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Nephron Count, Birth Weight &Hypertensive Renal Disease

$221,639R01FY2005DKNIH

University Of Mississippi Medical Center, Jackson MS

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Hypothesis: Increased rates of hypertension and hypertensive end-stage renal disease among African Americans (AA) are due to high rates of low birth weight (LBW) and decreased fetal nephron development. Individuals with low nephron numbers have increased renal perfusion rates through a reduced number of pre-glomerular arteries. In adulthood, obesity is associated with hypertension and with a further increase in renal perfusion rates. This accentuates the intrarenal arteriosclerosis leading to reduce glomerular perfusion, glomerular collapse, and ischemic glomerulosclerosis. Progressively severe arteriosclerosis and gIomerulosclerosis develops in this increasingly restricted vascular bed. Methods: Total glomerular number (Nglom) is estimated by the stereological physical disector/fractionator method using kidney tissue sampled from autopsies performed at the University of Mississippi Medical Center. The severity of renal arteriosclerosis and glomerulosclerosis is morphometrically evaluated on histologic sections of kidney. Specific Aims and Objectives: 1. To determine whether there is any correlation between hypertension, birth weight, Nglom, obesity, and the severity of renal arteriosclerosis and glomerulosclerosis. 2. To determine whether there are racial differences in any of these relationships that may underlie the increased risk among AA for hypertensive renal disease. A correlation between hypertension, low Nglom, LBW, and an increased severity of renal arteriosclerosis and glomerulosclerosis will support the hypothesis that glomerular number as determined by birth weight is an etiologic factor in the progressive renal injury of hypertension. If hypertension and racial disparities in hypertensive renal disease can be related to Nglom and birth weight, preventive strategies can be directed toward improving maternal factors that impair fetal development and lead to high rates of LBW. [unreadable] [unreadable]

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