Congenital Abnormalities of Kidneys and Urinary Tract in Children at the Dakar University Hospital

Congenital abnormalities of the kidneys and urinary tract (CAKUT) represent all the morphological abnormalities associated with a disorder of the embryonic development of the kidneys and their excretory tract. Its prevalence is underestimated in developing countries compared to developed countries. This was a cross-sectional and descriptive study between January 1st, 2015 and February 28th, 2020, carried out in the pediatric department of Aristide Le Dantec Hospital. The prevalence of CAKUT was 8.77% for all pediatric nephrologic pathologies (n = 58), the median age at diagnosis was 77.28 months and the sex ratio was 1.6. The circumstances of the discovery of CAKUT were dominated by urinary tract infection (n = 21), the antenatal diagnosis was poor (n = 13) and confusion between cysts and calyx dilation in antenatal was noted. Ultrasound was the main postnatal imaging test requested. The most common renal abnormality was kidney cysts (n = 18) (cystic kidneys and multicystic dysplastic kidney) and the most common urological abnormality was the posterior urethral valves (n = 8). Kidney failure was a pejorative factor in the evolution of these CAKUT.

Multi-modality imaging review of congenital abnormalities of kidney and upper urinary tract

Congenital abnormalities of the kidney and urinary tract(CAKUT) include a wide range of abnormalities ranging from asymptomatic ectopic kidneys to life threatening renal agenesis(bilateral). Many of them are detected in the antenatal or immediate postnatal with a significant proportion identified in the adult population with varying degree of severity. CAKUT can be classified on embryological basis in to abnormalities in the renal parenchymal development, aberrant embryonic migration and abnormalities of the collecting system. Renal parenchymal abnormalities include multi cystic dysplastic kidneys, renal hypoplasia, number(agenesis or supernumerary), shape and cystic renal diseases. Aberrant embryonic migration encompasses abnormal location and fusion anomalies. Collecting system abnormalities include duplex kidneys and Pelvi ureteric junction obstruction. Ultrasonography(US) is typically the first imaging performed as it is easily available, noninvasive and radiation free used both antenatally and postnatally. Computed tomography(CT) and magnetic resonance imaging(MRI) are useful to confirm the ultrasound detected abnormality, detection of complex malformations, demonstration of collecting system and vascular anatomy and more importantly for early detection of complications like renal calculi, infection and malignancies. As CAKUT are one of the leading causes of end stage renal disease, it is important for the radiologists to be familiar with the varying imaging appearances of CAKUT on US, CT and MRI, thereby helping in prompt diagnosis and optimal management.

Genetic Architecture of Childhood Kidney and Urological Diseases in China

Kidney disease is manifested in a wide variety of phenotypes,many of which have an important hereditary component.To delineate the genotypic and phenotypic spectrum of pediatric nephropathy,a multicenter registration system is being imple-mented based on the Chinese Children Genetic Kidney Disease Database(CCGKDD).In this study,all the patients with kidney and urological diseases were recruited from 2014 to 2020.Genetic analysis was conducted using exome sequencing for families with multiple affected individuals with nephropathy or clinical suspicion of a genetic kidney disease owing to early-onset or extrarenal features.The genetic diagnosis was confirmed in 883 of 2256(39.1%)patients from 23 provinces in China.Phenotypic profiles showed that the primary diagnosis included steroid-resistant nephrotic syndrome(SRNS,23.5%),glomerulonephritis(GN,32.2%),congenital anomalies of the kidney and urinary tract(CAKUT,21.2%),cystic renal disease(3.9%),renal calcinosis/stone(3.6%),tubulopathy(9.7%),and chronic kidney disease of unknown etiology(CKDu,5.8%).The pathogenic variants of 105 monogenetic disorders were identified.Ten distinct genomic disorders were identified as pathogenic copy number variants(CNVs)in 11 patients.The diagnostic yield differed by subgroups,and was highest in those with cystic renal disease(66.3%),followed by tubulopathy(58.4%),GN(57.7%),CKDu(43.5%),SRNS(29.2%),renal calcinosis/stone(29.3%)and CAKUT(8.6%).Reverse phenotyping permitted correct identification in 40 cases with clinical reassessment and unexpected genetic conditions.We present the results of the largest cohort of children with kidney disease in China where diagnostic exome sequencing was performed.Our data demonstrate the utility of family-based exome sequencing,and indicate that the combined analysis of genotype and phenotype based on the national patient registry is pivotal to the genetic diagnosis of kidney disease.

胎儿先天性泌尿系统异常的产前诊断及预后

先天性泌尿系统异常是一种常见的胎儿先天性畸形,是引起儿童肾功能不全以及终末期肾病的常见原因。先天性泌尿系统异常的临床表型多样,常常是由于胚胎时期肾发育异常或发育缺陷引起的,因而,胎儿泌尿系统结构异常也成为产前诊断和遗传咨询中常有的类型。泌尿系统异常的预后差异较大,胎儿出生后可能致命也可能轻度影响功能,需要及时做出准确的判断并进行适当的干预。因此,胎儿先天性泌尿系统异常的研究对优生优育有重要意义。随着多普勒超声等影像技术的发展,极大地降低了产前超声诊断胎儿结构异常的漏诊率,本文综述了常见胎儿泌尿系统畸形的诊断和预后,为临床咨询提供有效参考。

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.

染色体微阵列芯片在产前先天性泌尿系统畸形胎儿中的应用价值

目的探讨染色体微阵列分析(chromosome microarray analysis,CMA)在先天性泌尿系统畸形(congenital abnormalities of the kidmey and urinary tract,CAKUT)胎儿中的应用价值。方法回顾性收集2018年1月—2022年9月61例CAKUT的胎儿产前诊断资料,采用CMA检测CAKUT胎儿,同时进行染色体核型分析。结果在61例CAKUT胎儿中,染色体核型分析检出5例变异核型,变异检出率为8.20%。CMA检出15例拷贝数变异,变异检出率为24.59%。2组检测技术在致病变异检出率差异有统计学意义(χ^(2)=6.06,P<0.05)。CMA技术在染色体核型分析正常的胎儿中另检出11例CNVs,其中4例致病性CNVs和7例意义未明CNVs。按是否合并其他超声异常将病例分2组,孤立组与非孤立组复合致病异常率分别为22.45%和33.33%,差异无统计学意义(P>0.05)。结论CMA检出能够提高CNV异常检出率,对临床产前咨询具有价值。

儿童先天性肾脏及尿路畸形的研究现状

先天性肾脏及尿路畸形(congenital abnormalities of the kidmey and urinary tract,CAKUT)是由于各种原因所致的,以先天性泌尿系统解剖学异常为临床特征的表型多样的一组疾病,发生率较高.CAKUT是导致儿童慢性肾脏病(chronic kidney disease,CKD)的最主要原因,部分患者可隐匿进展至终末期肾病(end-stage renal disease,ESRD).儿童CAKUT的研究对优生优育有重要意义,其发病机制尚不完全明确,但不少研究证明该病的发病与基因突变、拷贝数变异及环境等多因素有关.另外,采用彩色多普勒超声检查对于发现儿童CAKUT具有明显优势,是筛查的首选方法,进而实行早期相应治疗干预,必将大大降低患儿肾功能的损伤程度,提高患儿的生存率,对于疾病预防意义重大.该文综述近年来儿童CAKUT的流行病学研究、病因学研究、彩超筛查及干预治疗,旨在使医务人员更全面地了解儿童CAKUT,并采取积极的干预措施,延缓CKD的进展从而防止ESRD发生.

CT尿路成像检查在儿童先天性肾脏和尿路畸形诊断中的应用

儿童先天性肾脏和尿路畸形(CAKUT)是由于胚胎期肾脏和泌尿道发育缺陷所致,以先天性泌尿系统解剖结构异常为主要临床特征、临床表型多样的一组疾病。CT尿路成像(CTU)是指利用多层螺旋CT进行全尿路造影检查,并对获得的图像进行后处理与重建,用于诊断各种泌尿系统疾病的影像学技术。受试儿肾排泄期,当泌尿系统充满碘造影剂时呈高密度显影,与周围低密度软组织形成良好对比,为CTU技术应用于CAKUT患儿检查提供依据。笔者拟就儿童CAKUT种类及发病机制,不同影像学诊断方法比较,CTU检查要点,以及降低CTU辐射剂量等的最新研究进展进行阐述,旨在为临床应用CTU诊断CAKUT患儿时,最大限度降低受试儿的电离辐射损伤提供参考。