Androgen deprivation therapy for prostate cancer associated with risk for acute kidney injury

In a study that included more than 10,000 men with nonmetastatic prostate cancer, use of androgen deprivation therapy (ADT) was associated with a significantly increased risk for acute kidney injury. Variations were observed with certain types of ADTs.

ADT is the mainstay treatment for patients with advanced prostate cancer. This therapy has traditionally been reserved for patients with advanced disease, but ADT is increasingly being used in patients with less severe forms of the cancer, such as those with biochemical relapse with no evidence of metastatic disease.

While ADT has been shown to have beneficial effects on prostate cancer progression, the article's background information explained that serious adverse events can occur during treatment. The article was published in JAMA (2013; 310(3):289-296).  The testosterone suppression associated with ADT may lead to a hypogonadal condition that can have detrimental effects on renal function. This raised the hypothesis that ADT-induced hypogonadism could potentially lead to acute kidney injury (AKI). Patients with AKI have a mortality rate of about 50%.

Francesco Lapi, PharmD, PhD, of Jewish General Hospital, Montreal, Canada, and colleagues conducted a study to determine whether the use of ADT was associated with an increased risk for AKI in patients newly diagnosed with prostate cancer. The researchers used medical information extracted from the UK Clinical Practice Research Datalink linked to the Hospital Episodes Statistics database. The study included men newly diagnosed with nonmetastatic prostate cancer between January 1997 and December 2008 who were followed up until December 2009. Cases were patients with incident AKI during follow-up who were randomly matched with up to 20 controls on age, calendar year of prostate cancer diagnosis, and duration of follow-up.

Analysis was conducted to estimate the odds ratios of AKI associated with the use of ADT. ADT 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.

A total of 10,250 patients met the study inclusion criteria. During follow-up, 232 cases with a first-ever AKI admission were identified. All cases were matched with at least one control. The researchers found that compared with never use, current use of ADT was significantly associated with a 2.5 times increased odds for AKI. They wrote, “This association was mainly driven by a combined androgen blockade consisting of gonadotropin-releasing hormone agonists with oral antiandrogens, estrogens, other combination therapies, and gonadotropin-releasing hormone agonists.”

“To our knowledge, this is the first population-based study to investigate the association between the use of ADT and the risk of AKI in men with prostate cancer. In this study, the use of ADT was associated with an increased risk of AKI, with variations observed with certain types of ADTs. This association remained continuously elevated, with the highest odds ratio observed in the first year of treatment. Overall, these results remained consistent after conducting several sensitivity analyses,” the authors wrote.
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