promega and Kidney-Failure--Chronic

Dialysis patients have an inordinate risk of cardiovascular events. Fish oils, rich in n-3 fatty acids, are believed to be beneficial in the prevention of atherosclerosis and thrombosis. Hence, the use of fish oils deserves consideration as a preventative or therapeutic intervention in dialysis patients. The suggestion has been made that n-3 fatty acids could increase the risk of bleeding, and thus, the safety of the use of these agents in dialysis patients must be established before long-term studies are undertaken. This study addresses the effect of n-3 fatty acids on the hemostatic profile of dialysis patients. Sixteen patients on chronic dialysis therapy were randomized to fish oil (MaxEPA) or placebo (olive oil) in a double-blind cross-over study. They received 3.6 g of n-3 fatty acids for 4 wk. Bleeding times were 4.8 +/- 0.4 min on MaxEPA and 4.5 +/- 0.3 min on placebo. Platelet aggregation to low-dose ADP or collagen also remained unchanged. There was a trend to lower serum triglyceride levels (2.7 +/- 0.5 versus 3.4 +/- 0.6 mmol/L, fish oil versus placebo) that did not reach statistical significance. Gastrointestinal side effects occurred in 10 of the 16 subjects and were severe in 5 patients. These side effects occurred in both the olive oil and the fish oil groups. The study had a 95% chance of detecting a clinically doubling significant increase in bleeding time, i.e., beta error less than 5%. In conclusion, n-3 fatty acids do not introduce a clinically important risk of bleeding for patients with end-stage renal disease.

Topics: Adult; Aged; Blood Pressure; Cardiovascular Diseases; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Female; Fish Oils; Hemostasis; Humans; Kidney Failure, Chronic; Lipids; Male; Middle Aged; Peritoneal Dialysis; Renal Dialysis

Dietary protein restriction and fish oil supplementation (MaxEPA) have been reported to have favourable effects on the remnant nephron model. In the present study female Munich-Wistar rats underwent 5/6 renal ablation (60 rats) or sham surgery (20 rats). The renal ablation rats were randomized one week post-surgery to receive a diet that contained either regular laboratory diet (RLD), 6% low protein diet (LPD) or 24% fish oil diet (FOD) supplementation. Mortality rates at 10 and 20 weeks post-surgery were not different amongst the RLD, LPD or FOD renal ablation cohorts. However the G.F.R. was significantly preserved in the FOD and LPD versus the RLD renal ablation rat groups. Both the LPD and FOD decreased albuminuria and gammaglobulinuria but LPD was more effective. Both dietary interventions prevented glomerulosclerosis but only LPD significantly reduced mesangial expansion. The FOD diet prevented intraglomerular fibrin formation and the LPD had no effect. The dyslipidemia noted at 20 weeks in the renal ablation group was significantly abrogated by both FOD and LPD, although only LPD prevented the heavy proteinuria. The LPD rats gained significantly less weight than the FOD and RLD cohorts. FOD exerted a significantly greater effect on blood pressure reduction than the LPD and also produced significant changes in the renal tissue phospholipids. These results indicate that protein restriction and fish oil supplementation preserve renal structure and function in the remnant nephron model but have different effects on mechanisms known to be co-factors in the progressive renal injury.

Topics: Animals; Blood Pressure; Dietary Proteins; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Female; Fish Oils; Fluorescent Antibody Technique; Glomerulosclerosis, Focal Segmental; Kidney Failure, Chronic; Kidney Glomerulus; Lipids; Nephrectomy; Nephrons; Phospholipids; Rats; Time Factors

Topics: Aspirin; Blood Pressure; Creatinine; Diabetic Nephropathies; Dipyridamole; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Female; Fish Oils; Glomerular Filtration Rate; Hemostasis; Humans; Hypertension; Kidney Failure, Chronic; Male; Platelet Aggregation Inhibitors; Proteinuria

It has been proposed that fish oil dietary supplementation in the chronic rat 5/6 renal ablation model may be either protective or toxic. These conflicting hypotheses were tested in rats who underwent renal ablation or sham surgery. Twenty rats received sham surgery, and 40 received 5/6 renal ablation. All rats were fed a regular laboratory diet up to 1 week postsurgery. At that time, one half of the renal ablation group was provided with an isocaloric diet supplemented with 24% MaxEPA (fish oil), 1% safflower oil, and antioxidants. The renal ablation rats developed hypertension, albuminuria, gammaglobulinuria, and a decline in glomerular filtration rate, which was less in the fish oil group compared with that in the regular laboratory diet group at 10 and 20 wk postsurgery. The fish oil renal ablation rats had significantly less glomerulosclerosis than did the regular laboratory diet renal ablation animals, and no more glomerular fibrin deposition than did the sham controls. The renal ablation regular laboratory diet rats had a significant dyslipidemia at 20 wk which was prevented in the fish oil renal ablation cohort. The fish oil renal ablation rats also demonstrated a significant decline in renal tissue arachidonic acid incorporation and a concomitant increase in eicosapentaenoic acid and docosahexaenoic acid incorporation. The mortality of the renal ablation group was greater than that of the sham controls but not significantly different for the fish oil or the regular laboratory diet groups. These results support the hypothesis that the fish oil diet containing specific antioxidant, vitamin E, and essential fatty acid supplementation is protective in the rat remnant nephron model and prevents the evolution of glomerulosclerosis with associated renal functional impairment, while preserving glomerular filtration.

Topics: Animals; Blood Pressure; Creatinine; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Female; Fish Oils; Glomerulonephritis; Immunoglobulin G; Inulin; Kidney; Kidney Failure, Chronic; Lipids; Nephrectomy; Phospholipids; Rats; Rats, Inbred Strains