Androgen deprivation therapy linked with renal damage
medwireNews: Men who receive androgen deprivation therapy (ADT) upon diagnosis of prostate cancer face an increased risk for acute kidney injury (AKI), researchers warn.
In a study involving more than 10,000 men, those who were currently receiving ADT for the management of nonmetastatic prostate cancer had a 2.5-fold increased risk for developing AKI as compared with never-users of ADT.
“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,” write Samy Suissa (Jewish General Hospital, Montreal, Quebec, Canada) and co-authors in JAMA.
In the study, Suissa’s team used two UK patient databases to identify all men newly diagnosed with nonmetastatic prostate cancer in the UK between January 1997 and December 2008. Of 10,250 such individuals, 232 men suffered a first-ever instance of AKI during 42,070 person–years of follow up. Each case was matched with up to 20 AKI-free men of similar age, year of cancer diagnosis, and duration of follow up.
After adjusting for potential confounders (comorbidities, medication use, alcohol use, smoking status, body mass index, and multiple clinical factors), men who were currently using ADT were at significantly increased risk for AKI (odds ratio [OR]=2.48) as compared with never-users. This translated into a rate difference of 4.43 per 1000 persons per year.
Secondary analyses revealed that the risk increase was not significant for past use of ADT (OR=1.25) but was significant for current use of combined androgen blockade consisting of gonadotropin-releasing hormone agonists with oral antiandrogens (OR=4.50), estrogens (OR=4.00), other combination therapies (OR=4.04), and gonadotropin-releasing hormone agonists (OR=1.93). There was no significant association with oral antiandrogens alone or bilateral orchiectomy and AKI.
Finally, sensitivity analyses supported the robustness of the association between current ADT use and AKI, finding consistent risk estimates in a variety of patient subgroups.
ADT is the mainstay of treatment for advanced prostate cancer but is increasingly being used in earlier stages of the disease. The therapy causes testosterone suppression, which has a range of potentially deleterious effects on the renal system, including disrupting both glomerular and tubular function, explain the authors.
Noting that “ADT and its hypogonadal effect have well-known consequences consistent with our findings,” the researchers conclude: “These findings require replication in other carefully designed studies as well as further investigation of their clinical importance.”
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By Joanna Lyford, medwireNews Reporter