Grant: Operating Grant

Among normal people, the number of functional nephrons varies widely from individual to individual (between 0.3 and 1.3 million nephrons per kidney). While this was once dismissed as a benign reflection of human diversity, recent evidence suggests that babies born with small kidneys may be at high risk for hypertension later in life. In preliminary studies, we found that babies born in India have smaller kidneys than babies in Montreal and hypothesize that this is due to a combination of inadequate vitamin A during pregnancy and inheritance of genes that influence the efficiency with which the fetus metabolizes vitamin A. In this project, we will first study a cohort of 300 newborns from Bangalore, India, to determine whether small kidney size is associated with maternal vitamin A deficiency plus an unfavorable combination of vitamin A pathway genes. We will then show that dysfunction of these specific genes lead to hypertension in mice. Finally we will test for an association between these genes and hypertension in a large cohort of adults from India and nearby regions. These studies should ascertain whether there is a link between vitamin A pathway genes and hypertension; if so, our studies will also provide a rationale for trials of vitamin A supplementation during pregnancy in the developing world.