血清氧化三甲胺与慢性肾脏病患者血管钙化的相关性研究

高佩茹; 崔彩侠; 吴雪平; 陈卫东

doi:10.3969/j.issn.1671-2390.2024.08.004

血清氧化三甲胺与慢性肾脏病患者血管钙化的相关性研究

Correlation between serum trimethylamine oxide and vascular calcification in patients with chronic kidney disease

摘要

摘要:
目的探讨血清氧化三甲胺（trimethylamine oxide，TMAO）水平与慢性肾脏病（chronic kidney disease，CKD）患者血管钙化的相关性及分析CKD患者血管钙化危险因素。
方法选取蚌埠医科大学第一附属医院肾病科CKD3～5期患者118例为实验组，并将其根据腹主动脉是否钙化分为钙化组和非钙化组，另选取60例年龄、性别相匹配的健康人群为对照组。ELISA法检测血清TMAO水平，收集并比较各组临床资料。
结果（1）实验组TMAO（6.49 ± 0.76）μmol/L、血磷（1.73 ± 0.62）mmol/L、钙磷乘积（3.66 ± 1.30）mmol²/L²、甲状旁腺激素（parathyroid hormone，PTH）232.90（96.90，521.60）ng/L、碱性磷酸酶（alkaline phosphatase，ALP）72.00（55.75，113.50）U/L、血肌酐（serum creatinine，Scr）684.50（511.25，921.00）μmol/L、C反应蛋白（C-reactive protein，CRP）5.00（1.28，21.88）mg/L高于对照组,TMAO（3.53 ± 0.77）μmol/L、血磷（1.02 ± 0.19）mmol/L、钙磷乘积（2.27±0.48）mmol²/L²、PTH46.78（40.63，49.26）ng/L、ALP55.50（46.00，65.75）U/L、 Scr65.00（56.00，79.50）μmol/L、 CRP0.85（0.53，1.58）mg/L（P＜0.05）；实验组血钙（2.13 ± 0.24）mmol/L、25羟维生素D23.67（16.84，30.06）μg/L、白蛋白（albumin，Alb）（37.35 ± 5.97）g/L、估算肾小球滤过率6.02（4.70，8.50）mL·min⁻¹·(1.73m²)⁻¹低于对照组血钙（2.22 ± 0.17）mmol/L、25羟维生素D37.02（34.83，39.01）μg/L、Alb（45.59 ± 2.21）g/L、估算肾小球滤过率100.61（90.64，110.65）mL·min⁻¹·(1.73 m²)⁻¹（P＜0.05）。（2）钙化组的TMAO（6.94 ± 0.61）μmol/L、年龄（60.05 ± 11.54）岁、血液透析人数比例（60.7%）、血钙（2.18 ± 0.25）mmol/L、CRP7.00（2.22，26.08）mg/L高于非钙化组TMAO（6.01 ± 0.90）μmol/L、年龄（47.81 ± 13.51）岁、血液透析人数比例（36.8%）、血钙（2.07 ± 0.21）mmol/L、CRP4.70（0.80，19.44）mg/L（P＜0.05）；两组在性别、基础疾病（高血压、糖尿病）、血磷、钙磷乘积、PTH、ALP、Alb、总胆固醇、三酰甘油、25羟维生素D、Scr、估算肾小球滤过率上差异无统计学意义（P＞0.05）。（3）CKD患者血管钙化与年龄（r = 0.446，P＜0.001）、TMAO（r = 0.614，P＜0.001）、血钙（r = 0.192，P = 0.038）、CRP（r = 0.208，P = 0.024）水平及血液透析（r = 0.238，P = 0.009）呈正相关。（4）二元Logistics分析示，年龄（OR = 1.069，95%CI：1.025～1.115，P = 0.002）和TMAO（OR = 19.295，95%CI：5.785～64.663，P＜0.001）是CKD患者发生血管钙化的危险因素。（5）受试者工作特征曲线结果显示，年龄、TMAO单独检测血管钙化时的受试者工作特征曲线下面积（area under curve，AUC）分别为0.758、0.855，二者联合检测血管钙化的AUC值为0.892，所对应截断值为0.499，敏感性为83.6%，特异度为80.7%。
结论（1）CKD患者的血清TMAO水平与血管钙化相关，TMAO有望成为辅助诊断CKD患者血管钙化的指标，但特异度较低，需与血管钙化的其他危险因素联合。（2）CKD患者血管钙化与年龄、TMAO、血钙、CRP、血液透析有关，其中年龄和血清TMAO水平是CKD患者发生血管钙化的危险因素。

Abstract:
Objective To evaluate the associations between serum level of trimethylamine oxide （TMAO） and vascular calcification and explore the risk factors of vascular calcification in patients with chronic kidney disease （CKD）.
Methods A total of 118 CKD3-5 patients were assigned into two experimental groups of calcification and non-calcification according to whether or not there was calcification of abdominal aorta. And 60 healthy people with matching age and gender were selected as control group. Serum level of TMAO was determined by enzyme-linked immunosorbent assay （ELISA）. The clinical data of two groups were compared.
Results TMAO（6.49 ± 0.76）μmol/L, serum phosphorus (1.73±0.62)μmol/L, calcium-phosphorus product(3.66±1.30), parathyroid hormone （PTH）232.90（96.90, 521.60）ng/L, alkaline phosphatase （ALP） 72.00（55.75, 113.50）U/L, serum creatinine （Scr）684.50（511.25, 921.00）μmol/L and C-reactive protein （CRP）5.00（1.28, 21.88）mg/L were higher in experimental group than those in control group （P＜0.05）. Serum calcium（Scr）(2.13±0.24)μmol/L, 25-hydroxyvitamin D23.67（16.84, 30.06）μg/L, albumin （Alb）(37.35±5.97)g/L and estimated glomerular filtration rate （eGFR）6.02（4.70, 8.50）mL·min^-1·（1.73m²）^-1 were lower in control group （P＜0.05）. TMAO(6.01±0.90)μmol/L, age(47.81±13.51)year, proportion of hemodialysis, serum calcium (2.07±0.21)μmol/L and CRP4.70（0.80, 19.44）mg/L were higher in calcification group than that in non-calcification group （P＜0.05）. No statistically significant inter-group difference existed in gender, basic diseases （hypertension & diabetes mellitus）, blood phosphorus, calcium-phosphorus product, PTH, ALP, Alb, total cholesterol （TC）, triglyceride （TG）, 25 hydroxyvitamin D, Scr and eGFR （P＞0.05）. Vascular calcification was correlated positively with age （r = 0.446, P＜0.001）, TMAO （r = 0.614, P＜0.001）, serum calcium （r = 0.192, P = 0.038）, CRP （r = 0.208, P = 0.024） and hemodialysis （r = 0.238, P = 0.009）. Logistic analysis revealed that age （OR = 1.069, 95%CI: 1.025-1.115, P = 0.002） and TMAO （OR = 19.295, 95%CI: 5.785-64.663, P＜0.001） were the independent risk factors for vascular calcification. ROC curve indicated that area under curve （AUC） of TMAO and serum calcium were 0.855 and 0.611 respectively for diagnosing vascular calcification. AUC of combination was 0.868 with a sensitivity of 85.2% and a specificity of 71.9%.
Conclusion Serum level of TMAO is correlated with vascular calcification in CKD patients. And TMAO is expected to become an adjunct to diagnosing vascular calcification. Due to a low specificity, it should be combined with other risk factors for assessing vascular calcification. The common risk factors for vascular calcification include age, TMAO, serum calcium, CRP and hemodialysis. And age and serum level of TMAO are independent risk factors for vascular calcification in CKD patients.

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