Nephritic factor and recurrence in the renal transplant of membranoproliferative glomerulonephritis type II

Animal models suggest a role for nephritic factor in the pathogenesis of glomerular disease, but evidence for a role in human disease is lacking. To assess its role, we applied a recently developed method that allows measurement of low levels of nephritic factor activity to stored serum specimens from three patients who had membranoproliferative glomerulonephritis (MPGN) type II. All three had had renal transplants, and one lost two of three transplants from recurrent disease. Evidence for a role for nephritic factor in human disease was a positive correlation between the level of nephritic factor activity and both the severity of recurrence and an increase in serum creatinine concentration. However, the hypocomplementemia was never severe; C3 levels of 49–76 mg/dl and nephritic factor levels of 89 U/ml were associated with severe recurrences. We have previously seen severe disease with mild hypocomplementemia. In contrast, patients with partial lipodystrophy often have severe hypocomplementemia and, presumably, high levels of nephritic factor yet have a mild glomerulonephritis. Disease severity and nephritic factor levels thus appear to be inversely related. The disease is progressive when only moderate amounts of nephritic factor have been circulating and C3 only mildly depressed.