Below Safety Limits, Every Unit of Glomerular Filtration Rate Counts: Assessing the Relationship Between Renal Function and Cancer-specific Mortality in Renal Cell Carcinoma

Abstract

BackgroundThe hypothesis that renal function could influence oncological outcomes is supported by anecdotal literature. ObjectiveTo determine whether estimated glomerular filtration rate (eGFR) is related to cancer-specific mortality (CSM) in patients who had undergone surgery for renal cell carcinoma (RCC). Design, setting, and participantsA retrospective analysis of 3457 patients who underwent radical (39%) or partial nephrectomy (61%) for cT1–2 RCC between 1990 and 2015. Outcome measurements and statistical analysisThe eGFR was calculated by the Chronic Kidney Disease Epidemiology Collaboration equation. CSM was analyzed in a multivariable competing-risk framework, estimating the subdistribution hazard ratio (SHR) accounting for deaths from other causes. The relationship between eGFR and CSM was investigated from multiple statistical approaches—extended Cox regression with eGFR incorporated as a time-dependent covariate, landmark analysis, and joint modeling. Other predictors were selected by competing-risk random forest method and backward elimination. Results and limitationsThe relationship between eGFR and CSM was graphically described by a linear spline, i.e. a continuous piecewise linear function with two lines joined by a knot. For eGFR treated as a time-dependent covariate, the knot was located at 65ml/min; at landmark analysis with eGFR at the baseline, 12 mo, and last functional follow-up, the knots were 85, 60, and 65ml/min, respectively. In multivariable competing-risk analysis, CSM was associated with eGFR only for values of eGFR below these cutoffs, with SHRs for every 10ml/min of reduction in eGFR of 1.25 (p=0.003), 1.16 (p=0.028), 1.44 (p=0.02), and 1.16 (p=0.042), corresponding to time-dependent eGFR, and eGFR at baseline, 12 mo, and last functional follow-up, respectively. Joint modeling confirmed these results. A retrospective design with inherent biases in data collection represents a limitation. ConclusionsIn patients undergoing surgery for RCC, renal function should be preserved in order to improve cancer-related survival. Patient summaryThe relationship between renal function and probability of dying due to renal cancer is complex. The present study found a correlation between glomerular filtration rate and cancer specific mortality that could reconsider the oncological role of renal function in patients undergoing surgery for renal cancer.