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.

A hemolytic method for the measurement of nephritic factor.

The absence of a simple and widely applicable test for the measurement of NF activity has hampered the accumulation of evidence bearing on its nephritogenicity. The extensive modification of a screening test for this autoantibody, reported here, has increased the range and precision of the test and made it less laborious. C3b deposited on sheep E by the reaction of NF with NHS forms a C5 convertase which, with addition of rat EDTA serum, leads to hemolysis of the cells proportionate under the right conditions to the concentration of NF in the reaction mixture. The calibration line is straight or slightly concave and passes through the origin. The method detects the activity of both the NF of the amplification loop, NFa, found in MPGN type II, and the NF of the terminal pathway, NFt, found in MPGN types I and III. Interday coefficients of variation ranged from 6.6% to 13.5% and intraday from 7.0% to 12.6%. Although serum C3 levels can be markedly depressed when NF levels are high, C3 levels and NF activity generally correlate poorly. The C3 level could be low and NF absent or, occasionally, NF present with the C3 level normal. NF activity was absent from the stored serum of patients with active SLE, AGN or with an IgA nephropathy.