Early Alteration in Glomerular Reserve in Humans at Genetic Risk of Essential Hypertension: Mechanisms and Consequences

Essential hypertension has a familial predisposition, but the phenotype of elevated blood pressure has delayed penetrance. Because the kidney is a crucial determinant of blood pressure homeostasis, we studied early glomerular alterations in still-normotensive young subjects at genetic risk of hypertension. Thirty-nine normotensive adults (mean age 29 to 31 years), stratified by genetic risk (parental family history [FH]) of hypertension (26 with positive FH [FH+], 13 with negative FH [FH−]), underwent intravenous infusion of mixed amino acids. Before and during amino acid administration, we measured glomerular filtration rate (GFR), putative second messengers of amino acids (nitric oxide [NO·] metabolites and cGMP), serum insulin and amino acid concentrations, and the FELi+ as an index of renal proximal tubular reabsorption. The FH+ group had a blunted GFR rise in response to amino acids (2.43±8.16% versus 31.0±13.4% rise, P =0.0126). The amino acid–induced change in GFR correlated (r =0.786, P