URINARY-EXCRETION OF PLATELET-ACTIVATING-FACTOR IN HUMAN AND EXPERIMENTAL NEPHROSIS

Background. Platelet-activating factor (PAF) is a phospholipid that ha s been implicated in the pathogenesis of glomerulonephritis and can be synthesized by glomerular cells in response to different stimuli. PAF increases glomerular permeability to proteins and urinary PAF has bee n determined to be of renal origin. In order to assess whether urinary PAF call be found augmented in situations of glomerular damage withou t glomerular leukocyte infiltration, urinary PAF was quantified in hum an and experimental nephrosis. Methods. Urinary PAF was quantified by platelet bioassay and glomerular PAF by incorporation of H-3-acetate i nto PAF. PAF was characterized by its behaviour on thin-layer chromato graphy and high performance liquid chromatography and the blockade of its bioactivity by specific receptor antagonists. Results. Urinary PAF excretion was significantly higher in patients with active idiopathic nephrotic syndrome than in controls (5.8+/-1.5 versus 1.7+/-0.75 ng/2 4 h; P<0.05) and patients in remission (1.63+/-0.75 ng/24 h; P<0.02). In rats with nephrosis induced by puromycin aminonucleoside there was an early increase in urinary PAF excretion (138+/-19 versus 49+/-22 pg /24 h in controls; P<0.035) that coincided with the augmented glomerul ar PAF synthesis (67+/-3.4 versus 36+/-1.2 DPM/mg protein in controls; P<0.003). Conclusions. These results suggest that the synthesis of PA F in the kidney may be involved in the pathogenesis of the proteinuria in idiopathic nephrotic syndrome and that urinary PAF excretion may b e a good marker of disease activity.