Gal-Moscovici Anca, Sprague Stuart M
Hadassah Hospital Medical Center, Hebrew University, Ein Keren, Jerusalem, Israel.
J Bone Miner Res. 2007 Dec;22 Suppl 2:V91-4. doi: 10.1359/jbmr.07s203.
Chronic kidney disease (CKD) has been recognized as a significant public health problem, with approximately 20 million Americans, or approximately 11% of the adult population, currently living with CKD. A significant source of morbidity associated with CKD is the development of disturbances of mineral metabolism, which occurs in virtually all patients during the progression of their disease, and is associated with bone loss and fractures, cardiovascular disease, immune suppression, and increased mortality. As kidney disease develops, there is decreased functional renal mass and a tendency to retain phosphorus. The reduction in functional renal mass and the retained phosphorus act to reduce renal 1alpha-hydroxylase activity and thus the renal production of calcitriol. Further compensation to maintain normal serum calcium and phosphorus homeostasis includes increased production and release of PTH and potentially other phosphaturic factors, such as fibroblast growth factor-23 (FGF23). This increase in FGF23 contributes to maintain normal serum phosphate independent of PTH but may worsen calcitriol deficiency by also inhibiting renal 1alpha-hydroxylase activity. The decrease in calcitriol also results in promoting further hyperparathyroidism and parathyroid gland hyperplasia, because calcitriol normally inhibits the production of prepro-PTH and parathyroid cell proliferation.
慢性肾脏病（CKD）已被公认为一个重大的公共卫生问题，目前约有2000万美国人，即约11%的成年人口患有CKD。与CKD相关的一个重要发病源是矿物质代谢紊乱的发生，几乎所有患者在疾病进展过程中都会出现这种情况，它与骨质流失和骨折、心血管疾病、免疫抑制以及死亡率增加有关。随着肾脏疾病的发展，功能性肾实质减少，磷潴留倾向增加。功能性肾实质的减少和潴留的磷会降低肾脏1α-羟化酶的活性，从而减少肾脏中骨化三醇的生成。为维持正常的血清钙和磷稳态而进行的进一步代偿包括甲状旁腺激素（PTH）以及可能的其他排磷因子（如成纤维细胞生长因子-23，FGF23）的生成和释放增加。FGF23的这种增加有助于在不依赖PTH的情况下维持正常的血清磷酸盐水平，但也可能通过抑制肾脏1α-羟化酶活性而加重骨化三醇缺乏。骨化三醇的减少还会导致进一步的甲状旁腺功能亢进和甲状旁腺增生，因为骨化三醇通常会抑制前甲状旁腺素原的生成和甲状旁腺细胞的增殖。
