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)

Ansquer, Jean-Claude; Foucher, Christelle; Rattier, Stephanie; Taskinen, Marja‐Riitta; Steiner, George

doi:10.1053/j.ajkd.2004.11.004

Cited by 231 publications

(139 citation statements)

References 20 publications

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“…However, we observed direct effects of lipids on renal function in both high-risk and low-risk models. Several proof-of-concept studies and post hoc analyses also sug-gested the potential benefits of lipid lowering, including the use of statins [36] and fibrates [37], on renal function.…”

Section: Effects Of Genotypes and Phenotypes On Renal Functionmentioning

confidence: 99%

Phenotype–genotype interactions on renal function in type 2 diabetes: an analysis using structural equation modelling

Song

Lee

et al. 2009

Diabetologia

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Aims/hypothesis Cardiovascular and renal diseases share common risk factors. We used structural equation modelling (SEM) to evaluate the independent and combined effects of phenotypes and genotypes implicated in cardiovascular diseases on renal function in type 2 diabetes.Methods 1,188 type 2 diabetic patients were stratified into high-risk and low-risk groups according to bimodal distributions of the logarithmically transformed (log e ) urinary albumin:creatinine ratio and plasma creatinine levels. Models for these groups, comprising continuous and non-ranking categorical data, were developed separately to evaluate the inter-relationships among measured variables and latent factors using non-linear SEMs, Bayesian estimation and model selection as assessed by a goodness-of-fit statistic. Results Inter-correlated measured variables (obesity, glycaemia, lipid, blood pressure) and variants of the genes encoding endothelial nitric oxide synthase (NOS), β-adrenergic receptor (ADRB), components of the reninangiotensin system (RAS) and lipid metabolism were loaded onto their respective latent factors of phenotypes and genotypes. In addition to direct and indirect effects, latent factors of obesity, lipid and BP interacted with latent factors of ADRB and RAS genotypes to influence renal function. Together with variants of the genes encoding peroxisome proliferator-activated receptor γ, atrial natriuretic peptide, adducin, G protein β 3 subunit, epithelial sodium channel α subunit and matrix metallopeptidase 3, these parameters explained 39-80% of the variance in renal function in the high-risk and low-risk models. Conclusions/interpretation SEM is a useful tool for confirming and quantifying multiple interactions of biological pathways with genetic determinants. The combined and interactive effects of blood pressure, lipid and obesity on renal function may have therapeutic implications, especially in type 2 diabetic individuals with genetic risk factors.

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Section: Effects Of Genotypes and Phenotypes On Renal Functionmentioning

confidence: 99%

Phenotype–genotype interactions on renal function in type 2 diabetes: an analysis using structural equation modelling

Song

Lee

et al. 2009

Diabetologia

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“…In the Cholesterol and Recurrent Events (CARE) study (10), patients with previous myocardial infarction, total cholesterol Ͻ240 mg/dl (6.21 mmol/l), and CKD had reduced rates of decline in renal function with pravastatin versus placebo. In the Diabetes Atherosclerosis Intervention Study (DAIS) (11) and in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial (12) in patients with type 2 diabetes, fenofibrate therapy reduced progression of albuminuria. Simvastatin in the Heart Protection Study (HPS) significantly decreased decline in glomerular filtration rate in diabetic subjects (13).…”

Section: Research Design and Methods -mentioning

confidence: 99%

Effect of LDL Cholesterol and Treatment With Losartan on End-Stage Renal Disease in the RENAAL Study

et al. 2008

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Renal pathology and dyslipidemia commonly coexist. Treatments that lower albuminuria/ proteinuria may lower lipids, but it is not known whether lipid lowering independent of lessening albuminuria/proteinuria slows progression of kidney disease. We examined the association between LDL cholesterol levels and treatment with losartan on end-stage renal disease (ESRD). Lipid levels and albuminuria measurements were obtained at baseline and at year 1 in a post hoc analysis from the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study, which compared the effects of losartan-versus placebobased antihypertensive therapy in patients with type 2 diabetes and nephropathy. LDL cholesterol lowering was associated with a lower risk of ESRD; however, this seemed to be largely an association with the reduction in albuminuria. Diabetes Care 31:445-447, 2008A pproximately 60% of patients with chronic kidney disease (CKD) have dyslipidemia (1,2). Elevated LDL cholesterol may be associated with CKD progression (2); however, patients with normal renal function and dyslipidemia do not develop renal insufficiency (3). Treatments that reduce albuminuria and slow CKD progression commonly lower lipids. It is unclear whether lipid lowering itself, rather than as a result of reduced albuminuria, slows CKD progression.We investigated the relationship of LDL cholesterol and albuminuria at baseline and/or year 1 and treatment with losartan on end-stage renal disease (ESRD) in the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study. RESEARCH DESIGN AND METHODS -The RENAAL study evaluated losartan-versus placebo-based therapy in 1,513 patients with type 2 diabetes and nephropathy (4). This post hoc analysis included LDL cholesterol (5) and albuminuria measurements at baseline and year 1 before ESRD. Patients were encouraged to control protein and salt intake, but there were no instructions regarding lipid management.Changes from baseline to year 1 are reported as the absolute difference for LDL cholesterol and as the percentage of change in the geometric mean ratio for albuminuria. Stratification for LDL cholesterol at baseline (Ͻ2.59, Ͼ2.59 to Յ3.10, Ͼ3.10 to Յ3.62, Ͼ3.62 to Յ4.14, Ͼ4.14 to Յ4.65, and Ͼ4.65 mmol/l) was based on clinical judgment and sample size/stratum. Event rates were calculated as number of endpoints per 1,000 patient-years of follow-up. Cox regression models were used to calculate hazard ratios (HRs), 95% CIs, and P values with LDL cholesterol Ͻ2.59 mmol/l as reference with/without adjustments for baseline albuminuria (log transformed), serum creatinine, serum albumin, and hemoglobin (6) and with/without additional adjustment for albuminuria at year 1. Similar analyses were done when treatment group was incorporated into the model with the placebo-administered LDL cholesterol increase group as reference. Change in albuminuria by group and by LDL cholesterol Ͻ and Ն3.10 mmol/l was assessed with adjustment for baseline albuminuria (log transformed), ...

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“…Several studies which have measured GFR in patients with creatinine elevation (up to a 20% increase) following fibrate treatment have not demonstrated glomerular impairment using inulin [8][9][10]. Significant direct nephrotoxicity induced by fibrates within the commonly observed range of creatinine increase is unlikely as no increase in proteinuria has previously been reported with these drugs; in fact a reduction in the rate of onset and progression of microalbuminuria has been described [27]. A recent animal study by Ovcharenko et al did not reveal any evidence of a direct nephrotoxic effect or deterioration in renal haemodynamics caused by either PPARα (fenofibrate) or dual PPARα/γ (tesaglitazar) agonists [28].…”

Section: Discussionmentioning

confidence: 99%

Factors Associated With Fibrate-Induced Creatinine Elevation: Observations in an Outpatient Setting

Аббас

2012

World J Nephrol Urol

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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)

Cited by 231 publications

References 20 publications

Phenotype–genotype interactions on renal function in type 2 diabetes: an analysis using structural equation modelling

Phenotype–genotype interactions on renal function in type 2 diabetes: an analysis using structural equation modelling

Effect of LDL Cholesterol and Treatment With Losartan on End-Stage Renal Disease in the RENAAL Study

Factors Associated With Fibrate-Induced Creatinine Elevation: Observations in an Outpatient Setting

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