title: Calciuric response to an acute acid load in healthy subjects and hypercalciuric calcium stone formers.
abstract: Excessive animal protein consumption is associated with a greater risk of occurrence of renal calcium stone, presumably because of the attendant endogenous acid production. Indeed, chronic acid load enhances urinary calcium excretion possibly through an increased bone calcium release. Because acute studies are best designed to elucidate the mechanism, renal or extra renal, underlying hypercalciuria in the setting of enhanced acid load, we examined the response of 9 healthy adults (8 males, 1 female, aged 38 +/- 3 years, weight 67 +/- 2 kg) and 34 hypercalciuric recurrent calcium stone formers (31 males, 3 females, aged 44 +/- 2 years, weight 72 +/- 2 kg), without any associated disease, to an oral acid load (NH4Cl 2 mmol/kg body wt). After an overnight fast, each patient and control was studied during one one-hour period before and three two-hour periods after their intake of the acid load. An additional group of four time-control subjects (4 males, aged 33 +/- 2 years, weight 66 +/- 2 kg) was studied as the experimental groups except that they did not receive the acid load. On baseline, the three groups exhibited similar glomerular filtration rates, net acid excretions, and plasma calcium and magnesium concentrations. However, fasting urine calcium and magnesium excretions were higher in hypercalciuric calcium stone formers than in healthy control or time-control subjects. In time-control subjects, plasma acid base status, net acid excretion, filtered loads of calcium and magnesium, and urinary calcium and magnesium excretions remained unchanged all over the study. By contrast, after the oral acute acid load, net acid excretion increased and urinary pH decreased similarly in patient and control groups; glomerular filtration rate did not change, as well as plasma calcium and magnesium concentrations. Nevertheless, urinary calcium and magnesium excretions markedly increased, in both groups, independently of changes in tubular sodium handling and in plasma parathyroid hormone concentration. The increase in urinary calcium and magnesium excretions that occurred in the absence of any change in the filtered load of calcium and magnesium was therefore mediated by a decrease in tubular calcium and magnesium reabsorption, independent of PTH, but dependent on changes in net acid excretion. A positive linear relationship between urinary calcium and magnesium excretions suggested that the target tubular site for acid load was the thick ascending limb of Henle's loop. Finally, a negative linear relationship was demonstrated between the acid load-induced increase in urinary calcium excretion and fasting urinary calcium excretion; indeed, the lowest calciuric responses were observed in patients with the highest fasting urinary calcium excretion. Thus there was no additional effect of the acid load-induced inhibition on intrinsic defect in tubular calcium reabsorption which suggests that the tubular target site for acid load and the site of calcium transport defect in idiopathic hypercalciuria may be the same.
authors.affiliation: Département de Physiologie, Université Pierre et Marie Curie, Hôpital Broussais, Institut National de la Santé et de la Recherche Médicale Unité 356, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Houillier
authors.forename: M
authors.initials: M
authors.lastname: Normand
authors.forename: M
authors.initials: M
authors.lastname: Froissart
authors.forename: A
authors.initials: A
authors.lastname: Blanchard
authors.forename: P
authors.initials: P
authors.lastname: Jungers
authors.forename: M
authors.initials: M
authors.lastname: Paillard
mesh_terms: D000138:Acidosis / Q000652:urine*; D000143:Acids / Q000494:pharmacology / Q000652:urine; D000328:Adult; D001639:Bicarbonates / Q000097:blood; D002118:Calcium / Q000652:urine*; D003710:Demography; D005260:Female; D006801:Humans; D007669:Kidney Calculi / Q000737:chemistry*; D008138:Loop of Henle / Q000187:drug effects / Q000378:metabolism; D008297:Male
chemical_list: D000143:Acids; D001639:Bicarbonates; D002118:Calcium