Anti-GBM antibody-induced proteinuria in isolated perfused rat kidney

The effect of anti-GBM antibody on protein excretion was studied in isolated rat kidneys perfused with 20 mg of sheep anti-rat GBM (experimental) or nonantibody sheep IgG (control). Six control kidneys excreted 176 +/- 31 micrograms/min of BSA initially, rising to 296 +/- 111 micrograms/min at 2 h. Fractional clearance of BSA rose from 0.51 to 1.70%. Eight experimental kidneys excreted 211 +/- 56 micrograms/min of BSA, increasing to 1,924 +/- 804 micrograms/min at 2 h. Fractional BSA clearance increased from 0.56 to 11.49%. After 60 min, BSA excretion in anti-GBM-perfused kidneys exceeded controls by a factor of 6.5-7.9 (P less than 0.05) and fractional BSA clearance exceeded controls by a factor of 5.8-7.1 (P less than 0.05). Studies with fluorescent markers indicated proteinuria to be of glomerular origin in antibody-perfused kidneys. There were no significant differences between anti-GBM-perfused and control kidneys in perfusion pressures, perfusate flow rates, urine flow rates, inulin clearance, or sodium reabsorption. Antibody to GBM can induce a marked increase in glomerular permeability to BSA and IgG without participation of other systemic humoral or cellular mediation systems.