What are the current EULAR (European League Against Rheumatism) guidelines for treating lupus nephritis?

Current EULAR Guidelines for Lupus Nephritis Treatment

The EULAR/ERA-EDTA 2012 guidelines recommend mycophenolic acid (MMF 3 g/day for 6 months) or low-dose intravenous cyclophosphamide (total 3 g over 3 months) combined with glucocorticoids as first-line treatment for class III/IV lupus nephritis, followed by maintenance therapy with MPA or azathioprine for at least 3 years. 1

Diagnostic Approach

Indications for Renal Biopsy

• Perform renal biopsy for any reproducible proteinuria ≥0.5 g/24 hours, especially with glomerular hematuria and/or cellular casts 1
• Clinical and serological tests cannot accurately predict biopsy findings, making histological diagnosis indispensable 1
• Use the ISN/RPS 2003 classification system to assess active and chronic glomerular/tubulointerstitial changes and vascular lesions 1

Treatment Goals

Target complete renal response: proteinuria <0.5 g/24 hours (UPCR <50 mg/mol) with normal or near-normal renal function 1

• Partial response (≥50% reduction in proteinuria to subnephrotic levels with normal/near-normal renal function) should be achieved by 6 months, but no later than 12 months 1
• Ultimate goals include long-term preservation of renal function, prevention of flares, avoidance of treatment-related harms, and improved quality of life and survival 1

Initial Treatment Regimens

Class III A/C and IV A/C (±V) Lupus Nephritis

First-line options (equal efficacy/toxicity ratio): 1

• Mycophenolic acid: MMF target dose 3 g/day for 6 months (or MPA sodium at equivalent dose)
• Low-dose IV cyclophosphamide: Total 3 g over 3 months

Alternative cyclophosphamide regimens: 1

• Monthly higher doses: 0.75–1 g/m² for 6 months
• Oral: 2–2.5 mg/kg/day

Patients with Adverse Prognostic Factors

For those with acute renal function deterioration, substantial cellular crescents, and/or fibrinoid necrosis, prescribe cyclophosphamide at higher doses 1

Glucocorticoid Protocol

Combine immunosuppression with: 1

• Three consecutive pulses of IV methylprednisolone 500–750 mg
• Followed by oral prednisone 0.5 mg/kg/day for 4 weeks
• Taper to ≤10 mg/day by 4–6 months

Pure Class V Nephritis with Nephrotic-Range Proteinuria

First-line: MPA (MMF target dose 3 g/day for 6 months) combined with oral prednisone 0.5 mg/kg/day 1

Alternative options for non-responders: 1

• Cyclophosphamide
• Calcineurin inhibitors (ciclosporin, tacrolimus)
• Rituximab

Azathioprine as Alternative

Consider azathioprine 2 mg/kg/day only in selected patients without adverse prognostic factors, or when MPA/CY are contraindicated, not tolerated, or unavailable 1

⚠️ Caveat: Azathioprine use is associated with higher flare risk 1

Maintenance/Subsequent Treatment

For patients improving after initial treatment: 1

• Continue immunosuppression for at least 3 years
• MPA at lower doses (initial target MMF dose 2 g/day) OR
• Azathioprine 2 mg/kg/day
• Combined with low-dose prednisone 5–7.5 mg/day

Critical principle: Patients who responded to initial MPA should remain on MPA for maintenance (not switch to azathioprine) unless pregnancy is contemplated 1

For pregnancy planning: Switch to azathioprine at least 3 months prior to conception 1

Drug withdrawal: Gradual withdrawal can be attempted after 3 years, with glucocorticoids withdrawn first 1

Refractory Disease Management

For patients failing MPA or cyclophosphamide (lack of effect or adverse events): 1

• Switch from MPA to CY, or CY to MPA
• OR give rituximab

Essential Adjunctive Therapies

Universal Recommendations

Hydroxychloroquine is recommended for all patients with lupus nephritis to reduce renal flares and limit accrual of renal and cardiovascular damage 1, 2

Proteinuria and Hypertension Management

• ACE inhibitors or ARBs for proteinuria (UPCR >50 mg/mmol) or hypertension 1

Cardiovascular Risk Reduction

• Statins for persistent dyslipidemia (target LDL-cholesterol <2.58 mmol/L or <100 mg/dL) 1

Thrombosis Prevention

• Acetyl-salicylic acid in patients with antiphospholipid antibodies 1
• Consider anticoagulation in nephrotic syndrome with serum albumin <20 g/L, especially if persistent or with antiphospholipid antibodies 1

Bone Health and Infection Prevention

• Calcium and vitamin D supplementation 1
• Immunizations with non-live vaccines 1

Monitoring Protocol

Regular Assessment (Every Visit)

Monitor the following parameters: 1

• Body weight and blood pressure
• Serum creatinine and eGFR
• Serum albumin
• Proteinuria
• Urinary sediment (microscopic evaluation)
• Serum C3 and C4
• Anti-dsDNA antibody levels
• Complete blood cell count

Intermittent Monitoring

• Antiphospholipid antibodies and lipid profile at baseline and intermittently 1

Visit Schedule

• Every 2–4 weeks for the first 2–4 months after diagnosis or flare 1
• Then according to treatment response
• Lifelong monitoring at least every 3–6 months for renal and extra-renal disease activity 1

Prognostic Indicators

Changes in serum creatinine (eGFR), proteinuria, hemoglobin levels, and blood pressure predict long-term outcome 1

Important Clinical Caveats

⚠️ Common pitfall: Do not use clinical or serological tests alone to guide treatment without renal biopsy confirmation, as they cannot accurately predict histological findings 1

⚠️ Treatment continuity: Management of lupus nephritis should not differ between children and adults 1

⚠️ Medication switching: Maintain consistency with initial responders—if MPA worked for induction, continue MPA for maintenance unless pregnancy is planned 1