Abstract
Background: Lupus nephritis is one of the most common severe organ manifestations of systemic lupus erythematosus (SLE). Despite the continuing advancement in therapy, up to 30% of patients progress to end-stage renal disease. The clinical manifestations of lupus nephritis are variable and screening all SLE patients for lupus nephritis is imperative. There has been substantial advancement in availability of biomarkers and therapeutic options. This review focuses on epidemiology, early screening, advances in the biomarkers and management of lupus nephritis.
Content: Lupus nephritis is a devastating consequence of SLE and disproportionately affects the minorities. Inter-ethnic variation in the prevalence and severity of lupus nephritis as well as tolerance and clinical response to various therapeutic regimens for LN has led to variation in screening and treatment of lupus nephritis in SLE patients. Periodic screening of lupus nephritis in patients with SLE is imperative for early detection. Urinalysis and urine protein-to-creatinine ratio are useful screening tests. Quantification can be performed by 24-h urine sample collection for protein. Renal biopsy remains the gold standard for diagnosis of lupus nephritis. Traditional serum biomarkers used to monitor lupus nephritis disease activity and flares include anti-double-stranded DNA antibodies and complement components 3 and 4. New biomarkers for lupus nephritis include anti-C1q and type 1 interferon regulatory genes, urinary monocyte chemoattractant protein 1, neutrophil gelatinase-associated lipocalin, tumor necrosis factor-like inducer of apoptosis, and vascular cell adhesion molecule 1. Therapeutic options that better lead to remission of lupus nephritis, preserve kidney function and reduce the toxicities of concomitant glucocorticoids are unmet needs in lupus nephritis. There are newly approved treatments as well as investigational drugs in the pipeline, including the newer generation calcineurin inhibitors, biologic agents and cellular therapeutic options. The choice of therapy depends on a numberof clinical considerations and should be tailored to individual patient circumstances. Molecular profiling, gene-signature fingerprints and urine proteomic panels might enhance the accuracy of patient stratification for treatment personalization in the future.
Summary: Promising advances have been made in screening and treatment of lupus nephritis. The use of traditional and alternative biomarkers has the potential to identify at risk patients and those having active flare-up but require validation in prospective studies. Renal remission rates in patients receiving standard of care therapy for induction and maintenance treatments have improved but remain low. Further research in newer therapeutic targets for lupus nephritis shows promising results.
Key points
- The development of biomarkers for early detection and novel therapeutics to improve the efficacy-to-toxicity balance for LN are current unmet needs.
- New serum and urinary biomarkers for LN can help screen and stratify the patients at risk and those having flare-up of LN.
- Biologic, belimumab and calcineurin inhibitor, voclosporin are recently approved drugs for the treatment of LN offering potential to provide early and sustained remission in LN.
- Options to better stratify patients and provide personalized treatment for patients with LN such as molecular profiling and urine proteomic panels are on the horizon.
- New-generation anti-CD20 biologic agents, type I interferon antagonists, combination of biologics and cellular therapies such as autologous anti-CD19 CAR-T cell show promise for the treatment of LN.