What is the treatment for membranous nephropathy?

Treatment of Membranous Nephropathy

The first-line treatment for primary membranous nephropathy with nephrotic syndrome should be rituximab due to its better safety profile compared to cyclophosphamide, particularly in younger patients or those concerned about fertility. 1

Risk Assessment and Treatment Indications

Treatment should be initiated when one of the following criteria is met:

• Urinary protein excretion persistently >4 g/day AND remains >50% of baseline value despite 6 months of conservative therapy 2, 1
• Severe, disabling, or life-threatening symptoms related to nephrotic syndrome 2
• Serum creatinine rise ≥30% within 6-12 months (with eGFR >30 ml/min/1.73m²) 2, 1

Risk Stratification

Patients should be categorized by risk of progression:

• Low risk: Normal renal function despite conservative therapy
• Medium risk: Proteinuria 4-8 g/day observed for up to 6 months
• High risk: Deteriorating renal function over 2-3 months and/or proteinuria >8 g/day 2

Treatment Algorithm

1. Conservative Management (Initial 6 months for all patients)

• ACE inhibitors and/or ARBs for blood pressure control (target <120/75 mm Hg) 2, 1
• Diuretics for edema management 2
• Dietary sodium restriction 2
• Lipid-lowering agents 1
• Counsel patients to hold ACEi/ARB and diuretics when at risk for volume depletion 2

2. Immunosuppressive Therapy (for patients meeting treatment criteria)

First-line options:

• Rituximab: 375 mg/m² weekly for 4 weeks or 1 g × 2 doses given 2 weeks apart 1
• Cyclophosphamide with corticosteroids: 6-month course of alternating monthly cycles of oral and IV corticosteroids with oral cyclophosphamide 2, 1
• Calcineurin inhibitors (tacrolimus or cyclosporine): Target tacrolimus levels at 8-10 ng/mL, continue for at least 12 months if remission occurs 2, 1

Treatment selection considerations:

• Rituximab: Preferred for younger patients, those concerned about fertility, or with contraindications to other therapies 1, 3
• Cyclophosphamide: Effective but associated with significant adverse effects including myelotoxicity, infections, and cancer risk 4
• Calcineurin inhibitors: Effective but associated with high relapse rates upon discontinuation and nephrotoxicity 3, 4

3. Monitoring and Treatment Duration

• Monitor proteinuria, serum albumin, and kidney function regularly 1
• For anti-PLA2R positive patients, monitor antibody levels every 3 months 1
• Continue treatment for at least 6-12 months before considering treatment failure 2, 1
• If using calcineurin inhibitors, continue for at least 12 months if remission occurs 1

4. Thrombosis Prevention

• Consider prophylactic anticoagulation with warfarin in patients with serum albumin <2.5 g/dl and additional risk factors for thrombosis 1, 5
• Venous thromboembolic disease is more common in membranous nephropathy than other nephrotic disorders, especially within the first 6 months of diagnosis 2

Response Assessment

• Complete remission: Taper immunosuppressive therapy over 2-4 months 2
• Partial remission: Continue therapy for at least 1-2 years 2
• No response: After 3-6 months at a non-toxic dose, consider alternative treatment 2

Important Considerations

• Spontaneous remission occurs in 20-30% of cases, which justifies the initial observation period 1, 6
• Remission may be delayed for up to 18-24 months (mean time 14.7 ± 11.4 months) 2, 1
• Always rule out secondary causes of membranous nephropathy before initiating immunosuppressive therapy 1, 5
• Dihydropyridine calcium channel blockers (amlodipine, nifedipine) may exacerbate edema and increase proteinuria 2

By following this treatment approach, clinicians can optimize outcomes for patients with membranous nephropathy while minimizing treatment-related complications.