What is the treatment for Systemic Lupus Erythematosus (SLE) nephritis?

From the Guidelines

Treatment of Systemic Lupus Erythematosus (SLE) nephritis involves a combination of immunosuppressive medications to control inflammation and protect kidney function, with the initial therapy including glucocorticoids plus mycophenolic acid analogs, low-dose intravenous cyclophosphamide, belimumab with either mycophenolic acid analogs or low-dose intravenous cyclophosphamide, or mycophenolic acid analogs with a calcineurin inhibitor for patients with active Class III or IV LN, as recommended by the KDIGO 2024 clinical practice guideline 1.

The standard approach begins with induction therapy using high-dose corticosteroids (prednisone 0.5-1 mg/kg/day) plus either mycophenolate mofetil (MMF, 2-3 g/day in divided doses) or low-dose intravenous cyclophosphosphate (500 mg × 6 biweekly doses), as outlined in the 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 1. This induction phase typically lasts 3-6 months.

Following successful induction, maintenance therapy continues with lower-dose corticosteroids (gradually tapered to 5-10 mg/day) plus either MMF (1-2 g/day) or azathioprine (1.5-2.5 mg/kg/day) for at least 3 years. For patients with class V membranous lupus nephritis, calcineurin inhibitors like tacrolimus or cyclosporine may be considered. Hydroxychloroquine (200-400 mg daily) should be included in all treatment regimens as it reduces flares and improves survival, as supported by the American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis 1.

Blood pressure control with ACE inhibitors or ARBs is essential to reduce proteinuria and slow kidney disease progression. Regular monitoring of kidney function, urinary protein, and medication side effects is crucial. Rituximab or belimumab may be considered for refractory cases. This aggressive immunosuppressive approach is necessary because lupus nephritis represents immune complex-mediated kidney damage that, if left untreated, can progress to end-stage renal disease requiring dialysis or transplantation.

Key considerations in the treatment of SLE nephritis include:

• The target of therapy is complete response (proteinuria <0.5–0.7 g/24 hours with (near-) normal glomerular filtration rate) by 12 months, as outlined in the EULAR/ERA-EDTA recommendations 1.
• The choice of agent depends on the initial regimen and plans for pregnancy, with mycophenolate mofetil (MMF) being preferable to cyclophosphamide (CYC) for patients who express a major concern with fertility preservation, as discussed in the American College of Rheumatology guidelines 1.
• Adjunctive treatments, such as hydroxychloroquine and blood pressure control with ACE inhibitors or ARBs, are crucial in reducing proteinuria and slowing kidney disease progression, as recommended by the American College of Rheumatology guidelines 1.

From the Research

Treatment Overview

The treatment for Systemic Lupus Erythematosus (SLE) nephritis typically involves a combination of medications to manage the disease and prevent further kidney damage.

• The primary treatment approach includes the use of glucocorticoids, such as prednisone, to reduce inflammation and suppress the immune system 2, 3, 4, 5, 6.
• In some cases, cytotoxic agents like cyclophosphamide may be used in addition to glucocorticoids to treat more severe forms of lupus nephritis 2, 3, 4.

Induction Therapy

Induction therapy is used to treat active lupus nephritis and may involve the use of:

• High-dose intravenous methylprednisolone followed by moderate doses of prednisone 2, 5.
• A combination of glucocorticoids with cyclophosphamide, mycophenolate mofetil, or calcineurin inhibitors as first-line options 3.
• An upfront combination of immunosuppressive drugs and biological agents may be considered in patients at significant risk of disease progression and renal function deterioration 3.

Maintenance Therapy

Maintenance therapy is used to prevent renal flares and may involve the use of:

• Lower dose mycophenolate mofetil and azathioprine 3, 4.
• Prednisolone or equivalent should be maintained at a dose of 5 mg/day or less 3.
• The treatment should continue for at least 3 years to reduce the risk of renal flares 3.

Comparison of Treatment Approaches

Studies have compared the efficacy and safety of different treatment approaches, including:

• Low versus high initial oral glucocorticoid dose for lupus nephritis, with findings suggesting that lower doses may be associated with fewer serious adverse events without compromising efficacy 6.
• The use of pulsed methylprednisolone therapy compared to high-dose prednisone, with findings suggesting that both approaches can be effective in treating active SLE nephritis 5.