Cyst number but not the rate of cystic growth is associated with the mutated gene in autosomal dominant polycystic kidney disease
Cyst number but not the rate of cystic growth is associated with the mutated gene in autosomal dominant polycystic kidney disease
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DOI：
10.1681/asn.2006080835
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发表时间：
2006-11-01
影响因子：
13.6
通讯作者：
Miller, J. Philip
中科院分区：
文献类型：
--
作者：
Harris, Peter C.;Bae, Kyongtae T.;Miller, J. Philip
来自PKD放射成像研究联盟（CRISP）常染色体显性多囊肾病（PKD）人群的连续肾脏磁共振成像数据显示，尽管在人群中存在异质性，但每个个体的囊性扩张发生率一致，并且较大的肾脏与更快的疾病进展相关。在CRISP队列的这项研究中分析了基因类型对疾病进展的意义。在183个家系（219例）中确定了基因型，156例（85.2%）为PKD 1，27例（14.8%）为PKD 2。PKD 1组肾脏明显较大，但囊性生长率（PKD 1组5.68%/年; PKD 2组4.82%/年）无差异（P = 0.24）。囊肿数量随年龄增长而增加，PKD 1组囊肿数量较多（P < 0.0001）。PKD 1更严重，因为更多的囊肿更早地发育，而不是因为它们生长得更快，这意味着疾病基因参与了囊肿的形成，而不是扩张。这些见解将为常染色体显性遗传性PKD的靶向治疗的发展提供信息。
Data from serial renal magnetic resonance imaging of the Consortium of Radiologic Imaging Study of PKD (CRISP) autosomal dominant polycystic kidney disease (PKD) population showed that cystic expansion occurs at a consistent rate per individual, although it is heterogeneous in the population, and that larger kidneys are associated with more rapid disease progression. The significance of gene type to disease progression is analyzed in this study of the CRISP cohort. Gene type was determined in 183 families (219 cases); 156 (85.2%) had PKD1, and 27 (14.8%) had PKD2. PKD1 kidneys were significantly larger, but the rate of cystic growth (PKD1 5.68%/yr; PKD2 4.82%/yr) was not different (P = 0.24). Cyst number increased with age, and more cysts were detected in PKD1 kidneys (P < 0.0001). PKD1 is more severe because more cysts develop earlier, not because they grow faster, implicating the disease gene in cyst initiation but not expansion. These insights will inform the development of targeted therapies in autosomal dominant PKD.