INCREASED LEVELS OF PLASMA 8-EPI-PGF(2-ALPHA) IN PATIENTS WITH END-STAGE RENAL-FAILURE

F-2-isoprostanes are a series of prostaglandin-F-2 like compounds spec ifically derived from peroxidation of arachidonic acid by a mechanism independent of the cyclooxygenase pathway. Of these, 8-epi PGF(2 alpha ) is shown to be a potent vasoconstrictor. In this study, we have anal ysed plasma 8-epi PGF(2 alpha) as a marker of oxidative stress in pati ents with end stage renal failure (ESRF) undergoing haemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). Plasma F-2-isopr ostanes were isolated by solid-phase extraction on a C-18 followed by an NH2 cartridge. Quantitative analysis of the F-2-isoprostanes as pen tafluorobenzyl (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(2 alpha) was 0.58 +/- 0.22 M; range 0.21-1.16 nM. 8-epi PGF(2 alpha) co ncentration in the patient groups was markedly higher (P<0.0005 by sep arate 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(2 alpha) in plasma from patients undergoing HD or CAPD, nor was t here any association with age, plasma lipids or plasma creatinine. The se data provide direct evidence of increased oxidative stress in indiv iduals with ESRF. This marker should be useful in clinical studies exa mining the degree of oxidative stress in vivo and the therapeutic impa ct of antioxidants.