Martin-Malo A, Rodriguez M, Martinez M E, Torres A, Felsenfeld A J
Unit of Investigation, Hospital Universitario Reina Sofia Cordoba, Spain.
Nephrol Dial Transplant. 1996 Aug;11(8):1553-8.
Renal failure results in decreased calcitriol production, a key factor in the development of secondary hyperparathyroidism. Phosphorus accumulation and high parathyroid hormone (PTH) levels, both inherent to renal failure, have different effects on calcitriol production; moreover, dietary calcium loading may have a separate inhibitory effect on calcitriol production. This study was designed to evaluate the relative effects of PTH and dietary phosphorus and calcium on serum calcitriol levels.
Renal failure was surgically induced and rats were divided into normal, moderate renal failure, and advanced renal failure based on the serum creatinine. Each group was subdivided and received either a high-phosphorus diet (HPD, 0.6% Ca, 1.2% P) or high-calcium diet (HCaD, 1.2% Ca, 0.6% P) for 14-16 days to determine the relative effects of dietary calcium and phosphorus loading on serum calcitriol. In addition the effect of PTH and phosphorus on calcitriol stimulation was determined with a 48-h PTH infusion combined with either a low (0.16%) or high (1%) phosphorus diet; both diets had negligible calcium (< 0.05%).
With decreasing renal function, PTH increased and was greater in rats fed the HPD than the HCaD; serum calcitriol decreased as renal function decreased and was lower in normal rats and rats with moderate renal failure fed a HCaD (P < 0.01). The calcitriol response to a PTH infusion decreased as renal function decreased (P < 0.05) but was greater on a low- (0.16%) than a high- (1%) phosphorus diet (P < 0.05).
Dietary calcium loading either directly decreases serum calcitriol or acts by modifying the stimulatory effect of PTH; the stimulatory effect of PTH on serum calcitriol is modified by dietary phosphorus; in moderate renal failure, serum calcitriol levels depend on a complex interaction between PTH and dietary calcium and phosphorus; and in advanced renal failure, serum calcitriol levels are low and are difficult to stimulate, presumably because of the loss of renal mass.
肾衰竭导致骨化三醇生成减少，这是继发性甲状旁腺功能亢进发展的关键因素。肾衰竭固有的磷蓄积和高甲状旁腺激素（PTH）水平对骨化三醇生成有不同影响；此外，饮食中钙负荷可能对骨化三醇生成有单独的抑制作用。本研究旨在评估PTH、饮食中的磷和钙对血清骨化三醇水平的相对影响。
通过手术诱导肾衰竭，并根据血清肌酐将大鼠分为正常组、中度肾衰竭组和重度肾衰竭组。每组再细分，分别给予高磷饮食（HPD，0.6%钙，1.2%磷）或高钙饮食（HCaD，1.2%钙，0.6%磷）14 - 16天，以确定饮食中钙和磷负荷对血清骨化三醇的相对影响。此外，通过48小时输注PTH并结合低磷（0.16%）或高磷（1%）饮食来确定PTH和磷对骨化三醇刺激的影响；两种饮食中的钙含量均可忽略不计（<0.05%）。
随着肾功能下降，PTH升高，且喂食HPD的大鼠中的PTH高于喂食HCaD的大鼠；血清骨化三醇随着肾功能下降而降低，正常大鼠和中度肾衰竭且喂食HCaD的大鼠中的血清骨化三醇水平较低（P<0.01）。随着肾功能下降，对PTH输注的骨化三醇反应降低（P<0.05），但在低磷（0.16%）饮食时的反应大于高磷（1%）饮食时的反应（P<0.05）。
饮食中钙负荷要么直接降低血清骨化三醇，要么通过改变PTH的刺激作用来发挥作用；PTH对血清骨化三醇的刺激作用会受到饮食中磷的影响；在中度肾衰竭时，血清骨化三醇水平取决于PTH与饮食中钙和磷之间的复杂相互作用；在重度肾衰竭时，血清骨化三醇水平较低且难以被刺激，可能是由于肾实质的丧失。
