Study: Mycophenolate Mofetil and Steroid as Alternative for Idiopathic Membranous Nephropathy Treatment

India: An article published in The Journal of the Association of Physicians of India found that both mycophenolate mofetil combined with steroids and the modified Ponticelli regimen had similar tolerability and effectiveness. However, the use of MMF was associated with the advantage of reduced steroid exposure.

Membranous nephropathy is responsible for more than 25% of nephrotic syndrome cases in adults, with an overall incidence of 1.2 per 100,000 annually. The peak occurrence is in the fourth and fifth decades of life. About three-quarters of these patients have idiopathic membranous nephropathy, characterized by varying outcomes: one-third experience spontaneous remission, another third continue with persistent proteinuria, and the remaining third advance to severe renal failure.

The modified Ponticelli regimen is commonly used as a first-line therapy for patients with idiopathic membranous nephropathy, though it is known for having a less favorable safety profile. Despite the Kidney Disease Improving Global Outcomes guidelines not recommending the combination of mycophenolate mofetil and steroids, this alternative treatment can be considered due to its higher tolerability and steroid-sparing benefits.

With this reference, Manjuri Sharma, Professor and Head of the Department of Nephrology at Gauhati Medical College and Hospital in Guwahati et. al. conducted a study comparing the safety and effectiveness of the mycophenolate mofetil + steroid regimen with the modified Ponticelli regimen in patients with idiopathic membranous nephropathy.

A randomized, open-label study was conducted involving patients diagnosed with adult-onset nephrotic syndrome and biopsy-confirmed idiopathic membranous nephropathy. Forty-two participants were divided into two treatment groups: mycophenolate mofetil + steroid group (mycophenolate mofetil 1 gram twice daily combined with oral prednisolone 0.5 mg/kg/day; n = 21) and the modified Ponticelli regimen group (which received methylprednisolone 1 gram intravenously for 3 days, followed by alternating monthly cycles of oral prednisolone 0.5 mg/kg/day for the subsequent 27 days, and cyclophosphamide 2 mg/kg/day for 6 months; n = 21). The primary outcome assessed was the change in the urinary protein-to-creatinine ratio.

The key findings of the study were as follows:

• At six months, both groups showed a significant increase in serum albumin levels and estimated glomerular filtration rate.
• Both groups demonstrated a notable decrease in 24-hour proteinuria, with the mycophenolate mofetil + steroid group and the modified      Ponticelli regimen group
• Both groups also exhibited a significant decrease in the urinary protein-to-creatinine ratio.
• The groups did not show significant differences in these parameters at any of the monthly follow-up visits.
• The composite remission rates were 61.91% for the mycophenolate mofetil + steroid group and 71.43% for the modified Ponticelli regimen group, with no significant difference between the groups.

Researchers concluded that 62% of patients with idiopathic membranous nephropathy responded positively to first-line therapy with mycophenolate mofetil + steroids. The mycophenolate mofetil + steroids treatment demonstrated similar tolerability and effectiveness compared to modified Ponticelli regimen, with the added benefit of reduced steroid exposure.

Reference

Sharma M, Roy A, Doley PK, et al. Mycophenolate Mofetil with Steroid, a Reasonable Alternative to Current First-line Therapy, for Idiopathic Membranous Nephropathy in Resource-constrained Settings: A Randomized, Open-label Study. J Assoc Physicians India 2024;72(6):15-19.