Lupus Nephritis Treatment Consensus and Future Directions

Several trials are investigating belimumab and rituximab combination therapy, the authors noted. CALIBRATE studied sequential administration of rituximab-cyclophosphamide and belimumab in patients with refractory LN. Patients experienced a decline in total and autoreactive naive B cells without an increase in adverse events compared with rituximab-cyclophosphamide alone. BEAT-LUPUS confirmed the safety of the combination of rituximab followed by belimumab in patients with refractory SLE. BLISS-BELIEVE examined rituximab as add-on treatment to subcutaneously administered belimumab in patients with active SLE without other immunosuppression. Patients with SLE with renal involvement achieved long-term proteinuric remission.

Investigators are also exploring an intensified dosage regimen of anifrolumab, a monoclonal antibody directed against the type I interferon receptor subunit 1 on T cells. Herpes zoster infection is a concern.

Dual-action monoclonal antibodies also show promise, according to the authors. Rozibafusp alfa is a first-in-class bispecific antibody-peptide conjugate that binds both BAFF and inducible T cell co-stimulator ligand (ICOSL). The drug blocks B cell maturation, T cell activation, and communication between T cells and B cells. It is being explored for nonrenal SLE. Ianalumab, a dual-action biologic that targets the BAFF receptor and mediates direct ADCC-mediated B cell depletion, is being explored in the SIRIUS-LN trial (NCT05126277), which is now recruiting.

A host of other drugs with cellular and cytokine targets are being investigated in trials. These target surface antigens and growth factors of B cells, surface molecules and intracellular proteins of T cells, surface molecules of dendritic cells, surface molecules and immunoproteasomes of plasma cells, cytokines and their receptors, intracellular downstream signaling pathways, complement pathways, and the neonatal Fc receptor.

Non-Immunosuppressive Therapies

Patients with lupus nephritis benefit from blood pressure control, reduction of albuminuria, and a healthy lifestyle involving healthy eating, exercise, and smoking cessation, the authors recapitulated. Clinicians should treat diabetes mellitus, hyperlipidemia, and metabolic syndrome, while avoiding nephrotoxic drugs, they noted. As with other kidney diseases, consider renin-angiotensin-aldosterone system inhibitors and sodium-glucose cotransporter-2 (SGLT2) inhibitors, unless contraindicated.

Precision Medicine

In addition to LN histological class, activity and chronicity, selection of LN therapy varies by age, ethnicity, LN history and course, kidney function, and comorbidities, the authors pointed out.

“Molecular profiling, gene-signature fingerprints and urine proteomic panels could enhance the accuracy of patient stratification for treatment personalization in the future,” Dr Mok and colleagues wrote.

Future guidelines are expected to address when to ‘step-up’ versus ‘step-down’ on LN treatment.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Mok CC, Teng YKO, Saxena R, Tanaka Y. Treatment of lupus nephritis: consensus, evidence and perspectives. Nat Rev Rheumatol. 19(4):227-238. doi:10.1038/s41584-023-00925-5

This article originally appeared on Renal and Urology News