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青少年首次肾移植后骨密度和微结构的变化:一项前瞻性研究。

Changes in bone density and microarchitecture in adolescents undergoing a first kidney transplantation: a prospective study.

机构信息

Centre de Référence Des Maladies Rénales Rares, Centre de Référence Des Maladies Rares du Calcium Et du Phosphore, Filières Maladies Rares ORKiD, OSCAR Et ERK-Net, Hôpital Femme Mère Enfant, 69677, Bron, France.

Clinical Investigation Center (CIC 1407), Hospices Civils de Lyon, 69677, Bron, France.

出版信息

Eur J Pediatr. 2024 Dec;183(12):5303-5312. doi: 10.1007/s00431-024-05777-z. Epub 2024 Oct 9.

Abstract

PURPOSE

Mineral bone disorder associated with chronic kidney disease (CKD-MBD) frequently persists after kidney transplantation (KTx), being due to pre-existing CKD-MBD, immunosuppressive therapies, and post-KTx hypophosphatemia. This study aimed to evaluate bone biomarkers and microarchitecture using high resolution peripheral quantitative computed tomography (HR-pQCT) at the time of KTx and 6 months thereafter and to compare these results with those of matched healthy controls (HC).

METHODS

This study presented the single-center subgroup of patients aged between 10 and 18 years included in the prospective "Bone Microarchitecture in the Transplant Patient" study (TRANSOS-NCT02729142). Patients undergoing a first KTx were matched (1:2) with HC from the "Vitamin D, Bones, Nutritional and Cardiovascular Status" cohort (VITADOS) on sex, pubertal stage, and age.

RESULTS

At a median (interquartile range, IQR) age of 15 [13; 16] years, 19 patients (6 girls, 7 pre-emptive KTx, 7 steroid-sparing immunosuppressive strategies) underwent a first KTx, with a median [IQR] parathyroid hormone level of 1.9 [1.4; 2.9] the upper limit of normal (ULN). Higher total and trabecular bone densities, along with superior trabecular microarchitecture, were observed at KTx compared to HC. Six months post-KTx, patients had significantly impaired trabecular parameters at the radius, while results were not significantly different at the weight-bearing tibia, neither cortical parameters at both sites. Six months post-KTx, 6 (32%) patients still present with metabolic acidosis, 10 (53%) persistent hyperparathyroidism (always < 2 ULN), and 5 (26%) elevated FGF23 levels; 11 (58%) received phosphate supplementation.

CONCLUSIONS

Bone density and microarchitecture at the time of KTx were superior compared to HC, but radial trabecular bone microarchitecture impairment observed 6 months post-KTx may reflect subtle albeit present post-KTx CKD-MBD. What is Known? • Mineral bone disorder associated with chronic kidney disease (CKD-MBD) frequently persists after kidney transplantation (KTx) and is associated with morbidity. However, biochemical parameters and dual X-ray absorptiometry (DXA) are poor predictors of the underlying bone disease. What is new? • The present study on 19 adolescent KTx recipients with adequate CKD-MBD control at the time of KTx reveals no significant bone disease compared to matched healthy controls. Microarchitecture impairment observes 6 months post-KTx may reflect subtle, albeit present, post-KTx CKD-MBD.

摘要

目的

慢性肾脏病(CKD)相关的矿物质骨代谢紊乱(CKD-MBD)在肾移植(KTx)后经常持续存在,这是由于先前存在的 CKD-MBD、免疫抑制治疗和 KTx 后低磷血症。本研究旨在使用高分辨率外周定量计算机断层扫描(HR-pQCT)评估 KTx 时和之后 6 个月的骨生物标志物和微结构,并将这些结果与匹配的健康对照组(HC)进行比较。

方法

本研究展示了前瞻性“移植患者的骨微结构”研究(TRANSOS-NCT02729142)中年龄在 10 至 18 岁之间的患者的单中心亚组。接受首次 KTx 的患者按性别、青春期阶段和年龄与“维生素 D、骨骼、营养和心血管状况”队列(VITADOS)中的 HC 进行(1:2)匹配。

结果

在中位(四分位距 IQR)年龄为 15 [13;16] 岁时,19 名患者(6 名女性,7 名预先 KTx,7 名类固醇保留免疫抑制策略)接受了首次 KTx,甲状旁腺激素水平中位值 [IQR] 为 1.9 [1.4;2.9] 正常上限(ULN)。与 HC 相比,KTx 时总骨和小梁骨密度更高,小梁骨微结构更优越。KTx 后 6 个月,患者桡骨的小梁参数显著受损,而承重胫骨的结果无明显差异,两个部位的皮质参数也无明显差异。KTx 后 6 个月,6(32%)名患者仍存在代谢性酸中毒,10(53%)名患者持续存在高甲状旁腺激素(始终 < 2 ULN),5(26%)名患者 FGF23 水平升高;11(58%)名患者接受了磷酸盐补充。

结论

KTx 时的骨密度和微结构优于 HC,但 KTx 后 6 个月观察到的桡骨小梁骨微结构受损可能反映了存在但微妙的 KTx 后 CKD-MBD。已知的是什么?• 慢性肾脏病(CKD)相关的矿物质骨代谢紊乱(CKD-MBD)在肾移植(KTx)后经常持续存在,并与发病率有关。然而,生化参数和双能 X 线吸收法(DXA)是对潜在骨病的预测不佳。新的是什么?• 本研究对 19 名接受 KTx 的青少年患者进行了研究,这些患者在 KTx 时具有足够的 CKD-MBD 控制,与匹配的健康对照组相比,没有明显的骨骼疾病。KTx 后 6 个月观察到的微结构受损可能反映了存在但微妙的 KTx 后 CKD-MBD。

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