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Lupus nephritis-related chronic kidney disease

Nature Reviews Rheumatology (2024)Cite this article

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Abstract

Lupus nephritis is a common complication of systemic lupus erythematosus (SLE) and a determinant of overall morbidity and mortality, as lupus nephritis-related chronic kidney disease (CKD) drives cardiovascular disease and secondary immunodeficiency. Two lines of action are required to prevent the progression of lupus nephritis-related CKD: suppression of autoimmune SLE activity, which is a risk factor for immunopathology-related irreversible kidney injury, and management of non-immune risk factors that contribute to CKD progression. As each episode or relapse of active lupus nephritis implicates CKD progression, preventing flares of lupus nephritis is a key treatment target. Non-immune risk factors of CKD mostly include causes of nephron hyperfiltration, such as obesity, hypertension, sodium- or protein-rich diets and type 2 diabetes mellitus, as well as pregnancy. Nephrotoxic agents and smoking also drive kidney cell loss. Intrinsic risk factors for CKD progression include poor nephron endowment because of prematurity at birth, nephropathic genetic variants, ageing, male sex and previous or concomitant kidney diseases. Care for lupus nephritis involves the control of all modifiable risk factors of CKD progression. In addition, remnant nephron overload can be reduced using early dual therapy with inhibitors of the renin–angiotensin system and sodium–glucose transporter-2, whereas further renoprotective drug interventions are underway. As patients with lupus nephritis are at risk of CKD progression, they would all benefit from interdisciplinary care to minimize the risk of kidney failure, cardiovascular disease and infections.

Key points

  • All patients with lupus nephritis have chronic kidney disease (CKD), which increases the risk of cardiovascular manifestations and secondary immunodeficiency.

  • To minimize the risk of CKD progression, both immune and non-immune factors should be addressed.

  • Suppressing autoimmune activity of systemic lupus erythematosus reduces repeated episodes of inflammatory kidney injury.

  • Assessment of non-modifiable non-immune risk factors for CKD progression and cardiovascular events, including genetic susceptibilities, poor nephron endowment because of preterm birth, previous kidney injuries or ageing, can help to tailor the monitoring and management of lupus nephritis-associated CKD to patient-specific conditions.

  • Management of modifiable non-immune risk factors, such as obesity or weight gain, type 2 diabetes mellitus, arterial hypertension, sodium- and protein-rich diets, exposure to smoking and nephrotoxic agents, can further help to minimize CKD progression and risk of cardiovascular disease.

  • Therapy with an inhibitor of the renin–angiotensin system at the maximal tolerated dose and potentially combined with an SGLT2 inhibitor might benefit patients with persistent proteinuria and a reduced estimated glomerular filtration rate.

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Fig. 1: Fundamental concepts about kidney reserve and healthy kidney ageing versus chronic kidney disease.
Fig. 2: Immune mechanisms of lupus nephritis-related chronic kidney disease.
Fig. 3: Non-immune mechanisms of lupus nephritis-related chronic kidney disease.
Fig. 4: Management of lupus nephritis-related chronic kidney disease.

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Acknowledgements

H.-J.A. was supported by the Deutsche Forschungsgemeinschaft AN372/29-1 and 30-1.

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  1. Department of Medicine IV, Hospital of LMU Munich, Munich, Germany

    Julia Lichtnekert & Hans-Joachim Anders

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All authors researched data for the article. All authors contributed substantially to discussion of the content. H.-J.A. wrote the first draft of the article. All authors reviewed and edited the manuscript before submission.

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Correspondence to Hans-Joachim Anders.

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H.-J.A. has received consultancy and lecture fees from Otsuka, GSK, AstraZeneca, Bayer, Boehringer Ingelheim, Roche, Novartis and SOBI. J.L. declares no competing interests.

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Lichtnekert, J., Anders, HJ. Lupus nephritis-related chronic kidney disease. Nat Rev Rheumatol (2024). https://doi.org/10.1038/s41584-024-01158-w

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