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肾移植后骨矿物质疾病。

Bone Mineral Disease After Kidney Transplantation.

机构信息

Nephrology & Renal Transplant Department - Hospital Clínic, Barcelona, Spain.

Universidad de Barcelona, Barcelona, Spain.

出版信息

Calcif Tissue Int. 2021 Apr;108(4):551-560. doi: 10.1007/s00223-021-00837-0. Epub 2021 Mar 25.

Abstract

Chronic kidney disease-mineral bone disorder (CKD-MBD) after kidney transplantation is a mix of pre-existing disorders and new alterations. The final consequences are reflected fundamentally as abnormal mineral metabolism (hypercalcemia, hypophosphatemia) and bone alterations [high or low bone turnover disease (as fibrous osteitis or adynamic bone disease), an eventual compromise of bone mineralization, decrease bone mineral density and bone fractures]. The major cause of post-transplantation hypercalcemia is the persistence of severe secondary hyperparathyroidism, and treatment options include calcimimetics or parathyroidectomy. On turn, hypophosphatemia is caused by both the persistence of high blood levels of PTH and/or high blood levels of FGF23, with its correction being very difficult to achieve. The most frequent bone morphology alteration is low bone turnover disease, while high-turnover osteopathy decreases in frequency after transplantation. Although the pathogenic mechanisms of these abnormalities have not been fully clarified, the available evidence suggests that there are a number of factors that play a very important role, such as immunosuppressive treatment, persistently high levels of PTH, vitamin D deficiency and hypophosphatemia. Fracture risk is four-fold higher in transplanted patients compared to general population. The most relevant risk factors for fracture in the kidney transplant population are diabetes mellitus, female sex, advanced age (especially > 65 years), dialysis vintage, high PTH levels and low phosphate levels, osteoporosis, pre-transplant stress fracture and high doses or prolonged steroids therapy. Treatment alternatives for CKD-MBD after transplantation include minimization of corticosteroids, use of calcium and vitamin D supplements, antiresorptives (bisphosphonates or Denosumab) and osteoformers (synthetic parathyroid hormone). As both mineral metabolism and bone disorders lead to increased morbidity and mortality, the presence of these changes after transplantation has to be prevented (if possible), minimized, diagnosed, and treated as soon as possible.

摘要

肾移植后慢性肾脏病-矿物质和骨异常(CKD-MBD)是既有紊乱和新出现改变的混合体。最终后果主要表现为矿物质代谢异常(高钙血症、低磷血症)和骨改变[高或低骨转换疾病(如纤维性骨炎或无动力性骨病)、骨矿化最终受损、骨密度降低和骨折]。移植后高钙血症的主要原因是严重继发性甲状旁腺功能亢进的持续存在,治疗选择包括钙敏感受体激动剂或甲状旁腺切除术。相反,低磷血症是由 PTH 血水平持续升高和/或 FGF23 血水平升高引起的,其纠正非常困难。最常见的骨形态改变是低骨转换疾病,而移植后高转换骨病的频率降低。尽管这些异常的发病机制尚未完全阐明,但现有证据表明,有许多因素发挥了非常重要的作用,如免疫抑制治疗、持续高水平的 PTH、维生素 D 缺乏和低磷血症。与普通人群相比,移植患者的骨折风险增加了四倍。肾移植人群骨折的最相关危险因素包括糖尿病、女性、高龄(尤其是>65 岁)、透析时间、高 PTH 水平和低磷水平、骨质疏松症、移植前应力性骨折和大剂量或长期类固醇治疗。移植后 CKD-MBD 的治疗选择包括尽量减少皮质类固醇的使用、使用钙和维生素 D 补充剂、抗吸收剂(双膦酸盐或地舒单抗)和骨形成剂(合成甲状旁腺激素)。由于矿物质代谢和骨紊乱都会导致发病率和死亡率增加,因此移植后必须预防(如果可能)、最小化、诊断和尽快治疗这些改变。

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