Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.
Clin J Am Soc Nephrol. 2012 May;7(5):820-8. doi: 10.2215/CJN.11721111. Epub 2012 Mar 1.
Primary prevention of disordered mineral metabolism in CKD necessitates knowledge of its early pathophysiology. This study evaluated daily fluctuations in mineral metabolites in patients with CKD stages 3 and 4 before and after short-term calcitriol treatment and tested the effects of dietary calcium and calcitriol supplementation on these parameters in the dynamic postprandial setting.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Twelve CKD patients received calcitriol (0.25 μg daily for 1 week) with hourly assessments of mineral metabolites made throughout the day and in the context of standardized meals before and after treatment. Calcium content (250 versus 500 mg) in the breakfasts constituted the dietary calcium intervention. Twelve healthy volunteers were used as controls.
At baseline, compared with controls, fasting CKD subjects had higher parathyroid hormone and fibroblast growth factor 23 levels and greater fractional excretion of phosphate. After breakfast, urinary calcium excretion increased and parathyroid hormone levels dipped transiently in both groups, but they rose soon thereafter, reaching higher peaks in CKD. Calcitriol decreased fasting parathyroid hormone levels, and when combined with dietary calcium load, it normalized the postprandial parathyroid and calcemic responses. Daily variability in mineral metabolites was preserved in CKD before and after calcitriol. Fibroblast growth factor 23 levels increased after calcitriol, although the response was heterogeneous.
Short-term treatment with calcitriol and dietary calcium supplementation normalizes the parathyroid and calcemic postprandial responses in patients with CKD, in whom the diurnal rhythms of mineral metabolites are preserved. Future studies should investigate the variable fibroblast growth factor 23 response to calcitriol in CKD.
慢性肾脏病(CKD)患者发生矿物质代谢紊乱的一级预防需要了解其早期的病理生理学变化。本研究评估了 CKD 3-4 期患者在短期骨化三醇治疗前后矿物质代谢物的日波动情况,并在动态餐后环境中检验了膳食钙和骨化三醇补充对这些参数的影响。
设计、地点、参与者和测量方法:12 例 CKD 患者接受骨化三醇(0.25 μg/日,治疗 1 周)治疗,治疗前后全天及标准化餐时每小时评估矿物质代谢物。早餐中的钙含量(250 毫克和 500 毫克)构成了膳食钙干预。12 名健康志愿者作为对照组。
与对照组相比,基线时 CKD 患者的甲状旁腺激素和成纤维细胞生长因子 23 水平较高,磷酸盐的分数排泄率较大。两组早餐后尿钙排泄增加,甲状旁腺激素水平短暂下降,但随后迅速上升,CKD 组上升幅度更高。骨化三醇降低了空腹甲状旁腺激素水平,与膳食钙负荷联合应用时,可使餐后甲状旁腺和血钙反应正常化。在接受骨化三醇治疗前后,CKD 患者的矿物质代谢物日间变异性得以保留。虽然骨化三醇的作用存在异质性,但它能增加成纤维细胞生长因子 23 水平。
短期骨化三醇和膳食钙补充可使 CKD 患者的甲状旁腺和血钙的餐后反应正常化,且矿物质代谢物的昼夜节律在 CKD 患者中得以保留。未来的研究应探讨 CKD 患者对骨化三醇可变的成纤维细胞生长因子 23 反应。