Mycophenolate Mofetil Therapy in Children With Idiopathic Nephrotic Syndrome: Does Therapeutic Drug Monitoring Make a Difference?

Abstract

Idiopathic nephrotic syndrome (INS) necessitates administration of corticosteroids or corticoid-sparing agents in 60% of the cases for prolonged periods resulting in serious adverse effects. To avoid these complications, we investigated the efficacy and safety of mycophenolate mofetil (MMF) in our retrospective single-center study with 15 patients presenting with complicated courses of INS and aspired to estimate a cutoff level for mycophenolic acid-area under the curve (MPA-AUC) values, which can predict relapses with high sensitivity. Seven of 15 patients stayed in remission while receiving MMF. Average frequency of relapses was 1.39 (0.28-2.5) per year. In case of relapses, patients had lower predose and estimated AUC0-12 levels of MPA (P = 0.02 and 0.001, respectively). Based on the results of receiver operating characteristic analysis, we consider an estimated MPA-AUC0-12 lower than 44.6 mg·h·L(-1) as a risk factor for future relapses (91% sensitivity, 57% specificity, P = 0.06) because the prevalence of relapse is significantly lower (0.07 versus 0.5, P = 0.02), if the estimated MPA-AUC0-12 is >44.6 mg·h·L(-1). During MMF administration, we did not detect any adverse event requiring discontinuation of treatment. In conclusion, we demonstrate MMF as an alternative treatment for children with complicated INS to maintain remission without serious side effects. Furthermore, we propose a higher therapeutic target range of MPA-AUC0-12 (>45 mg·h·L(-1)) than used in transplanted children underlining the crucial role of therapeutic drug monitoring.