Recent observations indicate that focal hyperplasia of renal tubular epithelium characterizes a variety of renal cystic disorders in man and in rat. These disorders encompass both heritable an acquired diseases. Morphological studies in animal models indicate that the outer medullary segment of collecting tubules is the preferential site and that hyperplasia occurs so focally along these segments that papillomas or tiny polyps result. The polyps appear to infringe on tubular lumens and reduce the diameter of the channel through which urine passes en route to the renal pelvis. Functional studies of renal cystic disease indicate that hydrostatic pressures are variably increased among cysts. Pressures are elevated in cystic nephrons of diphenylamine-exposed kidneys and that, while not elevated without manipulation in cystic nordihydroguaiaretic acid-exposed nephrons, pressures rise to greater degrees when these nephrons are microperfused. The present project seeks to establish whether or not micropolyps are present along outer medullary segments of collecting tubules which drain only those nephrons that exhibit elevated pressures. It will utilize Sprague Dawley rats fed 2% dietary nordihydroguaiaretic acid for a minimum of five weeks to induce renal cysts and rats of the Zucker strain, 6 months or age of older, in which renal cysts develop as an apparently recessive, heritable trait. Conventional micropuncture, microperfusion, microscopic and microdissection techniques will be employed. This project also will endeavor to: (1) catalogue the frequency and distribution of micropolyps in human renal cystic disease, (2) assess the intrarenal distribution of, and renal tissue affinity for, nordihydroguaiaretic acid by labeling the chemical with radioiodide, and (3) assess the impact of chronically evlevated or reduced urinary flows on the rate of renal cyst formation. Overall, the study is directed toward enhanced understanding of pathogenic mechanisms in human renal cystic disease.
NIH ExPorter
NIH ExPorter