Association of Fetuin-A with Mineral Metabolism and Cardiovascular Risk Markers in Chronic Kidney Disease: A Cross-Sectional Study from Iraq
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Chronic kidney disease (CKD) is linked with gradual renal dysfunction and metabolic dysfunctions. The liver-derived glycoprotein fetuin-A is suggested as a biomarker of biochemical changes in CKD. This study aimed at investigating the level of serum Fetuin-A and its correlation with some clinical and biochemical parameters in patients with chronic kidney disease (CKD) in Iraq. 50 participants were recruited, including 20 stage 3-4 CKD conservative therapy, 20 maintenance hemodialysis (HD), and 10 healthy controls. ELISA was used to measure Serum Fetuin-A and correlations and ROC analysis was used to determine the associations of Fetuin-A with laboratory parameters. The levels of serum Fetuin-A were significantly lower in the HD group (378 ± 50 ng/mL) as compared to conservatively treated CKD patients (490 ± 73 ng/mL) and controls (498 ± 58 ng/mL) (p < 0.001). There was a correlation between fetuin-A and markers of renal function, calcium and lipid profile parameters. Good discrimination was observed between CKD patients and controls by using the ROC analysis (AUC = 0.82). Low serum Fetuin-A levels are linked to renal dysfunction and metabolic abnormalities, suggesting that it may be a biomarker for biochemical events in CKD.
[1] J. R. Schelling, “Tubular atrophy in the pathogenesis of chronic kidney disease progression,” Pediatr. Nephrol., vol. 31, no. 5, pp. 693–706, 2016.
[2] D. G. Matsell, “Congenital urinary tract obstruction—Diagnosis and management in the fetus,” in Nephrology and Fluid/Electrolyte Physiology, Elsevier, pp. 391–409, 2019.
[3] W. Ju, V. Nair, S. Smith, L. Zhu, K. Shedden, P. X. Song, et al., “Tissue transcriptome-driven identification of epidermal growth factor as a chronic kidney disease biomarker,” Sci. Transl. Med., vol. 7, no. 316, Art. no. 316ra193, 2015.
[4] P. Jirak, L. Stechemesser, E. Moré, M. Franzen, A. Topf, M. Mirna, et al., “Clinical implications of fetuin-A,” Adv. Clin. Chem., vol. 89, pp. 79–130, 2019.
[5] P. Aghagolzadeh, M. Bachtler, R. Bijarnia, C. Jackson, E. R. Smith, A. Odermatt, et al., “Calcification of vascular smooth muscle cells is induced by secondary calciprotein particles and enhanced by tumor necrosis factor-α,” Atherosclerosis, vol. 251, pp. 404–414, 2016.
[6] K. Benz, I. Varga, D. Neureiter, V. Campean, C. Daniel, and K. Amann, “Vascular calcification in chronic kidney disease: The role of inflammation,” Int. J. Nephrol., 2018, Art. ID 4310379.
[7] J. A. Leopold, “Vascular calcification: Mechanisms of vascular smooth muscle cell calcification,” Trends Cardiovasc. Med., vol. 25, no. 4, pp. 267–274, 2015.
[8] L. Dai, E. Golembiewska, B. Lindholm, and P. Stenvinkel, “End-stage renal disease, inflammation and cardiovascular outcomes,” Contrib. Nephrol., vol. 191, pp. 32–43, 2017.
[9] M. Fasshauer and M. Blüher, “Adipokines in health and disease,” Trends Pharmacol. Sci., vol. 36, no. 7, pp. 461–470, 2015.
[10] Z. A. Massy and T. B. Drüeke, “Magnesium and outcomes in patients with chronic kidney disease: Focus on vascular calcification, atherosclerosis and survival,” Clin. Kidney J., vol. 5, Suppl. 1, pp. i52–i61, 2012.
[11] S. Ossareh, A. Alaei, and D. Saedi, “Carotid intima-media thickness in maintenance hemodialysis patients,” Nephrourol. Mon., vol. 3, pp. 138–143, 2011.
[12] M. Sato, Y. Kamada, Y. Takeda, S. Kida, Y. Ohara, H. Fujii, et al., “Fetuin-A negatively correlates with liver and vascular fibrosis in nonalcoholic fatty liver disease subjects,” Liver Int., vol. 35, no. 3, pp. 925–935, 2015.
[13] M. Kanbay, D. Goldsmith, M. E. Uyar, F. Turgut, and A. Covic, “Magnesium in chronic kidney disease: Challenges and opportunities,” Blood Purif., vol. 29, no. 3, pp. 280–292, 2010.
[14] K. Okasha, A. El Bendary, and A. Mourad, “Evaluation of peripheral vascular calcification and serum magnesium level in Egyptian hemodialysis patients,” Arab J. Nephrol. Transplant., vol. 3, no. 1, pp. 11–16, 2010.
[15] F. Turgut, M. Kanbay, M. R. Metin, E. Uz, A. Akcay, and A. Covic, “Magnesium supplementation helps to improve carotid intima-media thickness in patients on hemodialysis,” Int. Urol. Nephrol., vol. 40, no. 4, pp. 1075–1082, 2008.
[16] R. C. Shroff, R. McNair, N. Figg, J. N. Skepper, L. Schurgers, A. Gupta, et al., “Chronic mineral dysregulation promotes vascular smooth muscle cell adaptation and extracellular matrix calcification,” J. Am. Soc. Nephrol., vol. 21, no. 1, pp. 103–112, 2010.
[17] H. Uedono, M. Fujii, H. Takata, S. Yamada, K. Tsuruya, T. Kitazono, et al., “Effects of fetuin-A-containing calciprotein particles on posttranslational modifications of fetuin-A in HepG2 cells,” Sci. Rep., vol. 11, Art. no. 11865, 2021.
[18] N. X. Chen and S. M. Moe, “Pathophysiology of vascular calcification,” Curr. Osteoporos. Rep., vol. 13, no. 6, pp. 372–380, 2015.
[19] W. V. de Oliveira Junior, A. P. Sabino, R. C. Figueiredo, D. R. A. Rios, and M. G. Carvalho, “Association between dyslipidemia and CCL2 in hemodialysis patients,” Cytokine, vol. 125, Art. no. 154858, 2020.
[20] M. Ketteler, P. Bongartz, R. Westenfeld, J. E. Wildberger, A. H. Mahnken, R. Böhm, et al., “Low fetuin-A levels and cardiovascular mortality in dialysis patients,” Lancet, vol. 361, no. 9360, pp. 827–833, 2003.
[21] Z. Zhou, B. Sun, X. Li, and C. Zhu, “Circulating fetuin-A and all-cause mortality in CKD: A meta-analysis,” Front. Physiol., vol. 10, Art. no. 966, 2019.
[22] G. Favretto, A. Stasi, C. Divella, R. Franzin, P. Pontrelli, L. Gesualdo, et al., “Uremic endothelial-derived extracellular vesicles: Mechanisms of formation and role in inflammation and oxidative stress,” Toxicol. Lett., vol. 347, pp. 12–22, 2021.
[23] A. Galassi, M. Cozzolino, P. Ciceri, and F. Conte, “Current treatment options for secondary hyperparathyroidism in stage 3–4 CKD,” Expert Opin. Drug Saf., 2021.
[24] C. L. Lu, J. F. Shyu, T. H. Yen, C. F. Hung, and C. C. Wu, “Emerging role of nutritional vitamin D in secondary hyperparathyroidism in CKD,” Nutrients, vol. 10, no. 12, Art. no. 1890, 2018.
[25] G. Toft, U. Heide-Jørgensen, H. van Haalen, G. James, K. Hedman, H. Birn, et al., “Anemia and clinical outcomes in patients with severe chronic kidney disease,” J. Nephrol., vol. 33, no. 1, pp. 147–156, 2020.
[26] L. F. Fried, R. A. Kronmal, A. B. Newman, D. E. Bild, M. B. Mittelmark, J. F. Polak, et al., “Renal insufficiency as a predictor of cardiovascular outcomes in elderly individuals,” J. Am. Coll. Cardiol., vol. 41, no. 8, pp. 1364–1372, 2003.
[27] A. P. Guérin, G. M. London, S. J. Marchais, and F. Metivier, “Arterial stiffening and vascular calcifications in end-stage renal disease,” Nephrol. Dial. Transplant., vol. 15, no. 7, pp. 1014–1021, 2000.
[28] J. H. Ix, M. G. Shlipak, V. M. Brandenburg, S. Ali, M. Ketteler, and M. A. Whooley, “Association between fetuin-A and the metabolic syndrome,” Circulation, vol. 113, no. 14, pp. 1760–1767, 2006.
[29] Z. Sun, “Aging, arterial stiffness, and hypertension,” Hypertension, vol. 65, no. 2, pp. 252–256, 2015.
[30] M. Temmar, S. Liabeuf, C. Renard, S. Czernichow, N. E. Esper, I. Shahapuni, et al., “Pulse wave velocity and vascular calcification at different stages of chronic kidney disease,” J. Hypertens., vol. 28, no. 1, pp. 163–169, 2010.
[31] K.-U. Eckardt, R. Agarwal, A. Aswad, A. Awad, G. A. Block, M. R. Bacci, et al., “Safety and efficacy of vadadustat for anemia in patients undergoing dialysis,” N. Engl. J. Med., vol. 384, no. 17, pp. 1601–1612, 2021.
[32] P. E. Pergola, R. N. Woodward, A. Florez, S. Rai, P. Delafontaine, C. Bowers, et al., “Ziltivekimab for treatment of anemia of inflammation in patients on hemodialysis,” J. Am. Soc. Nephrol., vol. 32, no. 1, pp. 211–222, 2021.
