What is the diagnosis and treatment of Minimal Change Nephrotic Syndrome (MCNS)?

From the Guidelines

The first-line treatment for minimal change nephrotic syndrome (MCNS) is high-dose oral glucocorticoids, which should be given for no longer than 16 weeks, as recommended by the KDIGO 2021 guideline 1.

Treatment Approach

The treatment approach for MCNS involves the following:

• High-dose oral glucocorticoids as the initial treatment, unless there are contraindications, in which case alternatives such as cyclophosphamide, CNIs, MMF, and possibly rituximab can be considered 1.
• Tapering of glucocorticoids should start 2 weeks after remission, and the optimal glucocorticoid regimen is not well-defined, but high-dose treatment should not exceed 16 weeks 1.
• Infrequent relapses should be treated with glucocorticoids, while cyclophosphamide, rituximab, CNIs, or mycophenolic acid analogs (MPAA) should be employed for the treatment of frequently relapsing/glucocorticoid-dependent MCNS (Grade 1C) 1.

Key Considerations

Some key considerations in the treatment of MCNS include:

• The disease has an excellent long-term prognosis in most cases, though relapses are common (60-70% of patients), requiring monitoring of urine protein levels even after remission.
• Supportive care includes sodium restriction, diuretics for edema (furosemide 1-2 mg/kg/dose), and ACE inhibitors or ARBs to reduce proteinuria.
• MCNS is caused by T-cell dysfunction leading to podocyte injury and increased glomerular permeability.

Evidence-Based Recommendation

Based on the most recent and highest quality study, the KDIGO 2021 guideline 1, the recommended treatment approach for MCNS prioritizes high-dose oral glucocorticoids as the first-line treatment, with a focus on minimizing treatment duration and monitoring for relapses.

From the Research

Definition and Treatment of Minimal Change Nephrotic Syndrome

• Minimal change nephrotic syndrome (MCNS) is a type of nephrotic syndrome characterized by the loss of large amounts of protein in the urine, often leading to swelling, particularly in the legs and feet 2.
• The first-line treatment for MCNS is corticosteroids, but a prolonged course of treatment is often required, and relapse rates are high, leading to the search for alternative treatments 2, 3, 4.

Alternative Treatments to Corticosteroids

• Tacrolimus monotherapy has been shown to be an effective alternative treatment for patients with MCNS who wish to avoid steroid therapy 2.
• A study comparing tacrolimus and low-dose corticosteroid with high-dose corticosteroid for MCNS in adults found that the combination of tacrolimus and low-dose corticosteroid was noninferior to high-dose corticosteroid for complete remission induction, and relapse rates were significantly lower with maintenance tacrolimus and steroid compared with steroid alone 4.
• Another study found that treatment with low-dose prednisone plus enteric-coated mycophenolate sodium was not superior to a standard high-dose prednisone regimen to induce complete remission of MCNS 3.

Comparison of Different Treatments

• A review of interventions for MCNS in adults with nephrotic syndrome found that compared with prednisolone alone, calcineurin inhibitors (CNIs) with reduced-dose prednisolone or without prednisolone probably make little or no difference to the number achieving complete remission, but may reduce the risk of obesity or Cushing's Syndrome and the risk of acne 5.
• The same review found that enteric-coated mycophenolate sodium (EC-MPS) with reduced-dose prednisolone probably makes little or no difference to the number undergoing complete remission, but may have uncertain effects on diabetes or hyperglycaemia, hypertension, and acute kidney injury (AKI) 5.

Treatment Outcomes and Relapse Rates

• A study found that there was no significant difference in relapse rates between patients treated with tacrolimus and those treated with prednisolone, but the time from complete remission to relapse was similar in both groups 2.
• Another study found that the median time to relapse was similar in the test and control groups, and the incidence of serious adverse events was also similar 3.
• A review found that CNIs with reduced-dose prednisolone or without prednisolone probably make little or no difference to the number achieving complete remission, but may reduce the risk of relapse 5.