The findings are reported in the Annals of Internal Medicine for April 17 by Dr. Amit X. Garg, MD, at the London Health Sciences Centre, in London, Ontario, and colleagues. “The mechanism and clinical significance of the increase in serum creatinine level with fibrates is unclear,” they comment.
The authors point out that fibric acid derivatives prescribed for dyslipidemia have been shown to increase serum creatinine in clinical trials, but most such trials have excluded older patients and those with chronic kidney disease.
To examine the effect of fibrates in this population, they looked at renal outcomes within 90 days of a new prescription for a fibrate or ezetimibe (comparator drug) in patients 66 years of age or older, using linked healthcare databases in Ontario.
The team identified 19,072 new fibrate users and 61,831 new ezetimibe users. The primary outcome of hospitalization for an increase in serum creatinine occurred in 0.4% and 0.2% of the two cohorts, respectively. Although the absolute difference was just 0.22%, it was statistically significant and translated to an adjusted odds ratio of 2.4, the investigators found.
Among a subset of patients with serum creatinine measurements before and after starting the new drug, an increase of at least 50% in creatinine concentration was documented in 9.1% of fibrate users compared to just 0.3% of ezetimibe users, the report indicates. Furthermore, the rise in creatinine level was greater in those with reduced renal function.
However, there was no apparent effect on the need for dialysis or on mortality, Dr. Garg and colleagues report. They think this may be “because increases in creatinine levels from fibrate use do not represent true kidney injury.” Indeed, they note that fibrates may have long-term renal benefits
That said, they conclude: “Until we have a better understanding of the underlying mechanism by which fibrates increase serum creatinine level and its long-term renal effects, we believe that, when fibrates are prescribed to older patients, it would be prudent to start the prescription at a low dosage and arrange for close monitoring of renal function, as has been done in clinical trials.”