Plasma and Lp(a)-associated PAF-acetylhydrolase activity in uremic patients undergoing different dialysis procedures

Background. Platelet-activating factor (PAF) is a potent inflammatory media tor associated with several physiopathological conditions, including renal diseases. PAF is degraded to the inactive metabolite lyso-PAF by PAF-acetyl hydrolase (PAF-AH), which is considered as a potent anti-inflammatory and a nti-atherogenic enzyme associated with lipoproteins. In this study, we eval uated the plasma- and lipoprotein(a) [Lp(a)]associated PAF-AH activity in r elationship to plasma lipid parameters and Lp(a) isoform size in patients w ith mild/moderate chronic renal failure (CRF), as well as in hemodialysis ( HD) and chronic ambulatory peritoneal dialysis (CAPD) patients. Methods. We studied 74 patients undergoing maintenance HD, 44 patients unde rgoing CAPD, 56 patients with mild/ moderate CRF, and 98 healthy subjects w hose lipid profile, as well as plasma and high-density lipoprotein (I-IDL)- associated PAF-AI-I activity, was determined. Moreover, the effect of Lp(a) plasma levels on the distribution of PAF-API among plasma lipoproteins, as well as the specific activity and kinetic properties of PAF-AH on two diff erent Lp(a) isoforms, was measured in each studied group. Results. The plasma PAF-AH activity in all studied groups was significantly higher than in controls, and the increase was more profound in CAPD patien ts. The HDL-associated PAF-AH activity, expressed per milliliter of plasma. was similar among all studied groups; however, when it was expressed as ei ther per milligrams of HDL cholesterol or per milligrams of plasma apolipop rotein (apo) AI, the PAF-AH activity was significantly higher in all patien t groups compared with controls. All patient groups had significantly eleva ted plasma Lp(a) levels, which altered the distribution of PAF-AH among the plasma lipoproteins compared with that observed in subjects with very low plasma Lp(a) levels (<8 mg/dl). Additionally, in each studied group, the sp ecific activity as well as the apparent K-m and V-max values of the 19K4 ap o(a) isoform were significantly higher (P < 0.01) compared with the values of the 23K4 isoform. However, the specific activity, as well as the K-m and V-max values on either the 19K4 apo(a) isoform or the 23K4 isoform, was si gnificantly higher in CAPD patients compared with the other three groups. Conclusions. Plasma PAF-AH activity is increased in uremic patients. This e levation is more profound in CAPD patients, who also exhibit a more atherog enic lipid profile and more pronounced alterations in the specific activity and the kinetic constants of Lp(a)-associated PAF-AH.