Amelioration of metabolic acidosis with fludrocortisone therapy in hyporeninemic hypoaldosteronism

N Engl J Med. 1977 Sep 15;297(11):576-83. doi: 10.1056/NEJM197709152971104.


In four patients with renal hyperchloremic acidosis and hyperkalemia, hyporeninemic hypoaldosteronism and chronic renal insufficiency (glomerular filtration rates of 13, 31, 35 and 44 ml per minute per 1.73 m2), prolonged administration of fludrocortisone increased urinary potassium and net acid excretion, corrected hyperkalemia and substantially ameliorated acidosis. Except in the patient with the lowest glomerular filtration rate, the increased net acid excretion was due mostly to increased ammonium excretion. Urine pH decreased initially in each patient, but in the three patients with the highest filtration rates, it increased subsequently as ammonium excretion increased, indicating that renal ammonia production increased. Urinary ammonium excretion correlated inversely with serum potassium concentration and did not decrease on discontinuation of therapy if hyperkalemia was prevented from recurring. In patients with renal acidosis and hyporeninemic hypoaldosteronism, administration of mineralocorticoid hormone can augment both renal hydrogen-ion secretion and, by correction of hyperkalemia, renal ammonia production, and thereby ameliorate metabolic acidosis.

MeSH terms

  • Acidosis, Renal Tubular / classification
  • Acidosis, Renal Tubular / drug therapy*
  • Acidosis, Renal Tubular / metabolism
  • Acidosis, Renal Tubular / physiopathology
  • Adult
  • Aged
  • Aldosterone / blood*
  • Ammonia / metabolism
  • Fludrocortisone / therapeutic use*
  • Glomerular Filtration Rate
  • Humans
  • Hydrogen-Ion Concentration
  • Kidney Failure, Chronic / physiopathology
  • Male
  • Middle Aged
  • Nephritis, Interstitial / metabolism
  • Nephritis, Interstitial / physiopathology
  • Potassium / blood
  • Potassium / urine
  • Renin / blood*
  • Sodium Chloride / metabolism
  • Syndrome


  • Sodium Chloride
  • Aldosterone
  • Ammonia
  • Renin
  • Potassium
  • Fludrocortisone