Lopez-Hilker S, Dusso A S, Rapp N S, Martin K J, Slatopolsky E
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Am J Physiol. 1990 Sep;259(3 Pt 2):F432-7. doi: 10.1152/ajprenal.1990.259.3.F432.
Phosphorus is a well-known modulator of renal 1 alpha-hydroxylase activity. In early and moderate renal failure it is proposed that dietary Pi reduction ameliorates secondary hyperparathyroidism through increased circulating levels of calcitriol (i.e, 1 alpha, 25-dihydroxycholecalciferol). To gain further insight into the mechanisms by which a low-Pi diet ameliorates secondary hyperparathyroidism in advanced renal insufficiency, studies were performed in five dogs before and 6 mo after the induction of uremia by 5/6 nephrectomy. Glomerular filtration rate decreased from 69.0 +/- 2.3 to 10.5 +/- 0.5 ml/min, immunoreactive parathyroid hormone (irPTH) increased from 66.0 +/- 8.8 to 321.0 +/- 46 pg/ml, and calcitriol decreased from 39.0 +/- 10.4 to 27.0 +/- 6.2 pg/ml. Thereafter, dietary Pi was decreased gradually every 2 wk from 0.95% to 0.6, 0.45, and 0.3%, respectively. Dietary Ca was reduced from 1.6 to 0.6% to prevent development of hypercalcemia. Ionized Ca (ICa) decreased from 5.4 +/- 0.04 to 5.2 +/- 0.05 mg/dl (P less than 0.02), and plasma Pi decreased from 6.3 +/- 0.7 to 4.7 +/- 0.2 mg/dl (P less than 0.05). Calcitriol remained low (23.3 +/- 4.7 pg/ml). However, irPTH gradually decreased from 321.0 +/- 46.0 to 94.7 +/- 22.9 pg/ml (P less than 0.005). These studies indicate that a decrease in dietary Pi from 0.95 to 0.3% suppressed irPTH by approximately 70%. Reduction of irPTH was observed in the absence of a concomitant increase in levels of ICa or calcitriol. These studies suggest that reduction in dietary Pi in advanced renal insufficiency improves secondary hyperparathyroidism by a mechanism that is independent of the levels of calcitriol or plasma ICa.
磷是一种已知的肾1α-羟化酶活性调节剂。在早期和中度肾衰竭中，有人提出减少饮食中的磷通过增加循环中骨化三醇（即1α，25-二羟胆钙化醇）的水平来改善继发性甲状旁腺功能亢进。为了进一步深入了解低磷饮食改善晚期肾功能不全继发性甲状旁腺功能亢进的机制，对5只狗在5/6肾切除诱导尿毒症之前和之后6个月进行了研究。肾小球滤过率从69.0±2.3降至10.5±0.5 ml/分钟，免疫反应性甲状旁腺激素（irPTH）从66.0±8.8升至321.0±46 pg/ml，骨化三醇从39.0±10.4降至27.0±6.2 pg/ml。此后，饮食中的磷每2周逐渐从0.95%分别降至0.6%、0.45%和0.3%。饮食中的钙从1.6%降至0.6%以防止高钙血症的发生。离子钙（ICa）从5.4±0.04降至5.2±0.05 mg/dl（P<0.02），血浆磷从6.3±0.7降至4.7±0.2 mg/dl（P<0.05）。骨化三醇仍保持在低水平（23.3±4.7 pg/ml）。然而，irPTH逐渐从321.0±46.0降至94.7±22.9 pg/ml（P<0.005）。这些研究表明，饮食中的磷从0.95%降至0.3%可使irPTH降低约70%。在未伴随ICa或骨化三醇水平升高的情况下观察到irPTH降低。这些研究提示，晚期肾功能不全时减少饮食中的磷通过一种独立于骨化三醇或血浆ICa水平的机制改善继发性甲状旁腺功能亢进。
