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  • Review Article
  • Published:

Biologics for the treatment of autoimmune renal diseases

Nature Reviews Nephrology volume 12, pages 217–231 (2016)Cite this article

Subjects

Key Points

  • The introduction of biologics that are safer and less toxic than conventional immunosuppressive therapies has markedly improved patient outcomes for many common autoimmune diseases

  • Good evidence suggests that many biologics will be effective in autoimmune renal diseases, but their development and introduction into clinical practice has been remarkably slow

  • Clinical and basic research is required to define the dominant disease-promoting molecules that underlie autoimmune renal diseases and could be targeted by current and evolving biologics

  • An increase in the size of patient cohorts and the assembly of clinician networks will facilitate the design and execution of multicentre, multinational, randomized controlled trials for new biologics

  • A strategic approach must be adopted to define the appropriate patient subgroups that will help prioritize which biologics should be tested, based on the available evidence of likely efficacy

Abstract

Biological therapeutics (biologics) that target autoimmune responses and inflammatory injury pathways have a marked beneficial impact on the management of many chronic diseases, including rheumatoid arthritis, psoriasis, inflammatory bowel disease, and ankylosing spondylitis. Accumulating data suggest that a growing number of renal diseases result from autoimmune injury — including lupus nephritis, IgA nephropathy, anti-neutrophil cytoplasmic antibody-associated glomerulonephritis, autoimmune (formerly idiopathic) membranous nephropathy, anti-glomerular basement membrane glomerulonephritis, and C3 nephropathy — and one can speculate that biologics might also be applicable to these diseases. As many autoimmune renal diseases are relatively uncommon, with long natural histories and diverse outcomes, clinical trials that aim to validate potentially useful biologics are difficult to design and/or perform. Some excellent consortia are undertaking cohort studies and clinical trials, but more multicentre international collaborations are needed to advance the introduction of new biologics to patients with autoimmune renal disorders. This Review discusses the key molecules that direct injurious inflammation and the biologics that are available to modulate them. The opportunities and challenges for the introduction of relevant biologics into treatment protocols for autoimmune renal diseases are also discussed.

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Figure 1: Biologics that target critical molecular pathways in the development of B-cell and T-cell autoimmunity.
Figure 2: Biologics that target CD4+ T helper (TH)-cell subsets.
Figure 3: Biologics that attenuate effector responses in the kidney.

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Acknowledgements

Research in glomerular disease performed by S.R.H., P.Y.G., and A.R.K. is funded by project grants from the National Health and Medical Research Council of Australia (grant numbers 1048575, 1045065, 1046585, 1064112, and 1084869).

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Authors and Affiliations

  1. Department of Medicine, Centre for Inflammatory Diseases, Monash University, 3800, VIC, Australia

    Stephen R. Holdsworth, Poh-Yi Gan & A. Richard Kitching

  2. Department of Nephrology, Monash Health, 246 Clayton Road, Clayton, Melbourne, 3168, VIC, Australia

    Stephen R. Holdsworth & A. Richard Kitching

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A.R.K., P.Y.G., and S.R.H. researched data for the article, made substantial contributions to discussions of the content, wrote the article and reviewed and/or edited the manuscript before submission.

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A.R.K. has been a member of an advisory board for Roche Products, Australia. P.Y.G and S.R.H. declare no competing interests.

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Holdsworth, S., Gan, PY. & Kitching, A. Biologics for the treatment of autoimmune renal diseases. Nat Rev Nephrol 12, 217–231 (2016). https://doi.org/10.1038/nrneph.2016.18

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