Influence Factors Of Renal Toxicity In Children With Aplastic Anemia Treated With Cyclosporine A

OBJECTIVE To study the incidence rate and influence factors of cyclosporine A nephrotoxicity and provide theoretical basis for clinical rational drug use,reducing the occurrence of renal toxicity and improving the quality of the patient’s long-term survival.METHODS Collecting information of children with aplastic anemia who administrated with cyclosporine A in one year from 2015 to 2016,and the age was between one and thirteen year,and the detecting blood drug concentration at regular intervals,liver and kidney function,etc.The children were divided into two groups and the matched ratio was 1:2 in a similar age and same gender according to retrospective nested case-control study.Based on the PPK model of cyclosporine A,the parameters AUC was calculated by the Bayesian feedback.A total of 23 variables in the two groups of children were compared,such as biology characteristic,index of liver function,renal function indexes,drug dosage,trough level concentration,AUC,genotype and so on,and find out the significant variables(P<0.05).RESULTS Incidence rate of cyclosporine A nephrotoxicity was 24.36%,which moderate injury was 5.13%.There were four significant variables(P<0.05)between the case group and the control group: drug dosage(P=0.030),AUC(P=0.001),trough level concentration(P=0.001)and rs2789047 position(P=0.046),especially AA genotype(P=0.013).SNPs position(rs12527161,rs9320773)were not significant variables.The AUC and trough level concentration were closely related to the value of e GFR,and the maximum value of AUC and trough level concentration were 12mg·h·L-1and 200ng·ml-1after analysis.CONCLUSION Cyclosporine A nephrotoxicity has a high occurrence rate within a year,but the majority of children were mild injury.Risk factors of cyclosporine A induced nephrotoxicity were drug dosage and trough level concentration and AUC.The AUC and trough level concentration should be less than12mg·h·L-1and 200ng·m L-1for long-term medication.AA genotype in rs2789047 position was also one of risk factors,but SNPs position(rs12527161,rs9320773)were not relevant to cyclosporine A nephrotoxicity.