Predictive value of osteoprotegerin and heart fatty acid binding protein as biomarkers for heart failure in chronic kidney disease patients on hemodialysis: A case-control study

Year 2025, Volume: 29 Issue: 2, 682 - 691

Saddam Jaber Khudiar Rayah Sulaiman Baban Arif Sami Malik

https://doi.org/10.12991/jrespharm.1664898

Abstract

Heart failure (HF) is a major cause of mortality worldwide, especially among patients undergoing regular dialysis. The current research aimed to assess the potential of measuring osteoprotegerin (OPG) and HFABP levels as predictors for HF in a chronic kidney disease patients on hemodialysis in a case-control study that was conducted on 130 Iriqi patients with end stage renal disease (ESRD) undergoing hemodialysis who divided into two groups of hemodialysis patients: those without HF (group 1, n =80) and those with HF (group 2, n=50). The results revealed that age, Osteoprotogerin (OPG), Heart fatty acid binding protein (HFABP) , cholesterol, Trigelecirid (TG), Very Low Density Lipoprotein (VLDL) and Low Diensity Lipoprotein were higher in HF compared to the non-HF group. OPG and HFABP levels were more than doubled in the HF group, and these differences were highly statistically significant. Receiver operating characteristic analysis showed that OPG and HFABP performed well in differentiating between HF and non- HF patients, with area under the curve values of 0.922 and 0.860, respectively. Logistic regression revealed that OPG and HFABP were the strongest predictors of HF, with an odds ratio of 8.71 and 1.09, respectively. It was concluded that OPG and HFABP can be considered as biomarkers for predicting of HF in dialysis patients with OPG, in particularly, showed strong predictive value. These findings have implications for the development of improved diagnostic and management strategies for (HF) in ESRD.

Keywords

Osteoprotegerin, HFABP, Heart Failure, Hemodialysis

References

• [1] Modi ZJ, Lu Y, Ji N, Kapke A, Selewski DT, Dietrich X, Abbott K, Nallamothu BK, Schaubel DE, Saran R, Gipson DS. Risk of cardiovascular disease and mortality in young adults with end-stage renal disease: An Analysis of the US Renal Data System. JAMA Cardiol. 2019;4(4):353-362. https://doi.org/10.1001%2Fjamacardio.2019.0375
• [2] Nichols GA, Amitay EL, Chatterjee S, Steubl D. The Bidirectional Association of Chronic Kidney Disease, Type 2 Diabetes, Atherosclerotic Cardiovascular Disease, and Heart Failure: The Cardio-Renal-Metabolic Syndrome. Metab Syndr Relat Disord. 2023;21(5):261-266. https://doi.org/10.1089/met.2023.0006
• [3] McCullough KP, Morgenstern H, Saran R, Herman WH, Robinson BM. Projecting ESRD Incidence and Prevalence in the United States through 2030. J Am Soc Nephrol. 2019;30(1):127-135. https://doi.org/10.1681/asn.2018050531
• [4] Roehm B, Gulati G, Weiner DE. Heart failure management in dialysis patients: Many treatment options with no clear evidence. Semin Dial. 2020 May;33(3):198-208. https://doi.org/10.1111%2Fsdi.12878
• [5] Montagnana M, Lippi G, Danese E, Guidi GC. The role of osteoprotegerin in cardiovascular disease. Ann Med. 2013;45(3):254-264. https://doi.org/10.3109/07853890.2012.727019
• [6] Corallini F, Rimondi E, Secchiero P. TRAIL and osteoprotegerin: a role in endothelial physiopathology? Front Biosci. 2008;13:135-147. https://doi.org/10.2741/2665
• [7] Salman HD, Kadhim MM. Serum Levels of Receptor Activator of Nuclear Factor-κβ Ligand, Osteoprotegerin, Interlukin-17 and association with Receptor Activator of Nuclear Factor Kappa B/Osteoprotegerin Ratio in Patients with Osteoporosis. Ann Rom Soc Cell Biol. 2021;25(5):3805 - 3821.
• [8] Rochette L, Meloux A, Rigal E, Zeller M, Cottin Y, Vergely C. The Role of Osteoprotegerin and ıts ligands in vascular function. Int J Mol Sci. 2019;20(3):705. https://doi.org/10.3390%2Fijms20030705
• [9] Yun TJ, Tallquist MD, Aicher A, Rafferty KL, Marshall AJ, Moon JJ, Ewings ME, Mohaupt M, Herring SW, Clark EA. Osteoprotegerin, a crucial regulator of bone metabolism, also regulates B cell development and function. J Immunol. 2001;166(3):1482-1491. https://doi.org/10.4049/jimmunol.166.3.1482
• [10] Stępień E. Osteoprotegerin as a possible novel predictor of cardiovascular dysfunction. Kardiochirurgia i Torakochirurgia Polska/Polish J Thor Cardiovasc Surg. 2012;9(1):82-85.
• [11] Özkalaycı F, Gülmez Ö, Uğur-Altun B, Pandi-Perumal SR, Altun A. The Role of Osteoprotegerin as a Cardioprotective Versus Reactive Inflammatory Marker: the Chicken or the Egg Paradox. Balkan Med J. 2018;35(3):225-232. https://doi.org/10.4274/balkanmedj.2018.0579
• [12] Anand DV, Lahiri A, Lim E, Hopkins D, Corder R. The relationship between plasma osteoprotegerin levels and coronary artery calcification in uncomplicated type 2 diabetic subjects. J Am Coll Cardiol. 2006;47(9):1850-1857. https://doi.org/10.1016/j.jacc.2005.12.054
• [13] Zauli G, Corallini F, Bossi F, Fischetti F, Durigutto P, Celeghini C, Tedesco F, Secchiero P. Osteoprotegerin increases leukocyte adhesion to endothelial cells both in vitro and in vivo. Blood. 2007;110(2):536-543. https://doi.org/10.1182/blood-2007-01-068395
• [14] Kuźniewski M, Fedak D, Dumnicka P, Stępień E, Kuśnierz-Cabala B, Cwynar M, Sułowicz W. Osteoprotegerin and osteoprotegerin/TRAIL ratio are associated with cardiovascular dysfunction and mortality among patients with renal failure. Adv Med Sci. 2016;61(2):269-275. https://doi.org/10.1016/j.advms.2016.03.003
• [15] Dutka M, Bobiński R, Wojakowski W, Francuz T, Pająk C, Zimmer K. Osteoprotegerin and RANKL-RANK-OPG-TRAIL signalling axis in heart failure and other cardiovascular diseases. Heart Fail Rev. 2022;27(4):1395-1411. https://doi.org/10.1007/s10741-021-10153-2
• [16] Rezar R, Jirak P, Gschwandtner M, Derler R, Felder TK, Haslinger M, Kopp K, Seelmaier C, Granitz C, Hoppe UC, Lichtenauer M. Heart-Type Fatty Acid-Binding Protein (H-FABP) and its Role as a Biomarker in Heart Failure: What Do We Know So Far? J Clin Med. 2020;9(1):164. https://doi.org/10.3390/jcm9010164
• [17] Honma M, Nozaki H. Molecular Pathogenesis of Psoriasis and Biomarkers Reflecting Disease Activity. J Clin Med. 2021;10(15):3199. https://doi.org/10.3390/jcm10153199
• [18] Torres M, Prieto C, Ortiz R, Siguencia W, Durán P, Pérez J, Díaz MP, Rojas M, Chacin M, Cano C, Bermúdez V. The A54T polymorphism in the FABP2 gene and its relationship with obesity. Gac Méd Caracas. 2020;128(3):360-372. http://dx.doi.org/10.47307/GMC.2020.128.3.9
• [19] Varrone F, Gargano B, Carullo P, Di Silvestre D, De Palma A, Grasso L, Di Somma C, Mauri P, Benazzi L, Franzone A, Jotti GS, Bang ML, Esposito G, Colao A, Condorelli G, Catalucci D. The circulating level of FABP3 is an indirect biomarker of microRNA-1. J Am Coll Cardiol. 2013;61(1):88-95. https://doi.org/10.1016/j.jacc.2012.08.1003
• [20] Carrillo-Salinas FJ, Ngwenyama N, Anastasiou M, Kaur K, Alcaide P. Heart Inflammation: Immune Cell Roles and Roads to the Heart. Am J Pathol. 2019;189(8):1482-1494. https://doi.org/10.1016/j.ajpath.2019.04.009
• [21] Tang W, Zhang Y, Wang Z, Yuan X, Chen X, Yang X, Qi Z, Zhang J, Li J, Xie X. Development and validation of a multivariate model for predicting heart failure hospitalization and mortality in patients receiving maintenance hemodialysis. Ren Fail. 2023;45(2):2255686. https://doi.org/10.1080%2F0886022X.2023.2255686
• [22] Yu X, Zhang D, Chen J, Zhang H, Shen Z, Lv S, Wang Y, Huang X, Zhang X, Zhang C. Heart failure with preserved ejection fraction in haemodialysis patients: prevalence, diagnosis, risk factors, prognosis. ESC Heart Fail. 2023;10(5):2816-2825. https://doi.org/10.1002%2Fehf2.14447
• [23] Hsu PY, Wei YJ, Lee JJ, Niu SW, Huang JC, Hsu CT, Jang TY, Yeh ML, Huang CI, Liang PC, Lin YH, Hsieh MY, Hsieh MH, Chen SC, Dai CY, Lin ZY, Chen SC, Huang JF, Chang JM, Hwang SJ, Chuang WL, Huang CF, Chiu YW, Yu ML. Comedications and potential drug-drug interactions with direct-acting antivirals in hepatitis C patients on hemodialysis. Clin Mol Hepatol. 2021;27(1):186-196. https://doi.org/10.3350/cmh.2020.0180
• [24] Cafka M, Rroji M, Seferi S, Barbullushi M, Burazeri G, Spahia N, Idrizi A, Likaj E, Seiti J, Lazaj J, Goda A. Inflammation, Left Ventricular Hypertrophy, and Mortality in End-stage Renal Disease. Iran J Kidney Dis. 2016;10(4):217-23.
• [25] Nishiura R, Fujimoto S, Sato Y, Yamada K, Hisanaga S, Hara S, Nakao H, Kitamura K. Elevated osteoprotegerin levels predict cardiovascular events in new hemodialysis patients. Am J Nephrol. 2009;29(3):257-263. https://doi.org/10.1159/000157629
• [26] Collado S, Coll E, Nicolau C, Azqueta M, Pons M, Cruzado JM, de la Torre B, Deulofeu R, Mojal S, Pascual J, Cases A. Serum osteoprotegerin in prevalent hemodialysis patients: associations with mortality, atherosclerosis and cardiac function. BMC Nephrol. 2017;18(1):290. https://doi.org/10.1186%2Fs12882-017-0701-8
• [27] Zotos P, Kaldara E, Kapelios C, Sousonis V, Nana E, Agapitou V, Dimopoulos S, Kontogiannis CD, Chalazonitis A, Margari Z, Karga E, Terrovitis JV, Nanas JN. Bone metabolism in chronic heart failure. J Osteopor Phys Act. 2014;2(2):121. http://dx.doi.org/10.4172/2329-9509.1000121
• [28] Ostrowska Z, Ziora K, Oświęcimska J, Marek B, Świętochowska E, Kajdaniuk D, Strzelczyk J, Cieślicka A, Wołkowska-Pokrywa K, Kos-Kudła B. Selected pro-inflammatory cytokines, bone metabolism, osteoprotegerin, and receptor activator of nuclear factor-kB ligand in girls with anorexia nervosa. Endokrynol Pol. 2015;66(4):313-321. https://doi.org/10.5603/ep.2015.0040
• [29] Tisato V, Zauli G, Voltan R, Gianesini S, di Iasio MG, Volpi I, Fiorentini G, Zamboni P, Secchiero P. Endothelial cells obtained from patients affected by chronic venous disease exhibit a pro-inflammatory phenotype. PLoS One. 2012;7(6):e39543. https://doi.org/10.1371/journal.pone.0039543
• [30] Moran CS, Cullen B, Campbell JH, Golledge J. Interaction between angiotensin II, osteoprotegerin, and peroxisome proliferator-activated receptor-gamma in abdominal aortic aneurysm. J Vasc Res. 2009;46(3):209-217. https://doi.org/10.1159/000163019
• [31] Rodríguez-Calvo R, Granado-Casas M, Pérez-Montes de Oca A, Julian MT, Domingo M, Codina P, Santiago-Vacas E, Cediel G, Julve J, Rossell J, Masana L, Mauricio D, Lupón J, Bayes-Genis A, Alonso N. Fatty Acid Binding Proteins 3 and 4 Predict Both All-Cause and Cardiovascular Mortality in Subjects with Chronic Heart Failure and Type 2 Diabetes Mellitus. Antioxidants (Basel). 2023 4;12(3):645. https://doi.org/10.3390/antiox12030645
• [32] Legarra MI, Monzo JJB, Caravaca P, Rodríguez D, Cuadrado E, Farrero M, Maduell F. Cardıac Alteratıons Found In Patıents Who Start Dıalysıs. Nephrol Dial Transplant. 2023;38 (Supplement-1): gfad063d_6869. https://doi.org/10.1093/ndt/gfad063d_6869
• [33] Başar O, Akbal E, Köklü S, Tuna Y, Koçak E, Başar N, Tok D, Erbiş H, Senes M. Increased H-FABP concentrations in nonalcoholic fatty liver disease. Possible marker for subclinical myocardial damage and subclinical atherosclerosis. Herz. 2013;38(4):417-422. https://doi.org/10.1007/s00059-012-3714-x
• [34] Beysel S, Kizilgul M, Ozbek M, Caliskan M, Kan S, Apaydin M, Ozcelik O, Cakal E. Heart-type fatty acid binding protein levels in elderly diabetics without known cardiovascular disease. Clin Interv Aging. 2017;12:2063-2068. https://doi.org/10.2147%2FCIA.S137247
• [35] Putra IGBGP, Widodo S, Wita IW, Bakta IM, Sudarsa IW. The Comparison of Lipid Profile in Heart Failure Patients with and without Acute Renal Dysfunction. Biomed Pharmacol J . 2022;15(4):2323-2329. https://dx.doi.org/10.13005/bpj/2571
• [36] Bawakhan BH, Chandru M, Moger V. A study of lipid profile in maintenance hemodialysis patients. Int J Clin Biochem Res. 2020;7(2): 172-175. http://dx.doi.org/10.18231/j.ijcbr.2020.037
• [37] Theofilis P, Vordoni A, Koukoulaki M, Vlachopanos G, Kalaitzidis RG. Dyslipidemia in Chronic Kidney Disease: Contemporary Concepts and Future Therapeutic Perspectives. Am J Nephrol. 2021;52(9):693-701. https://doi.org/10.1159/000518456
• [38] Cao H, Zhu Y, Hu G, Zhang Q, Zheng L. Gut microbiome and metabolites, the future direction of diagnosis and treatment of atherosclerosis? Pharmacol Res. 2023;187:106586. https://doi.org/10.1016/j.phrs.2022.106586
• [39] Podkowińska A, Formanowicz D. Chronic Kidney Disease as Oxidative Stress- and Inflammatory-Mediated Cardiovascular Disease. Antioxidants (Basel). 2020;9(8):752. https://doi.org/10.3390/antiox9080752
• [40] Rochette L, Meloux A, Rigal E, Zeller M, Malka G, Cottin Y, Vergely C. The Role of Osteoprotegerin in Vascular Calcification and Bone Metabolism: The Basis for Developing New Therapeutics. Calcif Tissue Int. 2019;105(3):239-251. https://doi.org/10.1007/s00223-019-00573-6
• [41] Huang QX, Li JB, Huang N, Huang XW, Li YL, Huang FX. Elevated Osteoprotegerin Concentration Predicts Increased Risk of Cardiovascular Mortality in Patients with Chronic Kidney Disease: A Systematic Review and Meta-Analysis. Kidney Blood Press Res. 2020;45(4):565-575. https://doi.org/10.1159/000508978
• [42] Al-Shammari AH, Khudhur A, Abdulamir H. Effect of intralesional levofloxacin in the treatment of cutaneous leishmaniasis: intralesional levofloxacin for cutaneous leishmaniasis treatment. J Popul Ther Clin Pharmacol. 2023;30(1):e92–e100. http://dx.doi.org/10.47750/jptcp.2023.1028
• [43] Aldafaay AA, Amir HAA, Abdulhussain HA, Badry AS, Abdulsada AK. The use of urinary α-amylase level in a diagnosis of chronic renal failure. Res J Pharm Technol. 2021;14(3):1597-1600. http://dx.doi.org/10.5958/0974-360X.2021.00283.3
• [44] Jabur MS, Manna MJ, Mohammed HR, Baqir LS, Abdulamir HA. Ocular Hypotensive Effect for the Topical Amlodipine 0.5% Eye Drop. Lat Am J Pharm. 2023;42 (special issue): 311-314.