Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1970 Jun;49(6):1288–1300. doi: 10.1172/JCI106341

Effect of renal insufficiency on the active transport of calcium by the small intestine

Richard D Baerg 1,2,3, Daniel V Kimberg 1,2,3, Elaine Gershon 1,2,3
PMCID: PMC322593  PMID: 5422027

Abstract

The intestinal absorption of calcium is often depressed in patients with chronic renal insufficiency. Furthermore, the malabsorption of calcium and the osteodystrophy which occur in association with chronic renal disease are often “resistant” to vitamin D; the basis for this resistance remains uncertain however. Recent studies by others have emphasized the role of an abnormality in the metabolism of vitamin D in accounting for the alterations in the calcium absorption and the apparent vitamin D-resistance which accompany the uremic syndrome.

The present studies with an experimentally uremic animal model demonstrate a defect in the active transport of calcium by duodenal gut sacs in vitro. This abnormality is not due to the semistarvation associated with renal insufficiency and cannot be corrected by the administration of physiologic amounts of vitamin D3: it is reversed by massive doses of the vitamin.

Neither the metabolism of vitamin D3 nor the levels of calcium binding protein activity in the duodenal mucosa are affected by renal insufficiency under the conditions employed in the present studies. The results of the present studies strongly suggest that in addition to the recently proposed mechanism involving an interference with the metabolism of vitamin D renal insufficiency also affects the cellular mechanisms for calcium transport in a manner which, while opposite in direction to that of vitamin D, is independent of a direct interaction with the vitamin or its metabolites.

Full text

PDF
1288

Selected References

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

  1. Avioli L. V., Birge S., Lee S. W., Slatopolsky E. The metabolic fate of vitamin D3-3H in chronic renal failure. J Clin Invest. 1968 Oct;47(10):2239–2252. doi: 10.1172/JCI105909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Avioli L. V., Scott S., Lee S. W., De Luca H. F. Intestinal calcium absorption: nature of defect in chronic renal disease. Science. 1969 Nov 28;166(3909):1154–1156. doi: 10.1126/science.166.3909.1154. [DOI] [PubMed] [Google Scholar]
  3. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  4. BOUCOT N. G., NURSER E. K., MERRILL J. P. Carbohydrate metabolism in rats with chronic uremia. Am J Physiol. 1960 Apr;198:797–799. doi: 10.1152/ajplegacy.1960.198.4.797. [DOI] [PubMed] [Google Scholar]
  5. Blunt J. W., Tanaka Y., DeLuca H. F. The biological activity of 25-hydroxycholecalciferol, a metabolite of vitamin D3. Proc Natl Acad Sci U S A. 1968 Oct;61(2):717–718. doi: 10.1073/pnas.61.2.717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. CRANE R. K., MANDELSTAM P. The active transport of sugars by various preparations of hamster intestine. Biochim Biophys Acta. 1960 Dec 18;45:460–476. doi: 10.1016/0006-3002(60)91482-7. [DOI] [PubMed] [Google Scholar]
  7. Clayton E. M., Seligson D., Seligson H. Inhibition of protein synthesis by N-methyl-2-pyridone-5-formamidoacetic acid and other compounds isolated from uremic patients. Yale J Biol Med. 1965 Dec;38(3):273–281. [PMC free article] [PubMed] [Google Scholar]
  8. DENT C. E., HARPER C. M., PHILPOT G. R. The treatment of renal-glomerular osteodystrophy. Q J Med. 1961 Jan;30:1–31. [PubMed] [Google Scholar]
  9. DeLuca H. F. Mechanism of action and metabolic fate of vitamin D. Vitam Horm. 1967;25:315–367. doi: 10.1016/s0083-6729(08)60039-4. [DOI] [PubMed] [Google Scholar]
  10. DeLuca H. F. Recent advances in the metabolism and function of vitamin D. Fed Proc. 1969 Sep-Oct;28(5):1678–1689. [PubMed] [Google Scholar]
  11. Dell R. B., Winters R. W. Lactate gradients in the kidney of the dog. Am J Physiol. 1967 Aug;213(2):301–307. doi: 10.1152/ajplegacy.1967.213.2.301. [DOI] [PubMed] [Google Scholar]
  12. Ebel J. G., Taylor A. N., Wasserman R. H. Vitamin D-induced calcium-binding protein of intestinal mucosa. Relation to vitamin D dose level and lag period. Am J Clin Nutr. 1969 Apr;22(4):431–436. doi: 10.1093/ajcn/22.4.431. [DOI] [PubMed] [Google Scholar]
  13. FLETCHER R. F., JONES J. H., MORGAN D. B. BONE DISEASE IN CHRONIC RENAL FAILURE. Q J Med. 1963 Oct;32:321–329. [PubMed] [Google Scholar]
  14. HICKS J. M., YOUNG D. S., WOOTTON I. D. THE EFFECT OF URAEMIC BLOOD CONSTITUENTS ON CERTAIN CEREBRAL ENZYMES. Clin Chim Acta. 1964 Mar;9:228–235. doi: 10.1016/0009-8981(64)90099-3. [DOI] [PubMed] [Google Scholar]
  15. KESSNER D. M., EPSTEIN F. H. EFFECT OF RENAL INSUFFICIENCY ON GASTROINTESTINAL TRANSPORT OF CALCIUM. Am J Physiol. 1965 Jul;209:141–145. doi: 10.1152/ajplegacy.1965.209.1.141. [DOI] [PubMed] [Google Scholar]
  16. KIMBERG D. V., SCHACHTER D., SCHENKER H. Active transport of calcium by intestine: effects of dietary calcium. Am J Physiol. 1961 Jun;200:1256–1262. doi: 10.1152/ajplegacy.1961.200.6.1256. [DOI] [PubMed] [Google Scholar]
  17. Kaye M., Silverman M. Calcium metabolism in chronic renal failure. J Lab Clin Med. 1965 Oct;66(4):535–548. [PubMed] [Google Scholar]
  18. Krawitt E. L., Schedl H. P. In vivo calcium transport by rat small intestine. Am J Physiol. 1968 Feb;214(2):232–236. doi: 10.1152/ajplegacy.1968.214.2.232. [DOI] [PubMed] [Google Scholar]
  19. Lund J., DeLuca H. F. Biologically active metabolite of vitamin D3 from bone, liver, and blood serum. J Lipid Res. 1966 Nov;7(6):739–744. [PubMed] [Google Scholar]
  20. McCormick G. J., Shear L., Barry K. G. Alteration of hepatic protein synthesis in acute uremia. Proc Soc Exp Biol Med. 1966 May;122(1):99–102. doi: 10.3181/00379727-122-31062. [DOI] [PubMed] [Google Scholar]
  21. Neale R. J., Wiseman G. Active transport of L-glucose by isolated small intestine of the dietary-restricted rat. J Physiol. 1968 Oct;198(3):601–611. [PMC free article] [PubMed] [Google Scholar]
  22. Olson E. B., DeLuca H. F. 25-hydroxycholecalciferol: direct effect on calcium transport. Science. 1969 Jul 25;165(3891):405–407. doi: 10.1126/science.165.3891.405. [DOI] [PubMed] [Google Scholar]
  23. Ponchon G., Kennan A. L., DeLuca H. F. "Activation" of vitamin D by the liver. J Clin Invest. 1969 Nov;48(11):2032–2037. doi: 10.1172/JCI106168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. ROSCOE M. H. The estimation of creatinine in serum. J Clin Pathol. 1953 Aug;6(3):201–207. doi: 10.1136/jcp.6.3.201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Relman A. S. The acidosis of renal disease. Am J Med. 1968 May;44(5):706–713. doi: 10.1016/0002-9343(68)90252-0. [DOI] [PubMed] [Google Scholar]
  26. SAIFER A., GERSTENFELD S. The photometric microdetermination of blood glucose with glucose oxidase. J Lab Clin Med. 1958 Mar;51(3):448–460. [PubMed] [Google Scholar]
  27. SCHACHTER D., DOWDLE E. B., SCHENKER H. Accumulation of Ca45 by slices of the small intestine. Am J Physiol. 1960 Feb;198:275–279. doi: 10.1152/ajplegacy.1960.198.2.275. [DOI] [PubMed] [Google Scholar]
  28. SCHACHTER D., DOWDLE E. B., SCHENKER H. Active transport of calcium by the small intestine of the rat. Am J Physiol. 1960 Feb;198:263–268. doi: 10.1152/ajplegacy.1960.198.2.263. [DOI] [PubMed] [Google Scholar]
  29. SCHACHTER D., KIMBERG D. V., SCHENKER H. Active transport of calcium by intestine: action and bio-assay of vitamin D. Am J Physiol. 1961 Jun;200:1263–1271. doi: 10.1152/ajplegacy.1961.200.6.1263. [DOI] [PubMed] [Google Scholar]
  30. SCHACHTER D., ROSEN S. M. Active transport of Ca45 by the small intestine and its dependence on vitamin D. Am J Physiol. 1959 Feb;196(2):357–362. doi: 10.1152/ajplegacy.1959.196.2.357. [DOI] [PubMed] [Google Scholar]
  31. STANBURY S. W., LUMB G. A. Metabolic studies of renal osteodystrophy. I. Calcium, phosphorus and nitrogen metabolism in rickets, osteomalacia and hyperparathyroidism complicating chronic uremia and in the osteomalacia of the adult Fanconi syndrome. Medicine (Baltimore) 1962 Feb;41:1–34. [PubMed] [Google Scholar]
  32. Stanbury S. W. Bone disease in uremia. Am J Med. 1968 May;44(5):714–724. doi: 10.1016/0002-9343(68)90253-2. [DOI] [PubMed] [Google Scholar]
  33. Taylor A. N., Wasserman R. H. Vitamin D3-induced calcium-binding protein: partial purification, electrophoretic visualization, and tissue distribution. Arch Biochem Biophys. 1967 Mar;119(1):536–540. doi: 10.1016/0003-9861(67)90488-2. [DOI] [PubMed] [Google Scholar]
  34. Trummel C. L., Raisz L. G., Blunt J. W., Deluca H. F. 25-Hydroxycholecalciferol: stimulation of bone resorption in tissue culture. Science. 1969 Mar 28;163(3874):1450–1451. doi: 10.1126/science.163.3874.1450. [DOI] [PubMed] [Google Scholar]
  35. WILSON T. H., WISEMAN G. The use of sacs of everted small intestine for the study of the transference of substances from the mucosal to the serosal surface. J Physiol. 1954 Jan;123(1):116–125. doi: 10.1113/jphysiol.1954.sp005036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Wasserman R. H., Taylor A. N. Vitamin D-dependent calcium-binding protein. Response to some physiological and nutritional variables. J Biol Chem. 1968 Jul 25;243(14):3987–3993. [PubMed] [Google Scholar]
  37. Wasserman R. H., Taylor A. N. Vitamin d3-induced calcium-binding protein in chick intestinal mucosa. Science. 1966 May 6;152(3723):791–793. doi: 10.1126/science.152.3723.791. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES