PAF-acetylhydrolase Activity in Plasma of Patients with Chronic Kidney Disease. Effect of Long-term Therapy with Erythropoietin

Background: Platelet activating factor acetylhydrolase (PAF-AH) is a Ca2+-independent phospholipase A2 that is secreted mainly from monocytes/macrophages. In human plasma, PAF-AH is associated primarily with low-density lipoprotein (LDL), while a small proportion of enzyme is associated with high-density lipoprotein (HDL). The ratio of HDL-PAF-AH to total plasma enzyme activity may represent a potential marker of atherogenicity. We evaluated possible alterations of lipoprotein-associated enzyme activity in Chronic Kidney Disease (CKD) patients, stages 3-4, and further investigated whether long-term therapy with recombinant human erythropoietin (epoetin) has any influence on the plasma PAF-AH activity in vivo or on the enzyme activity secreted from peripheral blood monocytes (PBMs), in vitro.

Methods: Forty-eight patients, 28 men and 20 women, with CKD (stages 3-4) participated in the study. Patients were randomized into groups I and II. Patients of group I (n = 28) were administered subcutaneously epoetin, 50 units/kg once per week. The Hb target was 13 g/dl. In group II (n = 20), epoetin was initiated only when the Hb levels decreased during follow-up to less than 9 g/dl. All patients were seen on an outpatient basis at 2, 4 and 6 months. Twenty-two normolipidemic age- and sex-matched healthy volunteers also participated in the study and were used as controls.

Results: The PAF-AH activity in plasma of both patient groups at baseline was higher compared to controls, whereas no difference in the HDL-PAF-AH activity was observed among the studied groups. Thus, the ratio of HDL-PAF-AH to the plasma enzyme activity was significantly lower in both patient groups compared to controls. Epoetin administration in the patients of group I was associated with a significant increase in the plasma PAF-AH and in HDL-PAF-AH activities 2 months after treatment, which remained stable for up to 6 months of therapy, a phenomenon not observed in untreated patients of group II. Thus, the ratio of HDL-PAF-AH to the plasma enzyme activity was significantly increased in patients of group I compared to the baseline values, a phenomenon not observed in patients of group II. In vitro treatment with epoetin of PBMs from patients of group I (undergoing therapy with epoetin) resulted in a dose-dependent increase in total and secreted enzyme activity, a phenomenon not observed in patients of group II who did not receive therapy with epoetin. This suggests that the in vivo increase in lipoprotein-associated PAF-AH observed in patients treated with epoetin may be attributed to the drug-induced enhanced secretion of PAF-AH from PBMs of these patients.

Conclusions: CKD patients of stages 3-4 are characterized by an increase in plasma PAF-AH activity and a low ratio of HDL-PAF-AH to total plasma enzyme activity. Long-term therapy with epoetin may improve this atherogenic ratio thus this drug may play an important antiatherogenic role in CKD.