Evidence base treatment of renal osteodistropy

24-羟基酶是分布于1-羟基-25-二羟基维生素D_3[1-α，25(α)_2D_3]靶组织中的一种酶。该酶的两个功能已被报道：一是产生24，25-二羟基维生素D_3[24，25(OH)_2D_3]；二是使1，25(OH)_2D_3失活。为了阐明α24在体内的其他生理作用，我们先前建立了组成性表达该基因的大鼠。这些转基因(TG)大鼠出现了意想不到的表型，例如低水平的血浆24，25(OH)_2D_3、血脂和蛋白尿。在本研究中，我们阐明了导致低血浆24，25(OH)_2D_3水平和骨丢失的机制。TG大鼠排出大量维生素D结合蛋白(DBP)，这与白蛋白的丢失是一致的。在TG大鼠中，作为内吞受体的megalin在肾脏中的表达模式与野生型大鼠相同，该受体负责重新摄取尿蛋白如DBP和白蛋白。排出的白蛋白似乎竞争结合和重吸收DBP-25-羟基维生素D_3[25(OH)D_3]复合体，导致25(OH)D_3丢失到尿中，继而降低血浆24，25(OH)_2D_3。在这个突出的肾炎大鼠模型中，补充25(OH)D_3能有效地防止肾功能不全早期的骨丢失。

24-Hydroxylase (CYP24) is an enzyme distributed in the target tissues of 1α,25-dihydroxyvitamin D_3 [1α,25(OH)_2D_3]. Two functions for this enzyme have been reported: One is production of 24,25-dihydroxyvitamin D_3 [24,25(OH)_2D_3] and the other is inactivation of 1α,25(OH)_2D_3. To elucidate other physiologic roles of CYP24 in vivo, we previously generated rats that constitutively express the CYP24 gene. These transgenic (Tg) rats developed unexpected phenotypes, such as low plasma levels of 24,25(OH)_2D_3, lipidemia, and albuminuria. In this study, we elucidated the mechanisms for inducing low plasma 24,25(OH)_2D_3 levels and bone loss. Tg rats excreted massive amounts of vitamin D binding protein (DBP), which coincided with the loss of albumin. In Tg rats, the renal expression pattern of megalin, which serves as an endocytotic receptor responsible for the reuptake of urinary proteins such as DBP and albumin, was identical to that of the wild-type rats. Excreted albumin appeared to compete for the binding and reabsorption of the DBP-25-hydroxyvitamin D_3 [25(OH)D_3] complex with megalin, resulting in a loss of 25(OH)D_3 into the urine and subsequent reduction of plasma 24,25(OH)_2D_3. In this prominent rat model of nephritis, supplementation of 25(OH)D_3 was effective in preventing bone loss in an early stage of renal insufficiency.