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Fibrates and albuminuria progression
Pierre Delanaye (1), Andr J Scheen (2)
Department of Nephrology, Dialysis, Transplantation
Division of Diabetes, Nutrition and Metabolic Disorders and Clinical Pharmacology Unit
University of Lige, CHU Sart Tilman, 4000 Lige, 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) ADDIN REFMGR.CITE Jun20101802Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysisJournal1802Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysisJun,M.Foote,C.Lv,J.Neal,B.Patel,A.Nicholls,S.J.Grobbee,D.E.Cass,A.Chalmers,J.Perkovic,V.2010/5/29AlbuminuriaAustraliaClinical TrialsCreatinineHealthHeartHeart FailureMeta-AnalysisMethodsmortalityResearchRiskSerumStroketherapyNot in File18751884Lancet3759729The George Institute for International Health, University of Sydney, Sydney, AustraliaPM:20462635Lancet1(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 ADDIN REFMGR.CITE Hottelart20021100Fenofibrate increases creatininemia by increasing metabolic production of creatinineJournal1100Fenofibrate increases creatininemia by increasing metabolic production of creatinineHottelart,C.el Esper,N.Rose,F.Achard,J.M.Fournier,A.2002adverse effectsAgedAlanine TransaminaseanalysisAntilipemic AgentsAspartate AminotransferasesbloodCholesterolChromatography,High Pressure LiquidcomplicationsCreatineCreatine KinaseCreatininedrug therapyEnzymesetiologyFemaleFranceGlomerular Filtration RateHumansHyperlipidemiasKidney FailureL-Lactate DehydrogenaseMaleMiddle AgedMyoglobinNephrologyPlasmaProcetofenRenal Plasma FlowsecretiontherapyTriglyceridesNot in File536541Nephron923Department of Nephrology, CHU Amiens, FrancePM:12372935Nephron1(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 ADDIN REFMGR.CITE Jun20101802Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysisJournal1802Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysisJun,M.Foote,C.Lv,J.Neal,B.Patel,A.Nicholls,S.J.Grobbee,D.E.Cass,A.Chalmers,J.Perkovic,V.2010/5/29AlbuminuriaAustraliaClinical TrialsCreatinineHealthHeartHeart FailureMeta-AnalysisMethodsmortalityResearchRiskSerumStroketherapyNot in File18751884Lancet3759729The George Institute for International Health, University of Sydney, Sydney, AustraliaPM:20462635Lancet1(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 ADDIN REFMGR.CITE Keech20051803Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trialJournal1803Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trialKeech,A.Simes,R.J.Barter,P.Best,J.Scott,R.Taskinen,M.R.Forder,P.Pillai,A.Davis,T.Glasziou,P.Drury,P.Kesaniemi,Y.A.Sullivan,D.Hunt,D.Colman,P.d'Emden,M.Whiting,M.Ehnholm,C.Laakso,M.2005/11/26adverse effectsAgedAlbuminuriaanalysisAntilipemic AgentsbloodCardiovascular DiseasesCholesterolcomplicationsCoronary DiseaseDiabetes MellitusDiabetes Mellitus,Type 2DiseaseDouble-Blind Methoddrug therapyDyslipidemiasetiologyFemaleHeartHumansHydroxymethylglutaryl-CoA Reductase InhibitorsMaleMethodsMiddle AgedmortalityMulticenter StudiesMyocardial InfarctionPlasmaprevention & controlProcetofenResearchRiskStroketherapeutic usetherapyTriglyceridesNot in File18491861Lancet3669500PM:16310551Lancet1(4), it would be interesting to know whether creatininuria and albuminuria (measured in g/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
ADDIN REFMGR.REFLIST 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.
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