The use of androgen deprivation therapy was significantly associated with an increased risk of acute kidney injury among men with newly diagnosed nonmetastatic prostate cancer, according to a study published in JAMA. The study was motivated by the increasing use of androgen deprivation therapy in patients with earlier-stage disease and the high mortality rate (around 50%) in patients with acute kidney injury, the researchers noted. The testosterone suppression associated with androgen deprivation therapy “may lead to a hypogonadal condition that can have detrimental effects on renal function, thus raising the hypothesis that [androgen deprivation therapy]–induced hypogonadism could potentially lead to acute kidney injury,” they explained.
The United Kingdom Clinical Practice Research Datalink and the Hospital Episodes Statistics database were used to identify 10,250 patients. During a mean follow-up of 4.1 years, 232 incident cases of acute kidney injury were identified, an incidence rate of 5.5 per 1,000 person-years. These cases were randomly matched with up to 20 controls for age, calendar year of prostate cancer diagnosis, and duration of follow-up.
“[Androgen deprivation therapy] was categorized into 1 of 6 mutually exclusive groups: gonadotropin-releasing hormone agonists, oral antiandrogens, combined androgen blockade, bilateral orchiectomy, estrogens, and combination of the above,” the investigators explained.
Patients who were currently using any androgen deprivation therapy had an increased risk of acute kidney injury compared to those who never used any androgen deprivation therapy. The odds ratio was 2.48 (95% confidence interval [CI] = 1.61–3.82), “generating a rate difference of 4.43/1,000 persons per year (95% CI = 1.54-7.33),” the researchers reported. The odds ratio “was lower and not statistically significant” for former androgen deprivation therapy users (odds ratio [OR] = 1.25 [95% CI = 0.68–2.29]).
This association between use of androgen deprivation therapy and increased risk of acute kidney injury “was mainly driven by a combined androgen blockade consisting of gonadotropin-releasing hormone agonists with oral antiandrogens (OR = 4.50 [95% CI = 2.61–7.78]), estrogens (OR =4.00 [95% CI, 1.06-15.03]), other combination therapies (OR = 4.04 [95% CI = 1.88–8.69]), and gonadotropin-releasing hormone agonists (OR = 1.93 [95% CI = 1.20–3.10]),” the investigators noted.
The finding that the highest odds ratio was observed in patients taking combination therapies “suggests a possible additive effect exerted by [androgen deprivation therapy] on both receptor antagonism and reduction of testosterone excretion,” the researchers wrote. “Furthermore, the highest [odds ratio] of [acute kidney injury] was also observed in the earliest period of treatment, though the [odds ratio] remained continuously elevated with longer durations of use. The former might be related to an early and severe deteriorating effect of [androgen deprivation therapy] in susceptible patients who probably experience subtle reductions in kidney functions.” ■
Lapi F, et al: JAMA 310:289-296, 2013.