Provider Preparing To Perform A Kidney Biopsy

Quiz – Primary Membranous Nephropathy Treatment

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Background:

Patient presents to the nephrology office to discuss next steps after being newly diagnosed with membranous nephropathy on a kidney biopsy. The patient has chronic kidney disease stage 3A, hypertension, prediabetes, and dyslipidemia. Labs: urine albumin to creatinine ratio is 5000 mg, Anti-phospholipase A2 Receptor (Anti-PLA2R) is positive. The serum creatinine is 1.4 (baseline 1.3-1.5). The albumin is 3. Medications include: losartan, rosuvastatin, and empagliflozin.

Please answer the following questions:

Our patient has moderate-risk membranous nephropathy. What is the next step?
* Start rituximab
* Start prednisone
* Start cyclosporine
* Continue current for 3-6 months. Then reassess.

What is the purpose of the 3-6 month observation period for patients with primary membranous nephropathy on conservative therapy?
A
Minimize treatment costs
B
Accelerate disease progression
C
Allow time for spontaneous remission
D
Avoid further diagnostic tests

What is the best management option for a patient with persistent nephrotic-range proteinuria after completing conservative therapy if the goal is to induce a remission and maintain that remission?
A
Cyclosporine
B
Rituximab
C
Prednisone
D
Alkylating agents

Discussion:

Management of Membranous Nephropathy

Current Pharmacologic Regimen and Monitoring

The appropriate management for a patient with newly diagnosed primary membranous nephropathy (MN) involves continuing the current pharmacologic regimen, if the patient is not high risk.

Conservative management includes renin-angiotensin system blockers, statin therapy, edema management, and possibly SGLT2 management. Patients are typically observed for 3 to 6 months on conservative therapy before considering immunosuppression for those with persistent nephrotic-range proteinuria. Spontaneous remission can occur within 1 to 2 years in about 30% of patients.

Anti-PLA2R Antibodies and Diagnosis

Presence of anti-phospholipase A2 receptor (PLA2R) antibodies on kidney biopsy supports the diagnosis of primary MN, which is detected in approximately 75% of cases. These antibodies are rarely found in secondary forms of MN.

Treatment Options

  • Rituximab: Considered for patients with persistent nephrotic-range proteinuria after completing conservative therapy awaiting the observation period of 3-6 months to see what happens. Rituximab is non-inferior to cyclosporine in inducing remission and superior to cyclosporine in maintaining it with fewer adverse events. That is why rituximab therapy is usually the preferred therapy, chosen over the other immunosuppressive options listed below.
  • Cyclosporine: Effective in reducing proteinuria but should be started only after 6 to 12 months of conservative therapy (or after the observation period) because of higher relapse rates compared to alkylating agents
  • Cytotoxic therapy plus prednisone: Appropriate if nephrotic-range proteinuria persists after 6 to 12 months of conservative therapy (or after the observation period), not suitable at this stage. Consider if rituximab is unavailable.

Appropriate Management Decision

For the patient described above, one with moderate-risk membranous nephropathy, continuing the current pharmacologic regimen and monitoring is the best approach. The patient does not present with very high-risk features at this time: the serum creatinine is less than 1.5. The kidney function has been stable. And the patient does not have severe nephrotic syndrome. If nephrotic-range proteinuria persists after the 3- 6 month trial of conservative therapy, then immunosuppressive therapy, such as rituximab, may be considered.

That said, if the patient had high-risk features of membranous nephropathy, treatment might begin immediately. And if the patient presented with low-risk features of membranous nephropathy, supportive measures only are required, without using immunosuppressive therapy.

Inspiration: Advances in the Management of Primary Membranous Nephropathy and Rituximab-Refractory Membranous Nephropathy, National Library of Medicine

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