Acidosis and Urinary Calcium Excretion: Insights from Genetic Disorders

Abstract

Metabolic acidosis is associated with increased urinary calcium excretion and related sequelae, including nephrocalcinosis and nephrolithiasis. The increased urinary calcium excretion induced by metabolic acidosis predominantly results from increased mobilization of calcium out of bone and inhibition of calcium transport processes within the renal tubule. The mechanisms whereby acid alters the integrity and stability of bone have been examined extensively in the published literature. Here, after briefly reviewing this literature, we consider the effects of acid on calcium transport in the renal tubule and then discuss why not all gene defects that cause renal tubular acidosis are associated with hypercalciuria and nephrocalcinosis.

Nephrolithiasis secondary to inherited defects in the thick ascending loop of henle and connecting tubules

“…While nephrocalcinosis is almost a universal finding in inherited dRTA, the prevalence of nephrolithiasis is unknown and has not been reported in large cohort studies [105,104]. Hypercalciuria (due to increased release of Ca from bone and decreased renal Ca reabsorption), hypocitraturia (due to augmented proximal tubular citrate reabsorption) and alkaline urinary pH are the three principal prolithogenic factors in dRTA and favor CaP precipitation [117][118][119][120]. The typical renal calculus in dRTA consists of carbonate apatite and has a characteristic morphology with a smooth aspect and a glazed brown-yellow appearance with tiny cracks [121,122].…”

Treatment and long-term outcome in primary distal renal tubular acidosis

“…Hypokalaemia is common and has been attributed to the altered balance between potassium and proton secretion in the collecting duct in exchange for sodium reabsorption, potentially augmented by increased aldosterone levels (7,8). The excess acid in the blood is mainly buffered by the bone, leading to release of calcium from the skeleton, which, together with impaired tubular calcium reabsorption in acidosis, results in hypercalciuria that can be associated with nephrocalcinosis and/or nephrolithiasis (9). Faltering growth is a common presenting symptom in children with dRTA (10).…”

Circulating osteocalcin: A potential predictor of ketosis in type 2 diabetes

“…A possible explanation for the low 25(OH)D 3 level is that the acidotic state leads to a decreased vitamin‐D binding protein levels hence a corresponding decreasing in measured levels of 25(OH)D 3 . Negative calcium balance may be due to hypercalciuria induced by metabolic acidosis . Additionally, poor gastrointestinal absorption may also contribute to negative calcium balance …”