The objective of the proposed research is to gain new insights into the pathogenesis of renal disease mediated by immunologic mechanisms through a comprehensive study of the factors influencing and the consequences of tubular immune complex formation and clearance through an analysis of the kinetics of tubular deposition of antibodies to Tamm-Horsfall protein(TH). Specific objectives include evaluation of the effects of altered glomerular permeability and of urinary obstruction on the renal localization of anti-TH antibodies. These studies will include the use of immunologic, biochemical, ablative and naturally occurring models of glomerular injury in rats and cogenital hydronephrosis and ureteral ligation. They will include use of active immunization with TH and quantitative pair-label radioisotope techniques using affinity purified antibodies. Other proteins which interact with and are normally present in the same nephron segment as TH will also be studied. The methods employed will include quantitative biochemical, radioisotope, immunologic and immunopathologic techniques. These studies will be performed in rats, mice, and rabbits.
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