Role of aldosterone in the control of sodium excretion in patients with advanced chronic renal failure

The factors that regulate sodium and potassium excretion in patients with chronic renal failure have not been fully clarified. The role of aldosterone in the control of sodium and potassium excretion was therefore examined in eight normokalemic patients with chronic renal failure (mean creatinine clearance, 14.3 ml/min). With a normal sodium intake (120 to 151 mEq/24 hr), plasma aldosterone levels were above normal in five of the eight patients and in five of six patients with a creatinine clearance of less than 15 ml/min. Aldosterone levels were further increased in all eight patients by assumption of an upright posture (from a mean of 523 to 1,454 pg/ml, P<0.01). When seven of the patients were placed on a low sodium diet (10 to 20 mEq/24 hr), mean plasma aldosterone levels increased from 587 to 2,393 pg/ml; (P<0.02). The low sodium diet was also associated with a fall in mean body of 2.1 kg and a decrease in plasma sodium concentration from 140 to 131 mEq/liter (P<0.005)in all patients. To further define the physiologic role of the high aldosterone levels, we administered the aldosterone antagonist, spironolactone (300 mg/24 hr), to the patients while they were on a normal sodium diet. The administration of spironolactone was associated with a significant natriuresis, as mean sodium excretion increased from 142 to 173 mEq/24 hr (P<0.02)and mean body wt decreased by 1.4 kg (P<0.02). With the administration of spironolactone, the mean potassium excretion decreased from 47 to 41 mEq/24 hr (P<0.05) as plasma potassium rose from 4.6 to 5.4 mEq/liter (P<0.01). We conclude that (1) many normokalemic patients with advanced renal failure (creatinine clearance <15 ml/min) are in a state of hyperaldosteronism, (2) nevertheless, the secretion of aldosterone in these patients can be stimulated further by posture and volume depletion, and (3) aldosterone plays a physiologic role not only in the maintenance of serum potassium concentration but also as an antinatriuretic force in advanced chronic renal failure.