Relationship between androgen deprivation therapy and kidney function in patients with prostate cancer: An analysis of the RADICAL-PC study.

Abstract

115 Background: Androgen deprivation therapy (ADT) is an effective treatment for patients with advanced prostate cancer (PC). However, its impact on renal function remains underexplored. We evaluated the impact of ADT on kidney function in a cohort of patients with PC. Methods: We analyzed the RADICAL-PC study (Role of Androgen-Deprivation Therapy in Cardiovascular Disease—A Longitudinal Prostate Cancer study, NCT04127631), a prospective study of patients with PC in 10 countries. ADT use was assessed at baseline and follow-up visits. We quantified kidney function using glomerular filtration rate (GFR), calculated using the CKD-EPI equation and creatinine measurements obtained at annual visits. We used a linear mixed-effects regression model to analyze the association between ADT and change in GFR (ΔGFR), adjusting for age, diabetes, hypertension, renal disease, heart failure, chemotherapy, medications, alcohol use, and smoking. Using a Cox regression model, we assessed the association between ADT and acute kidney injury (AKI) as reported by sites. Results: Our analysis included 4119 participants with a median age of 68 (IQR 63-74) years. In 1791 (43%) participants using ADT at baseline, the ΔGFR over 2 years was -0.64 [95%CI -1.05 to -0.22] ml/min/1.73m 2 /year. In 2328 (57%) ADT-naïve participants at baseline, the ΔGFR was -1.00 [95%CI -1.34 to -0.64] ml/min/1.73m 2 /year. There was no significant difference in ΔGFR between the two groups (p=0.20). Age (β=-0.58, p<0.001), hypertension (β=-1.98, p<0.01), and anticoagulation use (β=-3.92, p<0.001) were associated with GFR decline. When analyzed as a time-varying covariate, ADT use was associated with less GFR decline than no ADT use (-0.21 vs. -1.07 ml/min/1.73m 2 /year, respectively, p<0.01). Duration of ADT use was not associated with ΔGFR (+0.04 [95%CI -0.02 to 0.10] ml/min/1.73m 2 /month, p=0.18). AKI developed in 91 (2.2%) participants over a median follow-up of 25 (IQR 12-36) months. Baseline ADT use was associated with an increased risk of AKI in univariate analysis (HR 2.58 [95%CI 1.67 to 3.98], p<0.001), but was not significant after adjustment for covariates (HR 1.37 [95%CI 0.83 to 2.26], p=0.22). Conclusions: This analysis suggests that ADT use is not associated with GFR decline or AKI incidence in patients with PC, challenging previous literature concerning ADT-related renal dysfunction. Further studies with longer follow-up periods are needed to confirm these findings.