Clinical Research Of Primary IgA Nephropathy In Children

Objective:IgA nephropathy(IgAN)is one of the most common primary glomerular diseases(PGD)worldwide and is common in children.20-40%of patients can progress to end-stage renal disease(ESRD).Studies have shown that this progression begins from childhood and has become the focus of attention for pediatric kidney disease researchers.Early detection of children at risk of progress,accurate management of children at different risks of standardized stratification and individualized treatment is very necessary.As a high incidence area of IgAN,the long-term prognosis,related risk factors and stratified individualized treatment of children's IgAN in China are still unclear.Therefore,this study intends to analyze the clinical,pathological,prognostic and related risk factors of IgAN children;further analysis of the outcome of hierarchical treatment according to the above risk factors,including the effect of glucocorticoid(GC)treatment on prognosis,the comparison of the efficacy of novel immunosuppressant tacrolimus(TAC)and mycophenolate mofetil(MMF)for the remission of proteinuria in refractory IgAN children,and provide evidence-based basis for rational clinical diagnosis and treatment of children's IgAN.Methods:Part I:the data of primary IgAN diagnosed by renal biopsy in our hospital from January 2000 to December 2017 were retrieved by electronic medical record system,and the clinicopathological features and outcomes were summarized.Part II:retrospective analysis of the treatment of the children included in the Part ?,compare the clinicopathological characteristics and prognosis of children with different renal function and proteinuria levels receiving GC combined RAS blockers(RASB)or receiving RASB alone,and analyze the effectiveness of GC treatment.Part III:Retrospective analysis of the patients who met the diagnostic criteria of refractory IgAN from January 2012 to December 2016.The patients were divided into TAC and MMF groups according to the treatment plan.The case-control matching method was used to match the two groups 1:1 to explore the clinical efficacy of the two groups in the treatment of children with refractory IgAN.The endpoint event used a composite endpoint,including eGFR decrease by more than 50%,or entry into the ESRD,or death.The Kaplan-Meier curve was used to compare the difference of renal survival rate in children.Cox regression model was used to analyze the risk factors of renal progression in children,and the working characteristic curve(ROC)of subjects was drawn to evaluate the predictive value of each risk factor.Results:(1)The median follow-up time of 1243 children was 86.8 months.During the follow-up period,82 children(6.46%)entered ESRD,171 children(13.76%)progression to complex endpoint events.The cumulative renal survival rates were 95.3%,90.3%and 84%in 5,10 and 15 years after renal biopsy.Cox regression and Kaplan-Meier analysis revealed that hypertension,high uric acid,high urinary protein quantification,low eGFR,high urinary C3 level,high urinary retinol binding protein(RBP),glomerular segmental sclerosis(S),and tubular atrophy/interstitial fibrosis(T)were independent risk factors for poor renal prognosis.Urinary RBP had the most desirable predictive value for renal prognosis.The area under the curve(AUC)for predicting progression to complex endpoint events in children was 0.899,and the optimal cut-off point is 0.7 ug/ml(sensitivity is 84.00%,specificity=86.00%).Children with urinary RBP?0.7 ug/ml were 2.513 times more at risk of progression to complex endpoint events than children with urinary RBP<0.7ug/ml(P=0.003)(2)This study found that GC treatment delayed progression of childhood IgAN,but that GC treatment only reduced the risk of progression to complex endpoint events in children with an initial eGFR>50 ml/min/1.73m2 and proteinuria?1 g/d.Increased GC treatment for patients with an initial eGFR?of 50 ml/min/1.73m2 or proteinuria<1 g/d had no additional benefit for renal cumulative survival.(3)TAC and MMF treatment of refractory IgAN had achieved good therapeutic results,but TAC could quickly induce urinary protein to reach remission level,and the remission rate was higher.Conclusion:At present,this study is the largest sample size of children IgAN survival data reported in China.The results showed that the 15 years cumulative renal survival rate of IgAN in Chinese children was 84%.That was 16%of children IgAN entered ESRD after 15 years of diagnosis,and found the risk factors affecting its progress.This study first found that urinary RBP?0.7ug/ml suggested poor renal prognosis.Additionally,the present study suggests that GC treatment can improve the prognosis of children with IgAN with proteinuria?1 g/d and initial eGFR>50 ml/min/1.73 m2.TAC has a more significant proteinuria remission effect for children with refractory IgAN than MMF.