CLUSTERIN DEPLETION ENHANCES IMMUNE GLOMERULAR INJURY IN THE ISOLATED-PERFUSED KIDNEY

Clusterin is a normal plasma protein, shown to be an inhibitor of reac tive complement hemolysis and a component of the fluid phase SC5b-9 te rminal complement complexes. It is a component of glomerular immune de posits in human and experimental glomerulonephritis. Using the complem ent-dependent isolated perfused rat kidney model of autologous phase p assive Heymann nephritis, we have studied the effect of clusterin depl etion of perfused plasma on the development of glomerular injury. Kidn eys with planted glomerular sheep anti-rat Fx1A antibody were perfused with human plasma either depleted of clusterin to less than or equal to 30%, or control plasma depleted of plasma fibronectin. Glomerular i njury was then initiated by the addition of guinea pig anti-sheep immu noglobulins to the perfusate. Kidneys perfused with clusterin depleted plasma developed significantly greater proteinuria at all time points when compared to control kidneys. Glomerular antibody binding and C3 deposition were similar in the two groups, but terminal complement com ponents were deposited in larger amounts in the clusterin depleted gro up. These data support a possible role for clusterin in vivo in the pr otection of complement-induced glomerular injury.