The Value Of Monitoring The Serum Concentration Of Mycophenolate Mofetil In Children With Nephrotic Syndrome

BACKGROUND:Mycophenolate mofetil(MMF)is an alternative treatment strategy in children with steroid sensitivity who have frequent relapses or steroid-dependent nephrotic syndrome(FRNS/SDNS).MMF was recommended in the 2012 KDIGO guidelines.The effective blood concentration of MPA,which is an active ingredient of MMF,is offen not monitored in current routine clinical aoolications.Recent studies have shown that an individualized adjustment of the MMFdoes based on the the area under the curve(AUC)for MPA or the MPA trough level(CO)helps improve drug efficacy and reduce the incidence of adverse reactions.By contrast,MPA-AUC monitoring may provide better clinical duidance.PURPOSE:Discuss the value of monitoring the serum concentration of mycophenolate mofetil in children with steroid-dependent/frequent relapsing nephrotic syndrome.The MPA-AUC and MPA-CO,which can better guide the clinical medication.Find the optimal MPA-AUC value.METHODS:From January 2009 to January 2015,31 cases of children with FRNS/SDNS were prospectively recruited and administered MMF and prednisone;then,serum samples were collected,and the area under the curve(AUC)of mycophenolic acid(MPA-AUC)was calculated.The 31 patients were then grouped according to the results of the MPA-AUC as follows:low-AUC group,<30 μg · h/ml and high-AUC group,≥30μg · h/ml.The two groups were re-grouped according to the MPA-C0,and the therapeutic effects were compared.Then the ROC curve were plotted according to the MPA-AUC and MPA-C0.RESULTS:1、A MPA-AUC of 27.99 μg · h/ml had a diagnostic sensitivity of 65.2%and a specificity of 87.5%in discriminating relapsing from non-relapsing patients(receiver operating characteristic-AUC 0.848).The results indicated that there was a significant difference in the remission rate between the groups(χ2=6.645,P=0.01)during the 6 months of follow-up.2、Compared with the results before MMF therapy,the steroid dosage in both groups was significantly reduced at the 6-and 12-month follow-ups.Furthermore,the steroid dose was reduced more significantly in the high-AUC group than in the low-AUC group(0.447 ± 0.254 vs.0.219 ± 0.161 mg/kg/day,P=0.006)at the 6-month follow-up.Additionlly,no significant difference was observed between the groups at the 1-year follow-up.3、Compared with the low-AUC group at the 6-month follow-up,the number of patients with relapse and relapse episodes in the high-AUC group were also significantly reduced(7/16 vs.1/15,P=0.037,and 15/27 vs.1/29,P=0.014,respectively).4、ROC curves were plotted based on the corresponding MPA-CO values.Based on the results,at the cotoff value of 0.87μg/ml,the AUC was 0.690,with 52.2%sensitivity and 87.5%specificity,witch indicates a relatives a relatively low diagnostic value of the MPA trough level.CONCLUSIONS:1、MMF is a reasonable treatment choice to reduce the number of relapse episodes and steroid administration in children with FRNS/SDNS.Moreover,children in the high-AUC group(MPA-AUC ≥30μg · h/ml)tended to require lower steroid doses and had greater remission rates than the patients in the low-AUC group(<30 μg · h/ml)at the 6-month follow-up.2、Monitoring the serum concentration of mycophenolate mofetil can better guide the clinical medication.