Division of Nephrology, Ambroise Paré Hospital, APHP, Versailles Saint-Quentin-en-Yvelines University (Paris-Ile-de-France-Ouest University, UVSQ), 9 avenue Charles de Gaulle, 92104, Boulogne Billancourt and Villejuif Cedex, France.
Inserm U-1018, Team 5, Paris-Sud University (UPS) and Versailles Saint-Quentin-en-Yvelines University (Paris-Ile-de-France-Ouest University, UVSQ), Villejuif, France.
J Nephrol. 2017 Oct;30(5):629-634. doi: 10.1007/s40620-017-0397-7. Epub 2017 Apr 12.
Chronic kidney disease (CKD) is complicated by disturbances of mineral and bone metabolism which start early in the course of the disease. It has long been assumed that high turnover bone lesions induced by secondary hyperparathyroidism are the predominant type of renal osteodystrophy from the start. However, there is increasing evidence in favor of the view that in early CKD stages low bone turnover is prevailing, with adynamic bone disease being the predominant form. Since serum parathyroid hormone levels increase progressively early on, and the most probable explanation is resistance to the skeletal action of this hormone. An early inhibition of the Wnt pathway with an increase in sclerostin and other inhibitors of Wnt signaling may be involved. Finally, a variety of other uremic toxins such as indoxyl sulfate and phosphate may play an important role in the pathogenesis of the low turnover bone disease observed in early stages of CKD. The optimal strategies to prevent and to treat adynamic bone disease in incipient CKD yet need to be defined. Targeting uremic toxins such as sclerostin, phosphate, and indoxyl sulfate may be relevant.
慢性肾脏病(CKD)常伴有矿物质和骨代谢紊乱,这些紊乱在疾病早期就已出现。长期以来,人们一直认为继发性甲状旁腺功能亢进引起的高转换骨病变是肾性骨营养不良的主要类型。然而,越来越多的证据表明,在 CKD 的早期阶段,低转换骨占主导地位,以动力缺失性骨病为主。由于血清甲状旁腺激素水平在早期逐渐升高,最可能的解释是该激素对骨骼的作用产生了抵抗。早期 Wnt 通路的抑制可能与骨硬化蛋白(sclerostin)和其他 Wnt 信号抑制剂的增加有关。最后,各种其他尿毒症毒素,如硫酸吲哚酚和磷酸盐,可能在 CKD 早期观察到的低转换骨病的发病机制中发挥重要作用。然而,仍需要确定预防和治疗早期 CKD 中动力缺失性骨病的最佳策略。针对尿毒症毒素,如骨硬化蛋白、磷酸盐和硫酸吲哚酚,可能具有相关性。