Original investigations
Pathogenesis and treatment of kidney disease and hypertension
Fenofibrate reduces progression to microalbuminuria over 3 years in a placebo-controlled study in type 2 diabetes: Results from the Diabetes Atherosclerosis Intervention Study (DAIS)

https://doi.org/10.1053/j.ajkd.2004.11.004Get rights and content

Background: Microalbuminuria is an early marker of diabetic nephropathy and an independent risk factor for cardiovascular disease. In the Diabetes Atherosclerosis Intervention Study (DAIS), treatment of people with type 2 diabetes with micronized fenofibrate for an average of 38 months reduced the progression of angiographically evaluated coronary artery disease and improved lipoprotein level abnormalities compared with placebo. The aim of this analysis is to study the influence of the treatment on changes in urinary albumin excretion. Methods: Microalbuminuria was measured on 2 to 3 occasions by using timed overnight samples at baseline and yearly thereafter in 314 DAIS participants (77 women, 237 men; average age, 56 years); all except 3 participants had either a normal albumin excretion rate (<20 μg/min; n = 214) or microalbuminuria (albumin, 20 to 200 μg/min; n = 97) before randomization. Tabulated shifts (between normal, microalbuminuria, and macroalbuminuria) from baseline to last observed values were compared between treatment groups by means of chi-square or Fisher’s exact test. Results: Fenofibrate significantly reduced the worsening of albumin excretion (fenofibrate, 8% versus placebo, 18%; P < 0.05). This effect was caused mostly by reduced progression from normal albumin excretion to microalbuminuria: 3 of 101 participants in the fenofibrate group versus 20 of 113 participants in the placebo group (P < 0.001). Overall, changes in albumin excretion were independent of age or changes in lipid or creatinine levels, weight, or blood pressure. Conclusion: Improvement in lipid profiles with fenofibrate in patients with type 2 diabetes was associated with reduced progression from normal albumin excretion to microalbuminuria.

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Study design and population

This study was performed in a representative sample of DAIS participants. DAIS is a randomized, double-blind, placebo-controlled, angiographic study. Participants were selected to be men or women of middle age, to have undergone coronary intervention or not, and to have mild to moderate lipid level abnormalities typical of patients with type 2 diabetes. Selection criteria and baseline characteristics have been published.9 Among selection criteria, participants were not to have significant renal

Baseline characteristics of participants

There were no differences in clinical and biochemical characteristics between the placebo and fenofibrate groups (Table 1, Table 2). There was no significant difference in age between participants with normal and abnormal albumin excretion or in the distribution of men, participants with previous coronary intervention, and smoking status (Table 1). However, body mass index (BMI) and blood pressure were significantly greater in the group with abnormal albumin excretion than in the group with

Discussion

The present study shows that treatment of people with type 2 diabetes with micronized fenofibrate reduces the progression of urinary albumin excretion. This was evidenced by a reduction in number of participants with microalbuminuria at the end of the treatment period and less progression from normoalbuminuria to microalbuminuria (Table 3) in a representative subset of participants with clinical and biochemical characteristics close to those of the DAIS population.8 In the placebo group, the

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Originally published online as doi:10.1053/j.ajkd.2004.11.004 on January 14, 2005.

A full list of DAIS investigators is provided in Lancet 357:905-910, 2001.

J-C.A., C.F., and S.R. are employees of Laboratoires Fournier SA, which manufactures fenofibrate. M-R.T. and G.S. are part of the DAIS study group that received unrestricted grants from Laboratoires Fournier SA to conduct the trial.

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