Pathophysiology of childhood polycystic kidney diseases: new insights into disease-specific therapy.
Pathophysiology of childhood polycystic kidney diseases: new insights into disease-specific therapy.
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DOI：
10.1038/pr.2013.191
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发表时间：
2014-01
影响因子：
3.6
通讯作者：
Avner, Ellis D.
中科院分区：
文献类型：
--
作者：
Sweeney, William E., Jr.;Avner, Ellis D.
ADPKD 和 ARPKD 是儿童和年轻人发病和死亡的重要原因。 ADPKD 的发病率为 1:400–1,000，影响全球超过 1300 万人，是成人终末期肾病 (ESRD) 的主要原因。然而，儿童中的症状性疾病越来越受到重视。 ARPKD 是一种双器官肝肾疾病，发病率为 1:20,000 至 1:40,000，杂合子携带率为 70 分之一。目前，尚无针对 ADPKD 或 ARPKD 的具有临床意义的疾病特异性治疗。 ADPKD 和 ARPKD 的遗传基础已被确定，对基本分子和细胞病理生理学的描述导致发现异常的 ADPKD 和 ARPKD 基因产物相互作用，在受影响细胞内的多个位点产生“多囊蛋白”复合物。这种复合物的整合信号传导导致异常的细胞增殖、改变的细胞运输和异常的基质血管生物学。本综述将重点关注异常囊性表型的分子和细胞基础，并回顾这种基本的临床转化。将数据转化为新疗法，有望改变患有遗传性多囊肾的儿童的疾病自然史。
ADPKD and ARPKD are a significant cause of morbidity and mortality in children and young adults. ADPKD with an incidence of 1:400–1,000 affects over 13 million individuals worldwide, and is a major cause of end-stage renal disease (ESRD) in adults. However, symptomatic disease is increasingly recognized in children. ARPKD is a dual organ hepatorenal disease with an incidence of 1:20,000 to 1:40,000 and a heterozygote carrier rate of 1 in 70. Currently, no clinically significant disease-specific therapy exists for ADPKD or ARPKD. The genetic basis of both ADPKD and ARPKD have been identified, and delineation of the basic molecular and cellular pathophysiology have led to the discovery that abnormal ADPKD and ARPKD gene products interact to create “polycystin" complexes” located at multiple sites within affected cells. The integrated signaling of such complexes leads to abnormal cellular proliferation, altered cellular transport, and abnormal matrix-vascular biology. This review will focus on the molecular and cellular basis of the abnormal cystic phenotype, and review the clinical translation of such basic data into new therapies, which promise to alter the natural history of disease for children with genetic PKDs.
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影响因子：
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作者：
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通讯作者：
Torres VE
DOI：
10.1152/ajprenal.00677.2011
发表时间：
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