Effectiveness of Mycophenolate Mofetil Trough Level Monitoring in Children with Relapsing Nephrotic Syndrome

The effectiveness of therapeutic drug monitoring (TDM) of mycophenolic acid (MPA) trough levels in children with steroid-dependent or frequently relapsing nephrotic syndrome (SDNS/FRNS) treated with mycophenolate mofetil (MMF) has not been adequately assessed. We performed an international, retrospective study including children with SDNS/FRNS, treated with MMF as the first-line steroid-sparing agent, and a follow-up of more than six months. Patients were categorized into two groups: TDM, if MPA trough levels were monitored, and No-TDM, if not. In the TDM group, MMF doses were adjusted to maintain MPA trough levels of more than 3 µg/ml, unless toxicity occurred. The primary outcome was relapse-free survival. A total of 167 patients were observed, 90 in the TDM and 77 in the No-TDM group. Relapse-free survival over the total follow-up was significantly longer in the TDM group (p=0.001, log-rank test) with an estimated relapse-free survival at six months of 73% for the TDM and 55% for the No-TDM group. After correcting for potential confounders, the association remained statistically significant (p<0.001). TDM patients also received lower doses of prednisone after MMF introduction. In the TDM group, children were more likely to modify their initial dose (90% vs 9%; p<0.001). While MMF dose was not associated with relapse (median 1186 vs 1298 mg/m 2 ; p=0.14), MPA trough levels were significantly higher in children who did not relapse (4.0 vs 2.7 µg/ml, p=0.001). Among children maintaining mean MPA levels more than 2.9 µg/ml, relapse-free survival at 6 months was 86%. Reported side effects were similar in both groups. Monitoring MPA trough levels was associated with an approximately 20% higher MMF effectiveness in maintaining remission at six months in children with SDNS/FRNS. Personalized MMF dosing, adjusted to maintain MPA levels more than 2.9 µg/ml, was both safe and effective. We recommend including MPA trough level monitoring in future studies comparing MMF with other steroid-sparing agents in SDNS/FRNS children.