Effect of mineralocorticoid replacement therapy on renal acid-base homeostasis in adrenalectomized patients

Abstract

Chronic balance studies were performed in six adrenalectomized patients to investigate the renal and systemic acid-base consequences of mineralocorticoid deficiency in the absence of either glucocorticoid deficiency or parenchymal renal disease. Constant glucocorticoid replacement was provided with dexamethasone, 750 to 875 micrograms/day, administered orally. Creatinine clearance averaged 98 +/- 8 ml/min/1.73 m2. Following a control period, mineralocorticoid replacement with fludrocortisone (100 to 200 micrograms/day) was either discontinued (N = 3) or initiated (N = 2). In an additional patient, mineralocorticoid replacement was initiated and sustained (5 days) by continuous i.v. infusion of aldosterone, at a dose approximating the normal secretion rate (120 micrograms/day). Net acid excretion (NAE) and plasma total carbon dioxide decreased in each patient in whom mineralocorticoid was discontinued and increased in each patient in whom mineralocorticoid was initiated. The cumulative change in NAE (sigma delta NAE) independent of direction averaged 66 +/- 20 mEq (P less than 0.05) by the fifth experimental day in the six patients, and the corresponding change in plasma total CO2 averaged 1.2 +/- 0.3 mmoles/liter (P less than 0.02). The magnitude of sigma delta NAE correlated with the basal rate of NAE (r = 0.87, P less than 0.05), which averaged 0.9 +/- 0.1 mEq/kg body wt per day. The change in plasma total CO2 correlated with sigma delta NAE (r = 0.83, P less than 0.05). The changes in NAE correlated positively with the corresponding changes in sodium balance and negatively with the corresponding changes in potassium balance. These findings provide the first evidence that renal acidification is under tonic stimulation by mineralocorticoid at levels not exceeding those in normal subjects ingesting acid-producing diets of normal sodium and potassium content. The extent to which the tonic stimulation of renal acidification is mediated by a direct effect of mineralocorticoid on renal hydrogen ion transport or by an indirect effect dependent on altered renal sodium and/or potassium transport requires further investigation. The findings implicate mineralocorticoid deficiency as a significant renal acidosis-producing condition not dependent on the presence of renal disease or glucocorticoid deficiency, and potentially amplified when endogenous acid production is increased by diet or disease.