NATURAL HISTORY OF POLYCYSTIC KIDNEY DISEASE

University Of Colorado Denver, Aurora CO

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Abstract

This project is to define the natural history of renal and extra-renal effects of ADPKD in a large population of ADPKD patients. The researchers hypothesize that the primary gene defect in ADPKD causes a defect in the gene product which affects cellular and/or extracellular processes which eventuate in an array of functional and structural systemic abnormalities. We hypothesize that the clinical progression of the phenotypic manifestations during subjects' lives will be variable even within the ADPKD1 gene group, but that differences in these manifestations will be detectable between the ADPKDI and the non-ADPKD1 groups. Specifically, different ADPKD genes will be characterized by different ages of onset, different disease severity and a different spectrum of systemic manifestations. We will test this by relating ADPKD gene types to clinical profiles. Elucidation of the phenotypes of the ADPKD1 and the non-ADPKD1 genes is critical for our understanding of the pathogenesis of the disorder and for effective genetic counseling of ADPKD families. To investigate these hypotheses we will examine the gastrointestinal tract and the cardiovascular system. In the study of the gastrointestinal system, the specific hypotheses are (1) that the progression of hepatic cystic disease relates to gender, pregnancy, use of contraceptive steroids and the structural and functional progression of the renal disease; (2) that ADPKD is associated with an increased frequency and severity of colonic diverticula. For the cardiovascular system, the specific hypotheses to be addressed are (1) that individuals with ADPKD from a family in which an affected person has an intracranial aneurysm (ICA) are at very high risk for aneurysm compared to individuals from families in which no ICA's have occurred; (2) that individuals from high-risk families may require serial studies of the intracranial circulation in order to detect all clinically important aneurysms. All subjects will undergo abdominal ultrasonography. Liver cyst number, maximal cyst size and renal volume will be obtained from ultrasonography and will be recorded. Subjects will undergo double-contrast barium enemas with glucagon. Studies will be interpreted by the gastrointestinal radiologist. The number, location, and size of all diverticula and any complicated diverticula will be recorded. All subjects will undergo a complete history and physical examination including a neurological exam. Subjects will be asked specifically about type and severity of headaches and any acute neurologic events. Subjects will undergo dynamic computed tomography (DCT) of the head. If findings indicate, subjects may undergo cerebral arteriography.