Responsible genes in children with primary vesicoureteral reflux: findings from the Chinese Children Genetic Kidney Disease Database

Background Primary vesicoureteral reflux(VUR)is a common congenital anomaly of the kidney and urinary tract(CAKUT)in childhood.The present study identified the possible genetic contributions to primary VUR in children.Methods Patients with primary VUR were enrolled and analysed based on a national multi-center registration network(Chinese Children Genetic Kidney Disease Database,CCGKDD)that covered 23 different provinces/regions in China from 2014 to 2019.Genetic causes were sought using whole-exome sequencing(WES)or targeted-exome sequencing.Results A total of 379 unrelated patients(male:female 219:160)with primary VUR were recruited.Sixty-four(16.9%)children had extrarenal manifestations,and 165(43.5%)patients showed the coexistence of other CAKUT phenotypes.Eighty-eight patient(23.2%)exhibited impaired renal function at their last visit,and 18 of them(20.5%)developed ESRD at the median age of 7.0(IQR 0.9–11.4)years.A monogenic cause was identified in 28 patients(7.39%).These genes included PAX2(n=4),TNXB(n=3),GATA3(n=3),SLIT2(n=3),ROBO2(n=2),TBX18(n=2),and the other 11 genes(one gene for each patient).There was a significant difference in the rate of gene mutations between patients with or without extrarenal complications(14.1%vs.6%,P=0.035).The frequency of genetic abnormality was not statistically significant based on the coexistence of another CAKUT(9.6%vs.5.6%,P=0.139,Chi-square test)and the grade of reflux(9.4%vs.6.7%,P=0.429).Kaplan–Meier survival curve showed that the presence of genetic mutations did affect renal survival(Log-rank test,P=0.01).PAX2 mutation carriers(HR 5.1,95%CI 1.3–20.0;P=0.02)and TNXB mutation carriers(HR 20.3,95%CI 2.4–168.7;P=0.01)were associated with increased risk of progression to ESRD.Conclusions PAX2,TNXB,GATA3 and SLIT2 were the main underlying monogenic causes and accounted for up to 46.4%of monogenic VUR.Extrarenal complications and renal function were significantly related to the findings of genetic factors in children with primary VUR.Like other types of CAKUT,several genes may be responsible for isolated VUR.

Evaluation of a new frequency-volume chart for children with primary monosymptomatic nocturnal enuresis:a prospective,comparative study

Introduction To improve compliance with voiding diaries in children with primary monosymptomatic nocturnal enuresis(PMNE),a new modified 3-day weekend frequency-volume chart(FVC)was designed,and the compliance and validity of this modified FVC was evaluated by comparing with the International Children's Continence Society(ICCS)recommended voiding diary.Methods A total of 1200 patients with PMNE were enrolled in the study from 13 centers in China and were randomly assigned to record this modified FVC or the ICCS-recommended voiding diary.The primary outcome measure was the compliance,assessed by comparing the completing index and the quality score of diaries between two groups.The secondary outcome measure was the validity,evaluated by comparing the constituent of subtypes,micturition parameters and response rate to desmopressin.Results Among the 1200 participants enrolled in the study,447 patients completed the ICCS-recommended voiding diary and 469 completed the modified diary.The diurnal completing index and the quality score of the modified FVC group were better than those of the ICCS group.In addition,there was no significant difference between these two groups in the subtype classification,or in the response rate to desmopressin.Conclusions The modified FVC could be applied to obtain the voiding characteristics of children with PMNE as the ICCS-recommended voiding diary does and offers a reasonable and better choice for children with PMNE from the unselected population in the future.