Overview
Lupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus (SLE) involving the kidneys 12. Guidelines provide evidence-based and expert guidance for the screening, treatment, and management of LN 123. Therapy for LN is considered continuous and ongoing, rather than consisting of discrete induction and maintenance phases 12.Management
Treatment Goals:
* Aim for remission or low disease activity and prevention of flares 4.
* Target complete renal response, defined as proteinuria <0.5-0.7 g/24 hours with (near-)normal glomerular filtration rate, by 12 months (extendable for patients with baseline nephrotic-range proteinuria) 3.
General Principles:
* Hydroxychloroquine is recommended for all patients with lupus, at a dose not exceeding 5 mg/kg real body weight, with regular ophthalmological monitoring 34.
Initial/Induction Treatment for Active Proliferative LN:
* Therapy should include pulse glucocorticoids followed by an oral glucocorticoid taper 12.
* Two additional immunosuppressive agents should be used for 3-5 years for those achieving complete renal response 12.
* Initial treatment options include mycophenolate mofetil (MMF 2-3 g/day or equivalent mycophenolic acid) or low-dose intravenous cyclophosphamide (500 mg x 6 biweekly doses), both combined with glucocorticoids (intravenous methylprednisolone pulses, then oral prednisone 0.3-0.5 mg/kg/day) 3.
* Alternatives for patients with nephrotic-range proteinuria and adverse prognostic factors include MMF/calcineurin inhibitor (especially tacrolimus) combination or high-dose cyclophosphamide 3.
Maintenance Treatment:
* Subsequent long-term maintenance treatment should follow with MMF or azathioprine 3.
* During chronic maintenance, glucocorticoids should be minimized to less than 7.5 mg/day (prednisone equivalent) and, when possible, withdrawn 34.
* Appropriate initiation of immunomodulatory agents (methotrexate, azathioprine, mycophenolate) can expedite glucocorticoid tapering or discontinuation 4.
Biologic Agents:
* Belimumab should be considered for persistently active or flaring extrarenal disease 4.
* Rituximab may be considered in organ-threatening, refractory disease 4.Key Recommendations
Lupus nephritis therapy should be continuous and ongoing, rather than consisting of discrete induction/initial and maintenance/subsequent therapies 12. (Evidence: Strong)
For patients achieving complete renal response, therapy should include pulse glucocorticoids followed by oral glucocorticoid taper and two additional immunosuppressive agents for 3-5 years 12. (Evidence: Strong)
Hydroxychloroquine is recommended for all patients with lupus, at a dose not exceeding 5 mg/kg real body weight, and requires regular ophthalmological monitoring 34. (Evidence: Strong)
The target of lupus nephritis therapy is complete renal response, defined as proteinuria <0.5-0.7 g/24 hours with (near-)normal glomerular filtration rate, to be achieved by 12 months (with potential extension for patients with baseline nephrotic-range proteinuria) 3. (Evidence: Strong)
For active proliferative lupus nephritis, initial treatment should involve mycophenolate mofetil (2-3 g/day or equivalent) or low-dose intravenous cyclophosphamide (500 mg x 6 biweekly doses), both combined with glucocorticoids (intravenous methylprednisolone pulses, then oral prednisone 0.3-0.5 mg/kg/day) 3. (Evidence: Strong)
During chronic maintenance treatment for SLE, glucocorticoids should be minimized to less than 7.5 mg/day (prednisone equivalent) and, when possible, withdrawn 34. (Evidence: Strong)References
1 Sammaritano LR, Askanase A, Bermas BL, Dall'Era M, Duarte-García A, Hiraki LT et al.. 2024 American College of Rheumatology (ACR) Guideline for the Screening, Treatment, and Management of Lupus Nephritis. Arthritis & rheumatology (Hoboken, N.J.) 2025. link
2 Sammaritano LR, Askanase A, Bermas BL, Dall'Era M, Duarte-García A, Hiraki LT et al.. 2024 American College of Rheumatology (ACR) Guideline for the Screening, Treatment, and Management of Lupus Nephritis. Arthritis care & research 2025. link
3 Fanouriakis A, Kostopoulou M, Cheema K, Anders HJ, Aringer M, Bajema I et al.. 2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis. Annals of the rheumatic diseases 2020. link
4 Fanouriakis A, Kostopoulou M, Alunno A, Aringer M, Bajema I, Boletis JN et al.. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Annals of the rheumatic diseases 2019. link