ROLE OF COMPLEMENT IN ACUTE TUBULOINTERSTITIAL INJURY OF RATS WITH AMINONUCLEOSIDE NEPHROSIS

The present work was designed to elucidate the in vivo role of complem ent in the proteinuria-associated tubulointerstitial injury. Rats were intravenously injected with puromycin aminonucleoside, and massive pr oteinuria was observed within 5 days, Prominent tubulointerstitial inj ury characterized by proximal tubular degeneration, tubular dilatation , and leukocyte infiltration were observed 7 days after injection, C3 and C5b-9 were observed in. the luminal side of proximal tubular cells . Renal function, assessed by inulin and para-aminohippurate clearance , was significantly decreased. To assess the role of complement in thi s model, rats were injected with either cobra venom factor or soluble recombinant human complement receptor type 1 starting at day 3. These manipulations significantly improved tubulointerstitial pathology and para-aminohippurate clearance without affecting the degree of proteinu ria, Deposition of C3 and C5b-9 was not detected in the kidney of rats depleted of complement by cobra venom factor, In rats treated with so luble complement receptor, C3 was still detected in the tubules, but d eposition of C5b-9 was not observed, Soluble complement receptor was d etected at the site of C3 deposition and in the urine. These data stro ngly suggest that complement plays a pivotal role in proteinuria-assoc iated tubulointerstitial injury and that systemic complement depletion or inhibition of complement in the tubular lumen may diminish the tub ulointerstitial damage.