Donor-derived hypouricemia in irrelevant recipients caused by kidney transplantation
Donor-derived hypouricemia in irrelevant recipients caused by kidney transplantation
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DOI：
10.21037/atm.2020.02.140
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发表时间：
2020-03
影响因子：
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通讯作者：
Lisha Teng;Yanling Zhang;Luxi Ye;J. Lv;You-ying Mao;Ronen Schneider;Jianghua Chen;Hong Jiang;Jianyong Wu
中科院分区：
文献类型：
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作者：
Lisha Teng;Yanling Zhang;Luxi Ye;J. Lv;You-ying Mao;Ronen Schneider;Jianghua Chen;Hong Jiang;Jianyong Wu
研究背景：遗传性肾性低尿酸血症（HRH）是一种遗传异质性疾病。HRH患者几乎无症状;但有些患者可能会发生运动性急性肾损伤（EAKI）和肾结石，这可能会引起对边缘肾供体风险-获益比的担忧。本研究检测了两例肾移植受者低尿酸血症的致病基因突变，为低尿酸血症的发病机制提供了初步证据。方法对2例患者进行详细的生化检查。从移植标本中提取DNA和RNA用于测序。通过全基因组测序和聚合酶链反应（PCR）扩增，确定致病基因。通过生物信息学分析验证了突变蛋白的功能效应。RNA测序（RNA-seq）用于研究低尿酸血症的转录组。结果两例受者的血尿酸（UA）水平均较低（45-65 μmol/l），UA排泄率较高（44%和75%），UA清除率升高（35.9和73.3 mL/min），移植肾功能正常。测序分析发现7种潜在的突变基因，其中SLC 22 A12基因上的两个新突变p.R89H和p.L181V可能是致病性的。结论SLC 22 A12基因存在两个新的突变。初步的功能分析揭示了这些突变在来自供体的移植物中的潜在有害作用，测序分析扩展了肾性低尿酸血症的分子机制。
Background Hereditary renal hypouricemia (HRH) is a genetically heterogenetic disease. Patients with HRH are almost asymptomatic; but some may experience exercise-induced acute kidney injury (EAKI) and nephrolithiasis which may bring concerns regarding the risk-benefit ratio as marginal kidney donors. This study examined the pathogenic mutations of hypouricemia in two recipients after receiving kidney transplantation, providing preliminary evidence for the mechanism of hypouricemia. Methods Two participants underwent detailed biochemical examinations. DNA and RNA were extracted from transplant specimens for sequencing. The whole-genome sequencing and polymerase chain reaction (PCR) amplification were performed to confirm the pathogenic genes. Functional effects of mutant proteins were verified by bioinformatics analysis. RNA-sequencing (RNA-seq) was used to study the transcriptome of hypouricemia. Results Both of the recipients had the low serum uric acid (UA) (45–65 µmol/l), high fraction excretion of UA (44% and 75%) and an increase in the UA clearance (35.9 and 73.3 mL/min) with a functioning graft. The sequencing analyses revealed 7 kinds of potential mutational genes in this case, two novel mutations p.R89H and p.L181V in SLC22A12 gene which were revealed by bioinformatics could be pathogenic in nature. Conclusions Two novel mutations of SLC22A12 were identified. Preliminary functional analysis revealed a potential deleterious effect of these mutations in the grafts derived from the donor and sequencing analysis expand the molecular mechanisms of renal hypouricemia.