Longitudinal changes in blood pressure are preceded by changes in albuminuria and accelerated by increasing dietary sodium intake

Abstract

Background: Dietary sodium is a well-known risk factor for cardiovascular and renal disease; however, direct evidence of the longitudinal changes that occur with aging, and the influence of dietary sodium on the age-associated alterations are scarce.

Methods: C57BL/6 mice were maintained for 13 months on a low (LS, 0.02 % Na⁺), normal (NS, 0.3 % Na⁺) or high (HS, 1.6 % Na⁺) salt diet. We assessed 1) the longitudinal trajectories for two markers of cardiovascular and renal dysfunction (blood pressure (BP) and albuminuria), as well as hormonal changes, and 2) end-of-study cardiac and renal parameters.

Results: The effect of aging on BP and kidney damage did not reach significance levels in the LS group; however, relative to baseline, there were significant increases in these parameters for animals maintained on NS and HS diets, starting as early as month 7 and month 5, respectively. Furthermore, changes in albuminuria preceded the changes in BP relative to baseline, irrespective of the diet. Circulating aldosterone and plasma renin activity displayed the expected decreasing trends with age and dietary sodium loading. As compared to LS - higher dietary sodium consumption associated with increasing trends in left ventricular mass and volume indices, consistent with an eccentric dilated phenotype. Functional and molecular markers of kidney dysfunction displayed similar trends with increasing long-term sodium levels: higher renovascular resistance, increased glomerular volumes, as well as higher levels of renal angiotensin II type 1 and mineralocorticoid receptors, and lower renal Klotho levels.

Conclusion: Our study provides a timeline for the development of cardiorenal dysfunction with aging, and documents that increasing dietary salt accelerates the age-induced phenotypes. In addition, we propose albuminuria as a prognostic biomarker for the future development of hypertension. Last, we identified functional and molecular markers of renal dysfunction that associate with long-term dietary salt loading.

Keywords: Aging; Albuminuria; Blood pressure; Dietary sodium.