The interplay between cell-free DNA, hepcidin, and interleukin-6 in chronic kidney disease induced inflammation and progression to a hemodialysis dependent state … Original Research Article … |
The Egyptian Journal of Immunology E-ISSN (2090-2506) Volume 32 (2), April 2025 Pages: 01–16. www.Ejimmunology.org https://doi.org/10.55133/eji.320201 |
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| Reham Hammad1, Mona A. Eldosoky1, Lamiaa Ismaiel2, Fatma M. Kotb2, Omaima I. Abo-Elkheir3, Hend G. Kotb2, Wafaa A. Emam4, Amena R. Mohammed4, Amany M. Tawfik5, Mona A. Raafat6, Doaa L. Ali6, Sarah F. Fahmy7, Rasha Elgamal8, Fatma EL-Zahraa Abd El Hakam9, and Sonia Distante10 |
| 1Department of Clinical Pathology, Faculty of Medicine (for Girls), Al-Azhar University, Cairo, Egypt.
2Department of Internal Medicine, Faculty of Medicine (for Girls), Al-Azhar University, Cairo, Egypt. 3Department of Community Medicine & Public Health, Faculty of Medicine (for Girls), Al-Azhar University, Cairo, Egypt. 4Department of Biochemistry, Faculty of Medicine (for Girls), Al-Azhar University, Cairo, Egypt. 5Department of Microbiology and Immunology, Faculty of Medicine (for Girls), Al-Azhar University, Cairo, Egypt. 6Department of Radiodiagnosis, Faculty of Medicine (for Girls), Al-Azhar University, Cairo, Egypt. 7Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. 8Department of Clinical Pathology, Faculty of Medicine, Suez University, Suez, Egypt. 9Department of Pharmacology, Faculty of Medicine (for Girls), Al-Azhar University, Cairo, Egypt. 10Department of Medical Biochemistry, Oslo |
Corresponding author: Reham Hammad, Department of Clinical Pathology, Faculty of Medicine (for Girls), Al-Azhar University, Cairo, Egypt, Egypt. Email: reham.hammad@azhar.edu.eg |
Abstract
Inflammation drives chronic kidney disease (CKD) progression to end-stage renal disease (ESRD). Cell-free DNA (cfDNA) release is linked to systemic inflammation. Pro-inflammatory interleukin-6 (IL-6) is believed to induce hepcidin, the master regulator of iron metabolism. This study attempts to assess the link between cfDNA, IL-6, and hepcidin in CKD induced inflammation and evaluate their usefulness as indicators for progression. This study included 90 participants, divided into three equal groups. Group 1 comprised non-dialysis dependent CKD (ND-CKD) patients (stages IV and V); Group 2 comprised hemodialysis dependent ESRD (HD-ESRD) patients; and Group 3 comprised study normal controls. cfDNA concentration was determined using the real-time quantitative polymerase chain reaction (RT-qPCR). Serum hepcidin and IL-6 were assessed using enzyme-linked immunosorbent assay (ELISA) kits. The HD-ESRD group showed significant up-regulation of cfDNA, IL-6, and hepcidin compared to the ND-CKD group (p =0.008, p< 0.001, and p< 0.001, respectively) and to the control group (p =0.007, p< 0.001, and p< 0.001, respectively). The ND-CKD group showed no significant up-regulation in cfDNA compared to the control group. cfDNA was positively correlated with IL-6, hepcidin, and carotid intima-media thickness (CIMT). IL-6 had the highest discriminative power to detect CKD progression [area under the curve (AUC) of 0.84, 83% sensitivity (SN) and 73% specificity (SP)], followed by hepcidin [AUC 0.77, SN = 80%, and SP = 63%] and cfDNA [AUC 0.67, SN = 70%, and SP = 50%]. Logistic regression analysis revealed that up-regulated IL-6 and hepcidin were independent predictors of HD-ESRD progression, (odds ratio = 1.005 and 1.006, respectively). In conclusion, cfDNA was associated with IL-6 and hepcidin in CKD. Up-regulated IL-6 and hepcidin can serve as predictors of HD-ESRD progression. cfDNA was associated with CIMT in renal patients. IL-6 and hepcidin up-regulations may act as predictors of HD-ESRD progression.
Keywords:
Cell-free DNA; interleukin-6; hepcidin; chronic kidney disease; end-stage renal disease
Date received:
23 May 2024; accepted: 10 February 2025
PMID:
40272917
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