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

Abstract

A B S T R A C T 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 wh ch 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 D:o; 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 v tamin or its metabolites.

Effect of cortisone treatment on the active transport of calcium by the small intestine

“…The serum and homogenates of liver and intestinal mucosa were prepared and analyzed for total tritium content after combustion as previously described (21). The radioactivity present in the liver, serum, and intestinal mucosa was extracted by the method of Bligh and Dyer (30) as modified by Lund and DeLuca (31).…”

“…The chloroform extracts were concentrated by evaporation with a stream of N2 and dissolved in n-hexane for chromatographic analysis on columns of activated silicic acid using the gradient elution scheme described by Ponchon, Kennan, and DeLuca (32). Tritium present in the 10-ml fractions obtained from the columns as well as that present in samples of the aqueous extracts was measured by previously described methods (21). Internal standards of toluene-3H were added to all samples and the total disintegrations per minute were calculated.…”

Effects of Cortisone Administration on the Metabolism and Localization of 25-Hydroxycholecalciferol in the Rat

“…Homogenates of intestinal mucosa (10%), liver (20%), and kidney (15%) were prepared in 0.25 M sucrose using a Waring blendor (Waring Products Div., Dynamics Corp. of America, New Hartford, Conn.) at medium speed for 30 s. Portions of the homogenates and plasma were analyzed for total tritium content after combustion (18). Determinations of protein and DNA content were performed by previously described methods (19)(20)(21).…”

“…The gelatinous film at the top of the tubes was removed with a spatula, the supernate discarded, and the nuclear pellets resuspended in isotonic sodium chloride (4.0 ml per g wet wt of mucosa). Portions of the original mucosal homogenates and of the final nuclear suspensions were removed for determination of protein (19), RNA (25), DNA (20,21), and total radioactivity (18).…”

Biologic effects of 1,25-dihydroxycholecalciferol (a highly active vitamin D metabolite) in acutely uremic rats

“…The intestinal absorption of calcium is impaired in uremic man (1,2), and diminished calcium transport has been shown in vitro in everted duodenal sacs from rats with acute or chronic uremia (3,4). The impaired calcium absorption, the hypocalcemia, and the osteomalacia which occur in uremia can be reversed with vitamin D but only when very large doses are employed (2).…”