High doses of erythropoiesis-stimulating agents (ESAs) are associated with an increased risk of cancer among patients on chronic dialysis, new findings suggest.

Canadian investigators led by Jean-Philippe Lafrance, MD, of the University of Montreal, conducted a case-control study in a cohort of 4574 patients who started chronic dialysis from January 1, 2001 to December 31, 2007 in Quebec. From this cohort, Dr Lafrance and his colleagues identified 419 cases of cancer and 3895 control patients without cancer and who were matched by age, gender, and other factors. The investigators categorized ESA use according to mean weekly dose: low dose (less than 30 µg/week), moderate dose (30–70 µg/week), or high dose (greater than 70 µg/week).

Patients treated with high-dose ESAs had a 77% increased likelihood of cancer compared with those not exposed to ESAs, Dr Lafrance’s team reported online in Nephrology Dialysis Transplantation.

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“Our results suggest an association between ESA use and the occurrence of new cancer among chronic dialysis patients,” the investigators wrote. “From our findings, this increased risk of cancer appears to be dose-related. While low and moderate doses were not correlated with a higher likelihood of new-onset malignancies, the dose-response analysis depicted an increment in risk starting at a mean weekly dose of 50 µg.”

Dr Lafrance and his collaborators noted that most of the evidence related to cancer and ESA use comes from populations without end-stage renal disease (ESRD). “Most randomized trials on this subject have studied the effect of ESAs on survival as a primary outcome in non-ESRD patients with a cancer-related anemia, showing an increased mortality associated with use of ESAs.”

The investigators noted that a main strength of their study was their sample size, which comprised a large population-based chronic dialysis cohort in a universal healthcare setting. “The capture of cancer events in the entire ESRD population of Quebec has enabled us to control for numerous potential confounders, including smoking.”

The researchers acknowledged that the study had limitations. For example, the observed association between cancer risk and ESA use could have been the result of reverse causality, “where an ESA has been prescribed for an early manifestation of cancer that has not been formerly detected and diagnosed.” They noted that they assessed ESA exposure at least 6 months prior to the initial diagnosis of cancer to avoid this potential bias.

Another limitation was a short surveillance period and lack of information about a prior history of cancer. “We were limited to a 2-year window before dialysis initiation to assess prior history of cancer, which may have misidentified new cancers from relapses of previous diagnoses.”

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