Androgen deprivation therapy and kidney function in patients with prostate cancer: an analysis of the RADICAL-PC cohort

Purpose: To evaluate the effect of androgen deprivation therapy (ADT) on kidney function in patients with prostate cancer (PC). Methods: We analyzed the RADICAL-PC cohort (NCT03127631), a prospective study of patients with PC in 10 countries. Patients were categorized as ADT-exposed or ADT-naïve at baseline. We quantified kidney function using estimated glomerular filtration rate (eGFR), calculated from creatinine measurements obtained at annual visits over a 2 year follow-up period. We used a linear mixed-effects regression model to analyze the association between ADT and eGFR, adjusting for covariates known to affect renal function. We assessed the association between ADT and kidney injury during hospitalization using Cox proportional-hazards regression. Results: This analysis included 4 742 patients. The rate of eGFR decline over the 2 year follow-up period was greater in ADT-naïve patients (−1.322 [95% CI, −1.649 to −0.995] ml/min/1.73m²/year, p < 0.001) than ADT-exposed patients (−0.706 [95% CI, −1.097 to −0.316] ml/min/1.73m²/year, p < 0.001, interaction p = 0.025). Age and heart failure were associated with worsening eGFR, while higher baseline eGFR was associated with preserved eGFR. Duration of ADT use was not associated with change in eGFR (+ 0.04 [95% CI, −0.03 to + 0.10] ml/min/1.73m²/year per month of ADT use, p = 0.260). Kidney injury during hospitalization occurred in 135 (2.8%) patients, with no significant association with ADT (HR 1.37 [95% CI, 0.91 to 2.07], p = 0.135). Conclusion: This analysis suggests that eGFR declines more modestly in patients initiating ADT than ADT-naïve patients. These findings do not preclude true kidney function decline due to ADT-mediated reduction in creatinine generation, and warrant further investigation.