title: Evidence for increased renal tubule and parathyroid gland sensitivity to serum calcium in human idiopathic hypercalciuria.
abstract: Patients with idiopathic hypercalciuria (IH) have decreased renal calcium reabsorption, most marked in the postprandial state, but the mechanisms are unknown. We compared 29 subjects with IH and 17 normal subjects (N) each fed meals providing identical amounts of calcium. Urine and blood samples were collected fasting and after meals. Levels of three candidate signalers, serum calcium (SCa), insulin (I), and plasma parathyroid hormone (PTH), did not differ between IH and N either fasting or fed, but all changed with feeding, and the change in SCa was greater in IH than in N. Regression analysis of fractional excretion of calcium (FECa) was significant for PTH and SCa in IH but not N. With the use of multivariable analysis, Sca entered the model while PTH and I did not. To avoid internal correlation we decomposed FECa into its independent terms: adjusted urine calcium (UCa) and UFCa molarity. Analyses using adjusted Uca and unadjusted Uca parallel those using FECa, showing a dominant effect of SCa with no effect of PTH or I. The effect of SCa may be mediated via vitamin D receptor-stimulated increased abundance of basolateral Ca receptor, which is supported by the fact PTH levels also seem more responsive to serum Ca in IH than in N. Although our data support an effect of SCa on FECa and UCa, which is more marked in IH than in N, it can account for only a modest fraction of the meal effect, perhaps 10-20%, suggesting additional mediators are also responsible for the exaggerated postprandial hypercalciuria seen in IH.
authors.affiliation: Nephrology Section MC 5100, Univ. of Chicago Medicine, 5841 South Maryland Ave., Chicago, IL 60637. eworcest@bsd.uchicago.edu.
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Worcester
authors.forename: Kristin J
authors.initials: KJ
authors.lastname: Bergsland
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Gillen
authors.forename: Fredric L
authors.initials: FL
authors.lastname: Coe
mesh_terms: D000328:Adult; D002118:Calcium / Q000097:blood* / Q000652:urine*; D005215:Fasting; D005260:Female; D006801:Humans; D053565:Hypercalciuria / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D007684:Kidney Tubules / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010280:Parathyroid Glands / Q000502:physiology*; D010281:Parathyroid Hormone / Q000097:blood*; D019518:Postprandial Period
chemical_list: D007328:Insulin; D010281:Parathyroid Hormone; D002118:Calcium
keywords: hypercalciuria; kidney stones; parathyroid hormone; serum calcium