Renin-Angiotensin-Aldosterone System

Whether estimated by the plasma renin level or renin activity, the basal renin level decreases by 30 to 50% in the elderly despite normal levels of renin substrate. Certain therapies and measures (eg, salt restriction, diuretic administration, upright posture), all designed to augment renin secretion, produce increases in plasma renin concentrations that remain 30 to 50% lower than those observed in younger persons under the same conditions.

The lower renin levels in elderly persons result in 30 to 50% reductions in plasma aldosterone levels; the secretion and clearance rates of aldosterone are comparably reduced. Plasma aldosterone and cortisol responses after corticotropin stimulation are not impaired with age. Therefore, aldosterone deficiency in the elderly is usually a function of the coexisting renin deficiency and is not secondary to intrinsic adrenal changes.

Age-related decreases in renin and aldosterone levels contribute to the development of various fluid and electrolyte abnormalities. For example, elderly persons on salt-restricted diets have a decreased ability to conserve sodium. Decreased angiotensin II production, which also can result from a lack of renin stimulation, has been reported to seriously impair tubular concentrating ability. Together, these conditions contribute to the increased tendency of elderly persons to develop volume depletion and dehydration. Still, the most important cause of dehydration, especially the hypernatremic dehydration that occurs when water loss is greater than sodium loss, is the loss of thirst, which is characteristic in the elderly in response to increased serum osmolality or volume contraction. Loss of thirst is especially important when elderly persons are confronted with an illness that increases demands for or limits the intake of salt and water (eg, an infection).

Age-related decreases in renin and aldosterone also contribute to the elderly's increased risk of hyperkalemia in various clinical settings.

Through its action on the distal renal tubule, aldosterone increases sodium reabsorption and facilitates potassium excretion. Aldosterone provides one of the major protective mechanisms in preventing hyperkalemia during periods of potassium challenge. Because glomerular filtration rate (another major determinant of potassium excretion) is impaired in the elderly, plasma potassium levels are likely to become seriously elevated, especially if gastrointestinal bleeding (a major abnormal source of potassium) occurs or if potassium salts are given orally or IV. The tendency toward hyperkalemia is enhanced by acidosis because the aging kidney is slow to correct an increase in acid load, resulting in prolonged depression of serum pH and a shift of potassium out of cells. Potent antagonists of renal potassium excretion (eg, spironolactone, triamterene, most nonsteroidal anti-inflammatory drugs, -blockers, angiotensin-converting enzyme inhibitors) should be administered cautiously to the elderly. The concomitant administration of these drugs with potassium supplements should be avoided.