肾移植候选者选择性基因检测的实用方法。
A pragmatic approach to selective genetic testing in kidney transplant candidates.
作者信息
Nissaisorakarn Pitchaphon, Fadakar Paul K, Safa Kassem, Lundquist Andrew L, Riella Cristian V, Riella Leonardo V
机构信息
Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Division of Nephrology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
出版信息
Front Transplant. 2024 Jan 16;2:1342471. doi: 10.3389/frtra.2023.1342471. eCollection 2023.
INTRODUCTION
Advances in the field of genetic testing have spurred its use in transplantation. Potential benefits of genetic testing in transplant nephrology include diagnosis, treatment, risk stratification of recurrent disease, and risk stratification in potential donors. However, it is unclear how to best apply genetic testing in this population to maximize its yield. We describe our transplant center's approach to selective genetic testing as part of kidney transplant candidate and donor evaluation.
METHODS
Transplant recipient candidates were tested if they had a history of ESRD at age <50, primary FSGS, complement-mediated or unknown etiology of kidney disease, or had a family history of kidney disease. Donors were tested if age <35, were related to their potential recipients with known genetic susceptibility or had a first-degree relative with a history of kidney disease of unknown etiology. A targeted NGS gene panel of 385 genes was used. Clinical implications and downstream effects were monitored.
RESULTS
Over 30% of recipients tested within the established criteria were positive for a pathogenic variant. The most common pathogenic variants were APOL1 high-risk genotypes as well as collagen 4-alpha-3, -4 and -5. Donor testing done according to our inclusion criteria resulted in about 12% yield. Positive test results in recipients helped with stratification of the risk of recurrent disease. Positive test results in potential donors guided informed decisions on when not to move forward with a donation.
DISCUSSION
Integrating targeted panel genetic testing into a kidney transplant clinic in conjunction with a selective criteria for testing donors and recipients ensured a reasonable diagnostic yield. The results had implications on clinical management, risk stratification and in some cases were instrumental in directing downstream changes including when to stop the evaluation process. Given the impact on management and transplant decisions, we advocate for the widespread use of genetic testing in selected individuals undergoing transplant evaluation and donation who meet pre-defined criteria.
引言
基因检测领域的进展推动了其在移植领域的应用。基因检测在移植肾病学中的潜在益处包括诊断、治疗、复发性疾病的风险分层以及潜在供体的风险分层。然而，目前尚不清楚如何在这一人群中最佳地应用基因检测以最大化其收益。我们描述了我们移植中心将选择性基因检测作为肾移植候选者和供体评估一部分的方法。
方法
如果移植受者候选人年龄<50岁时有终末期肾病病史、原发性局灶节段性肾小球硬化、补体介导的或病因不明的肾病，或者有肾病家族史，则对其进行检测。如果供体年龄<35岁、与具有已知遗传易感性的潜在受者有亲属关系或有一级亲属有病因不明的肾病病史，则对其进行检测。使用了一个包含385个基因的靶向二代测序基因panel。监测临床意义和下游效应。
结果
在既定标准内接受检测的受者中，超过30%的人有致病性变异呈阳性。最常见的致病性变异是APOL1高风险基因型以及胶原蛋白4-α-3、-4和-5。根据我们的纳入标准进行的供体检测阳性率约为12%。受者的阳性检测结果有助于复发性疾病风险的分层。潜在供体的阳性检测结果指导了关于何时不推进捐赠的明智决策。
讨论
将靶向panel基因检测与供体和受者检测的选择性标准相结合，纳入肾移植诊所，确保了合理的诊断阳性率。结果对临床管理、风险分层有影响，在某些情况下有助于指导下游变化，包括何时停止评估过程。鉴于对管理和移植决策的影响，我们主张在符合预定义标准的接受移植评估和捐赠的特定个体中广泛使用基因检测。
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