Association of androgen deprivation therapy and acute kidney injury in patients with prostate cancer: A systematic review and meta-analysis.

Abstract

111 Background: Androgen deprivation therapy (ADT) has been associated with cardiovascular risk in prostate cancer patients. Thus, we performed a systematic review and meta-analysis to assess the incidence of acute kidney injury (AKI) in prostate cancer patients under ADT. Methods: PubMed, Embase, and Cochrane Library were searched from inception to October 2024. A random-effects model was employed to compute mean differences for continuous endpoints. Heterogeneity was evaluated by prediction interval and I-squared statistics. All statistical analysis was conducted using R software 4.4.1. GRADE approach rated the certainty of the evidence and the results were reported following the PRISMA statement guidelines. Results: Four studies involving 72,980 patients with a mean age of 73.5 years were included. Over a mean follow-up of 6.7 years, ADT was associated with an increase in the AKI incidence in prostate cancer patients compared to patients not receiving ADT (RR 1.34; 95% CI 1.13-1.58; p<0.001). Among patients who developed AKI while receiving ADT, the use of GnRH agonists was not associated with AKI incidence (RR 4.32; 95% CI 0.60-30.97; p=0.146). Similarly, when comparing AKI risk between patients on GnRH agonists alone and those without ADT, no statistically significant difference was found (RR 1.24; 95% CI 0.73-2.11; p=0.424). Orchiectomized patients had a lower AKI incidence than GnRH agonist users (RR 1.16; 95% CI 1.04-1.3; p=0.009). All studies were limited by retrospective designs, introducing potential selection and therapeutic bias. Conclusions: In this meta-analysis, ADT was associated with an increased risk of AKI. No statistical association was found between GnRH agonist use and AKI. Orchiectomy presented a lower AKI risk compared to GnRH agonists. Further investigations, including post hoc analysis of randomized controlled trials, are warranted to confirm these findings. Characteristics of the included studies. Study Sample size (n) Mean age (years) ADT modality Control group AKI incidence (ADT) AKI incidence (control) Hazard ratio for GnRH use (95% CI) – sensitivity analyses Follow-up (years) Gandaglia 2014 31,408 78.6 GnRH agonist and Bilateral orchiectomy No ADT 30.7% 24.9% 1.73 (1.62-1.85) 10 Cardwell 2021 10,751 69.2 GnRH agonists, GnRH antagonist, oral antiandrogens, estrogens and orchiectomy No ADT 6.1% 5.2% 1.09 (0.88-1.34) 3.9 Sherer 2021 27,868 66 GnRH agonists, oral antiandrogens, and GnRH antagonist No ADT +Radiotherapy 10.5% 7.9% 1.25 (1.13-1.37) a 8.8 Lapi 2013 2,953 80.2 GnRH agonists, oral antiandrogens, GnRH agonists + oral antiandrogens, bilateral orchiectomy, estrogens, other combinations No ADT 9.2% 4.5% ≈ 1.54 (1.17-2.15) b / ≈ 1.04 (1.27-1.46) c 4.1 a Sensitivity analysis of all ADT modalities. b Adjusted analysis of current ADT modalities. c Adjusted analysis of past ADT modalities.