Kidney diseases. Issue 1 (12th November 2022)

• Record Type: Journal Article
• Authors: Daina, Erica; Cortinovis, Monica; Remuzzi, Giuseppe
• Is Part Of: Immunological reviews. Volume 313:Issue 1(2023)
• Page Start: 239
• Page End: 261
• Publication Date: 2022-11-12
• Subjects: alternative pathway of complement -- complement inactivating agents -- complement system -- glomerular diseases -- rare kidney diseases; Immunology -- Periodicals; Transplantation of organs, tissues, etc -- Periodicals; 616.079
• DOI: 10.1111/imr.13167
• Languages: English
• ISSNs: 0105-2896

Abstract

Summary: Dysregulation and accelerated activation of the alternative pathway (AP) of complement is known to cause or accentuate several pathologic conditions in which kidney injury leads to the appearance of hematuria and proteinuria and ultimately to the development of chronic renal failure. Multiple genetic and acquired defects involving plasma‐ and membrane‐associated proteins are probably necessary to impair the protection of host tissues and to confer a significant predisposition to AP‐mediated kidney diseases. This review aims to explore how our current understanding will make it possible to identify the mechanisms that underlie AP‐mediated kidney diseases and to discuss the available clinical evidence that supports complement‐directed therapies. Although the value of limiting uncontrolled complement activation has long been recognized, incorporating complement‐targeted treatments into clinical use has proved challenging. Availability of anti‐complement therapy has dramatically transformed the outcome of atypical hemolytic uremic syndrome, one of the most severe kidney diseases. Innovative drugs that directly counteract AP dysregulation have also opened new perspectives for the management of other kidney diseases in which complement activation is involved. However, gained experience indicates that the choice of drug should be tailored to each patient's characteristics, including clinical, histologic, genetic, and biochemical parameters. Successfully treating patients requires further research in the field and close collaboration between clinicians and researchers who have special expertise in the complement system.