Optimizing mycophenolic acid exposure for reduced relapse risk in paediatric nephrotic syndrome: An observational cohort study.

AIMS: Mycophenolic acid (MPA) effectively reduces relapse in paediatric nephrotic syndrome (NS), yet its pharmacokinetic variability hinders optimal dosing. This study aimed to define risk reference values of MPA area under the concentration-time curve (AUC0-12h) for relapse prevention during maintenance therapy.

METHODS

In this retrospective cohort study, 89 paediatric NS patients receiving MPA were enrolled. Factors influencing relapse were evaluated via binary logistic regression. Optimal cut-off threshold were determined using receiver operating characteristic (ROC) curves, while Kaplan-Meier and Cox regression analyses assessed relapse-free survival (RFS).

RESULTS

Lower MPA AUC0-12h levels strongly correlated with relapse (relapse group: 31.49 vs. non-relapse: 36.48 μg/h/mL, P < 0.001). Logistic regression confirmed MPA AUC0-12h as a protective factor (odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.88-0.99). ROC analysis identified 31.51 μg/h/mL as the optimal risk reference value (sensitivity = 87.5%, specificity = 51.02%). Cox regression further demonstrated subthreshold exposure as an independent relapse risk (hazard ratio [HR] = 0.24, 95% CI: 0.14-0.43, P < 0.001). Subgroup analyses validated this risk reference value across corticosteroid response, relapse frequency and rituximab use, though not in focal segmental glomerulosclerosis.

CONCLUSIONS

Maintaining MPA AUC0-12h ≥ 31.51 μg/h/mL significantly reduces relapse risk in paediatric NS. Individualized mycophenolate mofetil (MMF) dosing guided by therapeutic drug monitoring is critical for optimizing outcomes.