Members of the family under study have a variant of Bartter's syndrome characterized by renal potassium wasting and hypokalemia, mild extracellular metabolic alkalosis, hypercalciuria, hypocitraturia, and progressively worsening nephrocalcinosis and renal cystic disease. We postulate that the progressive renal damage is a consequence of the metabolic derangements resulting from intracellular potassium depletion and attendant potassium-depletion-induced intracellular acidosis. To test this hypothesis, we propose to orally administer to one subject supplements of potassium as the citrate salt chronically in doses sufficient to correct recognized biochemical markers of the potassium-depletion-induced metabolic derangements, and to follow the course of his progressive renal disease. This will be a 15-day diet-controlled inpatient metabolic study to examine the effect of orally administered potassium citrate on plasma and urine acid-base and electrolyte composition, creatinine clearance, and urine citrate excretion, in an affected member of this family with an inherited form of a variant of Bartter's syndrome. The GCRC nursing and laboratory staff will obtain and process the arterialized blood and urine collections and the dietary staff will provide a constant diet. Administration of potassium citrate to patients with nephrocalcinotic cystic variants of Bartter's syndrome is a novel approach to treatment based on understanding the pathophysiology of the complications of renal potassium wasting. Demonstration of the safety of potassium citrate administration in one member of the family, and its efficacy in correcting hypokalemia, reducing urinary calcium excretion, and increasing urinary citrate excretion in the short term would provide rationale for testing the effect of chronic potassium citrate administration on the progression of his renal disease (nephrocalcinosis, cyst formation, glomerular filtration rate). Justification would also be provided for recommending a trial of potassium citrate administration to the other affected family members and their physicians, and for consideration by other investigators of the appropriateness of the treatment in their kindreds.
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