Add on Mycophenolate mofetil to supportive care halts progression of IgA Nephropathy: JAMA

A new study published in the Journal of American Medical Association suggests that patients with progressive immunoglobulin A nephropathy (IgAN) had a substantially lower risk of disease progression when mycophenolate mofetil (MMF) was added to supportive care (SC) as opposed to SC alone.

Mycophenolate mofetil's function in the treatment of IgG Nephropathy is still up for debate. In order to assess the effectiveness and safety of MMF in patients with IgAN who are at high risk of renal function loss, Fan Fan Hou and colleagues undertook this study.

Adults with IgAN, proteinuria larger than 1.0 g/d, estimated glomerular filtration rate (eGFR) greater than 30 and less than 60 mL/min/1.73m2, or chronic hypertension participated in an open-label, blinded, randomized clinical study from September 2013 to December 2015. 238 patients got losartan and other optimal supportive treatment for a 3-month run-in period. Patients were included in the experiment for three years if they had a urinary protein excretion rate of 0.75 g/d or higher despite receiving 3 months of SC optimization. Following the experiment, survivors who did not obtain a transplant or dialysis were monitored for a median (IQR) of 60 (47-76) months. Data was examined between March and June 2022.

The two main outcomes were (1) development of chronic kidney disease and (2) a composite of doubling serum creatinine, end-stage renal disease (dialysis, transplant, or kidney failure without receiving kidney replacement treatment).

The key findings of this study were:

Out of 170 patients who were randomly assigned, 85 received MMF along with SC and 85 received SC alone. 168 patients (98.8%) finished the experiment, and 157 individuals (92.4%) survived without requiring dialysis or a transplant. 

The mean (SD) eGFR was 50.1 (17.9) mL/min/1.73m2 and the mean (SD) proteinuria level was 1.9 (1.7) g/d. 

Six patients (7.1%) in the MMF group and 18 patients (21.2%) in the SC group experienced primary composite outcome events. 

Seven participants (8.2%) in the MMF group and 23 participants (27.1%) in the SC group experienced chronic renal disease progression. 

There was no significant interaction for any of the predefined subgroups that the MMF therapy had on the key outcomes.

Annual eGFR loss increased following MMF withdrawal during post-trial follow-up; the mean (SD) annual eGFR loss throughout the study period in the MMF group was 2.9 (1.0) mL/min/1.73m2 and 6.1 (1.2) mL/min/1.73m2 among 66 individuals in the MMF group who stopped MMF after the trial. 

When compared to SC alone, serious side effects were not more common with MMF.

Reference: 

Hou, F. F., Xie, D., Wang, J., Xu, X., Yang, X., Ai, J., Nie, S., Liang, M., Wang, G., Jia, N., Zhao, H., Tao, X., Cao, Y., Su, L., Li, Y., Yuan, S., Zhou, Z., Tian, J., & Chen, T. (2023). Effectiveness of Mycophenolate Mofetil Among Patients With Progressive IgA Nephropathy. In JAMA Network Open (Vol. 6, Issue 2, p. e2254054). American Medical Association (AMA). https://doi.org/10.1001/jamanetworkopen.2022.54054