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Autosomal dominant polycystic kidney disease (ADPKD, autosomal dominant PKD or adult-onset PKD) is the most prevalent, potentially lethal, monogenic human disorder. It is associated with large interfamilial and intrafamilial variability, which can be explained to a large extent by its genetic heterogeneity and modifier genes.〔 It is also the most common of the inherited cystic kidney diseases — a group of disorders with related but distinct pathogenesis, characterized by the development of renal cysts and various extrarenal manifestations, which in case of ADPKD include cysts in other organs, such as the liver, seminal vesicles, pancreas, and arachnoid membrane, as well as other abnormalities, such as intracranial aneurysms and dolichoectasias, aortic root dilatation and aneurysms, mitral valve prolapse, and abdominal wall hernias.〔 Over 50% of patients with ADPKD eventually develop end stage kidney disease and require dialysis or kidney transplantation.〔 ADPKD is estimated to affect at least 1 in every 1000 individuals worldwide, making this disease the most common inherited kidney disorder with a diagnosed prevalence of 1:2000 and incidence of 1:3000-1:8000 in a global scale. ==Pathophysiology== In many patients with ADPKD, kidney disfunction is not clinically apparent until forty or fifty years of life.〔 There is, however, an increasing body of evidence that suggests the formation of renal cysts to start before birth while ''in utero''. Cysts initially form as small dilations in renal tubules, which then expand to form fluid-filled cavities of different sizes.〔 Factors suggested to lead to cystogenesis include a germline mutation in one of the polycystin gene alleles, a somatic second hit that leads to the loss of the normal allele, and a third hit, which can be anything that triggers cell proliferation, leading to the dilation of the tubules.〔 In the progression of the disease, continued dilation of the tubules through increased cell proliferation, fluid secretion, and separation from the parental tubule lead to the formation of cysts. ADPKD, together with many other diseases that present with renal cysts, can be classified into a family of diseases known as ciliopathies. Epithelial cells of the renal tubules, including all the segments of the nephron and the collecting ducts (with the exception of intercalated cells) show the presence of a single primary apical cilium. Polycystin-1, the protein encoded by the PKD1 gene, is present on these cilia and is thought to sense the flow with its large extracellular domains, activating the calcium channels associated with polycystin-2, the product of gene PKD2, as a result of the genetic setting of ADPKD as explained in the genetics sub-section below. Epithelial cell proliferation and fluid secretion that lead to cystogenesis are two hallmark features in ADPKD. During the early stages of cystogenesis, cysts are attached to their parental renal tubules and a derivative of the glomerular filtrate enters the cysts.〔 Once these cysts expand to approximately 2 mm in diameter, the cyst closes off from its parental tubule and after that fluid can only enter the cysts through transepithelial secretion, which in turn is suggested to increase due to secondary effects from an increased intracellular concentrations of cyclic AMP (cAMP).〔 Clinically, the insidious increase in the number and size of renal cysts translates as a progressive increment in kidney volume.〔〔 Trail-blazing studies led by Mayo Clinic professionals established that the total kidney volume (TKV) in a large cohort of ADPKD patients was 1060 ± 642ml with a mean increase of 204ml over three years, or 5.27% per year in the natural course of the disease, among other important, novel findings that were extensively studied for the first time. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Autosomal dominant polycystic kidney disease」の詳細全文を読む スポンサード リンク
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