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 ...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.展开更多
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 ...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.展开更多
目的:探讨新生儿先天性肾脏和泌尿道畸形(congenital anomalies of the kidney and urinary tract,CAKUT)的发病情况,评价出生后早期行泌尿系超声筛查的价值。方法:对2016年1月至2018年12月于清华大学附属北京清华长庚医院出生和就诊的...目的:探讨新生儿先天性肾脏和泌尿道畸形(congenital anomalies of the kidney and urinary tract,CAKUT)的发病情况,评价出生后早期行泌尿系超声筛查的价值。方法:对2016年1月至2018年12月于清华大学附属北京清华长庚医院出生和就诊的新生儿行泌尿系超声筛查并随访,同时对母孕产期资料进行分析,筛选与CAKUT发病相关的危险因素。结果:(1)本次筛查的2655例新生儿中,CAKUT阳性82例(男60例,女22例),阳性率为3.1%(82/2655),其中肾积水66例,重复肾6例,多发性肾囊肿2例,肾囊性发育不良2例,髓质海绵肾1例,小肾脏3例,孤立肾1例,马蹄肾1例。(2)66例肾积水患儿中有4例失访;8例目前随访尚不足6个月,肾积水无明显变化,继续随访观察中;54例完成随访1年,1年内恢复正常32例,减轻3例,加重7例,无变化12例,其中1例因反复泌感、肾功能下降接受手术治疗。(3)CAKUT高危因素以孕晚期胎儿泌尿系超声异常最多,胎儿泌尿系超声异常的高危新生儿有44例,生后筛查发现CAKUT病例35例,发生率为79.5%(35/44)。(4)本次筛查的2655例新生儿中,有2611例新生儿产前泌尿系超声检查是正常的,这些产前泌尿系超声检查正常的新生儿中,有47例出生后泌尿系B超筛查符合CAKUT诊断,发生率为1.8%(47/2611)。结论:新生儿最常见的CAKUT为肾积水,多数预后良好,但应定期随访;对新生儿尤其是母孕期胎儿泌尿系超声异常的高危新生儿行泌尿系统超声筛查,对于早期发现CAKUT有重要的临床意义。展开更多
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...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.展开更多
文摘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.
基金J.R.is supported by National Natural Science Foundation of China(NSFC-8182207)Shanghai Academic/Technology Research Leader(19XD1420600)Chinese Academy of Medical Sciences(2019-RC-HL_020).
文摘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.
文摘目的:探讨新生儿先天性肾脏和泌尿道畸形(congenital anomalies of the kidney and urinary tract,CAKUT)的发病情况,评价出生后早期行泌尿系超声筛查的价值。方法:对2016年1月至2018年12月于清华大学附属北京清华长庚医院出生和就诊的新生儿行泌尿系超声筛查并随访,同时对母孕产期资料进行分析,筛选与CAKUT发病相关的危险因素。结果:(1)本次筛查的2655例新生儿中,CAKUT阳性82例(男60例,女22例),阳性率为3.1%(82/2655),其中肾积水66例,重复肾6例,多发性肾囊肿2例,肾囊性发育不良2例,髓质海绵肾1例,小肾脏3例,孤立肾1例,马蹄肾1例。(2)66例肾积水患儿中有4例失访;8例目前随访尚不足6个月,肾积水无明显变化,继续随访观察中;54例完成随访1年,1年内恢复正常32例,减轻3例,加重7例,无变化12例,其中1例因反复泌感、肾功能下降接受手术治疗。(3)CAKUT高危因素以孕晚期胎儿泌尿系超声异常最多,胎儿泌尿系超声异常的高危新生儿有44例,生后筛查发现CAKUT病例35例,发生率为79.5%(35/44)。(4)本次筛查的2655例新生儿中,有2611例新生儿产前泌尿系超声检查是正常的,这些产前泌尿系超声检查正常的新生儿中,有47例出生后泌尿系B超筛查符合CAKUT诊断,发生率为1.8%(47/2611)。结论:新生儿最常见的CAKUT为肾积水,多数预后良好,但应定期随访;对新生儿尤其是母孕期胎儿泌尿系超声异常的高危新生儿行泌尿系统超声筛查,对于早期发现CAKUT有重要的临床意义。
基金This work was supported by the Grant NSFC-81800602 from National Natural Science Foundation of China(Dr.Jia-Lu Liu)the Grant 20184Y0176 from Shanghai Municipal Commission of Health and Family Planning Youth Research Program(Dr.Jia-Lu Liu)+2 种基金the Grant SHDC12016107 from Shanghai Shenkang Hospital Developmental Center(Dr.Hong Xu)the Grant NSFC-81670609 from National Natural Science Foundation of China(Dr.Hong Xu)the Grant 2018YFA0801102 from National Key Research and Development Project(Dr.Hong Xu).
文摘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.
