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Complement Activation in Progression of Chronic Kidney Disease

  • Su-Fang Chen
  • Min ChenEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1165)

Abstract

Chronic kidney disease (CKD) is a public health problem worldwide, with increasing incidence and prevalence. The mechanisms underlying the progression to end-stage renal disease (ESRD) is not fully understood. The complement system was traditionally regarded as an important part of innate immunity required for host protection against infection and for maintaining host hemostasis. However, compelling evidence from both clinical and experimental studies has strongly incriminated complement activation as a pivotal pathogenic mediator of the development of multiple renal diseases and progressive replacement of functioning nephrons by fibrosis. Both anaphylatoxins, i.e., C3a and C5a, and membrane attack complex (MAC) contribute to the damage that occurs during chronic renal progression through various mechanisms including direct proinflammatory and fibrogenic activity, chemotactic effect, activation of the renal renin–angiotensin system, and enhancement of T-cell immunity. Evolving understanding of the mechanisms of complement-mediated renal injury has led to the emergence of complement-targeting therapeutics. A variety of specific antibodies and inhibitors targeting complement components have shown efficacy in reducing disease in animal models. Moreover, building on these advances, targeting complement has gained encouraging success in treating patients with renal diseases such as atypical hemolytic uremic syndrome (aHUS). Nevertheless, it still requires a great deal of effort to develop inhibitors that can be applied to treat more patients effectively in routine clinical practice.

Keywords

Complement Chronic kidney disease Glomerular diseases Renal fibrosis 

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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Key Laboratory of Renal Disease, Renal Division, Department of Medicine, Peking University First HospitalInstitute of Nephrology, Ministry of Health of China, Peking UniversityBeijingChina

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