The Clinical and Genetic Features in Chinese Children With Steroid-Resistant or Early-Onset Nephrotic Syndrome: A Multicenter Cohort Study

Xiujuan Zhu; Yanqin Zhang; Zihua Yu; Li Yu; Wenyan Huang; Shuzhen Sun; Yingjie Li; Mo Wang; Yongzhen Li; Liangzhong Sun; Qing Yang; Fang Deng; Xiaoshan Shao; Ling Liu; Cuihua Liu; Yuanhan Qin; Shipin Feng; Hongtao Zhu; Fang Yang; Weimin Zheng; Wanqi Zheng; Rirong Zhong; Ling Hou; Jianhua Mao; Fang Wang; Jie Ding

doi:10.3389/fmed.2022.885178

The Clinical and Genetic Features in Chinese Children With Steroid-Resistant or Early-Onset Nephrotic Syndrome: A Multicenter Cohort Study

Front Med (Lausanne). 2022 Jun 9:9:885178. doi: 10.3389/fmed.2022.885178. eCollection 2022.

Authors

Xiujuan Zhu¹, Yanqin Zhang², Zihua Yu³, Li Yu⁴, Wenyan Huang⁵, Shuzhen Sun⁶, Yingjie Li⁷, Mo Wang⁸, Yongzhen Li⁹, Liangzhong Sun¹⁰, Qing Yang¹¹, Fang Deng¹², Xiaoshan Shao¹³, Ling Liu¹⁴, Cuihua Liu^{15

16}, Yuanhan Qin¹⁷, Shipin Feng¹⁸, Hongtao Zhu¹⁹, Fang Yang²⁰, Weimin Zheng²¹, Wanqi Zheng²², Rirong Zhong²³, Ling Hou²⁴, Jianhua Mao¹, Fang Wang², Jie Ding²

Affiliations

¹ Department of Nephrology, The Children Hospital of Zhejiang University School of Medicine, Hangzhou, China.
² Department of Pediatrics, Peking University First Hospital, Beijing, China.
³ Department of Pediatrics, Fuzong Clinical Medical College, Fujian Medical University, Fuzhou, China.
⁴ Department of Pediatrics, Guangzhou First People's Hospital, Guangzhou, China.
⁵ Department of Nephrology and Rheumatology, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai, China.
⁶ Department of Pediatric Nephrology and Rheumatism and Immunology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
⁷ Guangzhou Women and Children's Medical Center, Guangzhou, China.
⁸ Department of Nephrology, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
⁹ Department of Pediatrics, The Second Xiangya Hospital, Central South University, Changsha, China.
¹⁰ Department of Pediatrics, Nanfang Hospital, Southern Medical University, Guangzhou, China.
¹¹ Department of Nephrology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
¹² Department of Nephrology, Anhui Provincial Children's Hospital, Hefei, China.
¹³ Department of Nephrology and Immunization, Guiyang Maternal and Child Health Care Hospital, Guiyang, China.
¹⁴ Department of Nephrology and Rheumatology, Children's Hospital of Hebei Province, Shijiazhuang, China.
¹⁵ Department of Nephrology and Rheumatology, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China.
¹⁶ Zhengzhou Key Laboratory of Pediatric Kidney Disease Research, Zhengzhou, China.
¹⁷ Department of Pediatrics, The First Hospital of Guangxi Medical University, Nanning, China.
¹⁸ Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
¹⁹ Department of Pediatrics, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
²⁰ Department of Pediatrics, The First Affiliated Hospital of Jinan University, Guangzhou, China.
²¹ Department of Nephrology, Jiangxi Provincial Children's Hospital, The Affiliated Children's Hospital Nanchang University, Nanchang, China.
²² Department of Pediatrics, The Second Hospital of Dalian Medical University, Dalian, China.
²³ Department of Pediatrics, Fujian Provincial Hospital, Fuzhou, China.
²⁴ Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China.

Abstract

Steroid-resistant nephrotic syndrome (SRNS) is one of the major causes of end-stage kidney disease (ESKD) in children and young adults. For approximately 30% of children with SRNS results from a genetic cause. In this study, genotype-phenotype correlations in a cohort of 283 pediatric patients with SRNS or early-onset NS (nephrotic syndrome presenting within the first year of life) from 23 major pediatric nephrology centers in China were analyzed. All patients were performed with next-generation sequencing and Sanger sequencing. The overall mutation detection rate was 37.5% (106 of 283 patients). WT1 was the most frequently detected mutation, followed by NPHS1, NPHS2, and ADCK4, and these four major causative genes (WT1, NPHS1, NPHS2, and ADCK4) account for 73.6% of patients with monogenic SRNS. Thirteen of 106 individuals (12.3%) carried mutations in ADCK4 that function within the coenzyme Q10 biosynthesis pathway. In the higher frequently ADCK4-related SRNS, two mutations, c.737G>A (p.S246N) and c.748G>C (p.D250H), were the most prevalent. Our study provides not only definitive diagnosis but also facilitate available targeted treatment for SRNS, and prediction of prognosis and renal outcome. Our indications for genetic testing are patients with FSGS, initial SRNS, cases of positive family history or those with extra-renal manifestations.

Keywords: children; genetic testing; phenotype; prognosis; steroid-resistant nephrotic syndrome.