Abstract
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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Appel GB, Cook T, Hagaman G, Jennette JC, Kashgarten M, Kirschfink M, Lambris JD, Lanning L, Lutz HU, Meri S, Rose NR, Salant DJ, Sethi S, Smith RJH, Smoyer W, Tully HF, Tully SP, Walker P, Welsh M, Wurzner R, Zipfel PF (2005) Membranoproliferative glomerulonephritis type II (dense deposit disease): An Update. J Am Soc Nephrol 16:1392–1404
Pickering MC, Cook HT, Warren J, Bygrave AE, Moss J, Walport M, Bolte M (2002) Uncontrolled C3 activation causes membranoproliferative glomerulonephritis in mice deficient in complement factor H. Nat Genet 31:424–428
Schwertz R, de Jong R, Gretz N, Kirschfink M, Anders D, Schärer K, Arbeitsgemeinschaft Pädiatrische Nephrologie (1996) Outcome of idiopathic membranoproliferative glomerulonephritis in children. Acta Paediatr 85:308–312
Schwertz R, Rother U, Anders D, Gretz N, Scharer K, Kirschfink M (2001) Complement analysis in children with idiopathic membranoproliferative glomerulonephritis. Pediatr Allergy Immunol 12:166–172
Rother U (1982) A new screening test for C3 nephritis factor based on a stable cell bound convertase on sheep erythrocytes. J Immunol Methods 51:101–107
Leibowitch J, Halbwachs L, Wattel S, Gaillard M-H, Droz D (1979) Recurrence of dense deposits in transplanted kidney: II Serum complement and nephritic factor profiles. Kidney Int 15:396–403
di Belgiojoso B, Tarantino A, Colasanti G, Bazzi C, Guerra L, Durante A (1977) The prognostic value of some clinical and histological parameters in membranoproliferative glomerulonephritis. Nephron 19:250–258
Davis AE, Schneeberger EE, Grupe WE, McCluskey RT (1978) Membranoproliferative glomerulonephritis (MPGN type I) and dense deposit disease in children. Clin Nephrol 9:184–193
Bennett WM, Fassett RG, Walker RG, Fairley KF, d’Apice AJ, Kincaid-Smith P (1989) Mesangiocapillary glomerulonephritis type II (dense deposit disease): Clinical features of progressive disease. Am J Kidney Dis 13:469–476
West CD (2008) A hemolytic method for the measurement of nephritic factor. J Immunol Methods 335:1–7
Vallota EH, Forristal J, Spitzer RD, Davis NC, West CD (1971) Continuing C3 breakdown after bilateral nephrectomy in patients with membranoproliferative glomerulonephritis. J Clin Invest 50:552–558
West CD (1986) Childhood membranoproliferative glomerulonephritis. An approach to management. Kidney Int 29:1077–1093
Kincaid-Smith P (1972) Treatment of chronic mesangiocapillary glomerulonephritis with impaired renal function. Med J Aust 2:587–592
Vallota EH, Forristal J, Davis NC, West CD (1972) The C3 nephritic factor and membranoproliferative glomerulonephritis: Correlation of serum levels of the nephritic factor with C3 levels, with therapy, and with progression of the disease. J Pediatr 80:947–959
Vallota EH, Forristal J, Spitzer RE, Davis NC, West CD (1970) Characteristics of a non-complement-dependent C3 reactive complex formed from factors in nephritic and normal sera. J Exp Med 131:1306–1334
Sissons JGP, West RJ, Fallows J, Williams DG, Boucher BJ, Amos N, Peters DK (1976) The complement abnormalities of lipodystrophy. N Engl J Med 294:461–465
Sim RB, Twose TM, Paterson DS, Sim E (1981) The covalent-binding reaction of complement component C3. Biochem J 193:115–127
Sahu A, Pangburn MK (1996) Investigation of mechanism-based inhibitors of complement targeting the activated thioester of human C3. Biochem Pharmacol 51:797–804
Daha MR, Fearon DT, Austen KF (1976) C3 requirements for formation of alternative pathway C5 convertase. J Immunol 117:630–634
Latta H, Fligiel S (1985) Mesangial fenestrations, sieving, filtration, and flow. Lab Invest 52:591–598
Daha MR, Austen KF, Fearon DT (1977) The incorporation of C3 nephritic factor (C3NeF) into a stabilized C3 convertase, C3bBb (C3NeF), and its release after decay of convertase function. J Immunol 119:812–817
Acknowledgments
The authors thank Sudha Dastrola for her help in developing and applying the method for measurement of NF activity, and Mai Nguyen, M.D., for her tireless chart review.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
West, C.D., Bissler, J.J. Nephritic factor and recurrence in the renal transplant of membranoproliferative glomerulonephritis type II. Pediatr Nephrol 23, 1867–1876 (2008). https://doi.org/10.1007/s00467-008-0887-x
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-008-0887-x