Abstract
Membranoproliferative glomerulonephritis (MPGN), recognized since 1965, is now known to have three forms, designated types I, II, and III. The types are similar in the frequency of hypocomplementemia and clinical course but are dissimilar in glomerular ultrastructure, pathogenesis, mechanisms of complement activation, predisposition to recur in the renal transplant, and, to some extent, in clinical presentation. Although glomerular proliferation is usually diffuse, it may be focal and segmental particularly in mild cases of MPGN I. Hypocomplementemia, present in about 80% of patients, is the result of hypercatabolism of C3 by three mechanisms as well as of diminished C3 synthesis. The hypocomplementemia is unrelated to clinical course or prognosis. Although MPGN I and III both have a high frequency of an extended haplotype on chromosome 6, which has known associations with autoimmune phenomena, and both have a high frequency of inherited complement defects, they are nevertheless dissimilar in glomerular ultrastructure, complement profile, and immunohistology in ways which suggest a wide difference in pathogenesis. Abnormalities in humoral immunity appear not to be involved in MPGN III. Treatment with anticoagulant, antiplatelet and cytotoxic drugs have, in controlled trials, been either ineffective or marginally effective. Long-term use of alternate-day prednisone in high dosage appears to be the most efficacious regimen in both controlled and uncontrolled studies.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Weller RO, Nester B (1972) Histological reassessment of three kidneys originally described by Richard Bright in 1827-36. BMJ 2: 761–763
West CD, McAdams AJ, McConville JM, Davis NC, Holland NH (1965) Hypocomplementemic and normocomplementemic persistent (chronic) glomerulonephritis; clinical and pathologic characteristics. J Pediatr 67: 1089–1112
Habib R, Kleinknecht C, Gubler MC, Levy M (1973) Idiopathic membranoproliferative glomerulonephritis in children. Report of 105 cases. Clin Nephrol 1: 194–214
Strife CF, McEnery PT, McAdams AJ, West CD (1977) Membrano-proliferative glomerulonephritis with disruption of the glomerular basement membrane. Clin Nephrol 7: 65–72
Barbiano di Belgiojosa G, Baroni M, Pagliari B, Lavagni MG, Porri MT, Banfi G, Colasanti G, Confalonieri R (1985) Is membrano-proliferative glomerulonephritis really decreasing? A multicenter study of 1,548 cases of primary glomerulonephritis. Nephron 40: 380–381
Arbus G, Getu H, Baumal R, Mraz V, Jabs D, Eddy A (1987) Long-term follow-up, including renal transplantation, of children with membranoproliferative glomerulonephritis. In: Murakami K, Kitagawa T, Yabuta K, Sakai T (eds) Recent advances in pediatric nephrology. Excerpta Medica, Amsterdam pp 241–246
Watson AR, Poucell S, Thorner P, Arbus GS, Rance CP, Baumal R (1984) Membranoproliferative glomerulonephritis type I in children: correlation of clinical features with pathologic subtypes. Am J Kidney Dis 4: 141–146
Donadio JV Jr, Slack TK, Holley KE, Ilstrup DM (1979) Idiopathic membranoproliferative (mesangiocapillary) glomerulonephritis. A clinicopathologic study. Mayo Clin Proc 54: 141–150
Cameron JS, Turner DR, Heaton J, Gwyn Williams D, Ogg CS, Chantler C, Haycock GB, Hicks J (1983) Idiopathic mesangiocapillary glomerulonephritis. Comparison of types I and II in children and adults and long term prognosis. Am J Med 74: 175–192
Jackson EC, McAdams AJ, Strife CF, Forristal J, Welch TR, West CD (1987) Differences between membranoproliferative glomerulonephritis types I and III in clinical presentation, glomerular morphology, and complement perturbation. Am J Kidney Dis 9: 115–120
Churg J, Duffy JL, Bernstein J (1979) Identification of dense deposit disease. A report for the International Study of Kidney Diseases in Children. Arch Pathol Lab Med 103: 67–72
Nevins TE (1985) Lectin binding in membranoproliferative glomerulonephritis, evidence forN-acetylglucosamine in dense intramembranous deposits. Am J Pathol 118: 325–330
Strife CF, McAdams AJ, West CD (1982) Membranoproliferative glomerulonephritis characterized by focal, segmental proliferative lesions. Clin Nephrol 18: 9–16
Yoshikawa N, Yoshiara S, Yoshiya K, Matsuo T, Matsuyama S, Okada S (1988) Focal and diffuse membranoproliferative glomerulonephritis in children. Am J Nephrol 8: 102–107
Mandalenakis N, Mendoza N, Pirani CL, Pollak VE (1971) Lobular glomerulonephritis and membranoproliferative glomerulonephritis. A clinical and pathologic study based on renal biopsies. Medicine (Baltimore) 50: 319–355
Swainson CP, Robson JS, Thomson D, MacDonald MK (1983) Measangiocapillary glomerulonephritis: a long term study of 40 cases. J Pathol 141: 449–468
Anders D (1987) Cooperative long term follow-up study of children with membranoproliferative glomerulonephritis (MPGN, three types). In: Murakami K, Kitagawa T, Yabuta K, Sakai T (eds) Recent advances in pediatric nephrology. Excerpta Medica, Amsterdam, pp 253–259
Ohi H, Seki M, Hatano M (1989) Membranoproliferative glomerulonephritis in Japan. Nephron 51: 435
Varade WS, Forristal J, West CD (1990) Patterns of complement activation in idiopathic membranoproliferative glomerulonephritis, types I, II and III. Am J Kidney Dis 14: 196–206
McEnery PT, McAdams AJ, West CD (1986) The effect of prednisone in a high-dose alternate day regimen on the natural history of idiopathic membranoproliferative glomerulonephritis. Medicine (Baltimore) 401–425
West CD (1989) The complement profile in clinical medicine. Inherited and acquired conditions lowering the serum concentrations of complement component and control proteins. Complement Inflamm 6: 49–64
Edberg JC, Tosic L, Wright EL, Sutherland WM, Taylor RP (1988) Quantitative analysis of the relation between C3 consumption, C3b capture and immune inherence of complement-fixing antibody/DNA complexes. J Immunol 141: 4258–4265
Daha MR, Fearon DT, Austen KF (1976) C3 nephritic factor (C3NeF): stabilization of fluid phase and cell bound alternative pathway convertase. J Immunol 116: 1–7
Daha MR, Kok DJ, Van Es LA (1982) Regulation of the C3 nephritic factor stabilized C3/C5 convertase of complement by purified human erythrocyte C3b receptor. Clin Exp Immunol 50: 209–214
Sissons JGP, Liebowitch J, Amos W, Peters DK (1977) Metabolism of the fifth component of complement and its relation to the metabolism of the third component in patients with complement activation. J Clin Invest 59: 704–715
Clardy CW, Forristal J, Strife CF, West CD (1989) A properdin dependent nephritic factor slowly activating C3, C5, and C9 in membranoproliferative glomerulonephritis types I and III. Clin Immunol Immunopathol 50: 333–347
Mollnes TE, Ng YC, Peters DK, Lea T, Tschopp J, Harboe M (1986) Effect of nephritic factor on C3 and on the terminal pathway of complement in vivo and in vitro. Clin Exp Immunol 65: 73–79
Tanuma Y, Ohi H, Hatano M (1990) Two types of C3 nephritic factor: properdin-dependent C3NeF and properdin-independent C3NeF. Clin Immunol Immunopathol 56: 226–238
Halbwachs L, Leveille M, Lesavre P, Wattel S, Leibowitch J (1980) Nephritic factor of the classical pathway of complement. Immunoglobulin G autoantibody directed against the classical pathway C3 convertase enzyme. J Clin Invest 65: 1249–1256
Daha MR, Hazevoet HM, Van Es LA, Cats A (1980) Stabilization of the classical pathway C3 convertase C42, by a factor F-42 isolated from serum of patients with systemic lupus erythematosus. Immunology 40: 417–424
Tanuma Y, Ohi H, Watanabe S, Seki M, Hatano M (1989) C3 nephritic factor and C4 nephritic factor in the serum of two patients with hypocomplementemic membranoproliferative glomerulonephritis. Clin Exp Immunol 76: 82–85
Charlesworth JA, Gwyn Williams D, Sherington E, Lachmann PJ, Peters DK (1974) Metabolic studies of the third component of complement and the glycine-rich beta glycoprotein in patients with hypocomplementemia. J Clin Invest 53: 1578–1587
Welch TR, Beischel L, Balakrishnan K, Quinlan M, West CD (1986) Major-histocompatibility-complex extended haplotypes in membranoproliferative glomerulonephritis. N Engl J Med 314: 1476–1481
Ramm D, Awdeh Z, Yunis EJ, Alper CA, Gabbay KH (1984) Extended major histocompatibility complex haplotypes in type I diabetes mellitus. J Clin Invest 74: 449–454
Alper CA, Fleischnick E, Awdeh Z, Katz AJ, Yunis EJ (1987) Extended major histocompatibility complex haplotypes in patients with gluten-sensitive enteropathy. J Clin Invest 79: 251–256
Welch TR, Beischel L, Balakrishnan K, Quinlan M, West CD (1988) Major histocompatibility complex extended haplotypes in systemic lupus erythematosus. Dis Markers 6: 247–255
Coleman TH, Forristal J, Kosaka T, West CD (1983) Inherited complement component deficiencies in membranoproliferative glomerulonephritis. Kidney Int 24: 681–690
The Southwest Pediatric Nephrology Study Group (1985) Dense deposit disease in children: prognostic value of clinical and pathological indicators. Am J Kidney Dis 6: 161–169
Berry PL, McEnery PT, McAdams AJ, West CD (1981) Membranoproliferative glomerulonephritis in two sibships. Clin Nephrol 16: 101–106
Stutchfield PR, White RHR, Cameron AH, Thompson R, MacKintosh P, Wells L (1986) X-linked mesangiocapillary glomerulonephritis. Clin Nephrol 26: 150–156
Power DA, Ng WC, Simpson JG (1990) Familial incidence of C3 nephritic factor, partial lipodystrophy and membranoproliferative glomerulonephritis. Q J Med 75: 387–398
Sissons JGP, Peters DK (1979) Partial lipodystrophy, chapter 44. In: Hamburger J, Crosnier J, Grunfield J-P (eds) Nephrology. Wiley, New York, pp 681–687
Chartier S, Buzzanga JB, Paquin F (1987) Partial lipodystrophy associated with a type 3 form of membranoproliferative glomerulonephritis. J Am Acad Dermatol 16: 201–205
Michael AF, Herdman RC, Fish AJ, Pickering RJ, Vernier RL (1969) Chronic membranoproliferative glomerulonephritis with hypocomplementemia. Transplant Proc 1: 925–932
Strife CF, McDonald BM, Ruley EJ, McAdams AJ, West CD (1976) Shunt nephritis: the nature of the serum cryoglobulins and their relation to the complement profile. J Pediatr 88: 403–413
Cameron JS (1982) Glomerulonephritis in renal transplants. Transplantation 34: 237–245
Duvall-Young J, Short CD, Raines MF, Gokal R, Lawler W (1989) Fundus changes in mesangiocapillary glomerulonephritis type II: clinical and fluorescein angiographic findings. Br J Ophthalmol 73: 900–906
Leys A, Prosmans W, VanDamme-Lombaerts R, VanDamme B (1991) Specific eye fundus lesions in type II membranoproliferative glomerulonephritis. Pediatr Nephrol 5: 189–192
Ormos J, Magori A, Sonkodi S, Steitmann K (1979) Type 2 membranoproliferative glomerulonephritis with electron-dense basement membrane alteration in the spleen (letter). Arch Pathol Lab Med 103: 265–266
Thorner P, Baumal R (1982) Extraglomerular dense deposits in dense deposit disease. Arch Pathol Lab Med 106: 628–631
Rosen BS, Cook KS, Yaglom J, Groves DL, Volanakis JE, Damm D, White T, Spiegelman BM (1989) Adipisin and complement factor D activity: an immune-related defect in obesity. Science 244: 1483–1487
Sturfeld G, Truedsson L, Sjoholm A (1985) Complement factor D in uremia (letter). N Engl J Med 312: 1577
Flier JS, Cook KS, Usher P, Spiegelman BM (1987) Severely impaired adipisin expression in genetic and acquired obesity. Science 237: 405–408
Vargas R, Thomson KJ, Wilson D, Cameron JS, Turner DR, Gill D, Chantler C, Ogg CS (1976) Mesangiocapillary glomerulonephritis with dense “deposits” in the basement membranes of the kidney. Clin Nephrol 5: 73–82
Lamb V, Tisher CC, McCoy RC, Robinson RR (1977) Membranoproliferative glomerulonephritis with dense intramembranous alterations. A clinicopathological study. Lab Invest 36: 607–617
Falk RJ, Dalmasso AP, Kim Y, Tsai CH, Scheinman JI, Gewurz H, Michael AF (1983) Neoantigen of the polymerized minth component of complement: characterization of a monoclonal antibody and immunohistochemical localization in renal disease. J Clin Invest 72: 560–573
Cooper NR, Nemerow GR (1983) Complement, viruses and virus infected cells. Springer Semin Immunopathol 6: 327–347
Tiller DJ, Clarkson AR, Matthew T, Thompson N, Row G, Lauer C, Hobbs J, Seymour A (1981) A prospective randomized trial in the use of cyclophosphamide, dipyridamole and warfarin in membranous and mesangiocapillary glomerulonephritis. In: Zurukzoglu W, Papadimitriou M, Pyrpasotoulos M, Sion M, Zamboulis C (eds) Proceedings of the 8th International Congress of Nephrology: advances in basic and clinical nephrology. Karger, Basel, p 345
Cattran DC, Cardella CJ, Roscoe JM, Charron RC, Rance PC, Ritchie SM, Corey PN (1985) Results of a controlled drug trial in membranoproliferative glomerulonephritis. Kidney Int 27: 436–441
Zimmerman SW, Moorthy AV, Dreher WH, Friedman A, Varanasi U (1983) Prospective trial of warfarin and dipyridamole in patients with membranoproliferative glomerulonephritis. Am J Med 75: 920–927
Donadio JV Jr, Anderson CF, Mitchell JC III, Holley KE, Ilstrup DM, Fuster V, Chesebro JH (1984) Membranoproliferative glomerulonephritis: a prospective clinical trial of platelet-inhibitor therapy. N Engl J Med 310: 1421–1426
Donadio JV Jr, Offord KP (1989) Reassessment of treatment results in membranoproliferative glomerulonephritis, with emphasis on lifetable analysis. Am J Kidney Dis 14: 445–451
Baldwin DS (1982) Nephrology forum: Chronic glomerulonephritis: non-immunologic mechanisms of progressive glomerular damage. Kidney Int 21: 109–120
Brenner BM (1983) Nephrology forum: Hemodynamically mediated glomerular injury and the progressive nature of kidney disease. Kidney Int 23: 647–655
McEnery PT, McAdams AJ (1988) Regression of membranoproliferative glomerulonephritis type II (dense deposit disease): observations in 6 children. Am J Kidney Dis 12: 138–146
McEnery PT (1990) Membranoproliferative glomerulonephritis: the Cincinnati experience-cumulative renal survival from 1957 to 1989. J Pediatr 116: S109-S114
A report of the International Study of Kidney Disease in Children (1982) Alternate day steroid therapy in membranoproliferative glomerulonephritis: a randomized controlled clinical trial (abstract). Kidney Int 21: 150
Edelmann CM Jr (1987) Long term low dose prednisone ameliorates the course of membranoproliferative glomerulonephritis (MPGN). A report of the International Study of Kidney Disease in Children. Pediatr Res 21: 474A
Warady BA, Guggenheim SJ, Sedman A, Lum GM (1985) Prednisone therapy of membranoproliferative glomerulonephritis in children. J Pediatr 107: 702–707
Haycock GB (1988) The treatment of glomerulonephritis in children. Pediatr Nephrol 2: 247–255
Hasegawa O, Ito H (1987) Methylprednisolone pulse therapy (MPT) for children with type-I membranoproliferative glomerulonephritis (MPGN): significance of complement profile on the therapy. In: Murakami K, Kitagawa T, Yabuta K, Sakai T (eds) Recent advances in pediatric nephrology. Excerpta Medica, Amsterdam, pp 247–252
Urizar RE (1985) Membranoproliferative glomerulonephritis. NY State J Med 85: 571a-572a
Mota-Hernandez F, Gordillo-Paniagua G, Munoz-Arizpe R, Lopez-Arriaga JA, Barboza-Madueno L (1985) Prednisone versus placebo in membranoproliferative glomerulonephritis: long term clinicopathological correlations. Int J Pediatr Nephrol 6: 25–28
West CD (1986) Nephrology forum. Childhood membranoproliferative glomerulonephritis: an approach to management. Kidney Int 29: 1077–1093
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
West, C.D. Idiopathic membranoproliferative glomerulonephritis in childhood. Pediatr Nephrol 6, 96–103 (1992). https://doi.org/10.1007/BF00856851
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00856851