Department of Paediatric Nephrology, Great Ormond Street Hospital, London, UK.
NE Thames Regional Genetics Laboratory, GOSH NHS Foundation Trust, London, UK.
Pediatr Nephrol. 2023 Apr;38(4):1051-1056. doi: 10.1007/s00467-022-05569-3. Epub 2022 Jul 8.
Primary steroid resistant nephrotic syndrome (SRNS) is thought to have either genetic or immune-mediated aetiology. Knowing which children to screen for genetic causes can be difficult. Several studies have described the prevalence of genetic causes of primary SRNS to be between 30 and 40%, but these may reflect a selection bias for genetic testing in children with congenital, infantile, syndromic or familial NS and thus may overestimate the true prevalence in a routine clinical setting.
Retrospective electronic patient record analysis was undertaken of all children with non-syndromic SRNS and presentation beyond the first year of life, followed at our centre between 2005 and 2020.
Of the 49 children who met the inclusion criteria, 5 (10%) had causative variants identified, predominantly in NPHS2. None responded to immunosuppression. Of the 44 (90%) who had no genetic cause identified, 33 (75%) had complete or partial remission after commencing second-line immunosuppression and 67% of these had eGFR > 90 ml/min/1.73 m at last clinical follow-up. Of the children who did not respond to immunosuppression, 64% progressed to kidney failure.
In our cohort of children with non-syndromic primary SRNS and presentation beyond the first year of life, we report a prevalence of detectable causative genetic variants of 10%. Those with identified genetic cause were significantly (p = 0.003) less likely to respond to immunosuppression and more likely (p = 0.026) to progress to chronic kidney disease. Understanding the genetics along with response to immunosuppression informs management in this cohort of patients and variant interpretation. A higher resolution version of the Graphical abstract is available as Supplementary information.
原发性类固醇耐药性肾病综合征（SRNS）被认为具有遗传或免疫介导的病因。了解哪些儿童需要进行遗传原因筛查可能很困难。几项研究描述了原发性 SRNS 的遗传原因患病率在 30%至 40%之间，但这些可能反映了对具有先天性、婴儿期、综合征或家族性 NS 的儿童进行遗传检测的选择偏倚，因此可能高估了常规临床环境中的真实患病率。
对 2005 年至 2020 年期间在我们中心就诊的非综合征性 SRNS 且发病年龄超过 1 岁的所有儿童进行回顾性电子患者记录分析。
符合纳入标准的 49 名儿童中，有 5 名（10%）确定了致病变异，主要在 NPHS2 中。没有一个对免疫抑制有反应。在未确定遗传原因的 44 名（90%）儿童中，有 33 名（75%）在开始二线免疫抑制后完全或部分缓解，其中 67%的儿童在最后一次临床随访时 eGFR>90ml/min/1.73m。在未对免疫抑制有反应的儿童中，有 64%进展为肾衰竭。
在我们的非综合征性原发性 SRNS 且发病年龄超过 1 岁的儿童队列中，我们报告可检测到的致病遗传变异的患病率为 10%。那些有明确遗传原因的儿童对免疫抑制的反应明显（p=0.003）较低，更有可能（p=0.026）进展为慢性肾病。了解遗传学以及对免疫抑制的反应为该患者群体的管理提供了信息，并对变异进行了解读。图形摘要的更高分辨率版本可作为补充信息获得。
