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. 1974 Aug;54(2):387–400. doi: 10.1172/JCI107774

The Hypercalciurias CAUSES, PARATHYROID FUNCTIONS, AND DIAGNOSTIC CRITERIA

Charles Y C Pak 1, Masahiro Ohata 1, E Clint Lawrence 1, W Snyder 1
PMCID: PMC301566  PMID: 4367891

Abstract

The causes for the hypercalciuria and diagnostic criteria for the various forms of hypercalciuria were sought in 56 patients with hypercalcemia or nephrolithiasis (Ca stones), by a careful assessment of parathyroid function and calcium metabolism. A study protocol for the evaluation of hypercalciuria, based on a constant liquid synthetic diet, was developed. In 26 cases of primary hyperparathyroidism, characteristic features were: hypercalcemia, high urinary cyclic AMP (cAMP, 8.58±3.63 SD μmol/g creatinine; normal, 4.02±0.70 μmol/g creatinine), high immunoreactive serum parathyroid hormone (PTH), hypercalciuria, the urinary Ca exceeding absorbed Ca from intestinal tract (CaA), high fasting urinary Ca (0.2 mg/mg creatinine or greater), and low bone density by 125I photon absorption. The results suggest that hypercalciuria is partly secondary to an excessive skeletal resorption (resorptive hypercalciuria). The 22 cases with renal stones had normocalcemia, hypercalciuria, intestinal hyperabsorption of calcium, normal or low serum PTH and urinary cAMP, normal fasting urinary Ca, and normal bone density. Since their CaA exceeded urinary Ca, the hypercalciuria probably resulted from an intestinal hyperabsorption of Ca (absorptive hypercalciuria). The primacy of intestinal Ca hyperabsorption was confirmed by responses to Ca load and deprivation under a metabolic dietary regimen. During a Ca load of 1,700 mg/day, there was an exaggerated increase in the renal excretion of Ca and a suppression of cAMP excretion. The urinary Ca of 453±154 SD mg/day was significantly higher than the control group's 211±42 mg/day. The urinary cAMP of 2.26±0.56 μmol/g creatinine was significantly lower than in the control group. In contrast, when the intestinal absorption of calcium was limited by cellulose phosphate, the hypercalciuria was corrected and the suppressed renal excretion of cAMP returned towards normal. Two cases with renal stones had normocalcemia, hypercalciuria, and high urinary cAMP or serum PTH. Since CaA was less than urinary Ca, the hypercalciuria may have been secondary to an impaired renal tubular reabsorption of Ca (renal hypercalciuria). Six cases with renal stones had normal values of serum Ca, urinary Ca, urinary cAMP, and serum PTH (normocalciuric nephrolithiasis). Their CaA exceeded urinary Ca, and fasting urinary Ca and bone density were normal. The results support the proposed mechanisms for the hypercalciuria and provide reliable diagnostic criteria for the various forms of hypercalciuria.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arnaud C. D., Tsao H. S., Littledike T. Radioimmunoassay of human parathyroid hormone in serum. J Clin Invest. 1971 Jan;50(1):21–34. doi: 10.1172/JCI106476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. CAMERON J. R., SORENSON J. MEASUREMENT OF BONE MINERAL IN VIVO: AN IMPROVED METHOD. Science. 1963 Oct 11;142(3589):230–232. doi: 10.1126/science.142.3589.230. [DOI] [PubMed] [Google Scholar]
  3. Chase L. R., Aurbach G. D. Parathyroid function and the renal excretion of 3'5'-adenylic acid. Proc Natl Acad Sci U S A. 1967 Aug;58(2):518–525. doi: 10.1073/pnas.58.2.518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Coe F. L., Canterbury J. M., Firpo J. J., Reiss E. Evidence for secondary hyperparathyroidism in idiopathic hypercalciuria. J Clin Invest. 1973 Jan;52(1):134–142. doi: 10.1172/JCI107156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Forland M., Strandjord N. M., Paloyan E., Cox A. Bone density studies in primary hyperparathyroidism. Arch Intern Med. 1968 Sep;122(3):236–240. [PubMed] [Google Scholar]
  6. Gilman A. G. A protein binding assay for adenosine 3':5'-cyclic monophosphate. Proc Natl Acad Sci U S A. 1970 Sep;67(1):305–312. doi: 10.1073/pnas.67.1.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. HEANEY R. P., SKILLMAN T. G. SECRETION AND EXCRETION OF CALCIUM BY THE HUMAN GASTROINTESTINAL TRACT. J Lab Clin Med. 1964 Jul;64:29–41. [PubMed] [Google Scholar]
  8. HENNEMAN P. H., BENEDICT P. H., FORBES A. P., DUDLEY H. R. Idiopathic hypercaicuria. N Engl J Med. 1958 Oct 23;259(17):802–807. doi: 10.1056/NEJM195810232591702. [DOI] [PubMed] [Google Scholar]
  9. Kaminsky N. I., Broadus A. E., Hardman J. G., Jones D. J., Jr, Ball J. H., Sutherland E. W., Liddle G. W. Effects of parathyroid hormone on plasma and urinary adenosine 3',5'-monophosphate in man. J Clin Invest. 1970 Dec;49(12):2387–2395. doi: 10.1172/JCI106458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Liberman U. A., Sperling O., Atsmon A., Frank M., Modan M., Vries A. D. Metabolic and calcium kinetic studies in idiopathic hypercalciuria. J Clin Invest. 1968 Dec;47(12):2580–2590. doi: 10.1172/JCI105940. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Massry S. G., Friedler R. M., Coburn J. W. Excretion of phosphate and calcium. Physiology of their renal handling and relation to clinical medicine. Arch Intern Med. 1973 Jun;131(6):828–859. doi: 10.1001/archinte.131.6.828. [DOI] [PubMed] [Google Scholar]
  12. McCance R. A., Widdowson E. M., Lehmann H. The effect of protein intake on the absorption of calcium and magnesium. Biochem J. 1942 Sep;36(7-9):686–691. doi: 10.1042/bj0360686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Murad F., Pak C. Y. Urinary excretion of adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate. N Engl J Med. 1972 Jun 29;286(26):1382–1387. doi: 10.1056/NEJM197206292862604. [DOI] [PubMed] [Google Scholar]
  14. PRONOVE P., BELL N. H., BARTTER F. C. Production of hypercalciuria by phosphorus deprivation on a low calcium intake: a new clinical test for hyperparathyroidism. Metabolism. 1961 May;10:364–371. [PubMed] [Google Scholar]
  15. Pak C. Y., Delea C. S., Bartter F. C. Successful treatment of recurrent nephrolithiasis (calcium stones) with cellulose phosphate. N Engl J Med. 1974 Jan 24;290(4):175–180. doi: 10.1056/NEJM197401242900401. [DOI] [PubMed] [Google Scholar]
  16. Pak C. Y., East D. A., Sanzenbacher L. J., Delea C. S., Bartter F. C. Gastrointestinal calcium absorption in nephrolithiasis. J Clin Endocrinol Metab. 1972 Aug;35(2):261–270. doi: 10.1210/jcem-35-2-261. [DOI] [PubMed] [Google Scholar]
  17. Pak C. Y., East D., Sanzenbacher L., Ruskin B., Cox J. A simple and reliable test for the diagnosis of hyperparathyroidism. Arch Intern Med. 1972 Jan;129(1):48–55. [PubMed] [Google Scholar]
  18. Pak C. Y. Sodium cellulose phosphate: mechanism of action and effect on mineral metabolism. J Clin Pharmacol New Drugs. 1973 Jan;13(1):15–27. doi: 10.1002/j.1552-4604.1973.tb00064.x. [DOI] [PubMed] [Google Scholar]
  19. ROSE G. A., REED G. W., SMITH A. H. ISOTOPIC METHOD FOR MEASUREMENT OF CALCIUM ABSORPTION FROM THE GASTRO-INTESTINAL TRACT. Br Med J. 1965 Mar 13;1(5436):690–692. doi: 10.1136/bmj.1.5436.690. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Reis E., Canterbury J. M. A radioimmunoassay for parathyroid hormone in man. Proc Soc Exp Biol Med. 1968 Jun;128(2):501–504. doi: 10.3181/00379727-128-33050. [DOI] [PubMed] [Google Scholar]
  21. Samachson J., Scheck J., Spencer H. Radiocalcium absorption at different times of day. Am J Clin Nutr. 1966 Jun;18(6):449–451. doi: 10.1093/ajcn/18.6.449. [DOI] [PubMed] [Google Scholar]
  22. Taylor A. L., Davis B. B., Pawlson L. G., Josimovich J. B., Mintz D. H. Factors influencing the urinary excretion of 3',5'-adenosine monophosphate in humans. J Clin Endocrinol Metab. 1970 Mar;30(3):316–324. doi: 10.1210/jcem-30-3-316. [DOI] [PubMed] [Google Scholar]
  23. Wills M. R., Gill J. R., Jr, Bartter F. C. The interrelationships of calcium and sodium excretions. Clin Sci. 1969 Dec;37(3):621–630. [PubMed] [Google Scholar]
  24. Wills M. R., Pak C. Y., Hammond W. G., Bartter F. C. Normocalcemic primary hyperparathyroidism. Am J Med. 1969 Sep;47(3):384–391. doi: 10.1016/0002-9343(69)90222-8. [DOI] [PubMed] [Google Scholar]
  25. Wills M. R., Zisman E., Wortsman J., Evens R. G., Pak C. Y., Bartter F. C. The measurement of intestinal calcium absorption by external radioisotope counting: application to study of nephrolithiasis. Clin Sci. 1970 Jul;39(1):95–106. doi: 10.1042/cs0390095. [DOI] [PubMed] [Google Scholar]

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