Clinical And Pharmacogenomics Study Of Juvenile Lupus Nephritis

Objective:To analyze the clinical characteristics of juvenile lupus nephritis and to explore the relationship between genotype of cyclophosphamide(CTX)metabolic enzyme genes and the efficacy or adverse reactions.According to the testing results of genes to adjust treatment,then evaluate the impact of pharmacogenomics guidance on efficacy and adverse reactions.Methods:1.Collect clinical data of 62 LN children and describe the clinical characteristics.2.Thirty three type ? or ? LN children were included in the non-randomized controlled trials.CTX induction therapy 3 months was group A(n=12),therapy 6 months was group B(n=21).To analyze the efficacy and adverse reactions between the two groups.3.To analyze the clinical manifestations,laboratory findings and treatment outcomes of 79 children with Nephrotic Syndrome(NS)(n=31)and non-NS patients(n=48).4.Logistic regression was used to analyze the risk factors of early prognosis of 99 LN children.5.To explore the relationship between genes CYP2B6,CYP2C19,GSTP1 and CTX efficacy or adverse reactions in 46 LN children.6.Adjust the treatment according to the CTX drug gene results in 20 LN children,and evaluate the role of PGx guidance.Results:1.LN children in this center have a good prognosis.During the follow up process,we should pay attention to adverse drug reactions,such as hormone-related hypertension and ocular hypertension,especially the visual field defects caused by hydroxychloroquine.2.Sequencing of MMF after 3 months or 6 months of CTX treatment has no effect on efficacy and adverse effects for children with proliferative lupus nephritis.3.LN children with NS onset have more severe kidney damage.It takes longer to achieve clinical remission in NS group.4.Oral ulcer,high 24-hour urine protein and low serum albumin have a predictive value for the early poor outcome of juvenile LN.5.CYP2C19*2(rs4244285)and GSTP1(rs1659)site mutations can reduce the effect.Haplotype CYP2B6(rs4802101 mutant,rs8192709 wild,rs3745274 wild,rs2279343 wild),GSTP1(rs1695 wild),CYP2C19(rs4986893 wild,rs4244285 mutant)frequency is lower in effective group.6.CTX drug genetic guidance has no effect on the efficacy and adverse reactions of juvenile lupus nephritis.Conclusion:This study analyzed the clinical characteristics of juvenile lupus nephritis.And we found the relationship between CYP2B6,CYP2C19,GSTP1 genotypes and efficacy or adverse reactions of CTX.However,CTX gene guidance has no significant effect on the efficacy and adverse reactions.