Treatment of chronic hemodialysis patients with low-dose fenofibrate effectively reduces plasma lipids and affects plasma redox status

Dyslipidemia is common in chronic hemodialysis patients and its underlying mechanism is complex. Hemodialysis causes an imbalance between antioxidants and production of reactive oxygen species, which induces the oxidative stress and thereby may lead to accelerated atherosclerosis. Statins have been found to be little effective in end-stage kidney disease and other lipid-lowering therapies have been only scarcely studied. The study aimed to assess the effect of low-dose fenofibrate therapy on plasma lipids and redox status in long-term hemodialysis patients with mild hypertriglyceridemia. Twenty seven chronic hemodialysis patients without any lipid-lowering therapy were included in a double-blind crossover, placebo-controlled study. The patients were randomized into two groups and were given a sequence of either 100 mg of fenofibrate per each hemodialysis day for 4 weeks or placebo with a week-long wash-out period between treatment periods. Plasma lipids, high sensitive C-reactive protein (CRP), urea, creatinine, electrolytes, phosphocreatine kinase (CK), GOT, GPT and plasma thiols (total and free glutathione, homocysteine, cysteine and cysteinylglycine) were measured at baseline and after each of the study periods. Plasma aminothiols were measured by reversed phase HPLC with thiol derivatization with 2-chloro-1-methylquinolinium tetrafluoroborate. Fenofibrate therapy caused a significant decrease of total serum cholesterol, LDL cholesterol and triglycerides and an increase of HDL cholesterol. The treatment was well tolerated with no side-effects but there was a small but significant increase of CK not exceeding the upper limit of normal range. There were no changes of serum CRP, potassium, urea, and creatinine and liver enzymes during the treatment. Neither total nor total free cysteinylglycine and cysteine changed during the study but both total and free glutathione increased during the therapy with fenofibrate and the same was observed in case of plasma homocysteine. The study shows that a treatment with reduced fenofibrate dose is safe and effective in reducing serum triglycerides and cholesterol in chronic dialysis patients and may shift plasma aminothiol balance towards a more antioxidative pattern.