Nephron
Distinguished Scientists Lecture Series
Section Editors: J.C.M. Chan; R.J. Krieg, Jr.; J.I. Scheinmann, Richmond, Va.
The Complement System in Renal DiseasesWelch T.R.Division of Nephrology and Hypertension, Children’s Hospital Research Foundation and Department of Pediatrics, University of Cincinnati College of Medicine,
|
|
Nephron 2001;88:199–204
Log in to MyKarger to check if you already have access to this content.
KAB
Buy a Karger Article Bundle (KAB) and profit from a discount!
If you would like to redeem your KAB credit, please log in.
Save over 20% compared to the individual article price.
* The final prices may differ from the prices shown due to specifics of VAT rules.
Article / Publication Details
First-Page Preview
Published online: June 22, 2001
Issue release date: 2001
Number of Print Pages: 6
Number of Figures: 1
Number of Tables: 1
ISSN: 1660-8151 (Print)
eISSN: 2235-3186 (Online)
For additional information: https://www.karger.com/NEF
Abstract
The complement system has long been recognized as having a role in immune glomerular disease. This review provides an update on this association, some strategies for the clinical testing of complement in disease, and a brief commentary on current research directions. Evidence of complement activation in glomerulonephritis comes from characteristic patterns of a decrease in the serum concentrations of specific components, some of which are virtually diagnostic of certain nephritides. These patterns are often accompanied by the presence of complement components in the glomeruli and the detection of complement breakdown products in the circulation. In certain diseases, circulating complement-activating substances can be detected. Although there are over 20 complement proteins, clinical analysis is most often directed at C3 and C4, with occasional measurement of B and C5. Recently, a variety of mechanisms for complement-induced injury has been recognized. These mechanisms go far beyond simple passive lysis of erythrocytes, the earliest functional effect of complement studied. The role of such mechanisms in renal disease is just beginning to be studied. Local synthesis of complement components in the kidney may play a role both in host defense and in the promotion of interstitial inflammation and scarring. Such mechanisms will likely be defined more precisely with the availability of animals with specific complement deficiencies. Ultimately, an understanding of the role of complement in renal disease may permit specific targeted inhibition of one or more complement functions as a form of therapy.
© 2001 S. Karger AG, Basel
Related Articles:
References
- Wyatt RJ, Forristal J, West CD, Sugimoto S, Curd JG: Complement profiles in acute post-streptococcal glomerulonephritis. Pediatr Nephrol 1988;2:219–223.
- West CD: The complement profile in clinical medicine: Inherited and acquired conditions lowering the serum concentrations of complement component and control proteins. Complement Inflamm 1989;6:49–64.
- Varade WS, Forristal J, West CD: Patterns of complement activation in idiopathic membranoproliferative glomerulonephritis, type I, II, and III. Am J Kidney Dis 1990;16:196–206.
-
Abramson SB, Weissmann G: Complement split products and the pathogenesis of SLE. Hosp Pract 1988;23:45–56.
-
Mollnes TE, Haga HJ, Brun JG, Nielsen EW, Sjöholm A, Sturfeldt G, Martensson U, Bergh K, Rekvig OP: Complement activation in patients with systemic lupus erythematosus without nephritis. Rheumatology (Oxford) 1999;38:933–940.
External Resources
- Nagy G, Brozik M, Varga L, Fust G, Kirschfink M, Kiss E, Gergely P: Usefulness of detection of complement activation products in evaluating SLE activity. Lupus 2000;9:19–25.
- Daha MR, van Es LA: Further evidence for the antibody nature of C3 nephritic factor (C3NeF). J Immunol 1979;123:755–758.
- Daha MR, Hazevoet HM, Vanes LA, Cats A: Stabilization of the classical pathway C3 convertase C42, by a factor F-42, isolated from serum of patients with systemic lupus erythematosus. Immunology 1980;40:417–424.
- Mollnes TE, Ng YC, Peters DK, Lea T, Tschopp J, Harboe M: Effect of nephritic factor on C3 and on the terminal pathway of complement in vivo and in vitro. Clin Exp Immunol 1986;65:73–79.
- Sissons JG, West RJ, Fallows J, Williams DG, Boucher BJ, Amos N, Peters DK: The complement abnormalities of lipodystrophy. N Engl J Med 1976;294:461–465.
- West CD: Nephritic factors predispose to chronic glomerulonephritis [see comments]. Am J Kidney Dis 1994;24:956–963.
- West CD, McAdams AJ: Paramesangial glomerular deposits in membranoproliferative glomerulonephritis type II correlate with hypocomplementemia. Am J Kidney Dis 1995;25:853–861.
- Edberg JC, Tosic L, Wright EL, Sutherland WM, Taylor RP: Quantitative analyses of the relationship between C3 consumption, C3b capture, and immune adherence of complement-fixing antibody/DNA immune complexes. J Immunol 1988;141:4258–4265.
- Edberg JC, Kimberly RP, Taylor RP: Functional characterization of non-human primate erythrocyte immune adherence receptors: Implications for the uptake of immune complexes by the cells of the mononuclear phagocytic system. Eur J Immunol 1992;22:1333–1339.
- Walport MJ: Inherited complement deficiency – clues to the physiological activity of complement in vivo. Q J Med 1993;86:355–358.
-
Pascual M, Mach-Pascual S, Schifferli JA: Paraproteins and complement depletion: Pathogenesis and clinical syndromes. Semin Hematol 1997;34(suppl 1):40–48.
External Resources
-
Kashgarian M, Hayslett JP: Renal involvement in systemic lupus erythematosus; in Tischer C, Brenner B (eds): Renal Pathology. Philadelphia, Lippincott, 1989, p 389.
- McAdams AJ, Valentini RP, Welch TR: The nonspecificity of focal segmental glomerulosclerosis: The defining characteristics of primary focal glomerulosclerosis, mesangial proliferation, and minimal change. Medicine (Baltimore) 1997;76:42–52.
- Welch TR, McAdams J: Immunoglobulin M and C1q mesangial labeling in IgA nephropathy. Am J Kidney Dis 1998;32:589–592.
- Welch TR, Beischel L, Berry A, Forristal J, West CD: The effect of null C4 alleles on complement function. Clin Immunol Immunopathol 1985;34:316–325.
- Ohsawa I, Ohi H, Endo M, Fujita T, Matsushita M: Evidence of lectin complement pathway activation in poststreptococcal glomerulonephritis. Kidney Int 1999;56:1158–1159.
- Matsuda M, Shikata K, Wada J, Sugimoto H, Shikata Y, Kawasaki T, Makino H: Deposition of mannan binding protein and mannan binding protein-mediated complement activation in the glomeruli of patients with IgA nephropathy. Nephron 1998;80:408–413.
- Endo M, Ohi H, Ohsawa I, Fujita T, Matsushita M: Complement activation through the lectin pathway in patients with Henoch-Schönlein purpura nephritis. Am J Kidney Dis 2000;35:401–407.
- Cybulsky AV, Takano T, Papillon J, McTavish AJ: Complement C5b-9 induces receptor tyrosine kinase transactivation in glomerular epithelial cells. Am J Pathol 1999;155:1701–1711.
- Topham PS, Haydar SA, Kuphal R, Lightfoot JD, Salant DJ: Complement-mediated injury reversibly disrupts glomerular epithelial cell actin microfilaments and focal adhesions. Kidney Int 1999;55:1763–1775.
- Braun M, Davis AE 3rd: Cultured human glomerular mesangial cells express the C5a receptor. Kidney Int 1998;54:1542–1549.
- Zahedi R, Braun M, Wetsel RA, Ault HA, Welch TR, Frenzke M, Davis AE III: The C5a receptor is expressed by human renal proximal tubular epithelial cells. Clin Exp Immunol 2000;121:226–233.
- Nangaku M: Complement regulatory proteins in glomerular diseases. Kidney Int 1998;54:1419–1428.
- Witte DP, Welch TR, Beischel LS: Detection and cellular localization of human C4 gene expression in the renal tubular epithelial cells and other extrahepatic epithelial sources. Am J Pathol 1991;139:717–724.
- Welch TR, Beischel LS, Witte DP: Differential expression of complement C3 and C4 in the human kidney. J Clin Invest 1993;92:1451–1458.
- Welch TR, Beischel LS, Frenzke M, Witte D: Regulated expression of complement factor B in the human kidney. Kidney Int 1996;50:521–525.
-
Colten HR, Strunk RC, Perlmutter DH, Cole F: Regulation of complement protein biosynthesis in mononuclear phagocytes. C1ba Found Symp 1986;118:141–154.
- Passwell J, Schreiner GF, Nonaka M, Beuscher HU, Colten HR: Local extrahepatic expression of complement genes C3, factor B, C2, and C4 is increased in murine lupus nephritis. J Clin Invest 1988;82:1676–1684.
- Montinaro V, Gesualdo L, Ranieri E, Monno R, Grandaliano G, Schena FP: Renal cortical complement C3 gene expression in IgA nephropathy. J Am Soc Nephrol 1997;8:415–425.
-
Unanue ER, Dixon FJ: Experimental glomerulonephritis. IV. Participation of complement in nephrotoxic nephritis. J Exp Med 1964;119:965–982.
External Resources
- Schurman SJ, McAdams AJ, Beischel L, Davis AE 3rd, Welch TR: C3-independent glomerulonephritis in guinea pigs: Dependence upon primary humoral response. Clin Immunol Immunopathol 1995;74:51–58.
- Sawtell NM, Hartman AL, Weiss MA, Pesce AJ, Michael JG: C3 dependent, C5 independent immune complex glomerulopathy in the mouse. Lab Invest 1988;58:287–293.
- Mitchell DA, Taylor PR, Cook HT, Moss J, Bygrave AE, Walport MJ, Botto M: Cutting edge: C1q protects against the development of glomerulonephritis independently of C3 activation. J Immunol 1999;162:5676–5679.
- Quigg RJ, Lim A, Haas M, Alexander JJ, He C, Carroll MC: Immune complex glomerulonephritis in C4- and C3-deficient mice. Kidney Int 1998;53:320–330.
- Hebert MJ, Takano T, Papayianni A, Rennke HG, Minto A, Salant DJ, Carroll MC, Brady HR: Acute nephrotoxic serum nephritis in complement knockout mice: Relative roles of the classical and alternate pathways in neutrophil recruitment and proteinuria. Nephrol Dial Transplant 1998;13:2799–2803.
- Watanabe H, Garnier G, Circolo A, Wetsel RA, Ruiz P, Holers VM, Boackle SA, Colten HR, Gilkeson GS: Modulation of renal disease in MRL/lpr mice genetically deficient in the alternative complement pathway factor B. J Immunol 2000;164:786–794.
- Alexander JJ, Lim A, He C, MacDonald RL, Holers VM, Quigg RJ: Renal, central nervous system and pancreatic overexpression of recombinant soluble Crry in transgenic mice: A novel means of protection from complement-mediated injury. Immunopharmacology 1999;42:245–254.
- Quigg RJ: We need to inhibit complement in glomerular proteinuria. Kidney Int 1999;56:2314–2315.
- Mathieson PW: Is complement a target for therapy in renal disease? Kidney Int 1998;54:1429–1436.
Article / Publication Details
First-Page Preview
Published online: June 22, 2001
Issue release date: 2001
Number of Print Pages: 6
Number of Figures: 1
Number of Tables: 1
ISSN: 1660-8151 (Print)
eISSN: 2235-3186 (Online)
For additional information: https://www.karger.com/NEF
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
Get Permission
PubMed ID
