Studies of the Mechanism by Which Chronic Metabolic Acidosis Augments Urinary Calcium Excretion in Man*

TLDR

The authors performed renal clearance studies in nine healthy adults and four hypoparathyroid patients, inducing stable metabolic acidosis with NH₄Cl or acetazolamide and measuring calcium handling before, during, and after the acidotic challenge. Metabolic acidosis increased urinary calcium excretion by reducing renal tubular reabsorption, as evidenced by higher urine Ca despite a lower filtered load, persistence during recovery, and lack of association with natriuresis or anion excretion, findings replicated in hypoparathyroid patients.

Abstract

We carried out clearance studies in nine healthy adults and four patients with hypoparathyroidism before and after inducing stable metabolic acidosis with either NH(4)Cl or acetazolamide. Clearances were repeated in seven normal subjects and three of the patients 3 days after stopping these agents.During acidosis in the normal subjects, serum ultrafilterable calcium concentration rose significantly, but inulin clearance fell to a greater extent, so that the calculated filtered load of calcium fell significantly. Despite this, urinary calcium excretion rose. Urinary calcium excretion remained elevated in the recovery studies when the serum ultrafilterable calcium concentration and filtered load of calcium had returned to control levels. Evidence is presented indicating that the increased calcium excretion which occurred during acidosis and recovery clearances was not due to natriuresis or to increased excretion of complexing anions. The comparable results in the four patients with hypoparathyroidism, two of whom also had hypothyroidism, suggest that the capacity to alter secretion rates of parathyroid hormone, thyrocalcitonin or both is not a critical determinant of the augmented rates of calcium excretion during acidosis.We conclude that metabolic acidosis produces increased urinary calcium excretion by causing decreased renal tubular calcium reabsorption. Evidence is presented which suggests that this is a direct effect of metabolic acidosis on metabolic processes within renal tubular cells.