Nephropathy in blacks is related to the incidence of essential hypertension (EH) and non-insulin dependent diabetes mellitus (NIDDM). Insulin resistance is associated with EH and NIDDM in blacks as well as whites. In whites with insulin-dependent diabetes mellitus (IDDM) and elevated blood pressure (BP), an increase in activity of sodium-lithium countertransport (Na/Li Exc) measured in red blood cells (RBC) has been detected in patients with nephropathy. Na/Li Exc is a functional mode of sodium-hydrogen exchange (Na/H Exc). The activity of both Na/Li Exc and Na/H Exc are modulated by insulin. We have detected an increase in Na/H Exc activity in blacks with mild EH and insulin resistance; and we have found an increase in Na/Li Exc activity in blacks with insulin resistance. These alterations in young adult blacks in an early phase of EH, raise the possibility that cosegregation of the phenotypes insulin resistance and elevated sodium transport activity in RBCs could be markers for nephropathy. Our overall hypothesis is: Blacks with EH and insulin resistance are at risk for nephropathy. Blacks with EH and insulin resistance who exhibit early nephropathy, evidenced by increased urinary albumin excretion, will have increased activity of the RBC Na/Li Exc. Blacks with EH and insulin resistance may also have increased RBC Na/H Exc, but evidence of nephropathy will be present only if Na/Li Exc exhibits increased activity. In this project we will study RBC sodium transport and insulin resistance as determinants of nephropathy in blacks. The study population will consist of normotensive young adults, young adults with mild EH, and a sample of blacks with EH and NIDDM who also have clinically apparent nephropathy. We will 1) characterize insulin-stimulated glucose metabolism in the young adults (20-40 yr); 2) Measure the transmembrane sodium transporters Na/Li Exc and Na/H Exc in all subjects; 3) Examine urinary albumin excretion to determine if there is evidence of nephropathy in the young adults; 4) Determine if insulin resistance and alterations of Na/Li Exc or Na/H Exc are predictors of nephropathy in blacks. Results of these studies will determine if insulin resistance and sodium transport define risk for nephropathy. These data can lead to new insights on the mechanisms underlying nephropathy. Effective detection of individuals at risk for nephropathy will also lead to the development of strategies for prevention of progressive nephropathy in blacks.
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