Serum midkine, Reliable Biomarker for Early Detection of Atherosclerosis in Non-Dialysis CKD: Study

A new study published in the journal of BMC Nephrology showed that in non-dialysis chronic kidney disease (CKD) patients, serum midkine was found to be a valid marker for identifying asymptomatic coronary artery calcification (CAC) and carotid atherosclerosis, allowing for early identification and the avoidance of subsequent cardiovascular events.

Vascular calcification (VC), a pathological condition characterized by the accumulation of mineral deposits on artery walls, is one of the primary risk factors for the development of cardiovascular disease (CVD). Once coronary artery calcification appears, it is difficult to stop its development. Numerous disease processes, including cancer, acute and chronic renal disorders, and inflammatory illnesses, have been pathologically related to the 13 kDa cytokine midkine (MK). In non-dialysis CKD, this study measured serum MK levels and examined their associations with coronary artery calcification and carotid atherosclerosis.

A total of 185 adult patients with CKD at stages 3–5 who did not have cardiovascular illnesses and 80 controls made up the research. Based on the presence of a CAC score, the patients were divided into 2 groups as severe and mild to moderate. On the basis of carotid atherosclerosis, they were also separated into groups that were atherosclerotic and those who were not.

Phosphorus, lipid profile, intact parathyroid hormone (iPTH), kidney function tests, and CBC were evaluated. High-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and MK serum levels were quantitatively assessed by ELISA. To get the CAC score, a cardiac CT scan was performed. Plaques were identified, and carotid intima-media thickness (CIMT) was assessed using carotid ultrasonography.

As CKD deteriorated, all CKD categories (CKD-3, CKD-4, and CKD-5) exhibited increased frequencies of carotid plaques, elevated MK levels, and elevated CAC scores. Serum levels of MK, IL-6, TNF-α, hs-CRP, phosphorus, iPTH, total cholesterol (TC), and low density lipoprotein-cholesterol (LDL-C) were elevated in severe CAC patients as compared to mild to moderate CAC patients.

MK and serum creatinine were found to be reliable predictors of CAC using multivariate linear regression. Serum levels of MK, TNF-α, IL-6, hs-CRP, iPTH, phosphorus, TC, total triglycerides, and LDL-C were greater in individuals with carotid atherosclerosis. Serum MK, serum creatinine, age, iPTH, and IL-6 were all shown to be significant predictors of carotid atherosclerosis using multivariate logistic regression. Overall, based of this investigation, serum MK in non-dialysis CKD patients may serve as a trustworthy biomarker for these subclinical CVDs.

Source:

Mohamed, O. N., Mohamed, M. I., Kamel, S. F., Dardeer, A. M., Shehata, S., Mohammed, H. M., Kamel, A. K., Ismail, D. E., Abbas, N. I., Abdelsamie, M. A., Ziady, A. F. K., Sayed, M. M., Toni, N. D. M., Hafez, S. M., & Elsaghir, S. M. M. (2025). Serum midkine level and its association with subclinical coronary artery calcification and carotid atherosclerosis in chronic kidney disease. BMC Nephrology, 26(1), 185. https://doi.org/10.1186/s12882-025-04066-7