ASSOCIATION OF FETUIN-A AND OSTEOCALCIN WITH RENAL FUNCTION AND OTHER BIOMARKERS IN CHRONIC KIDNEY DISEASE PATIENTS FROM BAGHDAD

Main Article Content

Wissam Jabbar Hussein 1*, Hiba Abid Al-Hussein Hassan 2, Abbas Muhsin Gata 3

Keywords

Chronic kidney disease (CKD), Fetuin-A, osteocalcin, urea, creatinine, GFR.

Abstract

Objective: Chronic kidney disease is a condition that results in the gradual decline of kidney function, often leading to renal replacement therapy such as transplantation or dialysis. This investigation aims to determine if a correlation existed between the levels of Osteocalcin, Fetuin-A, and other biochemical markers, such as urea, creatinine, albumin, calcium, phosphate, vitamin D, and PTH, in patients with CKD compared to healthy people as controls. Fetuin-A is a glycoprotein that is involved in regulating calcium and phosphate metabolism, while osteocalcin is a protein that is involved in bone formation and remodeling. Both of these biomarkers have been studied in chronic kidney disease, and their levels are altered in patients with this condition. This information could help to better understand the pathophysiology of chronic kidney disease and potentially identify new targets for treatment or control progressions of the disease. Methods: one hundred eighty samples divided into one hundred twenty chronic kidney disease patients in end-stage (G5) and sixty healthy controls were taken between November 2022 and March 2023 from three major hospitals in Baghdad: Baghdad Teaching Hospital/Iraqi Center for Dialysis, National Center for Teaching Laboratories, and Ghazi AL-Hariri Surgical Specialties Hospital/Kidney Diseases and Transplantation Center. Chronic kidney disease was diagnosed using symptoms, biochemical testing, history, and clinical examination by specialized nephrologists. The blood urea, serum creatinine, calcium, Albumin, and phosphate were measured by an automated spectrophotometer (Roche Cobas C111). Furthermore, an automated spectrophotometer (Beckman coulter au480) was used to measure serum sodium and potassium levels. on the other hand, vitamin D3 level and PTH were measured by spectrophotometer (Roche Cobas E411). Moreover, Osteocalcin and Fetuin-A were done by ELISA technique. Results: The present study found that the male patients are more than females, (70) were men and (50) were women and the highest percentage of CKD cases were found in the age group of 50-59 years, with 55 out of 120 cases (45.8%). also indicates that the percentage of females with CKD was higher in the age group of 50-59 years, with 30 out of 50 cases (60.0%) compared to males in some age groups, where only 25 out of 70 males (35.7%). Also, the study results showed that the control group had a mean GFR of 92.58±1.98ml/min, while the chronic kidney disease stage 5 group had a significantly lower mean GFR of 5.61±0.20ml/min. The study found that out of 120 CKD patients, 37 cases (30.8%) were overweight with a BMI of 25-29.9 (Kg/m2), 18 cases (15.0%) suffered from obesity with BMI values >30 (Kg/m2), 57 cases (47.5%) had normal weight with BMI values between 18.5 to 24.9 (Kg/m2) (Kg/m2), and 8 cases (6.7%) were underweighted. this study indicates that there were significant differences in the levels of PTH, Fetuin-A, and Osteocalcin among CKD patients and the control p-values associated with these differences are all ≤0.001. also, indicates a strong positively correlated between the levels of Fetuin-A and GFR. while a moderate positively correlated between the levels of Fetuin-A with S. Ca, and Albumin. On the other hand, there is a weak positively correlated between the levels of Fetuin-A with BMI and Vit-D. Furthermore, the levels of Fetuin-A were found to be moderately negatively correlated with the levels of PTH and S.po4. also found that there is a strong negative correlation between the levels of Fetuin-A with creatinine, urea, and Osteocalcin, moreover, a strong negatively correlated between the level of Osteocalcin with GFR and Fetuin-A, also a moderate negatively correlated between the level of Osteocalcin with S. Ca and S. albumin. Furthermore, there is a weak negatively correlated between the levels of Osteocalcin with BMI and Vit-D. while a moderate positively correlated between the levels of Osteocalcin with S.po4 and PTH. the study also found that there is a strong positively correlated between the levels of Osteocalcin with blood urea and serum creatinine. Conclusion: Fetuin-A and Osteocalcin are two proteins that have been studied with CKD and its associated complications. While decreased Fetuin-A concentrations have been linked to increased calcification in the vasculature and mortality, increased Osteocalcin levels in CKD may not confer a protective effect against bone disorders. Further investigation is required to fully understand the roles of these proteins in CKD and to develop strategies for their clinical Use in the managing of CKD patients.

Downloads

References


[1] S. R. Vaidya and N. R. Aeddula, “Chapter 1: Definition and classification of CKD,” Kidney Int Suppl (2011), vol. 3, no. 1, pp. 19–62, Jan. 2013, doi: 10.1038/kisup.2012.64. [2] J.-C. Lv and L.-X. Zhang, “Prevalence and Disease Burden of Chronic Kidney Disease.,” Adv Exp Med Biol, vol. 1165, pp. 3–15, 2019, doi: 10.1007/978-981-13-8871-2_1. [3] N. G. Vallianou, S. Mitesh, A. Gkogkou, and E. Geladari, “Chronic Kidney Disease and Cardiovascular Disease: Is there Any Relationship?,” Curr Cardiol Rev, vol. 15, no. 1, pp. 55–63, 2019, doi: 10.2174/1573403X14666180711124825. [4] M. E. Suliman, E. García-López, B. Anderstam, B. Lindholm, and P. Stenvinkel, “Vascular calcification inhibitors in relation to cardiovascular disease with special emphasis on fetuin-A in chronic kidney disease.,” Adv Clin Chem, vol. 46, pp. 217–62, 2008, doi: 10.1016/s0065-2423(08)00406-x. [5] W. Jahnen-Dechent, A. Heiss, C. Schäfer, and M. Ketteler, “Fetuin-A regulation of calcified matrix metabolism,” Circ Res, vol. 108, no. 12, pp. 1494–1509, Jun. 2011, doi: 10.1161/CIRCRESAHA.110.234260. [6] J. Wei and G. Karsenty, “An overview of the metabolic functions of osteocalcin,” Reviews in Endocrine and Metabolic Disorders, vol. 16, no. 2. Kluwer Academic Publishers, pp. 93–98, Jul. 01, 2015. doi: 10.1007/s11154-014-9307-7. [7] T. Qaradakhi et al., “The Effect of Recombinant Undercarboxylated Osteocalcin on Endothelial Dysfunction,” Calcif Tissue Int, vol. 105, no. 5, pp. 546–556, Nov. 2019, doi: 10.1007/s00223-019-00600-6. [8] N. C. Kyriakidis, G. Cobo, L. Dai, B. Lindholm, and P. Stenvinkel, “Role of Uremic Toxins in Early Vascular Ageing and Calcification.,” Toxins (Basel), vol. 13, no. 1, p. 26, Jan. 2021, doi: 10.3390/toxins13010026. [9] A. Tacey, T. Qaradakhi, T. Brennan-Speranza, A. Hayes, A. Zulli, and I. Levinger, “Potential role for osteocalcin in the development of atherosclerosis and blood vessel disease,” Nutrients, vol. 10, no. 10. MDPI AG, Oct. 04, 2018. doi: 10.3390/nu10101426. [10] J. J. Carrero, M. Hecking, N. C. Chesnaye, and K. J. Jager, “Sex and gender disparities in the epidemiology and outcomes of chronic kidney disease.,” Nat Rev Nephrol, vol. 14, no. 3, pp. 151–164, Mar. 2018, doi: 10.1038/nrneph.2017.181. [11] S. Xu, Y. C. Li, and C. X. Chen, “The Prevalence of Chronic Kidney Disease in Hypertensive Patients in Primary Care in Hong Kong: A Cross-Sectional Study,” 2020, doi: doi.org/10.21203/rs.3.rs-74778/v1. [12] A. M. Kamil, S. A. Hassan, and R. A. Mahmoud, “Prevalence of chronic kidney disease and hypertension as a risk factor in Basrah province Iraq,” Ann Trop Med Public Health, vol. 24, no. 04, 2021, doi: 10.36295/asro.2021.24456. [13] L. Malekmakan, P. Khajehdehi, M. Pakfetrat, A. Malekmakan, H. Mahdaviazad, and J. Roozbeh, “Prevalence of Chronic Kidney Disease and Its Related Risk Factors in Elderly of Southern Iran: A Population-Based Study,” ISRN Nephrol, vol. 2013, pp. 1–6, Jul. 2013, doi: 10.5402/2013/427230. [14] A. Otero, A. de Francisco, P. Gayoso, F. García, and EPIRCE Study Group, “Prevalence of chronic renal disease in Spain: results of the EPIRCE study.,” Nefrologia, vol. 30, no. 1, pp. 78–86, 2010, doi: 10.3265/Nefrologia.pre2009.Dic.5732. [15] H. J. Kim et al., “Metabolic Acidosis Is an Independent Risk Factor of Renal Progression in Korean Chronic Kidney Disease Patients: The KNOW-CKD Study Results.,” Front Med (Lausanne), vol. 8, p. 707588, 2021, doi: 10.3389/fmed.2021.707588. [16] G. A. Nichols, A. Déruaz-Luyet, K. G. Brodovicz, T. M. Kimes, A. G. Rosales, and S. J. Hauske, “Kidney disease progression and all-cause mortality across estimated glomerular filtration rate and albuminuria categories among patients with vs. without type 2 diabetes.,” BMC Nephrol, vol. 21, no. 1, p. 167, May 2020, doi: 10.1186/s12882-020-01792-y. [17] E. Abdallah Hassan, “Biochemical Study in Iraqian Patients with Chronic Renal Failure Therapy by Regular Hemodialysis,” Diyala Journal For Pure Science, vol. 14, no. 4, pp. 1–13, Oct. 2018, doi: 10.24237/djps.1404.393a. [18] T.-J. Chang et al., “Relationship between body mass index and renal function deterioration among the Taiwanese chronic kidney disease population.,” Sci Rep, vol. 8, no. 1, p. 6908, May 2018, doi: 10.1038/s41598-018-24757-6. [19] L. L. Jun, K. Z. Kamyar, Z. Jennie, L. Darryl Quarles, and P. K. Csaba, “Association of body mass index with outcomes in patients with CKD,” Journal of the American Society of Nephrology, vol. 25, no. 9, pp. 2088–2096, Sep. 2014, doi: 10.1681/ASN.2013070754. [20] E. Habas, M. Eledrisi, F. Khan, and A.-N. Y. Elzouki, “Secondary Hyperparathyroidism in Chronic Kidney Disease: Pathophysiology and Management.,” Cureus, vol. 13, no. 7, p. e16388, Jul. 2021, doi: 10.7759/cureus.16388. [21] P. P. Centeno et al., “Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion.,” Nat Commun, vol. 10, no. 1, p. 4693, Oct. 2019, doi: 10.1038/s41467-019-12399-9. [22] N. S. Akimbekov, I. Digel, D. K. Sherelkhan, and M. S. Razzaque, “Vitamin D and Phosphate Interactions in Health and Disease,” in Advances in experimental medicine and biology, vol. 1362, 2022, pp. 37–46. doi: 10.1007/978-3-030-91623-7_5. [23] E. O. Chielle, K. A. Rigon, I. A. Arcari, V. Stein, and G. A. Dos Santos, “Influence of hemodialysis on the plasma concentration of adenosine deaminase in patients with chronic kidney disease,” J Bras Patol Med Lab, vol. 51, no. 3, pp. 153–157, May 2015, doi: 10.5935/1676-2444.20150026. [24] H. M. Kadhim, H. H. Al-Ghanimi, and R. M. Al-Dedah, “Haematological parameters and biochemical indices in patients with chronic kidney disease before haemodialysis Al-Furat Al-Awsat Governorates/Iraq,” in AIP Conference Proceedings, Dec. 2020, vol. 2290. doi: 10.1063/5.0027856. [25] V. Kolagal et al., “Determination of oxidative stress markers and their importance in early diagnosis of uremia-related complications.,” Indian J Nephrol, vol. 19, no. 1, pp. 8–12, Jan. 2009, doi: 10.4103/0971-4065.50673. [26] H. Faleh Hassen, M. Qassim Dawood Al-Lami, and A. J. Hashim Al-Saedi, “Evaluation some Biochemical Levels in Patients undergoing Hemodialysis in Baghdad Governorate,” 2018. [Online]. Available: https://e-journal.sospublication.co.in [27] Skorecki K, Green J, and Brenner B.M, Harrison’s principles of internal medicine .19th ed. New York: McGraw-Hill, 2006. [28] F. Huang et al., “The association between blood albumin level and cardiovascular complications and mortality risk in ICU patients with CKD.,” BMC Cardiovasc Disord, vol. 22, no. 1, p. 322, Jul. 2022, doi: 10.1186/s12872-022-02763-x. [29] J. Lang et al., “Association of serum albumin levels with kidney function decline and incident chronic kidney disease in elders,” Nephrology Dialysis Transplantation, vol. 33, no. 6, pp. 986–992, Jun. 2018, doi: 10.1093/ndt/gfx229. [30] C. J. Janmaat et al., “Lower serum calcium is independently associated with CKD progression.,” Sci Rep, vol. 8, no. 1, p. 5148, Mar. 2018, doi: 10.1038/s41598-018-23500-5. [31] P. H. Franca Gois, M. Wolley, D. Ranganathan, and A. C. Seguro, “Vitamin D Deficiency in Chronic Kidney Disease: Recent Evidence and Controversies.,” Int J Environ Res Public Health, vol. 15, no. 8, Aug. 2018, doi: 10.3390/ijerph15081773. [32] C. Fourtounas, “Phosphorus metabolism in chronic kidney disease.,” Hippokratia, vol. 15, no. Suppl 1, pp. 50–2, Jan. 2011, [Online]. Available: http://www.ncbi.nlm.nih.gov/pubmed/21897759 [33] A. Gluba-Brzózka, M. Michalska-Kasiczak, B. Franczyk-Skóra, M. Nocuń, M. Banach, and J. Rysz, “Markers of increased cardiovascular risk in patients with chronic kidney disease,” Lipids Health Dis, vol. 13, no. 1, Aug. 2014, doi: 10.1186/1476-511X-13-135. [34] I. Nessim, Amal Abd el Wahab, H. Madani, E. Waked, Ashraf Abd el Khalek, and Khaled Mabrouk, “Evaluation of serum osteoprotegerin and fetuin A levels in Egyptian patients with chronic kidney disease,” 2011. [35] R. Mehrotra et al., “Serum fetuin-A in nondialyzed patients with diabetic nephropathy: relationship with coronary artery calcification.,” Kidney Int, vol. 67, no. 3, pp. 1070–7, Mar. 2005, doi: 10.1111/j.1523-1755.2005.00172.x. [36] C. Schafer et al., “The serum protein alpha 2-Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification.,” J Clin Invest, vol. 112, no. 3, pp. 357–66, Aug. 2003, doi: 10.1172/JCI17202. [37] M. Ketteler et al., “Association of low fetuin-A (AHSG) concentrations in serum with cardiovascular mortality in patients on dialysis: a cross-sectional study.,” Lancet, vol. 361, no. 9360, pp. 827–33, Mar. 2003, doi: 10.1016/S0140-6736(03)12710-9. [38] M. S. Razzaque, “Osteocalcin: a pivotal mediator or an innocent bystander in energy metabolism?,” Nephrol Dial Transplant, vol. 26, no. 1, pp. 42–5, Jan. 2011, doi: 10.1093/ndt/gfq721. [39] M. Zhang, Z. Ni, W. Zhou, and J. Qian, “Undercarboxylated osteocalcin as a biomarker of subclinical atherosclerosis in non-dialysis patients with chronic kidney disease.,” J Biomed Sci, vol. 22, no. 1, p. 75, Sep. 2015, doi: 10.1186/s12929-015-0183-6. [40] X. Guo et al., “Osteocalcin association with vascular function in chronic kidney disease,” The Journal of Clinical Hypertension, vol. 24, no. 7, pp. 928–936, Jul. 2022, doi: 10.1111/jch.14523.