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. 2022 Dec 22;38(9):1981-1991.
doi: 10.1093/ndt/gfac338. Online ahead of print.

Genetic spectrum of CAKUT and risk factors for kidney failure: a pediatric multicenter cohort study

Jia-Lu Liu  1   2 , Xiao-Wen Wang  3 , Cui-Hua Liu  4 , Duan Ma Xiao-Jie Gao  5 , Xiao-Yun Jiang  6 , Jian-Hua Mao  7 , Guang-Hua Zhu  8 , Ai-Hua Zhang  9 , Mo Wang  10 , Xi-Qiang Dang  11 , Jie-Qiu Zhuang  12 , Yu-Feng Li  13 , Hai-Tao Bai  14 , Rui-Feng Zhang  15 , Tong Shen  16 , Yun-Li Bi  17 , Yu-Bo Sun  2   17 , Xiang Wang  2   17 , Bing-Bing Wu  17 , Jing Chen  1   2 , Jia Rao  1   2 , Xiao-Shan Tang  1   2 , Qian Shen  1   2 , Hong Xu  1   2 ; Chinese Children Genetic Kidney Disease Database (CCGKDD), “Internet Plus” Nephrology Alliance of the National Center for Children's Care Department of Nephrology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
Affiliations

Genetic spectrum of CAKUT and risk factors for kidney failure: a pediatric multicenter cohort study

Jia-Lu Liu et al. Nephrol Dial Transplant. .

Abstract

Background: Congenital anomalies of the kidney and urinary tracts (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 multicenter 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 wereobtained 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 out 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 (95% confidence interval, 12.4-13.6) years, and twenty-four 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.

Keywords: children; congenital anomalies of the kidney and urinary tract; human genetics; kidney failure; risk factors.

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Conflict of interest statement

The authors have no conflict of interest to declare.

Figures

Graphical Abstract
Graphical Abstract
Figure 1:
Figure 1:
Genotype–phenotype relationship in 925 children with CAKUT. (A) The genetic spectrum varies among different CAKUT subphenotypes. (B) The percentage and number of patients in whom the genetic diagnosis was established in more than one patient. (C) The clinical diagnostic spectrum of patients with genetic diagnosis. BRHD, bilateral renal hypodysplasia; DS, duplex collecting system; EK, ectopic kidney; HD, hydronephrosis; HSK, horseshoe kidney; SK, solitary kidney; URHD, unilateral renal hypodysplasia.
Figure 2:
Figure 2:
Kaplan‒Meier kidney survival curves for 584 children with CAKUT from the CCGKDD stratified according to (A) categories of genetic diagnosis; (B) the presence of certain variants (PAX2, TNXB, EYA1, HNF1B, GATA3 and 48,XXYY); (C) sex and (D) preterm or term birth.
Figure 3:
Figure 3:
Survival probabilities of 584 children with CAKUT from the CCGKDD stratified by CAKUT subphenotypes after adjustment for the presence of certain variants (PAX2, TNXB, EYA1, HNF1B, GATA3 and 48,XXYY) and premature birth.
See this image and copyright information in PMC

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