Familiar hyperkalaemic acidosis.
We evaluated a 26-year-old man with hyperkalaemic acidosis, apparently inherited as an autosomal dominant trait. Type II pseudohypoaldosteronism was suggested by normal aldosterone production and renal sodium conservation. The cause of acidosis in this syndrome is unknown. Both urinary ammonium excretion and bicarbonate threshold were low during hyperkalaemia. After correcting the hyperkalaemia ammonium excretion was normal, but bicarbonate threshold remained low. Maximum bicarbonate reabsorption, urine to blood pCO2 gradients, and minimum urine pH were normal. These findings suggest that hyperkalaemia might contribute to the acidosis by limiting urinary buffer, but that the primary defect is reduced mineralocorticoid effect on hydrogen ion secretion. When the poorly reabsorbed anion, sulphate, was infused, hydrogen ion and potassium secretion were normal. When the relatively reabsorbable anion, chloride, was infused, potassium secretion was decreased. These findings suggest that the attenuated mineralocorticoid effect on hydrogen ion secretion is due to increased reabsorptive avidity for chloride in the distal nephron. To determine if this defect caused resistance to mineralocorticoid we increased mineralocorticoid by dietary sodium restriction and later administered desoxycorticosterone and fludrocortisone. Both endogenous and exogenous mineralocorticoid caused increased net acid excretion and corrected the acidosis, indicating no resistance to mineralocorticoid. Hydrochlorothiazide 50 mg daily promptly corrected the acidosis and the hyperkalaemia by increased urinary potassium excretion. We conclude that the acidosis of type II pseudohypoaldosteronism is due in part to attenuation of the voltage-dependent moiety of mineralocorticoid-driven acidification caused by enhanced distal chloride reabsorption. Suppression of ammoniagenesis by hyperkalaemia exaggerates the acidosis. The acidosis and hyperkalemia are corrected by hydrochlorothiazide.
D000136:Acid-Base Equilibrium / Q000187:drug effects; D000141:Acidosis, Renal Tubular / Q000097:blood / Q000235:genetics*; D000328:Adult; D000450:Aldosterone / Q000097:blood; D003900:Desoxycorticosterone / Q000494:pharmacology; D004039:Diet, Sodium-Restricted; D005665:Furosemide / Q000494:pharmacology; D006801:Humans; D006852:Hydrochlorothiazide / Q000494:pharmacology; D006947:Hyperkalemia / Q000097:blood / Q000235:genetics*; D008297:Male; D010375:Pedigree; D011187:Posture; D011188:Potassium / Q000097:blood; D012083:Renin / Q000097:blood; D012964:Sodium / Q000097:blood; D013431:Sulfates / Q000494:pharmacology
D013431:Sulfates; D006852:Hydrochlorothiazide; C012036:sodium sulfate; D003900:Desoxycorticosterone; D000450:Aldosterone; D005665:Furosemide; D012964:Sodium; D012083:Renin; D011188:Potassium