Renal Section, Denver VA Medical Center, Denver, CO; Division of Renal Diseases and Hypertension, University of Colorado Denver Anschutz Medical Campus, Aurora, CO.
Division of Nephrology and Hypertension, Department of Medicine and Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.
Am J Kidney Dis. 2018 Jan;71(1):27-34. doi: 10.1053/j.ajkd.2017.06.017. Epub 2017 Aug 9.
Vascular calcification is common among patients with chronic kidney disease (CKD), and it is associated with all-cause and cardiovascular disease mortality. Deoxycholic acid, a metabolite of circulating bile acids, is elevated in CKD and induces vascular mineralization and osteogenic differentiation in animal models.
Cohort analysis of clinical trial participants.
SETTING & PARTICIPANTS: 112 patients with moderate to severe CKD (estimated glomerular filtration rate, 20-45mL/min/1.73m) who participated in a randomized controlled study to examine the effects of phosphate binders on vascular calcification.
Serum deoxycholic acid concentration.
Baseline coronary artery calcification (CAC) volume score and bone mineral density (BMD) and change in CAC volume score and BMD after 9 months.
Deoxycholic acid was assayed in stored baseline serum samples using liquid chromatography-tandem mass spectrometry, CAC was measured using a GE-Imitron C150 scanner, and BMD was determined using computed tomographic scans of the abdomen with calibrated phantom of known density.
Higher serum deoxycholic acid concentrations were significantly correlated with greater baseline CAC volume and lower baseline BMD. After adjusting for demographics, coexisting illness, body mass index, estimated glomerular filtration rate, and concentrations of circulating markers of mineral metabolism, including serum calcium, phosphorus, vitamin D, parathyroid hormone, and fibroblast growth factor 23, a serum deoxycholic acid concentration > 58ng/mL (the median) was positively associated with baseline CAC volume (β=0.71; 95% CI, 0.26-1.16; P=0.003) and negatively associated with baseline BMD (β = -20.3; 95% CI, -1.5 to -39.1; P=0.04). Serum deoxycholic acid concentration > 58ng/mL was not significantly associated with change in CAC volume score after 9 months (β=0.06; 95% CI, -0.09 to 0.21; P=0.4). The analysis for the relationship between baseline deoxycholic acid concentrations and change in BMD after 9 months was not statistically significant, but was underpowered.
The use of nonfasting serum samples is a limitation because deoxycholic acid concentrations may vary based on time of day and dietary intake. Few trial participants with complete data to evaluate the change in CAC volume score (n=75) and BMD (n=59). No data for changes in deoxycholic acid concentrations over time.
Among patients with moderate to severe CKD, higher serum deoxycholic acid concentrations were independently associated with greater baseline CAC volume score and lower baseline BMD.
血管钙化在慢性肾脏病（CKD）患者中很常见，与全因和心血管疾病死亡率相关。脱氧胆酸是循环胆汁酸的代谢产物，在 CKD 中升高，并在动物模型中诱导血管矿化和成骨分化。
临床试验参与者的队列分析。
112 名患有中重度 CKD（估计肾小球滤过率 20-45mL/min/1.73m）的患者参加了一项随机对照研究，以检查磷酸盐结合剂对血管钙化的影响。
血清脱氧胆酸浓度。
基线冠状动脉钙化（CAC）体积评分和骨密度以及 9 个月后 CAC 体积评分和骨密度的变化。
使用液相色谱-串联质谱法检测储存的基线血清样本中的脱氧胆酸，使用 GE-Imitron C150 扫描仪测量 CAC，使用腹部计算机断层扫描和校准的已知密度体模测量骨密度。
较高的血清脱氧胆酸浓度与较大的基线 CAC 体积和较低的基线 BMD 显著相关。在校正人口统计学、并存疾病、体重指数、估计肾小球滤过率以及包括血清钙、磷、维生素 D、甲状旁腺激素和成纤维细胞生长因子 23 在内的循环矿物质代谢标志物的浓度后，血清脱氧胆酸浓度>58ng/mL（中位数）与基线 CAC 体积呈正相关（β=0.71；95%CI，0.26-1.16；P=0.003），与基线 BMD 呈负相关（β=-20.3；95%CI，-1.5 至-39.1；P=0.04）。血清脱氧胆酸浓度>58ng/mL 与 9 个月后 CAC 体积评分的变化无显著相关性（β=0.06；95%CI，-0.09 至 0.21；P=0.4）。对 9 个月后基线脱氧胆酸浓度与 BMD 变化之间关系的分析不具有统计学意义，但统计效能不足。
使用非空腹血清样本是一个限制，因为脱氧胆酸浓度可能因一天中的时间和饮食摄入而有所不同。评估 CAC 体积评分变化（n=75）和 BMD 变化（n=59）的试验参与者数据不完整。没有脱氧胆酸浓度随时间变化的数据。
在患有中重度 CKD 的患者中，较高的血清脱氧胆酸浓度与较大的基线 CAC 体积评分和较低的基线 BMD 独立相关。
