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Genetic spectrum of CAKUT and risk factors for kidney failure: a paediatric multicentre cohort study

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of kidney failure in children with phenotypic and genotypic heterogeneity. Our objective was to describe the genetic spectrum and identify the risk factors for kidney failure in children with CAKUT. METHOD...

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Autores principales: Liu, Jia-Lu, Wang, Xiao-Wen, Liu, Cui-Hua, , Duan Ma, Gao, Xiao-Jie, Jiang, Xiao-Yun, Mao, Jian-Hua, Zhu, Guang-Hua, Zhang, Ai-Hua, Wang, Mo, Dang, Xi-Qiang, Zhuang, Jie-Qiu, Li, Yu-Feng, Bai, Hai-Tao, Zhang, Rui-Feng, Shen, Tong, Bi, Yun-Li, Sun, Yu-Bo, Wang, Xiang, Wu, Bing-Bing, Chen, Jing, Rao, Jia, Tang, Xiao-Shan, Shen, Qian, Xu, Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10468753/
https://www.ncbi.nlm.nih.gov/pubmed/36549658
http://dx.doi.org/10.1093/ndt/gfac338
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author Liu, Jia-Lu
Wang, Xiao-Wen
Liu, Cui-Hua
, Duan Ma
Gao, Xiao-Jie
Jiang, Xiao-Yun
Mao, Jian-Hua
Zhu, Guang-Hua
Zhang, Ai-Hua
Wang, Mo
Dang, Xi-Qiang
Zhuang, Jie-Qiu
Li, Yu-Feng
Bai, Hai-Tao
Zhang, Rui-Feng
Shen, Tong
Bi, Yun-Li
Sun, Yu-Bo
Wang, Xiang
Wu, Bing-Bing
Chen, Jing
Rao, Jia
Tang, Xiao-Shan
Shen, Qian
Xu, Hong
author_facet Liu, Jia-Lu
Wang, Xiao-Wen
Liu, Cui-Hua
, Duan Ma
Gao, Xiao-Jie
Jiang, Xiao-Yun
Mao, Jian-Hua
Zhu, Guang-Hua
Zhang, Ai-Hua
Wang, Mo
Dang, Xi-Qiang
Zhuang, Jie-Qiu
Li, Yu-Feng
Bai, Hai-Tao
Zhang, Rui-Feng
Shen, Tong
Bi, Yun-Li
Sun, Yu-Bo
Wang, Xiang
Wu, Bing-Bing
Chen, Jing
Rao, Jia
Tang, Xiao-Shan
Shen, Qian
Xu, Hong
author_sort Liu, Jia-Lu
collection PubMed
description BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of kidney failure in children with phenotypic and genotypic heterogeneity. Our objective was to describe the genetic spectrum and identify the risk factors for kidney failure in children with CAKUT. METHODS: Clinical and genetic data were derived from a multicentre network [Chinese Children Genetic Kidney Disease Database (CCGKDD)] and the Chigene database. A total of 925 children with CAKUT who underwent genetic testing from 2014 to 2020 across China were studied. Data for a total of 584 children were obtained from the CCGKDD, including longitudinal data regarding kidney function. The risk factors for kidney failure were determined by the Kaplan–Meier method and Cox proportional hazards models. RESULTS: A genetic diagnosis was established in 96 of 925 (10.3%) children, including 72 (8%) with monogenic variants, 20 (2%) with copy number variants (CNVs) and 4 (0.4%) with major chromosomal anomalies. Patients with skeletal abnormalities were more likely to have large CNVs or abnormal karyotypes than monogenic variants. Eighty-two patients from the CCGKDD progressed to kidney failure at a median age of 13.0 years (95% confidence interval 12.4–13.6) and 24 were genetically diagnosed with variants of PAX2, TNXB, EYA1, HNF1B and GATA3 or the 48,XXYY karyotype. The multivariate analysis indicated that solitary kidney, posterior urethral valves, bilateral hypodysplasia, the presence of certain variants and premature birth were independent prognostic factors. CONCLUSIONS: The genetic spectrum of CAKUT varies among different subphenotypes. The identified factors indicate areas that require special attention.
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spelling pubmed-104687532023-09-01 Genetic spectrum of CAKUT and risk factors for kidney failure: a paediatric multicentre cohort study Liu, Jia-Lu Wang, Xiao-Wen Liu, Cui-Hua , Duan Ma Gao, Xiao-Jie Jiang, Xiao-Yun Mao, Jian-Hua Zhu, Guang-Hua Zhang, Ai-Hua Wang, Mo Dang, Xi-Qiang Zhuang, Jie-Qiu Li, Yu-Feng Bai, Hai-Tao Zhang, Rui-Feng Shen, Tong Bi, Yun-Li Sun, Yu-Bo Wang, Xiang Wu, Bing-Bing Chen, Jing Rao, Jia Tang, Xiao-Shan Shen, Qian Xu, Hong Nephrol Dial Transplant Original Article BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of kidney failure in children with phenotypic and genotypic heterogeneity. Our objective was to describe the genetic spectrum and identify the risk factors for kidney failure in children with CAKUT. METHODS: Clinical and genetic data were derived from a multicentre network [Chinese Children Genetic Kidney Disease Database (CCGKDD)] and the Chigene database. A total of 925 children with CAKUT who underwent genetic testing from 2014 to 2020 across China were studied. Data for a total of 584 children were obtained from the CCGKDD, including longitudinal data regarding kidney function. The risk factors for kidney failure were determined by the Kaplan–Meier method and Cox proportional hazards models. RESULTS: A genetic diagnosis was established in 96 of 925 (10.3%) children, including 72 (8%) with monogenic variants, 20 (2%) with copy number variants (CNVs) and 4 (0.4%) with major chromosomal anomalies. Patients with skeletal abnormalities were more likely to have large CNVs or abnormal karyotypes than monogenic variants. Eighty-two patients from the CCGKDD progressed to kidney failure at a median age of 13.0 years (95% confidence interval 12.4–13.6) and 24 were genetically diagnosed with variants of PAX2, TNXB, EYA1, HNF1B and GATA3 or the 48,XXYY karyotype. The multivariate analysis indicated that solitary kidney, posterior urethral valves, bilateral hypodysplasia, the presence of certain variants and premature birth were independent prognostic factors. CONCLUSIONS: The genetic spectrum of CAKUT varies among different subphenotypes. The identified factors indicate areas that require special attention. Oxford University Press 2022-12-22 /pmc/articles/PMC10468753/ /pubmed/36549658 http://dx.doi.org/10.1093/ndt/gfac338 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the ERA. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Article
Liu, Jia-Lu
Wang, Xiao-Wen
Liu, Cui-Hua
, Duan Ma
Gao, Xiao-Jie
Jiang, Xiao-Yun
Mao, Jian-Hua
Zhu, Guang-Hua
Zhang, Ai-Hua
Wang, Mo
Dang, Xi-Qiang
Zhuang, Jie-Qiu
Li, Yu-Feng
Bai, Hai-Tao
Zhang, Rui-Feng
Shen, Tong
Bi, Yun-Li
Sun, Yu-Bo
Wang, Xiang
Wu, Bing-Bing
Chen, Jing
Rao, Jia
Tang, Xiao-Shan
Shen, Qian
Xu, Hong
Genetic spectrum of CAKUT and risk factors for kidney failure: a paediatric multicentre cohort study
title Genetic spectrum of CAKUT and risk factors for kidney failure: a paediatric multicentre cohort study
title_full Genetic spectrum of CAKUT and risk factors for kidney failure: a paediatric multicentre cohort study
title_fullStr Genetic spectrum of CAKUT and risk factors for kidney failure: a paediatric multicentre cohort study
title_full_unstemmed Genetic spectrum of CAKUT and risk factors for kidney failure: a paediatric multicentre cohort study
title_short Genetic spectrum of CAKUT and risk factors for kidney failure: a paediatric multicentre cohort study
title_sort genetic spectrum of cakut and risk factors for kidney failure: a paediatric multicentre cohort study
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10468753/
https://www.ncbi.nlm.nih.gov/pubmed/36549658
http://dx.doi.org/10.1093/ndt/gfac338
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