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.

Evidence of activation of the renal glutamate dehydrogenase pathway in intact acidotic dogs.

To determine if activity of the renal glutamate dehydrogenase (GD) pathway changes during chronic acidosis in intact dogs, we assessed the deamination of glutamate formed within renal cells during glutamine and alanine infusions. Infusing glutamine into chronically acidotic, normal and acutely alkalotic dogs enhanced renal ammonia production; more was formed as glutamine loading increased. In 4 acidotic dogs, the ratio of ammonia produced to glutamine extracted by the kidneys during exogenous glutamine loading was 1.93 compared with 0.99 for 5 alkalotic dogs and 1.23 for 2 control dogs. Little glutamate and alanine were released into the renal vein in acidotic dogs, whereas over 50% of the exogenous glutamine extracted in acutely alkalotic dogs could be accounted for as glutamate and alanine released into the renal vein. Renal glutamate concentrations were not elevated in acidosis compared with alkalosis despite greater deamidation. When glutamine infusions increased renal ammoniagenesis in acutely alkalotic and control dogs to levels seen in chronically acidotic dogs receiving no exogenous glutamine, approximately 4 to 6 times more glutamate was released from the kidneys. Infusing alanine into 7 chronically acidotic dogs enhanced ammoniagenesis significantly (p less than 0.01), but lesser augmentation was seen in 3 control dogs and no augmentation was seen in 6 acutely alkalotic dogs. The increases were secondary to enhanced glutamate deamination, not secondary to any changes in glutamine extraction and/or transaminase activity. We conclude that the glutamate dehydrogenase pathway is more active in intact acidotic dogs than it is in control and alkalotic dogs.

Tubulointerstitial diseases.

This group of disorders has a number of causes. Early in the course of the disease, tubular malfunction is out of proportion to glomerular disease. The early presentation may be inability to concentrate urine, salt wasting, distal or proximal renal tubular acidosis and/or Fanconi's syndrome. With early diagnosis and treatment, progression of the renal disorder can be prevented or at least delayed. One can easily discontinue the antibiotic or analgesic, remove the heavy metal, treat the electrolyte abnormality, lower the uric acid or remove the genitourinary tract obstruction.