Precise clinicopathologic findings for application of genetic testing in pediatric kidney transplant recipients with focal segmental glomerulosclerosis/steroid-resistant nephrotic syndrome
Precise clinicopathologic findings for application of genetic testing in pediatric kidney transplant recipients with focal segmental glomerulosclerosis/steroid-resistant nephrotic syndrome
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基因检测在局灶节段性肾小球硬化/类固醇抵抗性肾病综合征儿童肾移植受者中应用的精确临床病理结果
DOI：
10.1007/s00467-022-05604-3
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发表时间：
2022
影响因子：
3
通讯作者：
Hattori Motoshi
中科院分区：
文献类型：
--
作者：
Miura Kenichiro;Kaneko Naoto;Hashimoto Taeko;Ishizuka Kiyonobu;Shirai Yoko;Hisano Masataka;Chikamoto Hiroko;Akioka Yuko;Kanda Shoichiro;Harita Yutaka;Yamamoto Toshiyuki;Hattori Motoshi
背景：建立局灶节段性肾小球硬化(FSGS)/类固醇抵抗性肾病综合征（SRNS）的分子遗传学诊断有助于预测移植后复发。据报道，大约20-30%的FSGS/SRNS患者存在单基因病因。然而，可能有单基因原因的患者的特征仍有待确定。方法分析1999年至2019年期间在我中心接受首次肾移植的SRNS和/或活检证实的FSGS的儿科受者。排除继发性FSGS/SRNS患者。接受者分为三组：家族性/综合征性、推定原发性和未确定的FSGS/SRNS。符合以下所有标准的患者被归类为假定的原发性FSGS/SRNS:(i)肾病综合征，（ii）通过初始类固醇治疗和/或额外的免疫抑制治疗完全或部分缓解，（iii）原位肾活检电镜显示弥漫性足突消失。所有患者均采用下一代测序技术进行基因检测。结果本研究共分析了23个家庭的24例患者。FSGS/SRNS相关基因的致病性或可能致病性变异分别在家族性/综合征性、推定原发和未确定FSGS/SRNS的4个家族、8个家族中的0个和11个家族中的10个中被发现。移植后复发仅发生在推定为原发性FSGS/SRNS的患者中。结论基于精确的临床病理表现，包括肾病综合征、治疗反应和弥漫性足过程消退的系统方法可能有助于区分可能是单基因原因的FSGS/SRNS儿童肾移植受者，并预测移植后复发。图形摘要更高分辨率的图形摘要版本可作为补充信息。
BackgroundEstablishing a molecular genetic diagnosis of focal segmental glomerulosclerosis (FSGS)/steroid-resistant nephrotic syndrome (SRNS) can be useful for predicting post-transplant recurrence. Monogenic causes are reportedly present in approximately 20–30% of patients with FSGS/SRNS. However, the characteristics of patients who are likely to have a monogenic cause remain to be determined.MethodsPediatric recipients with SRNS and/or biopsy-proven FSGS who underwent their first kidney transplantation at our center between 1999 and 2019 were analyzed. Patients with secondary FSGS/SRNS were excluded. The recipients were divided into three groups: familial/syndromic, presumed primary, and undetermined FSGS/SRNS. Patients who met all of the following criteria were categorized as having presumed primary FSGS/SRNS: (i) nephrotic syndrome, (ii) complete or partial remission with initial steroid therapy and/or additional immunosuppressive therapies, and (iii) diffuse foot process effacement on electron microscopy in the native kidney biopsy. All patients underwent genetic testing using next-generation sequencing.ResultsTwenty-four patients from 23 families were analyzed in this study. Pathogenic or likely pathogenic variants in FSGS/SRNS-related genes were identified in four of four families, zero of eight families, and 10 of 11 families with familial/syndromic, presumed primary, and undetermined FSGS/SRNS, respectively. Post-transplant recurrence only occurred in patients with presumed primary FSGS/SRNS.ConclusionsOur systematic approach based on precise clinicopathological findings including nephrotic syndrome, treatment responses, and diffuse foot process effacement might be useful to differentiate pediatric kidney transplant recipients with FSGS/SRNS who are likely to have a monogenic cause from patients who are not, and to predict post-transplant recurrence.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information.
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影响因子：
3.9
作者：
Park, Eujin;Lee, Chung;Cheong, Hae Il
通讯作者：
Cheong, Hae Il
DOI：
10.2215/cjn.04120417
发表时间：
2018-01-06
影响因子：
9.8
作者：
Warejko, Jillian K.;Tan, Weizhen;Hildebrandt, Friedhelm
通讯作者：
Hildebrandt, Friedhelm
影响因子：
3
作者：
Fine, Richard N.
通讯作者：
Fine, Richard N.
一种新的从头截短 TRIM8 突变与儿童期发病的局灶节段性肾小球硬化症（不伴有癫痫性脑病）相关
DOI：
--
发表时间：
2021
期刊：
影响因子：
--
作者：
Shirai Y;Miura K;Kaneko N;Ishizuka K;Endo A;Hashimoto T;Kanda S;Harita Y;Hattori M
通讯作者：
Hattori M
DOI：
10.1007/s00467-017-3838-6
发表时间：
2019-03
期刊：
Pediatric nephrology (Berlin, Germany)
影响因子：
--
作者：
Preston R;Stuart HM;Lennon R
通讯作者：
Lennon R