Platelet-activating factor (PAF) is a potent inflammatory mediator which is released by various inflammatory cells and produced by certain tissues, including the kidney. PAF has been shown to increase glomerular permeability to
protein and to decrease glomerular filtration rate (GFR) by contracting mesangium. On the basis of these observations, it has been suspected that PAF may play a role as mediator of glomerular damage in glomerular
nephritis. To examine this possibility, we studied the effects of a specific PAF antagonist,
R-75,317, on the development of an experimental model of anti-glomerular basement membrane (
anti-GBM)
glomerulonephritis.
Glomerulonephritis was initiated by injecting rabbit anti-rat GBM serum into rats.
Proteinuria gradually developed after serum injection, plateaued at week 2, and remained at the high level of week 2 throughout the experimental period (6 wk). Chronic treatment with
R-75,317 (10 mg/kg/day i.p.) tended to delay the onset of
proteinuria and significantly accelerated the recovery phase.
Creatinine clearance (Ccr) fell to 40% at week 3.
R-75,317 treatment completely prevented this decline of Ccr. Histological changes in this model (glomerular
hypertrophy, proliferation of mesangial matrix and interstitial
fibrosis) were also ameliorated by the
R-75,317 treatment. The results suggest that PAF may play a role in the development of
glomerulonephritis and that PAF antagonists could be used in the treatment of human renal disease.