Fenofibrate AND nephropathy

CONTEXT: Fibrates, the ligands of peroxisome profileferator-activated receptor-α have been shown to have a renal protective action in diabetic nephropathy (DN). OBJECTIVE: This study aimed to elucidate the effect of fenofibrate on renal transforming growth factor-β1 (TGF-β1) and Smad3 in Streptozotocin (STZ)-induced DN. METHODS: Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (55 mg/kg). Diabetic rats were given fenofibrate (100 mg/kg, p...

The lipid lowering medication, fenofibrate (FF), is a peroxisome proliferator-activated receptor-alpha (PPARα) agonist, possessing beneficial effects for type 2 diabetic nephropathy (DN). We investigated whether FF can prevent the development of type 1 DN, and the underlying mechanisms. Diabetes was induced by a single intraperitoneal injection of streptozotocin in C57BL/6J mice. Mice were treated with oral gavage of FF at 100mg/kg every other day for 3 and 6 months. Diabetes-induced renal oxidative stress, inflammation, apoptosis, lipid and collagen accumulation, and renal dysfunction were accompanied by significant decrease in PI3K, Akt, and GSK-3β phosphorylation as well as an increase in the nuclear accumulation of Fyn [a negative regulator of nuclear factor (erythroid-derived 2)-like 2 (Nrf2)]...

Distal symmetric sensorimotor polyneuropathy (DSPN) is the most common neurological manifestation in diabetes. Major risk factors of DSPN include diabetes duration, hyperglycemia, and age, followed by prediabetes, hypertension, dyslipidemia, and obesity. Height, smoking, insulin resistance, hypoinsulinemia, and others represent an additional risk. Importantly, hyperglycemia, hypertension, dyslipidemia, obesity, and smoking are modifiable. Stringent glycemic control has been shown to be effective in type 1, but not to the same extent in type 2 diabetes...

INTRODUCTION: Fenofibrate/simvastatin combination is useful for patients with mixed dyslipidemia. Aim of this review is to critically present the safety aspects of the fenofibrate/simvastatin combination. AREAS COVERED: Current evidence regarding the adverse effects of fenofibrate/simvastatin combination is critically presented based on the results of large randomized controlled trials and other relevant studies. Additionally, clinical pharmacology, drug interactions and the effects of fenofibrate and simvastatin on metabolic variables and cardiovascular risk are briefly described...

AIMS/HYPOTHESIS: Baseline circulating fibroblast growth factor 21 (FGF21) levels can predict total cardiovascular disease events in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. This paper describes the relationship of baseline FGF21 levels and new on-study microvascular disease in patients with type 2 diabetes from the FIELD study. METHODS: Baseline FGF21 levels were measured in plasma by enzyme-linked immunosorbent assay in 9697 study participants...

This study was conducted to investigate whether the renoprotective effects of fenofibrate are mediated via attenuation of endothelial dysfunction and modulating the mRNA expression of adenosine monophosphate-activated protein kinase (AMPK) and its downstream kinase liver kinase B1 (LKB1) in rats with diabetic nephropathy (DN). Diabetes was induced by a single intraperitoneal injection of streptozotocin (55 mg kg(-1)). Fenofibrate (100 mg kg(-1), p.o.) was given to diabetic rats daily for 12 weeks. Treatment with fenofibrate significantly improved the renal function as revealed by the significant reductions in urinary albumin excretion and serum levels of creatinine and urea, in addition to the significant increase in creatinine clearance compared with the diabetic control group...

Although diabetes is mainly diagnosed based on elevated glucose levels, dyslipidemia is also observed in these patients. Chronic kidney disease (CKD), a frequent occurrence in patients with diabetes, is associated with major abnormalities in circulating lipoproteins and renal lipid metabolism. At baseline, most renal epithelial cells rely on fatty acids as their energy source. CKD, including that which occurs in diabetes, is characterized by tubule epithelial lipid accumulation. Whether this is due to increased uptake or greater local fatty acid synthesis is unknown...

OBJECTIVE: People with diabetes frequently develop vascular disease. We investigated the relationship between blood 25-hydroxyvitamin D (25OH-D) concentration and vascular disease risk in type 2 diabetes. RESEARCH DESIGN AND METHODS: The relationships between blood 25OH-D concentration at baseline and the incidence of macrovascular (including myocardial infarction and stroke) and microvascular (retinopathy, nephropathy, neuropathy, and amputation) disease were analyzed with Cox proportional hazards models and logistic regression in an observational study of patients in the 5-year Fenofibrate Intervention and Event Lowering in Diabetes trial...

Low-doses of fenofibrate and dipyridamole have pleiotropic renoprotective actions in diabetic rats. This study investigated their combined effect relative to their individual treatments and lisinopril in rats with diabetic nephropathy. Streptozotocin (55mg/kg, i.p., once)-administered diabetic rats were allowed for 10 weeks to develop nephropathy. Diabetic rats after 10 weeks developed nephropathy with discernible renal structural and functional changes as assessed in terms of increase in kidney weight to body weight ratio (KW/BW), and elevations of serum creatinine, urea and uric acid, which accompanied with elevated serum triglycerides and decreased high-density lipoproteins...

BACKGROUND: Kidney function progressively deteriorates in patients with familial juvenile hyperuricemiac nephropathy (FJHN, OMIN 162000) and chronic renal disease is commonly associated to dyslipidemia. We report for the first time abrupt renal insufficiency in a patient with FJHN and hypertrygliceridemia following fenofibrate administration. CASE REPORT: A 53-year-old man was diagnosed clinically with FJHN at age 24 years which was subsequently confirmed by genotypic analysis of the UMOD gene at age 40 years...

Diminished insulin sensitivity is a characteristic feature of various pathological conditions such as hypertension and activation of peroxisome proliferator activated receptor α (PPARα) has been shown to enhance insulin resistance and reduce capacity for glucose uptake in muscles. The present study was designed to evaluate the interactions of PPARα and GLUT4 in a model of hypertensive renal injury by studying deoxycorticosterone acetate (DOCA)-salt induced hypertension in wild-type (WT) and PPARα knockout (KO) mice...

Peroxisome proliferator-activated receptor (PPAR)-α, a lipid-sensing transcriptional factor, serves an important role in lipotoxicity. We evaluated whether fenofibrate has a renoprotective effect by ameliorating lipotoxicity in the kidney. Eight-week-old male C57BLKS/J db/m control and db/db mice, divided into four groups, received fenofibrate for 12 weeks. In db/db mice, fenofibrate ameliorated albuminuria, mesangial area expansion and inflammatory cell infiltration. Fenofibrate inhibited accumulation of intra-renal free fatty acids and triglycerides related to increases in PPARα expression, phosphorylation of AMP-activated protein kinase (AMPK), and activation of Peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α)-estrogen-related receptor (ERR)-1α-phosphorylated acetyl-CoA carboxylase (pACC), and suppression of sterol regulatory element-binding protein (SREBP)-1 and carbohydrate regulatory element-binding protein (ChREBP)-1, key downstream effectors of lipid metabolism...

Alpha(1D)-adrenergic receptor (α(1D)-AR) plays important roles in regulating physiological and pathological responses mediated by catecholamines, particularly in the cardiovascular and urinary systems. The present study was designed to investigate the expression profile of α(1D)-AR in the diabetic kidneys and its modulation by activation of peroxisome proliferator-activated receptors (PPARs). 12-week-old Zucker lean (ZL) and Zucker diabetic fatty (ZD) rats were treated with fenofibrate or rosiglitazone for 8-10 weeks...

There remains a need for strategies that are effective in preventing diabetic retinopathy (DR) or slowing down its progression, which is safe, well-tolerated, and more effective, have a lower risk profile, easy to perform, have more predictable results with less morbidity than the current regimens. Physicians caring for diabetic patients not only need to maximize glycemic control, but also closely monitor and treat other systemic conditions. The consistency of clinical data from the fenofibrate studies showed consistent beneficial effects with fenofibrate in slowing the progression of DR...

Excess mesangial extracellular matrix (ECM) and mesangial cell proliferation is the major pathologic feature of diabetic nephropathy (DN). Fenofibrate, a PPARα agonist, has been shown to attenuate extracellular matrix formation in diabetic nephropathy. However, the mechanisms underlying this effect remain to be elucidated. In this study, the effect of fenofibrate on high-glucose induced cell proliferation and extracellular matrix exertion and its mechanisms were investigated in cultured rat mesangial cells by the methylthiazoletetrazolium (MTT) assay, flow cytometry and western blot...

BACKGROUND: Fenofibrate has been used for the management of atherogenic dyslipidaemia for many years. Reports of fenofibrate-associated increases in serum creatinine (SCr) levels raised concerns regarding deleterious effects on renal function. DESIGN: In this narrative review, we discuss available literature on the effect of fenofibrate on the kidney. RESULTS: Most clinical studies showed a rapid (within weeks) raising effect of fenofibrate on SCr levels...

AIMS/HYPOTHESIS: Bilirubin has antioxidant and anti-inflammatory 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...

OBJECTIVE: To compare results of clinical trials that assessed the impact of near-normalization of glucose on microvascular complications in type 2 diabetes. METHODS: ACCORD (N = 10,234) and ADVANCE (N = 11,140) tested the hypothesis that near-normalization of glucose reduces microvascular complications in adults with established type 2 diabetes. Differences in incidence rates (intensive versus standard glucose control) for specific microvascular complications are expressed as 'number needed to treat' (NNT) to prevent one microvascular complication...

BACKGROUND: Small vessel disease is reported to be a more common cause of ischaemic stroke in people with diabetes than in others. However, population based studies have shown no difference between those with and those without diabetes in the subtypes of stroke. We determined the rates and predictors of risk of stroke and its subtypes in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial. METHODS: 9795 patients aged 50-75 years with type 2 diabetes were followed up for a median of 5 years...

We have previously shown that low-dose fenofibrate treatment has an ability to prevent diabetes-induced nephropathy in rats. We investigated here the comparative pre- and post-treatment effects of low-dose fenofibrate (30 mg/kg/day p.o.) in diabetes-induced onset of nephropathy. Rats were made diabetics by single administration of streptozotocin (STZ, 55 mg/kg i.p.). The development of diabetic nephropathy was assessed biochemically and histologically. Moreover, lipid profile and renal oxidative stress were assessed...