Increased levels of plasma 8-EPI-PGF(2α) in patients with end stage renal failure

Abstract

F2-isoprostanes are a series of prostaglandin-F2 like compounds specifically derived from peroxidation of arachidonic acid by a mechanism independent of the cyclooxygenase pathway. Of these, 8-epi PGF(2α) is shown to be a potent vasoconstrictor. In this study, we have analysed plasma 8-epi PGF(2α) as a marker of oxidative stress in patients with end stage renal failure (ESRF) undergoing haemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). Plasma F2-isoprostanes were isolated by solid-phase extraction on a C18 followed by an NH2 cartridge. Quantitative analysis of the F2-isoprostanes as pentafluorobenzyl (PFB) ester/trimethylsilyl (TMS) ether derivatives was carried out by gas chromatography-electron capture mass spectrometry. For 34 individuals with ESRF, the mean level of esterified 8-epi PGF(2α) was 0.58 ± 0.22 M; range 0.21-1.16 nM. 8-epi PGF(2α) concentration in the patient groups was markedly higher (P < 0.0005 by separate variance t-test) than that of control subjects (n = 15) 0.28 ± 0.17 nM; range 0.02-0.63 nM. There was no difference in levels of 8-epi PGF(2α) in plasma from patients undergoing HD or CAPD, nor was there any association with age, plasma lipids or plasma creatinine. These data provide direct evidence of increased oxidative stress in individuals with ESRF. This marker should be useful in clinical studies examining the degree of oxidative stress in vivo and the therapeutic impact of antioxidants.