Usefulness of mizoribine administration in children with frequently relapsing nephrotic syndrome, and the relationship between pharmacokinetic parameters and efficacy: a multicenter prospective cohort study in China

Background Mizoribine (MZR) is an immunosuppressant used to treat adult nephropathy.There is little experience with the drug in treating Chinese children with frequently relapsing nephrotic syndrome (FRNS).We investigated the efficacy and safety for treating MZR with FRNS.Furthermore,the relationship between efficacy and serum concentration was investigated.Methods A prospective multicenter observational 12-month study was performed for evaluating the usefulness of MZR with FRNS.Serum MZR concentration was measured,and the relationships between pharmacokinetic parameters (Cmax,AUC),number of relapses,and urinary protein were evaluated.Results Eighty-two pediatric patients from four hospitals were treated with MZR and prednisone.MZR treatment significantly reduced the number of relapses and steroid doses.A correlation between pharmacokinetic parameters and relapses was observed,which fits well with the sigmoidal Emax model.Even in the relationship between pharmacokinetic parameters and urinary proteins,it was recognized that there was a threshold in the pharmacokinetic parameters for the therapeutic effect similar to the results obtained with the sigmoidal Emax model.Eleven patients (13.4%) experienced mild adverse events.Conclusions MZR therapy was effective in reducing the number of relapses and steroid doses.No severe adverse reactions were observed.Therapeutically effective serum concentrations were estimated to be Cmax > about 2 μg/mL or AUC > about 10 lag h/mL.MZR and steroid treatment were effective and safe for pediatric FRNS.

Efficacy and safety of tacrolimus and low-dose prednisone in Chinese children with steroid-resistant nephrotic syndrome

Background Tacrolimus,a calcineurin inhibitor,is recommended by the recent guidelines from the Kidney Disease Improving Global Outcomes Group as the first-line treatment for steroid-resistant nephrotic syndrome(SRNS),but its clinical application in China is still limited.We investigated the efficacy and safety of tacrolimus combined with low-dose corticosteroids in a population of Chinese children with SRNS.Methods In this prospective non-randomized,non-controlled study,Chinese children with SRNS who failed the previous full-dose prednisone treatment were given tacrolimus(0.1 mg/kg/day)and low-dose prednisone(0.25-0.50 mg/kg/day).We compared the overall remission rate(ORR)and adverse events in the follow-up period with this therapeutic regimen.Results A total of 76 children were enrolled into the study with an average follow-up period of 18±6 months(maximum 36 months).ORR achieved by the first,third,and sixth months was 94.7%,94.7%,and 96.0%,respectively.All patients who attained an initial tacrolimus trough concentration(FK506C0)>6 ng/mL(60.3%)achieved remission.The relative risk of relapse at FK506C0<3 ng/mL compared to 3-6 ng/mL,6-9 ng/mL,and 9-12 ng/mL was 2.3,3.2,and 16.9,respectively.During the follow-up period,adverse effects that had been previously reported were rare.Conclusions Combination of tacrolimus and low-dose prednisone was safe and effective for the treatment of children with SRNS,with high remission rates observed as early as the first month.Relapses were infrequent,but tended to increase significantly with decreases in FK506C0.

Environmental factors for the development of fetal urinary malformations

Background:The development of the kidneys and other organs of the urinary tract also follow the natural rule of gene-environment-lifestyle interaction.Both intrinsic and extrinsic factors may be associated with the etiology of various kinds of urinary malformations.The environmental factors belong to extrinsic factors,which have attracted increasing attention from researchers.Methods:Publications about urinary malformations were searched from databases such as PubMed,Elsevier,Chemical Abstract,Excerpta Medica,Chinese Hospital Knowledge Database and Wanfang Database.Results:Urinary malformation is associated with low birth weight,maternal diseases,placental insufficiency,maternal drug exposure,and maternal exposure to environmental pesticides.Living environment and socioeconomic factors may also influence the incidence of urinary malformation.Conclusion:It is important to understand the association of environmental factors with the development of the renal system and urinary malformation in order to decrease the incidence of urinary malformations.