A B S T R A C T The effect of increased capillary perilmealility on1 glomerular immultine comiiplex localizationi was studied in rats immiluniized with proximial tul)ular anitigeni (Fx1A) to induce autologouis imnmunie complex nephropathy (AICN). AICN rats were made proteinuric 1)V-injection or uniilateral renal perfusion with amiiinoinucleoside of puromycin (PA) before developing sul)epithelial conmplex deposits. Control AICN kidneys developed diffuse granular deposits of IgG and Fx1A oIn the subepithelial surf'ace of the glomerular b)asement membrane (GBM) at 3 wk by immuiinofluiorescence and electron microscopy, and dep(isits increased in sul)-se(quienit weekly biopsies. In conitrast, PA-nephrotic AICN kidneys developed few or no GBM deposits and a significant increase in mesangial localization of IgG and FxlA during the period of PA-induced proteinuria. These alterationis in complex localizationi were documenited 1)oth in rats with PA nephrosis andl in unilaterally PA-inephrotic kidneys compared with conitralateral controls in the sanme animiials, thus excluidinig any effect of PA on the imnililiiopatlhogenetic mlechaniisnm in AICN as ani explaniation for these finidings. The absence of GBMi deposits closely correlated with reducedl stainiing for polyanionic glomierilar sialoproteini in proteinutiric kidneys, siniee PA-perfuised kidneys studied 2 wk after resdoltutioin of proteinutria demiion strated retuirni of niormlial staininig for sialoprotein Portionis of this work were presented at the 8th Ainutal

Immunologic mechanisms of proteinuria were investigated in guinea pigs (GP) injected with sheep antiserum (NTS) to GP glomerular basement membrane (GBM). Linear deposition of sheep gamma 1 and gamma 2 IgG led to a prompt but transient (36 hr) increase in albumin excretion from control values of 0.026 +/- 0.013 mg/hr to maximal values of 26+/-12.1 mg/rh at six hours without detectable histologic or electron microscopic changes except for decreased staining for glomerular polyanion and epithelial cell foot process fusion. GBM permeability to anionic ferritin was not increased during proteinuria. Anti-GBM antibody deposits did not fix GP C3 or C4 in vivo or in vitro. NTS-induced proteinuria was the same in guinea pigs that were normal, greater than 95% depleted of C3 through C9, genetically deficient in C4, and depleted of circulating polymorphonuclear leukocytes (PMN). Prior administration of antihistamines, steroids, azathioprine, colchicine, indomethacin, heparin, aprotinin (Trasylol), and niridazole also failed to reduced proteinuria. Initial proteinuria subsided by 36 hr, did not recur despite linear deposition of GP gemma 1 and gemma 2 after day seven, and antibody to GMB-bound sheep globlin. In the GP nephrotoxic nephritis model, anti-GBM antibody deposits apparently mediate increased permeability to albumin by a currently undefined mechanism which is independent of complement, PMN, and other know mediators of inflammation.

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