ACUTE EFFECTS OF ANTIGLOMERULAR BASEMENT-MEMBRANE ANTIBODY ON PROCESS OF GLOMERULAR-FILTRATION IN RAT

Nephron filtration rate (sngfr) and the factors controlling filtration were examined before and within 60 min of the i.v. infusion of 225-450 .mu.g of antiglomerular basement membrane antibody (AGBM Ab) (> 50% antigenic saturation) in plasma-expanded (2.5% body wt) Munich-Wistar rats. Pressures in glomerular capillaries (PG) and Bowman''s space (Pt) were measured with a servo-nulling device, systemic (.pi.A) and efferent arteriolar oncotic pressures (.pi.E) were measured by microprotein methods, and nephron plasma flow (rpf) and sngfr were measured by micropuncture techniques in control and post-AGBM Ab conditions in each rat. The sngfr fell from 52.7 .+-. 2.9 to 24.1 .+-. 1.9 nl/min per g kidney wt (n = 7, P < 0.001). Afferent and efferent arteriolar resistances increased, and rpf fell from 221 .+-. 25 to 90 .+-. 9 nl/min per g kidney wt (P < 0.001), but the hydrostatic pressure gradient across the glomerular membrane (.DELTA.P = PG - Pt) increased from 37 .+-. 1 to 50 .+-. 2 mm Hg (P < 0.001). The increase in .DELTA.P and a numerical decrease in .pi.A acted to maintain sngfr after AGBM Ab treatment, and effectively nullified the influence of decreased rpf upon sngfr. The mean effective filtration pressure .**GRAPHIC**. increased from 14 .+-. 2 to 30 .+-. 3 mm Hg (P < 0.001), while sngfr decreased. The major and critical reason for this reduction in sngfr was a decrease in the glomerular permeability coefficient from 0.077 .+-. 0.017 to 0.014 .+-. 0.001 nl/s per g kidney wt per mm Hg (P < 0.001), where sngfr = .**GRAPHIC**. Histologic sections revealed no proliferative changes, and capillary lumens were patent. From examination of light microscopy and EM the loss of capillary conduits and surface area was not adequate to explain the large reduction in LpA observed. Reduction in LpA must result from an acute decrease in local glomerular hydraulic permeability (Lp), probably as a result of swelling and separation of endothelial cells from the glomerular basement membrane observed by EM.