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ADT linked to acute kidney injury risk in nonmetastatic prostate cancer
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Androgen deprivation therapy was significantly associated with an increased risk for acute kidney injury among men with nonmetastatic prostate cancer, according to study results.
“Although ADT has been shown to have beneficial effects on prostate cancer progression, serious adverse events can occur during treatment,” Francesco Lapi, PharmD, PhD, of the Centre for Clinical Epidemiology, Jewish General Hospital, Montreal, and colleagues wrote. “By lowering testosterone to castration levels, ADT may antagonize the vasodilating effects of testosterone on renal vessels while also creating an estrogen deficiency, which can negatively affect renal tubular function. Thus, it is possible that through these mechanisms, the use of ADT may increase the risk of acute kidney injury.”
However, despite the increasing use of ADT in patients with earlier-stage disease and the high mortality rate in patients with acute kidney injury, there are no observational studies investigating this possible correlation, the researchers said.
To ascertain whether ADT was associated with an increased risk for acute kidney injury in patients newly diagnosed with prostate cancer, Lapi and colleagues conducted a nested case-control analysis using medical information extracted from the UK Clinical Practice Research Datalink linked to the Hospital Episodes Statistics database.
The study included 10,250 men newly diagnosed with nonmetastatic prostate cancer between 1997 and 2008. The men were followed until December 2009.
Patients identified with incident acute kidney injury were then matched for age, year of diagnosis and duration of follow-up with those who did not develop injury.
The researchers identified 232 incident cases of acute kidney injury, and they determined that current use of any ADT was associated with an increased risk for acute kidney injury (OR=2.48; 95% CI, 1.61-3.82) compared with patients who never received ADT.
This association was primarily driven by a combined androgen blockade, including:
- Gonadotropin-releasing hormone agonists with oral anti-androgens (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 use of ADT was associated with an increased risk of [acute kidney injury], with variations observed with certain types of ADTs,” Lapi and colleagues wrote. “This association remained continuously elevated, with the highest OR observed in the first year of treatment. These findings require replication in other carefully designed studies as well as further investigation of their clinical importance.”
Disclosure: The researchers report advisory board positions and research grants from Abbott, AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck, Novartis, Pfizer and Sanofi.
Perspective
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E. David Crawford, MD
This study dealt with yet another complication of androgen deprivation therapy (ADT). We are familiar with the usual complications of weight gain, loss of libido, osteoporosis, mental changes and hot flashes. It is unclear why this acute kidney injury occurs. Fortunately, relative increase is small (4.43 per 1,000 person-years). It may be related to the loss of the protective effects of testosterone on renal blood flow or as a consequence of the metabolic syndrome. Regardless of the cause, it should encourage clinicians to limit the use of ADT to men with a clear benefit.
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