Genetic studies on familial interstitial nephritis

慢性肾脏病（CKD）是临床异质性疾病，可能进展为终末期肾衰竭的风险较高。CKD正在成为一个全球性的健康问题，因为它确实在八分之一的成年人中非常普遍。肾小管间质损伤作为肾小球损伤的主要始动因素和/或继发性加重改变，在CKD的发病机制中起重要作用。然而，早期肾小管间质损伤往往认识不足，因为患者几乎没有明显的蛋白尿和肾功能不全。为了改善慢性肾脏病的治疗，有必要阐明新的疾病生物标志物和肾小管间质疾病的遗传危险因素。本研究旨在确定一个显性肾小管间质性肾炎大家族的疾病基因。连锁分析和下一代测序的联合方法显示，两种新的单核苷酸变异可能解释间质性肾炎的易感性。

Chronic kidney disease(CKD) is clinically heterogeneous groups of diseases at a higher risk of potentially progressing to the end stage renal failure. The CKD is becoming a global health problem since it is indeed highly prevalent at one in eight adult individuals. The tubule-interstitial injuries significantly contribute to the pathogenesis of CKD as a primary initiating factor and/or a secondary exacerbating changes resulting from the glomerular insults. However, earlier tubule-interstitial injuries are often under-recognized because the patients barely manifest overt proteinuria and renal dysfunction. To improve the treatment for CKD, there is a need for elucidation of new disease biomarkers and genetic risk factors underlying tubule-interstitial diseases.This study aimed to identify the disease genes underling a large dominant family with tubule-interstitial nephritis. A combined approach of linkage analysis and next generation sequencing revealed that two novel single nucleotide variants may explain the susceptibility for interstitial nephritis.