Fibrates and albuminuria progression Pierre Delanaye (1), André J Scheen (2)
(1) Department of Nephrology, Dialysis, Transplantation
(2) Division of Diabetes, Nutrition and Metabolic Disorders and Clinical Pharmacology Unit
University of Liège, CHU Sart Tilman, 4000 Liège, Belgium
Sir,
In their recent meta-analysis, Jun et al have shown that fibrate therapy had a beneficial effect on progression of albuminuria (14% reduction versus placebo; p=0.028)(1). This positive renal effect is seen even if serum creatinine classically increases in subjects treated with fibrates. This creatinine increase is linked neither to a reduction in glomerular filtration rate (GFR)(no modification of inulin clearance) nor to an effect on tubular creatinine secretion (no modification of creatinine clearance). A potential explanation may be an increased creatinine production. As a consequence, creatininuria rises in parallel to serum creatinine (2). The two largest trials – ACCORD (3) and FIELD (4) - among the three studies included in the
“progression of albuminuria” meta-analysis used the albuminuria to creatininuria ratio (ACR) as albuminuria measurement (1). If creatininuria is increasing due to a “non-renal” effect of fibrates, the ACR will automatically decrease, independently of any direct effect of
albuminuria, so that this ACR reduction might be considered as an artifact. If the rise in serum creatinine is reversible after stopping fenofibrate therapy (4), it would be interesting to know
whether creatininuria and albuminuria (measured in µg/min and not in mg/g creatinine) were also modified concomitantly. The potential positive effect of fibrates on kidney is actually based on a surrogate marker, ACR. We need to better understand the reason why serum creatinine is increasing with fibrates. We need also trials studying the effect of fibrates (and other lipid-lowering agents) either on “true” GFR measurements or on “hard” endpoints (as need to dialysis).
We declare that we have no conflict of interest
Reference List
1. Jun M, Foote C, Lv J, Neal B, Patel A, Nicholls SJ et al. Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet 2010;375(9729):1875-84.
2. Hottelart C, el Esper N, Rose F, Achard JM, Fournier A. Fenofibrate increases creatininemia by increasing metabolic production of creatinine. Nephron 2002;92(3):536-41.
3. Ginsberg HN, Elam MB, Lovato LC, Crouse JR, III, Leiter LA, Linz P et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N.Engl.J Med.
2010;362(17):1563-74.
4. Keech A, Simes RJ, Barter P, Best J, Scott R, Taskinen MR et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 2005;366(9500):1849-61.
