AKI) at any time post-operatively between patients undergoing NSS and RNU and evaluated the effect of AKIs on long term renal function. We found the incidence of AKI to be greater in our RNU cohort (73% RNU vs. 52% NSS). Recurrent AKI (defined as 2 or greater AKI events) was found to be associated with worse long-term renal function. Post-operative AKI has been shown to be associated with long term renal dysfunction,2 and our results add to a growing body of literature on the negative renal effects of AKIs.

Overall, our results show that NSS in UTUC may provide a renal function benefit to some, but not all patients – especially those with medical factors at baseline contributing to CKD (i.e. the very people we are trying to help with NSS). The importance of both oncologic and expected renal function outcomes are necessary when counseling patients on treatment options in UTUC.

Written by: John V. Dudinec, David I. Ortiz-Melo, Michael E. Lipkin, Michael R. Abern, Ankeet M. Shah, Brant A. Inman

Division of Urology, Duke University Medical Center, Durham, NC., Division of Nephrology, Duke University School of Medicine, Durham, NC., Division of Urology, Duke Cancer Institute, Duke University Medical Center, Durham, NC., Division of Urology, Duke Cancer Institute, Duke University Medical Center, Durham, NC.

References:

  1. Lane BR, Demirjian S, Derweesh IH, Takagi T, Zhang Z, Velet L, et al. Survival and Functional Stability in Chronic Kidney Disease Due to Surgical Removal of Nephrons: Importance of the New Baseline Glomerular Filtration Rate. European Urology. 2015;68:996-1003.
  2. Long TE, Helgason D, Helgadottir S, Sigurdsson GH, Palsson R, Sigurdsson MI, et al. Mild Stage 1 post-operative acute kidney injury: association with chronic kidney disease and long-term survival. Clin Kidney J. 2021;14:237-44.
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