Serum Levels of Fibroblast Growth Factor 23 in People Living with HIV

Author(s): Yusuke Yoshino*, Kazunori Seo, Takatoshi Kitazawa, Yasuo Ota

Journal Name: Current HIV Research

Volume 17 , Issue 3 , 2019

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Graphical Abstract:


Background: Fibroblast growth factor (FGF) 23 is a well-known phosphaturic hormone produced mainly by bone cells to maintain phosphate and mineral homeostasis. Serum FGF23 levels are elevated in patients with chronic kidney disease (CKD), and elevated FGF23 might increase the risk of cardiovascular disease (CVD). Several reports have documented an increased incidence of risk factors for osteopenia, CKD, and CVD in people living with HIV (PLWH). However, few reports related to FGF23 in PLWH have been published.

Methods: Male HIV patients who presented to the outpatient clinic of Teikyo University Hospital, Tokyo, Japan, in 2015 and were treated with antiretroviral therapy (ART) for > 6 months were enrolled in the study. In addition to serum FGF23 measurements, the clinical factors assessed included age, ART regimens, and laboratory data. Spearman correlation and multiple regression analysis were performed to determine factors significantly associated with FGF23.

Results: In total, 67 patients were enrolled in the present study. The median age was 43.7 years, the median CD4 count was 529 cells/μL, and the median serum FGF23 level was 36.0 pg/mL. Based on correlation and multiple regression analyses, serum FGF23 levels were significantly correlated with HIV RNA > 50 copies (correlation analysis: t = 3.4259, P = 0.0011 / multiple regression analysis: P = 0.00106) or abacavir (ABC)/lamivudine (3TC) use (t = 2.8618, P = 0.0057 / P = 0.02704).

Conclusion: Factors significantly associated with elevated serum FGF23 levels included poor virologic control and ABC/3TC use.

Keywords: Fibroblast Growth Factor (FGF) 23, HIV, Abacavir, Cardiovascular disease risk, Antiretroviral Treatment (ART), Chronic Kidney Disease (CKD).

Mondy K, Overton ET, Grubb J, et al. Metabolic syndrome in HIV-infected patients from an urban, midwestern US outpatient population. Clin Infect Dis 2007; 44(5): 726-34.
[] [PMID: 17278068]
Grunfeld C, Delaney JA, Wanke C, et al. Preclinical atherosclerosis due to HIV infection: carotid intima-medial thickness measurements from the FRAM study. AIDS 2009; 23(14): 1841-9.
[] [PMID: 19455012]
Palau L, Menez S, Rodriguez-Sanchez J, et al. HIV-associated nephropathy: links, risks and management. HIV AIDS (Auckl) 2018; 10: 73-81.
[] [PMID: 29872351]
McDonald CL, Kaltman JR. Cardiovascular disease in adult and pediatric HIV/AIDS. J Am Coll Cardiol 2009; 54(13): 1185-8.
[] [PMID: 19761941]
Hadigan C, Meigs JB, Corcoran C, et al. Metabolic abnormalities and cardiovascular disease risk factors in adults with human immunodeficiency virus infection and lipodystrophy. Clin Infect Dis 2001; 32(1): 130-9.
[] [PMID: 11118392]
Wolf M. Update on fibroblast growth factor 23 in chronic kidney disease. Kidney Int 2012; 82(7): 737-47.
[] [PMID: 22622492]
Celik E, Guzel S, Abali R, Guzelant AY, Celik Guzel E, Kuçukyalcin V. The relationship between fibroblast growth factor 23 and osteoporosis in postmenopausal women. Minerva Med 2013; 104(5): 497-504.
[PMID: 24101107]
Mirza MA, Karlsson MK, Mellström D, et al. Serum fibroblast growth factor-23 (FGF-23) and fracture risk in elderly men. J Bone Miner Res 2011; 26(4): 857-64.
[] [PMID: 20928885]
Leifheit-Nestler M, Haffner D. Paracrine Effects of FGF23 on the Heart. Front Endocrinol (Lausanne) 2018; 9: 278.
[] [PMID: 29892269]
Gutiérrez OM, Mannstadt M, Isakova T, et al. Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 2008; 359(6): 584-92.
[] [PMID: 18687639]
Batra J, Buttar RS, Kaur P, Kreimerman J, Melamed ML. FGF-23 and cardiovascular disease: review of literature. Curr Opin Endocrinol Diabetes Obes 2016; 23(6): 423-9.
[] [PMID: 27652999]
Faul C, Amaral AP, Oskouei B, et al. FGF23 induces left ventricular hypertrophy. J Clin Invest 2011; 121(11): 4393-408.
[] [PMID: 21985788]
Richter B, Haller J, Haffner D, Leifheit-Nestler M. Klotho modulates FGF23-mediated NO synthesis and oxidative stress in human coronary artery endothelial cells. Pflugers Arch 2016; 468(9): 1621-35.
[] [PMID: 27448998]
Luetkens JA, Homsi R, Dabir D, et al. Comprehensive cardiac magnetic resonance for short-term follow-up in acute myocarditis. J Am Heart Assoc 2016; 5(7): 5.
[] [PMID: 27436306]
Qin Z, Liu X, Song M, et al. Fibroblast growth factor 23 as a predictor of cardiovascular and all-cause mortality in prospective studies. Atherosclerosis 2017; 261: 1-11.
[] [PMID: 28411494]
Kanjilal S, Rao VS, Mukherjee M, et al. Application of cardiovascular disease risk prediction models and the relevance of novel biomarkers to risk stratification in Asian Indians. Vasc Health Risk Manag 2008; 4(1): 199-211.
[] [PMID: 18629375]
Francis C, David V. Inflammation regulates fibroblast growth factor 23 production. Curr Opin Nephrol Hypertens 2016; 25(4): 325-32.
[] [PMID: 27191351]
Domingo P, Lamarca MK, Gallego-Escuredo JM, et al. Circulating fibroblast growth factor 23 (FGF23) levels are associated with metabolic disturbances and fat distribution but not cardiovascular risk in HIV-infected patients. J Antimicrob Chemother 2015; 70(6): 1825-32.
[] [PMID: 25700720]
Chen KY, Wang CH, Lin TY, et al. Monitoring early developed low bone mineral density in HIV-infected patients by intact parathyroid hormone and circulating fibroblast growth factor 23. J Microbiol Immunol Infect 2018; S1684-1182(18): 30219-6.
[] [PMID: 30293926]
Atta MG, Estrella MM, Fine DM, et al. Correlates and Longitudinal Renal and Cardiovascular Implications of FGF23 Levels in HIV-Positive Individuals. PLoS One 2016; 11(5)e0155312
[] [PMID: 27176000]
Sabin CA, Worm SW, Weber R, et al. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration. Lancet 2008; 371(9622): 1417-26.
[] [PMID: 18387667]
Sabin CA, Reiss P, Ryom L, et al. Is there continued evidence for an association between abacavir usage and myocardial infarction risk in individuals with HIV? A cohort collaboration. BMC Med 2016; 14: 61.
[] [PMID: 27036962]
Ding X, Andraca-Carrera E, Cooper C, et al. No association of abacavir use with myocardial infarction: findings of an FDA meta-analysis. J Acquir Immune Defic Syndr 2012; 61(4): 441-7.
[] [PMID: 22932321]
Brothers CH, Hernandez JE, Cutrell AG, et al. Risk of myocardial infarction and abacavir therapy: no increased risk across 52 GlaxoSmithKline-sponsored clinical trials in adult subjects. J Acquir Immune Defic Syndr 2009; 51(1): 20-8.
[] [PMID: 19282778]
Bavinger C, Bendavid E, Niehaus K, et al. Risk of cardiovascular disease from antiretroviral therapy for HIV: a systematic review. PLoS One 2013; 8(3)e59551
[] [PMID: 23555704]
Alvarez A, Orden S, Andújar I, et al. Cardiovascular toxicity of abacavir: A clinical controversy in need of a pharmacological explanation. AIDS 2017; 31(13): 1781-95.
[] [PMID: 28537935]
Young J, Mucsi I, Rollet-Kurhajec KC, Klein MB. Fibroblast growth factor 23: associations with antiretroviral therapy in patients co-infected with HIV and hepatitis C. HIV Med 2016; 17(5): 373-9.
[] [PMID: 26307135]
Havens PL, Stephensen CB, Van Loan MD, et al. Decline in Bone Mass With Tenofovir Disoproxil Fumarate/Emtricitabine Is Associated With Hormonal Changes in the Absence of Renal Impairment When Used by HIV-Uninfected Adolescent Boys and Young Men for HIV Preexposure Prophylaxis. Clin Infect Dis 2017; 64(3): 317-25.
[] [PMID: 28013265]
Saeedi R, Jiang SY, Holmes DT, Kendler DL. Fibroblast growth factor 23 is elevated in tenofovir-related hypophosphatemia. Calcif Tissue Int 2014; 94(6): 665-8.
[] [PMID: 24706031]
Bech A, Van Bentum P, Nabbe K, Gisolf J, Richter C, De Boer H. Fibroblast growth factor 23 in hypophosphataemic HIV-positive adults on tenofovir. HIV Med 2012; 13(9): 558-63.
[] [PMID: 22462533]
Saidenberg-Kermanac’h N, Souabni L, Prendki V, Prie D, Boissier MC. Normal plasma FGF23 levels kinetic in tenofovir-related hypophosphatemic osteomalacia in an HIV-infected patient with von Recklinghausen disease. Joint Bone Spine 2011; 78(3): 306-8.
[] [PMID: 21185214]

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Article Details

Year: 2019
Published on: 22 October, 2019
Page: [198 - 203]
Pages: 6
DOI: 10.2174/1570162X17666190903231203
Price: $65

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