Risk factors for renal outcomes in children with antineutrophil cytoplasmic antibody-associated vasculitis:a nationwide retrospective study in China

Background Pediatric antineutrophil cytoplasmic antibody-associated vasculitis(AAV)is a life-threatening systemic vasculitis featured by liability to renal involvement.However,there are few studies on the risk factors and predictive models for renal outcomes of AAV in children.Methods Data from 179 AAV children in multiple centers between January 2012 and March 2020 were collected retrospectively.The risk factors and predictive model of end-stage renal disease(ESRD)in AAV were explored.Results Renal involvement was the most typical manifestation(95.5%),and the crescent was the predominant pathological lesion(84.9%).The estimated glomerular filtration rate(eGFR)was evaluated in 114 patients,of whom 59.6%developed ESRD,and the median time to ESRD was 3.20 months.The eGFR[P=0.006,odds ratio(OR)=0.955,95%confidence interval(CI)=0.924–0.987]and the percentages of global glomerulosclerosis(pGGS;P=0.018,OR=1.060,95%CI=1.010–1.112)were independent risk factors for ESRD of renal biopsy.Based on the pGGS and eGFR at renal biopsy,we developed three risk grades of ESRD and one predictive model.The Kaplan‒Meier curve indicated that renal outcomes were significantly different in different risk grades(P<0.001).Compared with serum creatinine at baseline,the predictive model had higher accuracy(0.86 versus 0.58,P<0.001)and a lower coefficient of variation(0.07 versus 0.92)in external validation.Conclusions Renal involvement is the most common manifestation of pediatric AAV in China,of which more than half deteriorates into ESRD.The predictive model based on eGFR at renal biopsy and the pGGS may be stable and accurate in speculating the risk of ESRD in AAV children.

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.