The young, the uremic and the broken.
The young, the uremic and the broken.
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年轻人、尿毒症患者和破碎者。
DOI：
10.1093/ndt/gfaa068
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Nickolas,ThomasL
中科院分区：
文献类型：
--
作者：
Khairallah,Pascale;Nickolas,ThomasL
慢性肾脏疾病（CKD）影响美国> 3700万人，全球> 8.5亿人[1，2]。CKD与许多主要并发症相关，包括骨病[3]。CKD-矿物质和骨病（MBD）在早期CKD患者中很常见，在晚期CKD和透析患者中普遍存在[3]。甲状旁腺激素，成纤维细胞生长因子23，1，25-二羟维生素D和o-klotho调节钙和磷水平，确保这些矿物质的可用性骨重建。肾性骨营养不良（ROD）是指影响肾脏无法维持矿物质代谢产物和维生素D稳态的患者的骨组织学病变[3]。在早期CKD中，MBD和伴随的ROD通常未被识别，因为疾病是无症状的。随着CKD的进展，骨丢失和骨折发生，严重程度增加，肾功能不全程度更严重[4]。在CKD患者和透析患者中进行的研究[5-10]均表明，与非CKD患者相比，肾病患者的骨折风险增加2- 100倍。1989年至1996年美国肾脏数据系统的数据报告称，接受透析的男性和女性髋部骨折的相对风险分别是一般人群的4.0倍和4.44倍[5]。令人担忧的是，尽管MBD的治疗有所改善，但髋部骨折的风险在随后的几年中显著增加[11]。髋部骨折风险在2004年达到峰值，比1996年透析患者高出43%。到2009年，风险有所下降，但仍比1996年高出27%。此外，与皮质骨缺损相关的外周骨折的发生率在同一时间间隔内翻了一番[11]。骨折会使人衰弱，并导致死亡率过高和医疗保健相关费用增加。30天和1年死亡率分别高达16%[11]和64%[7]。从这个角度来看，一般人群中髋部骨折后的1年死亡率为20%-虽然这很高，但仍明显低于CKD患者[7]。据报道，维持髋部骨折的透析患者的中位生存时间为289天，而年龄、心血管疾病和透析持续时间匹配的无髋部骨折的对照组为714天[12]。除了高死亡率外，骨折还使人衰弱，并与长期康复和长期疼痛有关。在髋部骨折的幸存者中，只有一半恢复了活动能力，并达到了骨折前的独立水平[13]。CKD 3-5D级患者骨折管理的年度成本估计高达5.56亿美元[3]。一个值得注意的知识差距是我们对CKD轻度时骨骼疾病的理解。在本期《肾脏透析移植》杂志中，Desbiens等。[14]使用CARTAGENE研究，一项前瞻性的基于人群的中年至老年人的调查，以确定早期CKD和骨折风险之间的关联。作者包括最初在CARTAGENE研究中招募的19990名个体中的19391名。他们将慢性肾脏病流行病学协作方程应用于单一肌酐测量，并将患者分为CKD类别。在纳入本研究的参与者中，9114例CKD 2级，756例CKD 3级。9114例（4.4%）CKD 2级受试者中有400例和756例（6.5%）CKD 3级受试者中有49例发生骨折。分类分析提示CKD患者骨折风险增加。
Chronic kidney disease (CKD) affects> 37 million individuals in the USA and> 850million individuals worldwide [1, 2]. CKD is associated with a number of major complications, including bone disease [3]. CKD–mineral and bone disease (MBD) is common in patients with early CKD and is universally present in patients with advanced CKD and on dialysis [3]. Parathyroid hormone, fibroblast growth factor 23, 1, 25-dihydroxyvitamin D and o-klotho regulate calcium and phosphorus levels, ensuring the availability of these minerals for bone remodeling. Renal osteodystrophy (ROD) refers to the bone histological lesions that affect patients whose kidneys are unable to maintain mineral metabolite and vitamin D homeostasis [3]. In early CKD, MBD and the accompanying ROD often go unrecognized since the disease is asymptomatic. As CKD progresses, bone loss and fractures occur and increase in severity with more severe degrees of kidney dysfunction [4]. Studies in patients with CKD and in patients on dialysis [5–10] all demonstrate that patients with kidney disease have a 2-to 100-fold increase in fracture risk compared with individuals without CKD. Data from the US Renal Data System between 1989 and 1996 reported that the relative risk of hip fractures in males and females on dialysis was, respectively, 4.0 and 4.44 times higher than that in the general population [5]. Alarmingly, despite improvements in the treatment of MBD, the risk for hip fractures increased considerably over the consequent years [11]. Hip fracture risk peaked in 2004 and was 43% higher than that in dialysis patients in 1996. The risk decreased by 2009 but remained 27% higher compared with 1996. Furthermore, the incidence of peripheral fractures, which are linked to defects in cortical bone, doubled over the same time interval [11]. Fractures are debilitating and result in excess mortality and healthcare-associated costs. The 30-day and 1-year mortality rates are as high as 16%[11] and 64%[7], respectively. To put this into perspective, the 1-year mortality rate following hip fracture in the general population is 20%—while this is high, it remains remarkably lower than for patients with CKD [7]. Dialysis patients who sustain a hip fracture were reported to have a median survival time of 289days as compared with 714 days in age-, cardiovascular disease–and dialysis duration–matched controls without a hip fracture [12]. In addition to high mortality, fractures are debilitating and associated with prolonged rehabilitation and long-term pain. Of those who survived a hip fracture, only half regained their mobility and attained their prefracture level of independence [13]. The annual cost for management of fractures in patients with CKD Grades 3–5D is estimated to be as high as US $556 million [3]. A notable knowledge gap is our understanding of bone disease when CKD is mild. In this issue of Nephrology Dialysis Transplantation, Desbiens et al.[14] used the CARTaGENE study, a prospective population-based survey of middle-aged to older individuals, to identify associations between early CKD and fracture risk. The authors included 19 391 of 19 990 individuals who were originally recruited in the CARTaGENE study. They applied the Chronic Kidney Disease Epidemiology Collaboration equation to a single creatinine measurement and stratified patients into CKD categories. Of those participants included in this investigation, 9114 had CKD Grade 2 and 756 had CKD Grade 3. Four hundred of the 9114 (4.4%) participants with CKD Grade 2 and 49 of the 756 (6.5%) participants with CKD Grade 3 sustained a fracture. The categorical analysis suggested that fracture risk was increased for CKD …