Intravenous immunoglobulin protects against experimental thrombotic microangiopathy

Background. Intravenous immunoglobulin (IVIG) has been utilized in several forms of vasculitis and has many potential mechanisms of action, including the inhibition of C3 activation. We have previously demonstrated that IVIG can reduce glomerular injury in a model of membranous nephropathy mediated by C5b-9 [1]. C5b-9 has also been shown to mediate the thrombotic microangi opathy (TMA) induced by antibody to glomerular endothelial cells leading to a hemolytic uremic syndrome-type lesion [2]. Methods. To test the hypothesis that IVIG might be effective in treating an tibody-induced TMA, male uninephrectomized rats underwent right renal arter y perfusion with goat anti-rat glomerular endothelial cell (GEN) antibody ( 20 mg/kg). Sheep IgG (200 mg/kg) was administered either 30 minutes before the renal artery perfusion (group I, N = 6) or 30 minutes postperfusion (gr oup II, N = 9). A third control group received phosphate-buffered saline (P BS; group III, N = 12). A survival biopsy was performed at 15 minutes, and the animals were sacrificed on day 2. Results. There were no significant differences in proteinuria or hematocrit between the groups. Animals pretreated with IVIG had significantly improve d survival and renal function, which was associated with a decrease in glom erular C3 deposition. The protective effect of IVIG was abolished if the ad ministration was delayed 30 minutes after perfusion. Conclusions. IVIG is effective in reducing injury in experimental TMA only if given prophylactically. The effect is mediated by inhibition of local in traglomerular complement activation.