The aging hypertensive kidney: pathophysiology and therapeutic options

Abstract

The aging kidney undergoes hemodynamic changes characterized by reductions in glomerular filtration rate and effective renal plasma flow. These functional changes are associated with loss of renal mass related to changes in the intrarenal vasculature. The reduced glomerular filtration surface area and subsequent microcirculatory adaptations enhance the risk for development of renal diseases associated with systemic diseases. Hypertensive nephrosclerosis accounts for 26% of all end-stage renal disease in the United States; the median age of those affected is 67 years. Hemodynamic and structural changes observed in the essential hypertensive kidney suggest an accentuation of the physiologic aging process. Initially observed hemodynamic changes, which may be reversible with specific drug therapy, suggest that excessive production of angiotensin II plays a role. Progressive renal impairment may occur despite control of systemic hypertension. Renal protection appears to require therapeutic normalization of both systemic and glomerular capillary pressures. The latter may depend on a drug's ability to attenuate the intrarenal effects of angiotensin II on the renal microcirculation. Drug classes with renal protective potential include angiotensin-converting enzyme inhibitors and calcium antagonists. However, long-term clinical trials are required to assess the potential advantages of specific drug therapies in preventing the development and/or progression of hypertensive arteriolar nephrosclerosis.