Treatment of Membranous Glomerulonephritis with High ACR
For patients with membranous glomerulonephritis (MGN) and high albumin-to-creatinine ratio (ACR) of 88, initial management should include conservative therapy with ACE inhibitors or ARBs for at least 6 months before considering immunosuppressive therapy, unless severe symptoms or rapidly deteriorating kidney function are present.
Initial Approach and Risk Assessment
- All patients with MGN should undergo risk assessment by evaluation of proteinuria (as indicated by the high ACR), blood pressure, and eGFR at diagnosis and during follow-up 1
- A high ACR of 88 indicates significant proteinuria, which is a risk factor for disease progression 1
- Conservative therapy should be the first approach and includes:
Indications for Immunosuppressive Therapy
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 1
First-Line Immunosuppressive Treatment
When immunosuppressive therapy is indicated:
- The recommended first-line therapy is a 6-month course of alternating monthly cycles of corticosteroids combined with oral alkylating agents (modified Ponticelli regimen) 1
- Cyclophosphamide is preferred over chlorambucil for initial therapy due to better safety profile 1
- The modified Ponticelli regimen includes:
Alternative Therapies
- For patients who cannot tolerate or have contraindications to the cyclophosphamide/steroid regimen, calcineurin inhibitors (CNIs) can be considered 1
- CNIs (cyclosporine or tacrolimus) should be started at a dose that achieves target blood levels and continued for at least 6 months 1
- In cases refractory to standard immunosuppressive therapy, rituximab has shown promise, though it's not mentioned in the primary guidelines provided 2
Thrombosis Prophylaxis
- Patients with MGN, nephrotic syndrome, serum albumin <2.5 g/dl, and additional risk factors for thrombosis should be considered for prophylactic anticoagulant therapy with oral warfarin 1
Monitoring and Assessment of Treatment Response
- Regular monitoring of proteinuria, serum albumin, and kidney function is essential to assess treatment response 1
- After completing the 6-month immunosuppressive regimen, patients should be managed conservatively for at least another 6 months before being considered treatment failures 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
Important Considerations and Cautions
- 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, unless there is crescentic MGN with rapidly deteriorating kidney function 1
- The benefits of immunosuppressive therapy must be weighed against potential adverse effects, including infections, bone marrow suppression, and malignancy risk 2
- Long-term immunosuppressive therapy may be required in some patients with refractory disease 3
Special Situations
- In cases with rapidly deteriorating kidney function or crescentic features on biopsy, more aggressive immunosuppression may be warranted 4
- For patients with refractory disease, alternative approaches such as LDL apheresis might be considered in specialized centers, though evidence is limited to case reports 3