Clinical and Experimental Nephrology

, Volume 22, Issue 1, pp 3–14 | Cite as

Complement regulation and kidney diseases: recent knowledge of the double-edged roles of complement activation in nephrology

  • Masashi MizunoEmail author
  • Yasuhiro Suzuki
  • Yasuhiko Ito
Review article


The complement activation system plays important roles to maintain homeostasis in the host and to fight foreign invaders to protect the host. Therefore, the complement system is considered a core part of innate immunity which also cross-talks to acquired immunity. In the history of nephrology, the complement system is familiar to us, because complement protein or fragment deposition, including C3, C4, C1q, and/or C4d, is routinely estimated by immunohistochemistry to diagnose renal pathologies. The relationships between pathological mechanisms and complement activation have been investigated for renal diseases such as post-infectious glomerulonephritis, lupus nephritis, and primary membranoproliferative glomerulonephritis, which are usually accompanied by hypocomplementemia. However, unregulated complement activation in local areas might be associated with progression of various renal injuries even in the normocomplementemic patient. Recently, attention has focused on dysfunction of complement regulation in various diseases including renal diseases such as atypical hemolytic uremic syndrome and C3 glomerulopathy. Some mechanisms associated with complement activation in these diseases were clarified. In addition, lots of anti-complement agents were developed and some of the agents have become clinically available. Now, anti-complement therapies represent a realistic choice of therapeutic approaches for complement-related diseases. Research on roles of complement activation is proceeding into new stages in the field of nephrology and in other fields involving both basic and clinical research. We herein summarize relationships between the complement activation and regulation systems, their physiological effects and roles in maintenance of homeostasis in the host, and how dysregulation of the complement system triggers disease, especially renal disease.


Complement Complement regulator Complement dysregulation 



The authors profoundly thank Prof B. Paul Morgan for editing this manuscript. This work was in part supported in part by the Ministry of Education, Culture, Sports, Science and Technology in Japan (Grants-in-Aid 24591227). Mizuno M, Suzuki Y and Ito Y worked in the Department of Renal Replacement Therapy as positions endowed by Baxter Japan at Nagoya University Graduate School of Medicine.

Conflict of interest



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Copyright information

© Japanese Society of Nephrology 2017

Authors and Affiliations

  1. 1.Renal Replacement Therapy, Division of NephrologyNagoya University Graduate School of MedicineNagoyaJapan

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