July 25, 2013
Androgen-Deprivation Therapy More Than Doubled Risk of Acute Kidney Injury

Montreal—Androgen-deprivation therapy (ADT), increasingly used in patients with less severe prostate cancer, is linked with a significantly increased risk of acute kidney injury, according to a new study.

The report, published recently in the Journal of the American Medical Association, said variations were observed with certain types of ADTs. The study included more than 10,000 men with nonmetastatic prostate cancer.

“Androgen deprivation therapy is the mainstay treatment for patients with advanced prostate cancer. While this therapy has been traditionally reserved for patients with advanced disease, ADT is increasingly being used in patients with less severe forms of the cancer, such as in patients with biochemical relapse who have no evidence of metastatic disease,” according to the authors, led by Francesco Lapi, PharmD, PhD, of Jewish General Hospital in Montreal, Canada.

“Although ADT has been shown to have beneficial effects on prostate cancer progression, serious adverse events can occur during treatment,” according to background information in the article. “…the testosterone suppression associated with this therapy may lead to a hypogonadal condition that can have detrimental effects on renal function, thus raising the hypothesis that ADT-induced hypogonadism could potentially lead to acute kidney injury (AKI).”

Patients with AKI have a high mortality rate of about 50%, the study says.

For the study, researchers sought to determine whether the use of ADT was associated with an increased risk of AKI in patients newly diagnosed with prostate cancer. Using medical information extracted from the UK Clinical Practice Research Datalink linked to the Hospital Episodes Statistics database, the study included men with recent diagnoses for nonmetastatic prostate cancer between January 1997 and December 2008, with follow-up until December 2009.

Patients with incident AKI during follow-up were randomly matched with up to 20 controls on age, calendar year of prostate cancer diagnosis, and duration of follow-up. Analysis estimated the odds ratios of AKI incidence associated with the use of ADT, which was categorized as one of the following: gonadotropin-releasing hormone agonists, oral anti-androgens, combined androgen blockade, bilateral orchiectomy, estrogens, or a combination of those.

With 10,250 men meeting the study inclusion criteria, 232 cases with a first-ever AKI admission were identified during follow-up; all cases were matched with at least one control.

Researchers found that compared with never using ADT, current use was significantly associated with a 2.5 times increased odds of developing AKI.

“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 note.

“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,” according to the report.

Authors suggest that their research was the first population-based study “to investigate the association between the use of ADT and the risk of AKI in men with prostate cancer,” adding, “These findings require replication in other carefully designed studies as well as further investigation of their clinical importance."

U.S. Pharmacist Social Connect