Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic kidney disease and is caused by heterozygous germ-line mutations in eitherPKD1(85%) orPKD2(15%). It is characterised by the formation of numerous fluid-filled renal cysts and leads to adult-onset kidney failure in ~50% of patients by 60 years. Kidney cysts in ADPKD are focal and sporadic, arising from the clonal proliferation of collecting-duct principal cells, but in only 1–2% of nephrons for reasons that are not clear. Previous studies have demonstrated that further postnatal reductions inPKD1(orPKD2) dose are required for kidney cyst formation, but the exact triggering factors are not clear. A growing body of evidence suggests that DNA damage, and activation of the DNA damage response pathway, are altered in ciliopathies. The aims of this review are to: (i) analyse the evidence linking DNA damage and renal cyst formation in ADPKD; (ii) evaluate the advantages and disadvantages of biomarkers to assess DNA damage in ADPKD and finally, (iii) evaluate the potential effects of current clinical treatments on modifying DNA damage in ADPKD. These studies will address the significance of DNA damage and may lead to a new therapeutic approach in ADPKD.

中文翻译：

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DNA损伤作为常染色体显性遗传多囊肾病治疗靶点的作用

常染色体显性遗传多囊肾病 (ADPKD) 是最常见的单基因肾病，由任一基因的杂合子系突变引起。PKD1(85%) 或PKD2（15%）。它的特点是形成大量充满液体的肾囊肿，并导致约 50% 的患者在 60 岁时出现成人肾功能衰竭。ADPKD 中的肾囊肿是局灶性和散发性的，由集合管主细胞的克隆性增殖引起，但仅在 1-2% 的肾单位中出现，原因尚不清楚。以前的研究表明，产后进一步减少PKD1（要么PKD2) 肾囊肿形成需要剂量，但确切的触发因素尚不清楚。越来越多的证据表明 DNA 损伤和 DNA 损伤反应通路的激活在纤毛病中发生了改变。本综述的目的是：(i) 分析 ADPKD 中 DNA 损伤与肾囊肿形成相关的证据；(ii) 评估生物标志物评估 ADPKD 中 DNA 损伤的优缺点，最后，(iii) 评估当前临床治疗对修饰 ADPKD 中 DNA 损伤的潜在影响。这些研究将解决 DNA 损伤的重要性，并可能导致 ADPKD 的新治疗方法。