Pharmacological monitoring of mycophenolic acid in blood in children with nephrotic syndrome

Abstract

Idiopathic nephrotic syndrome in children is the most common glomerular disease in pediatric practice and frequently requires long-term immunosuppressive therapy because of steroid dependence and frequent relapses. Mycophenolate mofetil has emerged as a preferred steroid-sparing agent in international guidelines due to its favorable safety profile and proven efficacy in reducing relapse rates in steroid-dependent and frequently relapsing nephrotic syndrome in children. Its active metabolite, mycophenolic acid, exhibits marked interindividual pharmacokinetic variability influenced by age, serum albumin, kidney and liver function, concomitant therapies, and genetic factors, which underpins the need for therapeutic drug monitoring. This narrative review summarizes current evidence on the pharmacokinetics and pharmacodynamics of mycophenolic acid in pediatric nephrotic syndrome, focusing on target exposure parameters such as area under the concentration–time curve (AUC) and trough levels (C0) and their association with clinical efficacy and relapse risk. Particular attention is given to limited sampling strategies enabling reliable estimation of mycophenolic acid exposure from a small number of timed blood samples, as well as to population pharmacokinetic modeling as tools to individualize dosing in clinical practice. The potential role of inosine monophosphate dehydrogenase activity as a pharmacodynamic biomarker is discussed, and key gaps are highlighted, including the need for prospective trials to define optimal target exposure ranges for mycophenolic acid in children with steroid-dependent and frequently relapsing nephrotic syndrome.