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Aims/hypothesis 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 sub-study. Methods Type 2 diabetic patients (n=9,795) aged 50 to 75 years were randomly assigned to fenofibrate (n=4,895) or placebo (n=4,900) for 5 years, after 6 weeks fenofibrate run-in. Albuminuria (urinary albumin/creatinine ratio measured at baseline, year 2 and close-out) and estimated GFR, measured four to six monthly according to the Modification of Diet in Renal Disease Study, were pre-specified endpoints. Plasma creatinine was re-measured 8 weeks after treatment cessation at close-out (washout sub-study, n=661). Analysis was by intention-to-treat. Results During fenofibrate run-in, plasma creatinine increased by 10.0 μmol/l (p<0.001), but quickly reversed on placebo assignment. It remained higher on fenofibrate than on placebo, but the chronic rise was slower (1.62 vs 1.89 μmol/l annually, p=0.01), with less estimated GFR loss (1.19 vs 2.03 ml min −1 1.73 m −2 annually, p<0.001). After washout, estimated GFR had fallen less from baseline on fenofibrate (1.9 ml min −1 1.73 m −2 , p=0.065) than on placebo (6.9 ml min −1 1.73 m −2 , p<0.001), sparing 5.0 ml min

Aims/hypothesis We investigated effects of renal function and albuminuria on cardiovascular outcomes in 9,795 lowrisk patients with diabetes in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Methods Baseline and year 2 renal status were examined in relation to clinical and biochemical characteristics. Outcomes included total cardiovascular disease (CVD), cardiac and non-cardiac death over 5 years. Results Lower estimated GFR (eGFR) vs eGFR ≥90 ml min . CVD risk was further modified by renal status changes over the first 2 years. In multivariable analysis, 77% of the effect of eGFR and 81% of the effect of albumin:creatinine ratio were accounted for by other variables, principally low HDL-cholesterol and elevated blood pressure. Conclusions/interpretation Reduced eGFR and albuminuria are independent risk factors for cardiovascular events and mortality rates in a low-risk population of mainly European ancestry. While their independent contributions to CVD risk appear small when other risk factors are considered, they remain excellent surrogate markers in clinical practice because they capture risk related to a number of other characteristics. Therefore, both should be considered when assessing prognosis and treatment strategies in patients with diabetes, and both should be included in risk models.

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Aims/hypothesis Bilirubin has antioxidant and antiinflammatory activities. Previous studies demonstrated that higher bilirubin levels were associated with reduced prevalence of peripheral arterial disease (PAD). However, the relationship between bilirubin and lower-limb amputation, a consequence of PAD, is currently unknown. We hypothesised that, in patients with type 2 diabetes, bilirubin concentrations may inversely associate with lower-limb amputation.Methods The relationship between baseline plasma total bilirubin levels and amputation events was analysed in 9,795 type 2 diabetic patients from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. The analysis plan was pre-specified. Lower-limb amputation was adjudicated blinded to treatment allocation. Relevant clinical and biochemical data were available for analyses. Amputation was a pre-specified tertiary endpoint. Results Bilirubin concentrations were significantly inversely associated with lower-limb amputation, with a greater than M. K. C. Ng and A. C. Keech are joint senior authors of this study Electronic supplementary material The online version of this article