Protecting the kidney in systemic lupus erythematosus: from diagnosis to therapy

Lupus nephritis (LN) is a common manifestation of systemic lupus erythematosus that can lead to irreversible renal impairment. Although the prognosis of LN has improved substantially over the past 50 years, outcomes have plateaued in the USA in the past 20 years as immunosuppressive therapies have failed to reverse disease in more than half of treated patients. This failure might reflect disease complexity and heterogeneity, as well as social and economic barriers to health-care access that can delay intervention until after damage has already occurred. LN progression is still poorly understood and involves multiple cell types and both immune and non-immune mechanisms. Single-cell analysis of intrinsic renal cells and infiltrating cells from patients with LN is a new approach that will help to define the pathways of renal injury at a cellular level. Although many new immune-modulating therapies are being tested in the clinic, the development of therapies to improve regeneration of the injured kidney and to prevent fibrosis requires a better understanding of the mechanisms of LN progression. This mechanistic understanding, together with the development of clinical measures to evaluate risk and detect early disease and better access to expert health-care providers, should improve outcomes for patients with LN. Lupus nephritis is a serious and currently irreversible complication of systemic lupus erythematosus that is a leading cause of mortality. New biomarkers and therapies are being developed to improve the monitoring and treatment of this disease. Key points Lupus nephritis (LN) is a heterogeneous complication of systemic lupus erythematosus that remains a considerable unmet medical need. Genetic and epigenetic factors confer risks of LN incidence and progression. Single-cell analyses and enhanced microscopic analyses of renal tissues are yielding new information about LN pathogenesis and the progression of chronic kidney disease. Improvements in risk assessment using genetic or transcriptomic biomarkers could enable the design of clinical trials to prevent LN onset and progression. Trials might need to be tailored according to the genetic profile of the patient, a biomarker-based evaluation of their renal tissue and/or the mechanism of action of each new drug. Developments in the understanding of tubulointerstitial injury and repair are yielding new strategies for preserving renal function and preventing fibrosis.