Multiple factors are thought to give rise to common, recurrent kidney stone disease, but for monogenic stone disorders a firm diagnosis is possible through genetic testing. The autosomal recessive primary hyperoxalurias (PH) are rare but important forms of monogenic kidney stone disease. All 3 types of PH are caused by inborn errors of glyoxylate metabolism in the liver, leading to hepatic oxalate overproduction and excessive renal urinary oxalate excretion. The conditions are characterized by kidney stones, nephrocalcinosis, progressive chronic kidney disease (CKD), and eventually kidney failure. Systemic oxalosis, the extra-renal deposition of oxalate resulting in severe morbidity and mortality, occurs in the setting of CKD when oxalate clearance by the kidneys declines. Novel small interfering RNA-based therapeutics targeting the liver to reduce urinary oxalate excretion have been approved, introducing precision medicine to treat primary hyperoxaluria type 1 (PH1). Increased access to genetic testing facilitates early detection of PH and other monogenic causes of kidney stone disease so that individualized care can be instituted promptly. This narrative review addresses the benefits and practicalities of genetic testing for suspected monogenic kidney stone disease and the critical roles of a multidisciplinary team. We share our procedures, education, training, and workflows to help other clinicians integrate genetic assessment into their diagnostic routines. This information may ensure more timely diagnoses so that patients with suspected monogenic kidney stone disease gain access to an expanded range of services and enrollment in clinical trials and registries.

中文翻译：

---

基因检测在单基因肾结石病中不断变化的作用：聚焦原发性高草酸尿症。


人们认为多种因素会导致常见的复发性肾结石病，但对于单基因结石病，可以通过基因检测进行明确诊断。常染色体隐性遗传性原发性高草酸尿症 （PH） 是罕见但重要的单基因肾结石病。所有 3 种类型的 PH 都是由肝脏乙醛酸代谢的先天性缺陷引起的，导致肝脏草酸盐分泌过多和肾尿草酸盐排泄过多。这些疾病的特征是肾结石、肾钙质沉着症、进行性慢性肾病 （CKD），最终导致肾衰竭。系统性草酸贮积，即草酸盐在肾外沉积导致严重并发症和死亡，发生在 CKD 的情况下，当肾脏对草酸盐的清除率下降时。靶向肝脏以减少尿草酸盐排泄的新型基于小干扰 RNA 的疗法已获得批准，引入了精准医学来治疗 1 型原发性高草酸尿症 （PH1）。基因检测的可及性增加有助于早期发现 PH 和其他肾结石病的单基因原因，以便及时进行个体化护理。本叙述性综述讨论了基因检测对疑似单基因肾结石病的益处和实用性，以及多学科团队的关键作用。我们分享我们的程序、教育、培训和工作流程，以帮助其他临床医生将基因评估整合到他们的诊断程序中。这些信息可以确保更及时的诊断，以便疑似单基因肾结石病患者能够获得更广泛的服务，并参加临床试验和登记。