Current treatment of lupus nephritis: an overview of the new guidelines

Sales, Gabriel Teixeira Montezuma; Macedo, Natália Janoni; Reis Neto, Edgard Torres dos; Kirsztajn, Gianna Mastroianni

doi:10.1590/2175-8239-JBN-2025-0092en

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Review Article • Braz. J. Nephrol. 47 (4) • Oct-Dec 2025 • https://doi.org/10.1590/2175-8239-JBN-2025-0092en linkcopy

Current treatment of lupus nephritis: an overview of the new guidelines

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Introduction: Given the relevance of renal involvement in systemic lupus erythematosus (SLE) and new approaches to the disease and its treatment, this article aimed to synthesize the main updates in the diagnosis, management, and treatment of lupus nephritis (LN), based on recent publications of international reference guidelines in nephrology and rheumatology, in addition to highlighting aspects of interest from the 2024 national guidelines of the Brazilian Society of Rheumatology (SBR). The treatments for each class of lupus nephritis are described, as well as the therapeutic targets, underlining similarities and differences between the guidelines. In general, they recommend that induction (“initial”) treatment of proliferative classes be performed with monotherapy using mycophenolate or intravenous cyclophosphamide, or with multitarget regimens, using corticosteroids, mycophenolate or cyclophosphamide, and a calcineurin inhibitor or belimumab as a third drug. A change in therapy should be considered if the expected response target is not achieved, which presents subtle differences among current consensus guidelines. Maintenance (“subsequent”) treatment should preferably be performed with mycophenolate, azathioprine, or multi-target therapies. Emerging scientific evidence has provided treatment options that impact the management of lupus nephritis, thereby justifying the publication of new guidelines in recent months. Critically analyzing these guidelines may assist in decision-making for the individualized treatment of individuals with this disease.

Keywords:
Lupus Nephritis; Systemic Lupus Erythematosus; Guidelines; KDIGO; Immunosuppression; Glomerulopathies; Therapeutic Targets

1st Biopsy – perform whenever possible, when:
Proteinuria ≥ 0.5 g/24h (with or without other accompanying symptoms) Elevated serum creatinine with no other apparent cause
Rebiopsy – possible indications:	Observations
Support in deciding whether to discontinue maintenance therapy (after at least 3 years, including both induction and maintenance phases). Recurrence of renal activity for class reassessment, especially if initial presentation with nonproliferative class. LN refractory to induction therapy, usually after 24 weeks, if other associated diagnoses are suspected or if progression to chronicity occurs. Individualization is required.	Sustained histological activity, even with complete clinical response, suggests continuing maintenance immunosuppression.

Options for first-line induction therapy in proliferative classes	Observations
Cyclophosphamide monotherapy	Preference for a reduced dose of 500 mg every 14 days for 3 months, corresponding to the Euro-Lupus regimen
Mofetil mycophenolate monotherapy	Dose of 2-3 g/day
Belimumab in combination	Dose of 10 mg/kg IV on D0, D14, D28, and every 28 days thereafter With mycophenolate or cyclophosphamide Not indicated if eGFR < 30 ml/min/1.73m²
Voclosporin associated with mycophenolate mofetil 2 g/day	Alternatives: mycophenolate mofetil 1 g + tacrolimus (0.05–0.1 mg/day, divided into 2 doses, adjusted according to serum levels) or cyclosporine (3 mg/kg/day, divided into 2 doses, adjusted according to serum levels), in the absence of voclosporin. Not indicated if eGFR < 45 ml/min/1.73m²

	MMF	CYC NIH	CYC Euro-Lupus	AZA	TAC	CsA	BEL	RTX
Promotes adherence		X	X
Ease of access	X	X	X	X		X
Need for infusion center		X	X				X	X
Severity or refractoriness		X					X	X
Pregnancy/lactation				X	X	X
Risk of infertility		X	X
High cost					X		X	X

Types of responses	Definition
Complete renal response	Reduction of proteinuria to <0.5 g/g P/C or 24-hour proteinuria Stabilization or improvement of renal function (value within ±10%–15% of baseline eGFR) Within 6 to 12 months after initiation of therapy
Primary efficacy renal response	P/C < 0.7 g/g Maximum reduction in eGFR of 20% from baseline or eGFR > 60 ml/min/1.73 m² No use of rescue therapy Associated with better renal outcomes
Partial renal response	Reduction in proteinuria by at least 50% and to <3 g/g P/C or 24-hour proteinuria Stabilization or improvement in renal function (±10%–15% of baseline) Within 6 to 12 months after initiation of therapy
No response	No CR or PR criteria after 6–12 months of ISS

Target renal response – proteinuria
Reduction ≥ 25% in 3 months
Reduction ≥ 50% in 6 months
Reduction to < 0.7–0.8 g/24h in 12 months

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[1] Abbreviations – TAC: Tacrolimus; CsA: Cyclosporine A; MMF: Mycophenolate Mofetil; AZA: Azathioprine; CYC: Cyclophosphamide; BEL: Belimumab; RTX: Rituximab. Note – Adapted from SBR table.