Supplementary Material for: Successful Living Kidney Donation from Heterozygous Carrier Parents to Siblings with Coenzyme Q8B Nephropathy: Two Case Series

Introduction:
Coenzyme Q8B (COQ8B) nephropathy is an autosomal recessive hereditary disorder caused by primary coenzyme Q10 (CoQ10) deficiency. It manifests as a genetic steroid-resistant nephrotic syndrome (SRNS), typically of childhood-onset. CoQ10 supplementation is a treatment option; however, it is not always effective in an entire patient population, leading to end-stage kidney disease. Kidney transplantation (KTx) is an effective treatment option for genetic SRNS; however, living KTx within biologically related members is associated with increased risk of allograft failure in recipients and future kidney dysfunction in donors. Here, we present two successful cases of living kidney donations from heterozygous carrier parents to their siblings with COQ8B nephropathy.

Case presentation:
The family comprised two parents and three siblings. Two of the daughters were diagnosed with proteinuria at 11 and 8 years of age, respectively. COQ8B nephropathy diagnosis was confirmed by next-generation and Sanger sequencing analysis, which revealed a novel compound heterozygous mutation in the COQ8B gene (c.737G>A and c.1468C>T). An older sister missed an opportunity for CoQ10 supplementation due to late diagnosis, whereas a younger sister did not respond to CoQ10 supplementation. Living kidney donation from father to the older sister and from mother to the younger sister was successfully performed without posttransplant recurrence in recipients or kidney dysfunction in donors within 5 and 2 years of follow-up.

Conclusion:
Parent-to-child KTx may be an effective treatment option within family members affected with COQ8B nephropathy.

引言：
辅酶Q8B（Coenzyme Q8B, COQ8B）肾病是一种由原发性辅酶Q10（Coenzyme Q10, CoQ10）缺乏引发的常染色体隐性遗传性疾病，临床表现为遗传性类固醇抵抗型肾病综合征（steroid-resistant nephrotic syndrome, SRNS），多起病于儿童阶段。辅酶Q10补充治疗为可选干预手段，但并非对所有患者群体均有效，部分患者仍会进展为终末期肾病。肾移植（Kidney transplantation, KTx）是治疗遗传性SRNS的有效方案，但亲缘关系间的活体肾移植会增加受者的移植物功能丧失风险，同时提升供者未来发生肾功能异常的概率。本文报告2例成功的活体肾移植病例：由携带杂合突变的父母向其患有COQ8B肾病的同胞供肾。

病例报告：
该家系包含2名父母与3名同胞兄妹。两名女儿分别于11岁和8岁时确诊蛋白尿。通过下一代测序与桑格测序分析，证实为COQ8B肾病，检出COQ8B基因新型复合杂合突变（c.737G>A及c.1468C>T）。长姐因诊断延迟错失辅酶Q10补充治疗时机，而小妹对辅酶Q10补充治疗无应答。分别实施父亲向长姐、母亲向小妹的活体肾移植手术，术后随访5年及2年期间，受者均未出现移植肾复发，供者均未发生肾功能异常。

结论：
父母向子女的肾移植或许可为受累于COQ8B肾病的家庭成员提供有效的治疗选择。