What is the preferred immunosuppressive therapy for Nephrotic Syndrome (NS)?

From the Guidelines

The preferred initial immunosuppressive therapy for most cases of primary nephrotic syndrome in adults is oral prednisone. Typical regimen:

• Start with prednisone 1 mg/kg/day (maximum 80 mg/day) for 4-16 weeks
• Then taper slowly over 2-6 months For steroid-resistant or frequently relapsing cases, consider adding:
• Cyclophosphamide: 2-2.5 mg/kg/day for 8-12 weeks
• Or cyclosporine: 3-5 mg/kg/day in two divided doses for 6-12 months Alternatively, tacrolimus or mycophenolate mofetil may be used in place of cyclosporine. This approach is based on the evidence from 1, which suggests that immunosuppressive therapy can improve proteinuria and slow progression to ESRD in patients with nephrotic syndrome.

The use of prednisone as the initial therapy is supported by its ability to suppress the immune response that damages the glomeruli, reducing proteinuria and often inducing remission 1. In cases of steroid resistance or intolerance, the addition of cyclosporine or other immunosuppressants can help maintain remission and reduce steroid dependence by targeting specific immune pathways involved in the disease process 1. It is essential to monitor patients closely for side effects and adjust dosage as needed, with regular blood tests to check kidney function, electrolytes, and drug levels (for cyclosporine or tacrolimus) 1.

While other studies, such as 1, provide recommendations for the management of lupus nephritis, the focus of the question is on nephrotic syndrome, and the evidence from 1 is more directly relevant to this condition. Therefore, the recommended approach prioritizes the use of prednisone as the initial immunosuppressive therapy, with the addition of other agents as needed to manage steroid-resistant or frequently relapsing cases.

Key considerations in the management of nephrotic syndrome include:

• The importance of careful assessment for potential clinical and pathologic clues to differentiate idiopathic from secondary FSGS 1
• The need for prolonged therapy to maintain remission and reduce relapses 1
• The potential for significant side effects with immunosuppressive therapy, particularly with high-dose prolonged corticosteroids and calcineurin inhibitors 1

From the Research

Immunosuppressive Therapy for Nephrotic Syndrome (NS)

The preferred immunosuppressive therapy for Nephrotic Syndrome (NS) varies depending on the specific condition and patient response.

• A long-term corticosteroid therapy is often the first therapeutic approach for patients with NS 2.
• In patients who have contraindication to steroids or do not respond to steroids, immunosuppressive agents such as cyclosporine, mizoribine, azathioprine, and cyclophosphamide may be used 2.
• For minimal change nephrotic syndrome (MCNS), a low-dose corticosteroid plus enteric-coated mycophenolate sodium may be considered, although it was not found to be superior to a standard high-dose corticosteroid regimen in one study 3.
• Rituximab, a chimeric murine/human monoclonal immunoglobulin G1 antibody, has shown beneficial effects in patients with steroid-dependent MCNS, with sustained remission or reduction of proteinuria 4, 5.
• Low-dose rituximab regimens may be beneficial for the treatment of relapsing MCNS in adults, with fewer side effects 4.
• Conventional treatment of idiopathic nephrotic syndrome and membranous nephropathy in adults often involves corticosteroid and immunosuppressive treatment, with alternatives such as intravenous high-dose steroid pulses, alternate-day prednisone, and long-term administration of azathioprine 6.

Specific Treatment Options

• Cyclosporine, mizoribine, azathioprine, and cyclophosphamide may be used as immunosuppressive agents in patients who do not respond to steroids 2.
• Mycophenolate sodium may be used in combination with low-dose corticosteroids for MCNS 3.
• Rituximab may be used for steroid-dependent MCNS, with a low-dose regimen potentially being beneficial for relapsing MCNS in adults 4, 5.
• Corticosteroids and immunosuppressive agents such as azathioprine and chlorambucil may be used for membranous nephropathy 6.

Considerations

• The choice of immunosuppressive therapy should be based on the specific condition, patient response, and potential side effects 2, 3, 4, 6, 5.
• Further studies are needed to find more effective and less toxic treatment approaches for patients with primary glomerulonephritis 6.
• Controlled randomized trials are required to prove the efficacy and safety of rituximab and to evaluate the cost-effectiveness of rituximab treatment for MCNS in adults 5.