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  • Review Article
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Redefining lupus nephritis: clinical implications of pathophysiologic subtypes

Key Points

  • The main purposes of renal biopsy in patients with systemic lupus erythematosus are to confirm the diagnosis of lupus nephritis, to assess disease activity and/or chronicity, guide therapeutic strategy, and provide prognostic information

  • Although the 2003 International Society of Nephrology/Renal Pathology Society (ISN/RPS) lupus nephritis classification system has been widely accepted, some additional lesions reflect the underlying disease pathogenesis and should be included or otherwise recognized

  • The ISN/RPS classification system is based on histology and not necessarily on the underlying pathogenesis, which needs to be the focus of treatment

  • The presence of glomerular crescents, podocyte injury, tubulointerstitial lesions and thrombotic microangiopathy, in particular, are indicative of underlying disease processes and should be considered when assessing patients with lupus nephritis

  • The current management of lupus nephritis is based on steroids and non-selective immunosuppressive drugs; novel agents that specifically interfere with the underlying pathophysiologic mechanisms of lupus nephritis are needed to improve disease outcomes

Abstract

Systemic lupus erythematosus (SLE) is associated with a broad spectrum of clinical and immunologic manifestations, of which lupus nephritis is the most common cause of morbidity and mortality. The development of nephritis in patients with SLE involves multiple pathogenic pathways including aberrant apoptosis, autoantibody production, immune complex deposition and complement activation. The 2003 International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification system for lupus nephritis was widely accepted with high intraobserver and interobserver concordance to guide therapeutic strategy and provide prognostic information. However, this classification system is not based on the underlying disease pathophysiology. Some additional lesions that contribute to disease presentation, including glomerular crescents, podocyte injury, tubulointerstitial lesions and vascular injury, should be recognized. Although outcomes for patients with lupus nephritis have improved over the past 30 years, treatment of this disease remains challenging and is best approached on the basis of the underlying pathogenesis, which is only partially represented by the various pathological phenotypes defined by the ISN/RPS classification. Here, we discuss the heterogeneous mechanisms involved in the pathogenesis of lupus nephritis and how improved understanding of underlying disease mechanisms might help guide therapeutic strategies.

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Figure 1: Pathological features of lupus nephritis subtypes.
Figure 2: Cell-mediated disease mechanisms of lupus nephritis.
Figure 3: Therapeutic targets in systemic lupus erythematosus (SLE) and lupus nephritis.
Figure 4: Proposed treatment algorithm for various pathological subtypes of lupus nephritis.

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Acknowledgements

We gratefully acknowledge the contributions of Hong Chu, Ying Tan, Chen Wang and Su-xia Wang, Peking University First Hospital, Beijing, for collecting data discussed in this Review. This work is supported by grants of National Natural Science Foundation of China to Innovation Research Group (No. 81621092) and National Natural Science Foundation of China (No. 81470932, No.81500526, No. 81670640 and No. 81670639).

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All authors researched data for the article, provided substantial contributions to discussions of its content, wrote the article, and reviewed and/or edited of the manuscript before submission.

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Correspondence to Ming-Hui Zhao.

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R.G. consults for Genentech. The other authors declare no competing interests.

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Glossary

Segmental lesions

A lesion that involves less than half the glomerular tuft.

Global lesions

A glomerular lesion that affects more than 50% of the glomerular tuft.

Pauci-immune

A pattern associated with minimal evidence of staining for immunoglobulins on glomeruli by immunofluorescence.

Renal flares

Defined by an increase in urine sediment, protein excretion, and serum creatinine value from baseline.

Tertiary lymphoid organs

Highly organized lymph node-like structures.

Vascular rarefaction

Loss of capillaries.

Perinuclear-ANCA

A category of ANCA originally described on the basis of their immunofluorescence patterns around the nucleus.

In situ adaptive immunity

A process in which infiltrate organizes into well-circumscribed aggregates of B cells and T cells (in germinal centres). These germinal centres contain follicular dendritic cells and enable intrarenal B cells to undergo clonal expansion and somatic hypermutation.

Plasmablast foci

Plasmablast aggregates in an organ.

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Yu, F., Haas, M., Glassock, R. et al. Redefining lupus nephritis: clinical implications of pathophysiologic subtypes. Nat Rev Nephrol 13, 483–495 (2017). https://doi.org/10.1038/nrneph.2017.85

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