Dabbagh S, Epley M, Diven W, Chen T, Virji M, Ellis D
Children's Hospital of Pittsburgh, University of Pittsburgh Medical School, Pa.
Miner Electrolyte Metab. 1989;15(5):283-90.
Vitamin D deficiency is associated with a generalized aminoaciduria which has been shown to be independent of parathyroid hormone (PTH) and urinary cyclic AMP excretion. To further characterize the mechanism underlying the tubulopathy, weanling rats were placed on one of the following diets for 5 weeks: (1) control [0.7% phosphorus (P), 5.5 micrograms % vitamin D]; (2) D-P- (0.1% P, 0 vitamin D); (3) D+P- (0.1% P, 5.5 micrograms % vitamin D); (4) D-P+ (0.3% P, 0 vitamin D); (5) D-P++ (0.7% P, 0 vitamin D). All diets contained 1.2% calcium (Ca). A group of rats raised on D-P++ for 4 weeks were fed D-P- for 7 days after which they received 500 pmol of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3; SUPP] or an equal volume of the vehicle (ETH). The above diets resulted in partial vitamin D depletion in that 1,25(OH)2D levels were 50.25-79 pg/ml in the presence of very low 25(OH)D concentrations. Augmentation in the urinary excretion of 6 out of 8 amino acids measured was observed in P depletion irrespective of vitamin D status. For the most part, acute supplementation with 1,25(OH)2D3 did not ameliorate the tubulopathy. Plasma PTH and Ca concentrations remained normal in all diets, except D+P-, where plasma Ca was 15.88 +/- 0.54 mg/dl. P depletion was associated with hypercalciuria, hypophosphatemia, avid reabsorption of P and growth retardation, irrespective of vitamin D status. Using taurine as a representative of the amino affected, there was a strong correlation between urinary taurine on the one hand and dietary P content (r = 0.613), plasma P (r = 0.399) and 1,25(OH)2D levels (r = -0.576) on the other. The present study suggests that the aminoaciduria of vitamin D deficiency is not related to elevated levels of PTH. A similar defect may be produced by P depletion, suggesting the possibility of a common pathway for the effect.
维生素D缺乏与全身性氨基酸尿有关,已证明这种氨基酸尿与甲状旁腺激素(PTH)和尿中环磷酸腺苷(cAMP)排泄无关。为了进一步阐明肾小管病变的潜在机制,将断乳大鼠分为如下几组,每组给予相应饮食5周:(1)对照组[0.7%磷(P),5.5微克/毫升维生素D];(2)低维生素D低磷组(0.1% P,0维生素D);(3)低磷高维生素D组(0.1% P,5.5微克/毫升维生素D);(4)高磷低维生素D组(0.3% P,0维生素D);(5)高磷高维生素D组(0.7% P,0维生素D)。所有饮食均含1.2%钙(Ca)。一组在高磷高维生素D组喂养4周的大鼠,在接下来7天给予低维生素D低磷饮食,之后分别给予500皮摩尔1,25 - 二羟维生素D3 [1,25(OH)2D3;补充剂]或等体积溶媒(赋形剂)。上述饮食导致维生素D部分缺乏,因为在25(OH)D浓度极低时,1,25(OH)2D水平为50.25 - 79皮克/毫升。无论维生素D状态如何,磷缺乏时所测8种氨基酸中有6种的尿排泄量增加。在大多数情况下,急性补充1,25(OH)2D3并不能改善肾小管病变。除低磷高维生素D组血浆钙为15.88±0.54毫克/分升外,所有饮食组血浆PTH和钙浓度均保持正常。无论维生素D状态如何,磷缺乏与高钙尿症、低磷血症、磷的强烈重吸收和生长迟缓有关。以牛磺酸作为受影响氨基酸的代表,尿牛磺酸一方面与饮食中磷含量(r = 0.613)、血浆磷(r = 0.399)和1,25(OH)2D水平(r = -0.576)密切相关。本研究提示,维生素D缺乏所致的氨基酸尿与PTH水平升高无关。磷缺乏可能产生类似缺陷,提示存在共同作用途径的可能性。