Mycophenolate mofetil-based regimen as effective as conventional steroids therapy in immunoglobulin A nephropathy

In a single-centre study on IgAN patients with active lesions, significant urinary abnormalities, and an increased risk of complications ( glucocorticosteroid-related), a mycophenolate mofetil-based regimen showed comparable outcomes in complete responses and relapse rates at 1 and 5 years compared to a conventional glucocorticosteroid-based protocol, while significantly reducing glucocorticosteroid cumulative doses. This study is published in the Journal of Nephrology.

The effectiveness and safety of a combination of mycophenolate mofetil and a short course of glucocorticosteroids for patients with histologically active immunoglobulin A nephropathy need further investigation. In the present study, a team of researchers compared the efficacy and safety of this combination therapy to conventional glucocorticosteroid therapy in patients with active lesions and major urinary abnormalities.

Thirty patients had IgA nephropathy with active histological lesions. Fifteen patients were treated with both mycophenolate mofetil 2 g/day for six months and 3 pulses of 15 mg/kg methylprednisolone. This was followed by a short tapering schedule of oral prednisone.

The control group had 15 patients treated with glucocorticosteroids alone, 1 g of methylprednisolone given intravenously for three consecutive days, followed by oral prednisone 0.5 mg/kg every other day for six months. All patients had urinary protein excretion > 1 g/24 h and microscopic hematuria at diagnosis.

Key findings from this study are:

• At the end of the first year of follow-up of 30 patients and after five years of follow-up of 17 patients, no difference was reported between the two groups related to urinary abnormalities and functional parameters.
• Both regimens achieved a significant reduction in 24-hour urinary protein excretion and a reduction of microscopic hematuria.
• Mycophenolate mofetil-based regimen allowed a cumulative sparing dose of 6 g of glucocorticosteroids.

Study limitations include the absence of randomization, the retrospective nature, heterogeneity in follow-up duration and small sample size.

The strength of the study includes patient selection. The therapy targeted active lesions and excluded patients with chronic lesions which could obscure the benefits of anti-inflammatory and immunosuppressive therapy.

This study found that an MMF-based regimen was as effective as steroids recommended by KDIGO guidelines for IgAN patients with active lesions. It also showed substantial steroid-sparing effects, suggesting an alternative strategy for reducing steroid-related morbidity in patients with metabolic syndrome, diabetes risk, or severe osteoporosis. Benefits were confirmed at five years of follow-up.

Reference:

Roccatello, D., Careddu, A., Ferro, M. et al. The steroid-sparing effects of a mycophenolate mofetil-based regimen in the management of immunoglobulin A nephropathy in patients with histologically active lesions: A comparison with a control cohort receiving conventional therapy. J Nephrol 36, 2223–2231 (2023). https://doi.org/10.1007/s40620-023-01636-6