Urine of Patients with Nephrotic Syndrome Contains the Plasma Type of PAF-Acetylhydrolase Associated with Lipoproteins

Abstract

Background: Platelet-activating factor (PAF) is a proinflammatory phospholipid mediator involved in the pathogenesis of glomerulonephritis (GN). In plasma, PAF is hydrolyzed and inactivated by PAF-acetylhydrolase (PAF-AH), an enzyme associated with lipoproteins, mainly with the low-density lipoprotein. PAF-AH activity has been found in urine of patients with primary GN, however the source and type of urinary PAF-AH remain unknown. We characterized the type of PAF-AH excreted in the urine of patients with primary GN and studied the possible relationship of this enzyme with the lipiduria and proteinuria observed in these patients. Methods: Eighteen patients with primary GN (8 with nephrotic syndrome (NS) and 10 with non-nephrotic range proteinuria (NNRP)) and 20 normolipidemic age- and sex-matched controls participated in the study. PAF-AH activity in plasma, in urine and in individual lipoprotein particles was determined by the trichloroacetic acid precipitation procedure, whereas the PAF-AH protein was detected by Western blotting analysis. Plasma and urine lipoproteins were fractionated by gradient ultracentrifugation and characterized by Western blotting analysis. Results: Plasma PAF-AH activity was higher in NS patients compared with NNRP patients and controls, whereas the enzyme activity associated with high-density lipoprotein was significantly lower in both patient groups compared with controls. PAF-AH was detected only in the urine of NS patients. It was the plasma type of PAF-AH and was associated with lipoprotein particles. Enzyme activity was also positively correlated with urine cholesterol levels. Conclusion: Urine of NS patients contains the plasma type of PAF-AH, which is related to the extent of lipiduria and is associated with urine lipoproteins.