Identification of biomarkers that predict renal flare in childhood-onset lupus nephritis with mycophenolate acid.

Abstract

Children-onset lupus nephritis (cLN) occurs>50% of patients with systemic lupus erythematosus. Mycophenolic acid (MPA) is the first-line agent for the induction and maintenance treatment of LN. This study was to explore the predictors of renal flare in cLN. Data from 90 patients were included in population pharmacokinetic (PK) models to predict MPA exposure. Cox regression models and restricted cubic spline were performed in 61 patients to identify the risk factors for renal flare, baseline clinical characteristics and MPA exposures as potential covariates. PK best fitted a two-compartment model of first-order absorption and linear elimination, with delayed absorption. Clearance increased with weight and immunoglobulin G (IgG), but decreased with albumin and serum creatinine. During follow-up of 1040 (658-1359) days, 18 patients experienced a renal flare, after a median time of 932.5 (663.5-1316) days. Each 1-mg·h/L increase of MPA-AUC was associated with a 6% decreased risk of an event (HR=0.94; 95% CI: 0.90-0.98), while IgG significantly increased this risk (HR=1.17; 95% CI: 1.08-1.26). ROC analysis showed that MPA-AUC0-12h<35mg·h/L and IgG>17.6g/L had a good prediction of renal flare. Of restricted cubic spline, the risk of renal flares decreased with higher MPA exposure but reached a plateau when AUC0-12h>55mg·h/L, while substantially increases when IgG is>18.2g/L. Monitoring MPA exposure together with IgG could be very useful during clinical practice to identify patients with a potential high risk of renal flare. This early risk assessment would allow for the treat-to-target and tailored medicine.