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. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK065970-03
Application #
7111867
Study Section
Pathobiology of Kidney Disease Study Section (PBKD)
Program Officer
Moxey-Mims, Marva M
Project Start
2004-09-01
Project End
2008-02-29
Budget Start
2006-09-01
Budget End
2008-02-29
Support Year
3
Fiscal Year
2006
Total Cost
$214,779
Indirect Cost
Name
University of Mississippi Medical Center
Department
Pathology
Type
Schools of Medicine
DUNS #
928824473
City
Jackson
State
MS
Country
United States
Zip Code
39216
Hughson, Michael D; Hoy, Wendy E; Mott, Susan A et al. (2018) APOL1 Risk Variants Independently Associated With Early Cardiovascular Disease Death. Kidney Int Rep 3:89-98
Hughson, Michael D; Hoy, Wendy E; Mott, Susan A et al. (2016) APOL1 Risk Alleles are Associated with More Severe Arteriosclerosis in Renal Resistance Vessels with Aging and Hypertension. Kidney Int Rep 1:10-23
Hoy, Wendy E; Hughson, Michael D; Kopp, Jeffrey B et al. (2015) APOL1 Risk Alleles Are Associated with Exaggerated Age-Related Changes in Glomerular Number and Volume in African-American Adults: An Autopsy Study. J Am Soc Nephrol 26:3179-89
Puelles, Victor G; Bertram, John F (2015) Counting glomeruli and podocytes: rationale and methodologies. Curr Opin Nephrol Hypertens 24:224-30
Puelles, Victor G; Douglas-Denton, Rebecca N; Zimanyi, Monika A et al. (2014) Glomerular hypertrophy in subjects with low nephron number: contributions of sex, body size and race. Nephrol Dial Transplant 29:1686-95
Hughson, Michael D; Puelles, Victor G; Hoy, Wendy E et al. (2014) Hypertension, glomerular hypertrophy and nephrosclerosis: the effect of race. Nephrol Dial Transplant 29:1399-409
Puelles, Victor G; Zimanyi, Monika A; Samuel, Terence et al. (2012) Estimating individual glomerular volume in the human kidney: clinical perspectives. Nephrol Dial Transplant 27:1880-8
Hughson, Michael D; Hoy, Wendy E; Douglas-Denton, Rebecca N et al. (2011) Towards a definition of glomerulomegaly: clinical-pathological and methodological considerations. Nephrol Dial Transplant 26:2202-8
Bertram, John F; Douglas-Denton, Rebecca N; Diouf, Boucar et al. (2011) Human nephron number: implications for health and disease. Pediatr Nephrol 26:1529-33
McNamara, Bridgette J; Diouf, Boucar; Douglas-Denton, Rebecca N et al. (2010) A comparison of nephron number, glomerular volume and kidney weight in Senegalese Africans and African Americans. Nephrol Dial Transplant 25:1514-20

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