Serum midkine level and its association with subclinical coronary artery calcification and carotid atherosclerosis in chronic kidney disease

Abstract Background 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 calci...

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Main Authors: Osama Nady Mohamed, Marwa Ibrahim Mohamed, Shaimaa F. Kamel, Ahmed M. Dardeer, Sayed Shehata, Hassan MH Mohammed, Asmaa Khalf Kamel, Doaa Elzaeem Ismail, Nehal I. Abbas, Mohamed Ahmed Abdelsamie, Ahmed Fathy Kamel Ziady, Manar M. Sayed, Nermeen Dahi Mohammed Toni, Shaimaa Moustafa Hafez, Shereen Mohammed Mohammed Elsaghir
Format: Article
Language:English
Published: BMC 2025-04-01
Series:BMC Nephrology
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Online Access:https://doi.org/10.1186/s12882-025-04066-7
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author Osama Nady Mohamed
Marwa Ibrahim Mohamed
Shaimaa F. Kamel
Ahmed M. Dardeer
Sayed Shehata
Hassan MH Mohammed
Asmaa Khalf Kamel
Doaa Elzaeem Ismail
Nehal I. Abbas
Mohamed Ahmed Abdelsamie
Ahmed Fathy Kamel Ziady
Manar M. Sayed
Nermeen Dahi Mohammed Toni
Shaimaa Moustafa Hafez
Shereen Mohammed Mohammed Elsaghir
author_facet Osama Nady Mohamed
Marwa Ibrahim Mohamed
Shaimaa F. Kamel
Ahmed M. Dardeer
Sayed Shehata
Hassan MH Mohammed
Asmaa Khalf Kamel
Doaa Elzaeem Ismail
Nehal I. Abbas
Mohamed Ahmed Abdelsamie
Ahmed Fathy Kamel Ziady
Manar M. Sayed
Nermeen Dahi Mohammed Toni
Shaimaa Moustafa Hafez
Shereen Mohammed Mohammed Elsaghir
author_sort Osama Nady Mohamed
collection DOAJ
description Abstract Background 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. Methods 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. Results 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. Conclusions 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. Trial registration The trial number was 1138 and its registration was approved by the hospital’s Research Ethics Committee in 4/2024.
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spelling doaj-art-623e749e405443ae935e6a44e5330fc92025-08-20T02:17:01ZengBMCBMC Nephrology1471-23692025-04-0126111810.1186/s12882-025-04066-7Serum midkine level and its association with subclinical coronary artery calcification and carotid atherosclerosis in chronic kidney diseaseOsama Nady Mohamed0Marwa Ibrahim Mohamed1Shaimaa F. Kamel2Ahmed M. Dardeer3Sayed Shehata4Hassan MH Mohammed5Asmaa Khalf Kamel6Doaa Elzaeem Ismail7Nehal I. Abbas8Mohamed Ahmed Abdelsamie9Ahmed Fathy Kamel Ziady10Manar M. Sayed11Nermeen Dahi Mohammed Toni12Shaimaa Moustafa Hafez13Shereen Mohammed Mohammed Elsaghir14Department of Internal Medicine, Faculty of Medicine, Minia UniversityDepartment of Internal Medicine, Faculty of Medicine, Minia UniversityDepartment of Internal Medicine, Faculty of Medicine, Minia UniversityDepartment of Cardiology, Faculty of Medicine, Minia UniversityDepartment of Cardiology, Faculty of Medicine, Minia UniversityDepartment of Cardiology, Faculty of Medicine, Minia UniversityDepartment of Clinical Pathology, Faculty of Medicine, Minia UniversityDepartment of Clinical Pathology, Faculty of Medicine, Minia UniversityDepartment of Clinical Pathology, Faculty of Medicine, Minia UniversityDepartment of Radiology, Faculty of Medicine, Minia UniversityDepartment of Radiology, Faculty of Medicine, Minia UniversityDepartment of Radiology, Faculty of Medicine, Minia UniversityDepartment of Public and Preventive Medicine, Faculty of Medicine, Minia UniversityDepartment of Public and Preventive Medicine, Faculty of Medicine, Minia UniversityDepartment of Internal Medicine, Faculty of Medicine, Minia UniversityAbstract Background 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. Methods 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. Results 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. Conclusions 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. Trial registration The trial number was 1138 and its registration was approved by the hospital’s Research Ethics Committee in 4/2024.https://doi.org/10.1186/s12882-025-04066-7Chronic kidney diseaseAtherosclerosisVascular calcificationMidkine
spellingShingle Osama Nady Mohamed
Marwa Ibrahim Mohamed
Shaimaa F. Kamel
Ahmed M. Dardeer
Sayed Shehata
Hassan MH Mohammed
Asmaa Khalf Kamel
Doaa Elzaeem Ismail
Nehal I. Abbas
Mohamed Ahmed Abdelsamie
Ahmed Fathy Kamel Ziady
Manar M. Sayed
Nermeen Dahi Mohammed Toni
Shaimaa Moustafa Hafez
Shereen Mohammed Mohammed Elsaghir
Serum midkine level and its association with subclinical coronary artery calcification and carotid atherosclerosis in chronic kidney disease
BMC Nephrology
Chronic kidney disease
Atherosclerosis
Vascular calcification
Midkine
title Serum midkine level and its association with subclinical coronary artery calcification and carotid atherosclerosis in chronic kidney disease
title_full Serum midkine level and its association with subclinical coronary artery calcification and carotid atherosclerosis in chronic kidney disease
title_fullStr Serum midkine level and its association with subclinical coronary artery calcification and carotid atherosclerosis in chronic kidney disease
title_full_unstemmed Serum midkine level and its association with subclinical coronary artery calcification and carotid atherosclerosis in chronic kidney disease
title_short Serum midkine level and its association with subclinical coronary artery calcification and carotid atherosclerosis in chronic kidney disease
title_sort serum midkine level and its association with subclinical coronary artery calcification and carotid atherosclerosis in chronic kidney disease
topic Chronic kidney disease
Atherosclerosis
Vascular calcification
Midkine
url https://doi.org/10.1186/s12882-025-04066-7
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