Dabbagh S, Chesney R, Gusowski N, Mathews M C, Padilla M, Theissen M, Slatopolsky E
Department of Pediatrics, University of Wisconsin Center for the Health Sciences, Madison.
Miner Electrolyte Metab. 1989;15(4):221-32.
Aminoaciduria and secondary hyperparathyroidism accompany vitamin D deficiency. However, the degree of aminoaciduria and PTH elevation have not been studied relative to different calcium and phosphorus dietary intakes. Weanling rats were fed 5 vitamin D deficient diets for 4-6 weeks: very low Ca (VLC) 0.02% Ca, 0.3% P; VLC + 1,25-dihydroxyvitamin D [1,25(OH)2D3], same + 500 pmol i.p. for 2 days; low Ca (LC) 0.45% Ca, 0.3% P; very low P (VLP) 1.2% Ca, 0.1% P; high Ca (HC) 2.5% Ca, 0.3% P, and control 1.2% Ca, 0.70% P + 2.5 micrograms% vitamin D. Amino acids, serum 25-hydroxyvitamin D [25(OH)D3], 1,25(OH)2D3, and PTH, using a specific antirat PTH antibody, were measured. A significant generalized aminoaciduria (11 amino acids) was found in all vitamin D-deficient groups. Furthermore, it was independent of plasma Ca and PTH, and urinary cAMP excretion irrespective of diet. Serum 25(OH)D and 1,25(OH)2D were significantly reduced in all vitamin D-deficient groups. VLC and VLC + 1,25(OH)2D3 were associated with the highest PTH levels (10- and 13-fold increase, respectively) and urinary cAMP (2.3-fold increase in each) and the lowest serum Ca. LC rats had an 8.8- and a 1.7-fold increase in PTH and urinary cAMP, respectively. Phosphate depletion was found in VLP rats documented by insignificantly elevated PTH, normal urinary cAMP, hypercalciuria, and percent tubular reabsorption of phosphate of greater than 99%. While dietary Ca and P affect plasma and urinary Ca and P plasma PTH and urinary cAMP, it appears that dietary P affects the aminoaciduria observed in this study via mechanisms that remain unclear. The possibility that the mechanism for the tubulopathy is multifactorial should be entertained.
氨基酸尿症和继发性甲状旁腺功能亢进与维生素D缺乏症相伴。然而,尚未针对不同的钙和磷饮食摄入量研究氨基酸尿症的程度和甲状旁腺激素(PTH)升高的情况。将断奶大鼠喂食5种维生素D缺乏饮食4至6周:极低钙(VLC),钙含量0.02%,磷含量0.3%;VLC + 1,25 - 二羟基维生素D [1,25(OH)2D3],即在VLC基础上腹腔注射500 pmol,持续2天;低钙(LC),钙含量0.45%,磷含量0.3%;极低磷(VLP),钙含量1.2%,磷含量0.1%;高钙(HC),钙含量2.5%,磷含量0.3%,以及对照组,钙含量1.2%,磷含量0.70% + 2.5微克%维生素D。使用特异性抗大鼠PTH抗体测量氨基酸、血清25 - 羟基维生素D [25(OH)D3]、1,25(OH)2D3和PTH。在所有维生素D缺乏组中均发现显著的全身性氨基酸尿症(11种氨基酸)。此外,它与血浆钙和PTH以及尿cAMP排泄无关,且不受饮食影响。所有维生素D缺乏组的血清25(OH)D和1,25(OH)2D均显著降低。VLC组和VLC + 1,25(OH)2D3组的PTH水平最高(分别升高10倍和13倍),尿cAMP水平也最高(每组均升高2.3倍),而血清钙最低。LC组大鼠的PTH和尿cAMP分别升高8.8倍和1.7倍。在VLP组大鼠中发现了磷缺乏,表现为PTH轻度升高、尿cAMP正常、高钙尿症以及肾小管对磷的重吸收率大于99%。虽然饮食中的钙和磷会影响血浆和尿液中的钙和磷、血浆PTH和尿cAMP,但饮食中的磷似乎通过尚不清楚的机制影响本研究中观察到的氨基酸尿症。肾小管病变的机制可能是多因素的,这一可能性应予以考虑。