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  • Review Article
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What is damaging the kidney in lupus nephritis?

Nature Reviews Rheumatology volume 12, pages 143–153 (2016)Cite this article

Subjects

Key Points

  • Nephritis remains a major cause of morbidity and mortality in systemic lupus erythematosus (SLE), with both extrinsic and intrinsic renal factors influencing long-term prognosis

  • Renal injury involves local immune responses and aberrant responses by the renal parenchyma; some of these responses are not reversed by immunosuppressive therapy and might require targeting of nonimmune mechanisms

  • Although lupus nephritis is initiated by immune complex deposition, the response to injury in individuals varies owing to differences in immune mechanisms, inflammation versus metabolic changes, hypoxia, and tissue repair and fibrosis

  • Disease phenotyping based on mechanism of renal injury, which are being discovered by genetic analyses, molecular profiling and proteomic analyses, could suggest new and more individualized therapeutic approaches

  • Studies in mouse models show that progression to chronic kidney disease is not inevitable even if systemic autoimmunity persists, and that several checkpoints in the progression pathway are amenable to therapy

  • Because clinical remission and renal histologic remission are not always correlated, improved disease monitoring and/or repeated biopsies could help identify patients at risk of progression and in need of high-intensity maintenance therapy

Abstract

Despite marked improvements in the survival of patients with severe lupus nephritis over the past 50 years, the rate of complete clinical remission after immune suppression therapy is <50% and renal impairment still occurs in 40% of affected patients. An appreciation of the factors that lead to the development of chronic kidney disease following acute or subacute renal injury in patients with systemic lupus erythematosus is beginning to emerge. Processes that contribute to end-stage renal injury include continuing inflammation, activation of intrinsic renal cells, cell stress and hypoxia, metabolic abnormalities, aberrant tissue repair and tissue fibrosis. A deeper understanding of these processes is leading to the development of novel or adjunctive therapies that could protect the kidney from the secondary non-immune consequences of acute injury. Approaches based on a molecular–proteomic–lipidomic classification of disease should yield new information about the functional basis of disease heterogeneity so that the most effective and least toxic treatment regimens can be formulated for individual patients.

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Figure 1: Glomerular injury in lupus nephritis.
Figure 2: Interstitial injury in lupus nephritis.
Figure 3: Shared pathogenic pathways identified in the kidneys of the three different lupus-prone mouse strains.

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Acknowledgements

The author's work is supported by NIH R01 DK085241-01.

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    Anne Davidson

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Davidson, A. What is damaging the kidney in lupus nephritis?. Nat Rev Rheumatol 12, 143–153 (2016). https://doi.org/10.1038/nrrheum.2015.159

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