Authors: T M E Davis R Ting J D Best M W Donoghoe P L Drury D R Sullivan A J Jenkins R L O’Connell M J Whiting P P Glasziou R J Simes Y A Kesäniemi V J Gebski R S Scott A C Keech on behalf of the FIELD Study investigators
Publish Date: 2010/11/04
Volume: 54, Issue: 2, Pages: 280-290
Abstract
Fenofibrate caused an acute sustained plasma creatinine increase in the Fenofibrate Intervention and Event Lowering in Diabetes FIELD and Action to Control Cardiovascular Risk in Diabetes ACCORD studies We assessed fenofibrate’s renal effects overall and in a FIELD washout substudyType 2 diabetic patients n = 9795 aged 50 to 75 years were randomly assigned to fenofibrate n = 4895 or placebo n = 4900 for 5 years after 6 weeks fenofibrate runin Albuminuria urinary albumin/creatinine ratio measured at baseline year 2 and closeout and estimated GFR measured four to six monthly according to the Modification of Diet in Renal Disease Study were prespecified endpoints Plasma creatinine was remeasured 8 weeks after treatment cessation at closeout washout substudy n = 661 Analysis was by intentiontotreatDuring fenofibrate runin plasma creatinine increased by 100 μmol/l p 0001 but quickly reversed on placebo assignment It remained higher on fenofibrate than on placebo but the chronic rise was slower 162 vs 189 μmol/l annually p = 001 with less estimated GFR loss 119 vs 203 ml min−1 173 m−2 annually p 0001 After washout estimated GFR had fallen less from baseline on fenofibrate 19 ml min−1 173 m−2 p = 0065 than on placebo 69 ml min−1 173 m−2 p 0001 sparing 50 ml min−1 173 m−2 95 CI 23–77 p 0001 Greater preservation of estimated GFR with fenofibrate was observed with baseline hypertriacylglycerolaemia n = 169 vs 491 without alone or combined with low HDLcholesterol n = 140 vs 520 without and reductions of ≥048 mmol/l in triacylglycerol over the active runin period prerandomisation n = 356 vs 303 without Fenofibrate reduced urine albumin concentrations and hence albumin/creatinine ratio by 24 vs 11 p 0001 mean difference 14 95 CI 9–18 p 0001 with 14 less progression and 18 more albuminuria regression p 0001 than in participants on placebo Endstage renal event frequency was similar n = 21 vs 26 p = 048Fenofibrate reduced albuminuria and slowed estimated GFR loss over 5 years despite initially and reversibly increasing plasma creatinine Fenofibrate may delay albuminuria and GFR impairment in type 2 diabetes patients Confirmatory studies are merited
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