Shanks Josiah, Butler Grainne, Cheng Daryl, Jayasinghe Kushani, Quinlan Catherine
Department of Nephrology, Royal Children's Hospital, Melbourne, Australia.
Digital Health, Melbourne Children's Centre for Health Analytics, Melbourne, Australia.
Pediatr Nephrol. 2023 Aug;38(8):2623-2630. doi: 10.1007/s00467-022-05846-1. Epub 2023 Jan 30.
Microscopic haematuria in children is associated with the risk of progression to chronic kidney disease. Genetic disease is an important potential aetiology. Genomic sequencing presents the most effective diagnostic route for these conditions, but access remains inequitable internationally.
We conducted a retrospective review of the electronic medical records of a Kidney Genomics Clinic (KGC) from January 2016 to December 2021.
Sixty patients were referred to the KGC with haematuria over this period. Forty-three percent of patients had analysis of a limited haematuria panel (COL4A1, COL4A3, COL4A4, COL4A5, MYH9) with 58% receiving a genetic diagnosis. Forty-two percent of referred patients had further analysis of genes implicated in the development of kidney disease, and 36% received a diagnosis. Eight percent of patients underwent cascade testing for a known familial variant, and all received a diagnosis. Children with the highest levels of haematuria (> 500 × 10/L red blood cells) had the highest diagnostic yield (67%). Proteinuria, defined as a urinary protein to creatinine ratio > 20, increased the diagnostic yield from 31 to 65%. Importantly, negative genetic analysis can still have significant clinical utility for patients by altering surveillance and further management; the genetic result had clinical utility in 60% of patients.
Our KGC review highlights the substantial clinical utility and diagnostic yield of genomic analysis for microscopic haematuria in paediatric patients. Whilst the management of variants of uncertain significance can be challenging, a multidisciplinary team including genetic counselling can help ensure these patients are followed up meaningfully. A higher resolution version of the Graphical abstract is available as Supplementary information.
儿童镜下血尿与进展为慢性肾脏病的风险相关。遗传疾病是一个重要的潜在病因。基因组测序是诊断这些疾病最有效的途径，但在国际上获取该技术的机会仍然不平等。
我们对一家肾脏基因组诊所（KGC）2016年1月至2021年12月的电子病历进行了回顾性分析。
在此期间，60例血尿患者被转诊至KGC。43%的患者对有限的血尿检测组（COL4A1、COL4A3、COL4A4、COL4A5、MYH9）进行了分析，其中58%获得了基因诊断。42%的转诊患者对与肾脏疾病发生相关的基因进行了进一步分析，36%获得了诊断。8%的患者针对已知的家族性变异进行了级联检测，所有患者均获得了诊断。血尿水平最高（>500×10/L红细胞）的儿童诊断率最高（67%）。蛋白尿定义为尿蛋白与肌酐比值>20，可使诊断率从31%提高到65%。重要的是，阴性基因分析通过改变监测和进一步管理仍可为患者带来显著临床价值；基因检测结果在60%的患者中具有临床价值。
我们对KGC的回顾强调了基因组分析对儿科患者镜下血尿具有显著的临床价值和诊断率。虽然对意义未明变异的管理可能具有挑战性，但包括遗传咨询在内的多学科团队有助于确保对这些患者进行有意义的随访。更高分辨率的图形摘要版本可作为补充信息获取。
