What is the treatment for membranous glomerulonephritis?

Treatment of Membranous Glomerulonephritis

The recommended treatment for membranous glomerulonephritis (MGN) consists of initial observation for 6 months with supportive care, followed by immunosuppressive therapy with cyclophosphamide and corticosteroids in patients who meet specific criteria for treatment initiation. 1

Initial Approach and Patient Selection

• Patients with MGN should initially receive conservative management with supportive care for at least 6 months before considering immunosuppressive therapy 1

• Supportive care includes diuretics, sodium restriction, and ACE inhibitors/ARBs, although their efficacy in MGN is unproven 1

• Immunosuppressive therapy should only be initiated when at least one of the following conditions is met:

  • Persistent nephrotic syndrome with urinary protein excretion >4 g/day that remains >50% of baseline value despite 6 months of conservative therapy 1
  • Presence of severe, disabling, or life-threatening symptoms related to nephrotic syndrome 1
  • Serum creatinine has risen by ≥30% within 6-12 months from diagnosis (but eGFR remains ≥25-30 ml/min/1.73m²) 1

• Immunosuppressive therapy should NOT be used in patients with:

  • Serum creatinine persistently ≥3.5 mg/dl (or eGFR ≤30 ml/min/1.73m²) AND reduced kidney size on ultrasound 1
  • Concomitant severe or potentially life-threatening infections 1

First-Line Immunosuppressive Treatment

• The recommended initial therapy consists of a 6-month course of alternating monthly cycles of oral and IV corticosteroids, combined with oral alkylating agents 1
• Cyclophosphamide is preferred over chlorambucil for initial therapy 1
• The "modified Ponticelli" regimen includes:
  • Month 1: IV methylprednisolone followed by oral prednisone
  • Month 2: Oral cyclophosphamide
  • Month 3: Repeat month 1 regimen
  • Month 4: Repeat month 2 regimen
  • Month 5: Repeat month 1 regimen
  • Month 6: Repeat month 2 regimen 1
• Cyclophosphamide dosing should be adjusted according to the patient's age and eGFR 1

Assessment of Treatment Response

• After completing the 6-month immunosuppressive regimen, patients should be managed conservatively for at least another 6 months before being considered treatment failures 1
• Treatment failure should only be declared if there is no remission AND either:
  • Kidney function is deteriorating, OR
  • Severe, disabling, or life-threatening symptoms related to nephrotic syndrome are present 1
• A repeat kidney biopsy should only be performed if the patient has rapidly deteriorating kidney function (doubling of serum creatinine over 1-2 months) in the absence of massive proteinuria (≥15 g/day) 1

Alternative and Second-Line Therapies

• For patients resistant to alkylating agent/steroid-based initial therapy, calcineurin inhibitors (CNIs) are recommended as second-line therapy 1
• For patients resistant to CNI-based initial therapy, an alkylating agent/steroid-based therapy is recommended 1
• CNIs (cyclosporine or tacrolimus) should be started at a dose that achieves target blood levels and continued for at least 6 months 1
• CNI blood levels should be monitored regularly during the initial treatment period and whenever there is an unexplained rise in serum creatinine 1
• Monotherapy with corticosteroids or mycophenolate mofetil (MMF) is NOT recommended for initial therapy of MGN 1

Treatment of Relapses

• Relapses of nephrotic syndrome should be treated by reinstituting the same therapy that resulted in the initial remission 1
• If a 6-month cyclical corticosteroid/alkylating-agent regimen was used for initial therapy, this regimen should be repeated only once for treatment of a relapse 1

Special Considerations

• Patients with MGN and nephrotic syndrome with marked reduction in serum albumin (<2.5 g/dl) and additional risk factors for thrombosis should be considered for prophylactic anticoagulant therapy with oral warfarin 1
• Children with MGN should follow the same treatment recommendations as adults, but no more than one course of the cyclical corticosteroid/alkylating-agent regimen should be given 1
• In refractory cases, newer therapies such as rituximab may be considered, although evidence is limited compared to established protocols 2
• Long-term outcomes are significantly better in patients who receive immunosuppressive therapy compared to those managed conservatively when renal function begins to decline 3

Monitoring and Follow-up

• Regular monitoring of proteinuria, serum albumin, and kidney function is essential to assess treatment response 1
• A decline in proteinuria to 50% of baseline during the first year of follow-up, even if still in the nephrotic range, significantly predicts spontaneous remission 1
• Complete remission is significantly associated with the absence of chronic histological changes on kidney biopsy 4