Baerg R D, Kimberg D V, Gershon E
J Clin Invest. 1970 Jun;49(6):1288-300. doi: 10.1172/JCI106341.
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 D(3): it is reversed by massive doses of the vitamin. Neither the metabolism of vitamin D(3) 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.
慢性肾功能不全患者的肠道钙吸收常受抑制。此外,与慢性肾病相关的钙吸收不良和骨营养不良通常对维生素D“抵抗”;然而,这种抵抗的基础尚不确定。其他人最近的研究强调了维生素D代谢异常在解释钙吸收改变和尿毒症综合征伴随的明显维生素D抵抗中的作用。目前用实验性尿毒症动物模型进行的研究表明,十二指肠肠囊体外钙的主动转运存在缺陷。这种异常并非由于与肾功能不全相关的半饥饿状态,且给予生理剂量的维生素D(3)无法纠正:大剂量维生素可使其逆转。在本研究采用的条件下,肾功能不全既不影响维生素D(3)的代谢,也不影响十二指肠黏膜中钙结合蛋白的活性水平。本研究结果强烈表明,除了最近提出的涉及干扰维生素D代谢的机制外,肾功能不全还以一种与维生素D作用方向相反、且独立于与维生素或其代谢产物直接相互作用的方式影响钙转运的细胞机制。