Mohamed Osama Nady, Mohamed Marwa Ibrahim, Kamel Shaimaa F, Dardeer Ahmed M, Shehata Sayed, Mohammed Hassan Mh, Kamel Asmaa Khalf, Ismail Doaa Elzaeem, Abbas Nehal I, Abdelsamie Mohamed Ahmed, Ziady Ahmed Fathy Kamel, Sayed Manar M, Toni Nermeen Dahi Mohammed, Hafez Shaimaa Moustafa, Elsaghir Shereen Mohammed Mohammed
Department of Internal Medicine, Faculty of Medicine, Minia University, Taha Hussein street, Minia, Egypt.
Department of Cardiology, Faculty of Medicine, Minia University, Minia, Egypt.
BMC Nephrol. 2025 Apr 10;26(1):185. doi: 10.1186/s12882-025-04066-7.
There are no studies investigating the role of midkine (MK) in vascular calcification (VC) or vascular disease associated with chronic kidney disease (CKD). This study assessed serum MK level and investigated its relationship with carotid atherosclerosis and coronary artery calcification (CAC) in non-dialysis CKD.
The study comprised 80 controls and 185 adult patients with CKD at stages 3-5 who were free of cardiovascular diseases. Acute renal failure, chronic hemodialysis, severe liver disease, inflammatory states, anticoagulation therapy and cancer were excluded. The patients were classified based on presence of CAC score into severe and mild to moderate CAC groups. They were also divided into atherosclerotic and non-atherosclerotic groups based on carotid atherosclerosis. CBC, kidney function tests, lipid profile, intact parathyroid hormone (iPTH), and phosphorus were assessed. Serum levels of MK, tumor necrosis factor- α (TNF- α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP) were quantitatively tested using ELISA. Cardiac CT scan was done to calculate CAC score. Carotid ultrasonography was used to evaluate carotid intima media thickness (CIMT) and identify plaques.
All CKD categories, including CKD-3, CKD-4, and CKD-5, showed higher rates of carotid plaques (p = 0.007, p < 0.001, and p < 0.001, respectively), higher levels of MK (p < 0.001 for each), and higher CAC scores (p < 0.001 for each) as CKD worsened. Compared to mild to moderate CAC patients, severe CAC patients showed increased CIMT (p < 0.001) and raised serum levels of MK (p < 0.001), TNF-α (p = 0.001), IL-6 (p = 0.002), hs-CRP (p = 0.003), iPTH (p = 0.02), phosphorus (p < 0.001), total cholesterol (TC), and low density lipoprotein-cholesterol (LDL-C). Multivariate linear regression revealed that CAC was reliably predicted by MK (p = 0.008) and serum creatinine (p = 0.001). Carotid atherosclerotic patients had higher serum levels of MK, TNF-α, IL-6, hs-CRP, iPTH, phosphorus, TC, total triglycerides and LDL-C (p < 0.001 for each). Multivariate logistic regression showed that serum MK (p = 0.001), serum creatinine (p = 0.005), age (p < 0.001), iPTH (p = 0.007), and IL-6 (p = 0.024) were significant predictors of carotid atherosclerosis.
As CKD worsened, MK levels, carotid atherosclerosis and CAC increased. Serum MK was a reliable biomarker for asymptomatic carotid atherosclerosis and CAC in non-dialysis CKD, allowing prompt early diagnosis to avert cardiovascular morbidity and death in the future.
The trial number was 1138 and its registration was approved by the hospital's Research Ethics Committee in 4/2024.
尚无研究调查中期因子（MK）在血管钙化（VC）或与慢性肾脏病（CKD）相关的血管疾病中的作用。本研究评估了非透析CKD患者的血清MK水平，并探讨其与颈动脉粥样硬化和冠状动脉钙化（CAC）的关系。
本研究纳入80名对照者和185例3-5期成年CKD患者，这些患者均无心血管疾病。排除急性肾衰竭、慢性血液透析、严重肝病、炎症状态、抗凝治疗和癌症患者。根据CAC评分将患者分为重度和轻度至中度CAC组。还根据颈动脉粥样硬化情况将患者分为动脉粥样硬化组和非动脉粥样硬化组。评估血常规、肾功能、血脂、全段甲状旁腺激素（iPTH）和磷水平。采用酶联免疫吸附测定（ELISA）法定量检测血清MK、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和高敏C反应蛋白（hs-CRP）水平。进行心脏CT扫描以计算CAC评分。采用颈动脉超声评估颈动脉内膜中层厚度（CIMT）并识别斑块。
所有CKD类别，包括CKD-3、CKD-4和CKD-5，随着CKD病情加重，颈动脉斑块发生率更高（分别为p = 0.007、p < 0.001和p < 0.001），MK水平更高（各p < 0.001），CAC评分更高（各p < 0.001）。与轻度至中度CAC患者相比，重度CAC患者的CIMT增加（p < 0.001），血清MK（p < 0.001）、TNF-α（p = 0.001）、IL-6（p = 0.002）、hs-CRP（p = 0.003）、iPTH（p = 0.02）、磷（p < 0.001）、总胆固醇（TC）和低密度脂蛋白胆固醇（LDL-C）水平升高。多变量线性回归显示，MK（p = 0.008）和血清肌酐（p = 0.001）可可靠预测CAC。颈动脉粥样硬化患者的血清MK、TNF-α、IL-6、hs-CRP、iPTH、磷、TC、总甘油三酯和LDL-C水平更高（各p < 0.001）。多变量逻辑回归显示，血清MK（p = 0.001）、血清肌酐（p = 0.005）、年龄（p < 0.001）、iPTH（p = 0.007）和IL-6（p = 0.024）是颈动脉粥样硬化的重要预测因素。
随着CKD病情加重，MK水平、颈动脉粥样硬化和CAC增加。血清MK是未透析CKD患者无症状颈动脉粥样硬化和CAC的可靠生物标志物，有助于早期诊断，以避免未来心血管疾病的发病和死亡。
试验编号为1138，其注册于2024年4月获得医院研究伦理委员会批准。
