MIF在慢性肾脏病患者中发生心血管事件的相关性
The Correlation between MIF and Cardiovascular Events in Patients with Chronic Kidney Disease
DOI: 10.12677/ACM.2023.13112440, PDF,   
作者: 李思莹, 刘 珍:新疆医科大学第一附属医院肾脏病中心,新疆 乌鲁木齐
关键词: 慢性肾脏病心血管疾病综述MIFChronic Kidney Disease Cardiovascular Disease Overview MIF
摘要: 慢性肾脏病(CKD)现在被认为是心血管疾病(CVD)的独立危险因素。而慢性肾脏病发生心血管事件的机制主要包括:肾素–血管紧张素–醛固酮系统异常激活(RAAS)、氧化应激、炎症反应、组织纤维化、贫血、自主神经系统功能紊乱、尿毒症毒素、代谢紊乱等。对于慢性肾脏病患者并发心血管事件,巨噬细胞迁移抑制因子(MIF)在其中扮演什么角色仍然没有统一的结论。MIF仍是目前研究的热点炎症因子。
Abstract: Chronic kidney disease (CKD) is now considered an independent risk factor for cardiovascular dis-ease (CVD). The mechanisms of cardiovascular events in chronic kidney disease mainly include: ab-normal activation of the renin angiotensin aldosterone system (RAAS), oxidative stress, inflamma-tory response, tissue fibrosis, anemia, dysfunction of the autonomic nervous system, uremic toxins, metabolic disorders, etc. There is still no unified conclusion on the role of macrophage migration in-hibitory factor (MIF) in cardiovascular events in patients with chronic kidney disease. MIF is still a hot research topic for inflammatory factors.
文章引用:李思莹, 刘珍. MIF在慢性肾脏病患者中发生心血管事件的相关性[J]. 临床医学进展, 2023, 13(11): 17420-17427. https://doi.org/10.12677/ACM.2023.13112440

参考文献

[1] Obrador, G.T., Levin, A., et al. (2019) CKD Hotspots: Challenges and Areas of Opportunity. Seminars in Nephrology, 39, 308-314. [Google Scholar] [CrossRef] [PubMed]
[2] Formentini, I., Bobadilla, M., Haefliger, C., et al. (2012) Current Drug Development Challenges in Chronic Kidney Disease (CKD)—Identification of Individualized Determinants of Renal Progression and Premature Cardiovascular Disease (CVD). Nephrology Dialysis Transplantation, 27, iii81-iii88. [Google Scholar] [CrossRef] [PubMed]
[3] El-Mahdy, R.I., et al. (2021) Functional Variants in the Promoter Region of Macrophage Migration Inhibitory Factor rs755622 Gene (MIF G173C) among Patients with Heart Failure: Association with Echocardiographic Indices and Disease Severity. Heart & Lung: The Journal of Critical Care, 50, 92-100. [Google Scholar] [CrossRef] [PubMed]
[4] Chin, C.G., Chen, Y.C., Lin, Y.K., et al. (2022) Effect of Mac-rophage Migration Inhibitory Factor on Pulmonary Vein Arrhythmogenesis through Late Sodium Current. Europace, 25, 698-706. [Google Scholar] [CrossRef] [PubMed]
[5] Bruchfeld, A., Carrero, J.J., Qureshi, A.R., et al. (2009) Elevated Serum Macrophage Migration Inhibitory Factor (MIF) Concentrations in Chronic Kidney Disease (CKD) Are Associated with Markers of Oxidative Stress and Endothelial Activation. Molecular Medicine, 15, 70-75. [Google Scholar] [CrossRef] [PubMed]
[6] Luo, J.Y., Fang, B.B., Du, G.L., et al. (2021) Association be-tween MIF Gene Promoter rs755622 and Susceptibility to Coronary Artery Disease and Inflammatory Cytokines in the Chinese Han Population. Scientific Reports, 11, Article No. 8050. [Google Scholar] [CrossRef] [PubMed]
[7] Liu, Y., Zhang, X., Liu, G., et al. (2016) Expressions of Macro-phage Migration Inhibitory Factor in Patients with Chronic Kidney Disease. Nigerian Journal of Clinical Practice, 19, 778-783. [Google Scholar] [CrossRef] [PubMed]
[8] Bernhagen, J., Calandra, T., Mitchell, R.A., et al. (1993) MIF Is a Pituitary-Derived Cytokine That Potentiates Lethal Endotoxaemia. Nature, 365, 756-759. [Google Scholar] [CrossRef] [PubMed]
[9] Aeberli, D., Yang, Y., Mansell, A., et al. (2006) Endogenous Macrophage Migration Inhibitory Factor Modulates Glucocorticoid Sensitivity in Macrophages via Effects on MAP Kinase Phospha-tase-1 and p38 MAP Kinase. FEBS Letters, 580, 974-981. [Google Scholar] [CrossRef] [PubMed]
[10] Calandra, T. and Roger, T. (2003) Macrophage Migration Inhib-itory Factor: A Regulator of Innate Immunity. Nature Reviews Immunology, 3, 791-800. [Google Scholar] [CrossRef] [PubMed]
[11] Bacher, M., Meinhardt, A., Lan, H.Y., et al. (1998) MIF Expression in the Rat Brain: Implications for Neuronal Function. Molecular Medicine (Cambridge, Mass.), 4, 217-230. [Google Scholar] [CrossRef
[12] Bernhagen, J., Calandra, T., Cerami, A., et al. (1994) Macrophage Mi-gration Inhibitory Factor Is a Neuroendocrine Mediator of Endotoxaemia. Trends in Microbiology, 2, 198-201. [Google Scholar] [CrossRef
[13] Nishio, Y., Minami, A., Kato, H., et al. (1999) Identification of Macrophage Migration Inhibitory Factor (MIF) in Rat Peripheral Nerves: Its Possible Involvement in Nerve Regener-ation. Biochimica et Biophysica Acta (BBA)—Molecular Basis of Disease, 1453, 74-82. [Google Scholar] [CrossRef
[14] Wada, S., Fujimoto, S., Mizue, Y., et al. (1997) Macrophage Migration Inhibitory Factor in the Human Ovary: Presence in the Follicular Fluids and Production by Granulosa Cells. IUBMB Life, 41, 805-814. [Google Scholar] [CrossRef] [PubMed]
[15] Meyer-Siegler, K.L., Vera, P.L., Iczkowski, K.A., et al. (2007) Macrophage Migration Inhibitory Factor (MIF) Gene Polymorphisms Are Associated with Increased Prostate Cancer In-cidence. Genes & Immunity, 8, 646-652. [Google Scholar] [CrossRef] [PubMed]
[16] Wistow, G.J., Shaughnessy, M.P., Lee, D.C., et al. (1993) A Mac-rophage Migration Inhibitory Factor Is Expressed in the Differentiating Cells of the Eye Lens. Proceedings of the Nation-al Academy of Sciences, 90, 1272-1275. [Google Scholar] [CrossRef] [PubMed]
[17] Waeber, G., Calandra, T., Roduit, R., et al. (1997) Insulin Secretion Is Regulated by the Glucose-Dependent Production of Islet β Cell Macrophage Migration Inhibitory Factor. Proceedings of the National Academy of Sciences, 94, 4782-4787. [Google Scholar] [CrossRef] [PubMed]
[18] Bernhagen, J., Bacher, M., Calandra, T., et al. (1996) An Essential Role for Macrophage Migration Inhibitory Factor in the Tuberculin Delayed-Type Hypersensitivity Reaction. The Journal of Experimental Medicine, 183, 277-282. [Google Scholar] [CrossRef] [PubMed]
[19] Schober, A., Bernhagen, J. and Weber, C. (2008) Chemokine-Like Functions of MIF in Atherosclerosis. Journal of Molecular Medicine, 86, 761-770. [Google Scholar] [CrossRef] [PubMed]
[20] Denkinger, C., Metz, C., Fingerle-Rowson, G., et al. (2004) Macrophage Migration Inhibitory Factor and Its Role in Autoimmune Diseases. Archivum Immunologiae et Therapiae Experimentalis, 52, 389-400.
[21] Pan, J.H., Lindholt, J.S., Sukhova, G.K., et al. (2003) Macrophage Migration Inhibi-tory Factor Is Associated with Aneurysmal Expansion. Journal of Vascular Surgery, 37, 628-635. [Google Scholar] [CrossRef] [PubMed]
[22] Donnelly, S.C., Haslett, C., Reid, P.T., et al. (1997) Regulatory Role for Macrophage Migration Inhibitory Factor in Acute Respiratory Distress Syndrome. Nature Medicine, 3, 320-323. [Google Scholar] [CrossRef] [PubMed]
[23] Zhang, L., Wang, F., Wang, L., 等. 中国慢性肾脏病的流行病学调查: 横断面研究[J]. 中华肾病研究电子杂志, 2012(2): 127.
[24] Parfrey, P.S., Foley, R.N., Harnett, J.D., et al. (1996) Outcome and Risk Factors for Left Ventricular Disorders in Chronic Uraemia. Nephrology, Dialysis, Transplantation, 11, 1277-1285. [Google Scholar] [CrossRef] [PubMed]
[25] Hallan, S.I., Dahl, K., Oien, C.M., et al. (2006) Screening Strategies for Chronic Kidney Disease in the General Population: Follow-Up of Cross Sectional Health Survey. BMJ: British Medical Journal, 333, Article No. 1047. [Google Scholar] [CrossRef
[26] Kelsey, R. (2012) Chronic Kidney Disease: A Risk Factor for Stroke and Bleeding in Patients with Atrial Fibrillation. Nature Reviews Nephrology, 8, 551-551. [Google Scholar] [CrossRef] [PubMed]
[27] 陈牧, 李毅刚. 生物标志物与心房颤动卒中风险分层[J]. 中国心脏起搏与心电生理杂志, 2014, 28(2): 161-163.
[28] Xu, G.S., Luo, K.P., Liu, H.X., et al. (2015) The Progress of In-flammation and Oxidative Stress in Patients with Chronic Kidney Disease. Renal Failure, 37, 45-49.
[29] Yu, C.M., et al. (2001) Elevation of Plasma Level of Macrophage Migration Inhibitory Factor in Patients with Acute Myocardial In-farction. The American Journal of Cardiology, 88, 774-777. [Google Scholar] [CrossRef
[30] Yu, C.M., Lai, K.W.H., Chen, Y.X., et al. (2003) Expression of Macrophage Migration Inhibitory Factor in Acute Ischemic Myocardial Injury. Journal of Histochemistry & Cyto-chemistry, 51, 625-631. [Google Scholar] [CrossRef] [PubMed]
[31] Takahashi, M. (2001) Macrophage Migration Inhibitory Factor as a Redox-Sensitive Cytokine in Cardiac Myocytes. Cardiovascular Research, 52, 438-445. [Google Scholar] [CrossRef
[32] Lopez, A.D., Mathers, C.D., Ezzati, M., et al. (2006) Global and Regional Burden of Disease and Risk Factors, 2001: Systematic Analysis of Population Health Data. The Lancet (London, England), 367, 1747-1757. [Google Scholar] [CrossRef
[33] Petrovsky, N., Socha, L., Silva, D., et al. (2003) Macrophage Migration Inhibitory Factor Exhibits a Pronounced Circadian Rhythm Relevant to Its Role as a Glucocorticoid Coun-ter-Regulator. Immunology and Cell Biology, 81, 137-143. [Google Scholar] [CrossRef] [PubMed]
[34] 郑猛, 单志新, 林秋雄, 等. GRK2调控血管紧张素II诱导产生MIF[C]//第七届海峡两岸心血管科学研讨会论文集. 中国病理生理学会, 中国药理学会, 中国生理学会, 台湾急诊医学会, 香港大学心脏血管研究所, 中华医学会心血管专业委员会. 2009: 57.
[35] Tilstam, P.V., Qi, D., Leng, L., et al. (2017) MIF Family Cytokines in Cardio-vascular Diseases and Prospects for Precision-Based Therapeutics. Expert Opinion on Therapeutic Targets, 21, 671-683. [Google Scholar] [CrossRef] [PubMed]
[36] Shi, X., Leng, L., Wang, T., et al. (2006) CD44 Is the Sig-naling Component of the Macrophage Migration Inhibitory Factor-CD74 Receptor Complex. Immunity, 25, 595-606. [Google Scholar] [CrossRef] [PubMed]
[37] Lue, H., Thiele, M., Franz, J., et al. (2007) Macrophage Migra-tion Inhibitory Factor (MIF) Promotes Cell Survival by Activation of the Akt Pathway and Role for CSN5/JAB1 in the Control of Autocrine MIF Activity. Oncogene, 26, 5046-5059. [Google Scholar] [CrossRef] [PubMed]
[38] Leng, L., Metz, C.N., Fang, Y., et al. (2003) MIF Signal Transduction Initiated by Binding to CD74. Journal of Experimental Medicine, 197, 1467-1476. [Google Scholar] [CrossRef] [PubMed]
[39] Choi, S., Liu, X., Pan, Z., et al. (2018) Zinc Deficiency and Cellular Oxidative Stress: Prognostic Implications in Cardiovascular Diseases. Acta Pharmacologica Sinica, 39, 1120-1132. [Google Scholar] [CrossRef] [PubMed]
[40] Miyazaki, K., Isbel, N.M., Lan, H.Y., et al. (1997) Up-Regulation of Macrophage Colony-Stimulating Factor (M-CSF) and Migration Inhibitory Factor (MIF) Expression and Monocyte Recruitment during Lipid-Induced Glomerular Injury in the Exogenous Hypercholesterolaemic (ExHC) Rat. Clinical and Experimental Immunology, 108, 318-323. [Google Scholar] [CrossRef] [PubMed]
[41] Christine, K., Bishan, Y., Sabrina, R., et al. (2023) Pathways Linking Aging and Atheroprotection in Mif-Deficient Atherosclerotic Mice. FASEB Journal: Official Publica-tion of the Federation of American Societies for Experimental Biology, 37, e22752. [Google Scholar] [CrossRef
[42] Krammer, C., Kontos, C., Dewor, M., et al. (2021) A MIF-Derived Cyclopeptide that Inhibits MIF Binding and Atherogenic Signaling via the Chemokine Receptor CXCR2. Chembiochem, 22, 1012-1019. [Google Scholar] [CrossRef] [PubMed]
[43] Liu, X.Q., Jiang, T.T., Wang, M.Y., et al. (2022) Using Machine Learning to Evaluate the Role of Microinflammation in Cardiovascular Events in Patients with Chronic Kidney Disease. Frontiers in Immunology, 12, Article ID: 796383. [Google Scholar] [CrossRef] [PubMed]
[44] Ruiz-Ortega, M., Rupérez, M., Esteban, V., et al. (2006) Angio-tensin II: A Key Factor in the Inflammatory and Fibrotic Response in Kidney Diseases. Nephrology Dialysis Transplan-tation, 21, 16-20. [Google Scholar] [CrossRef] [PubMed]
[45] Lan, H.Y., Mu, W., Yang, N., et al. (1996) De Novo Re-nal Expression of Macrophage Migration Inhibitory Factor during the Development of Rat Crescentic Glomerulonephritis. The American Journal of Pathology, 149, 1119-1127.
[46] Lan, H.Y., Yang, N., Brown, F.G., et al. (1998) Macro-phage Migration Inhibitory Factor Expression in Human Renal Allograft Rejection. Transplantation, 66, 1465-1471. [Google Scholar] [CrossRef] [PubMed]
[47] Lan, H.Y., Yang, N., Nikolic-Paterson, D.J., et al. (2000) Expression of Macrophage Migration Inhibitory Factor in Human Glomerulonephritis. Kidney International, 57, 499-509. [Google Scholar] [CrossRef] [PubMed]
[48] Brown, F.G., Nikolic-Paterson, D.J., Hill, P.A., et al. (2002) Urine Macrophage Migration Inhibitory Factor Reflects the Severity of Renal Injury in Human Glomerulonephri-tis. Journal of the American Society of Nephrology, 13, S7-S13. [Google Scholar] [CrossRef
[49] Burton, J.D., Ely, S., Reddy, P.K., et al. (2004) CD74 Is Ex-pressed by Multiple Myeloma and Is a Promising Target for Therapy. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 10, 6606-6611. [Google Scholar] [CrossRef
[50] Otterstrom, C., Soltermann, A., Opitz, I., et al. (2014) CD74: A New Prognostic Factor for Patients with Malignant Pleural Mesothelioma. British Journal of Cancer, 110, 2040-2046. [Google Scholar] [CrossRef] [PubMed]
[51] Datta, M.W., Shahsafaei, A., Nadler, L.M., et al. (2000) Expression of MHC Class II-Associated Invariant Chain (Ii;CD74) in Thymic Epithelial Neoplasms. Applied Immunohistochemistry & Molecular Morphology: AIMM, 8, 210-215. [Google Scholar] [CrossRef] [PubMed]
[52] Beswick, E.J., Das, S., Pinchuk, I.V., et al. (2005) Hel-icobacter pylori-Induced IL-8 Production by Gastric Epithelial Cells Up-Regulates CD74 Expression. Journal of Immu-nology (Baltimore, Md.: 1950), 175, 171-176. [Google Scholar] [CrossRef] [PubMed]
[53] Martín-Ventura, J.L., Madrigal-Matute, J., Muñoz-Garcia, B., et al. (2009) Increased CD74 Expression in Human Atherosclerotic Plaques: Contribution to Inflammatory Responses in Vascular Cells. Cardiovascular Research, 83, 586-594. [Google Scholar] [CrossRef] [PubMed]
[54] Heinrichs, D., Knauel, M., Offermanns, C., et al. (2011) Macrophage Migration Inhibitory Factor (MIF) Exerts Antifibrotic Effects in Experimental Liver Fibrosis via CD74. Proceedings of the National Academy of Sciences of the United States of America, 108, 17444-17449. [Google Scholar] [CrossRef] [PubMed]
[55] Miller, E.J., Li, J., Leng, L., et al. (2008) Mac-rophage Migration Inhibitory Factor Stimulates AMP-Activated Protein Kinase in the Ischaemic Heart. Nature, 451, 578-582. [Google Scholar] [CrossRef] [PubMed]
[56] Sanchez-Niño, M.D., Sanz, A.B., Ruiz-Andres, O., et al. (2013) MIF, CD74 and Other Partners in Kidney Disease: Tales of a Promiscuous Couple. Cytokine & Growth Factor Reviews, 24, 23-40. [Google Scholar] [CrossRef] [PubMed]
[57] Lawrance, I.C., Fiocchi, C. and Chakravarti, S. (2001) Ulcera-tive Colitis and Crohn’s Disease: Distinctive Gene Expression Profiles and Novel Susceptibility Candidate Genes. Hu-man Molecular Genetics, 10, 445-456. [Google Scholar] [CrossRef] [PubMed]
[58] Momburg, F., Koch, N., Möller, P., et al. (1986) Differential Expression of Ia and Ia-Associated Invariant Chain in Mouse Tissues after in Vivo Treatment with IFN-Gamma. Journal of Immu-nology (Baltimore, Md.: 1950), 136, 940-948. [Google Scholar] [CrossRef
[59] Su, H., Na, N., Zhang, X., et al. (2017) The Biological Function and Significance of CD74 in Immune Diseases. Inflammation Research, 66, 209-216. [Google Scholar] [CrossRef] [PubMed]
[60] Esteban, V., Ruperez, M., Sánchez-López, E., et al. (2005) Angiotensin IV Activates the Nuclear Transcription Factor-kappaB and Related Proinflammatory Genes in Vas-cular Smooth Muscle Cells. Circulation Research, 96, 965-973. [Google Scholar] [CrossRef
[61] Kim, J., Montagnani, M., Koh, K.K., et al. (2006) Re-ciprocal Relationships between Insulin Resistance and Endothelial Dysfunction: Molecular and Pathophysiological Mechanisms. Circulation, 113, 1888-1904. [Google Scholar] [CrossRef
[62] Prasad, A.S. (2008) Clinical, Immunological, An-ti-Inflammatory and Antioxidant Roles of Zinc. Experimental Gerontology, 43, 370-377. [Google Scholar] [CrossRef] [PubMed]
[63] Beattie, J.H., Gordon, M.J., Duthie, S.J., et al. (2012) Suboptimal Dietary Zinc Intake Promotes Vascular Inflammation and Atherogenesis in a Mouse Model of Atherosclerosis. Molecu-lar Nutrition & Food Research, 56, 965-973. [Google Scholar] [CrossRef] [PubMed]
[64] Wong, C.P. and Ho, E. (2012) Zinc and Its Role in Age-Related In-flammation and Immune Dysfunction. Molecular Nutrition & Food Research, 56, 77-87. [Google Scholar] [CrossRef] [PubMed]
[65] Cardozo, L.F.M.F. and Mafra, D. (2020) Don’t Forget the Zinc. Nephrology Dialysis Transplantation, 35, 1094-1098. [Google Scholar] [CrossRef] [PubMed]
[66] Mahajan, S.K., Bowersox, E.M., Rye, D.L., et al. (1989) Factors Under-lying Abnormal Zinc Metabolism in Uremia. Kidney International. Supplement, 27, S269-S273.
[67] Nakatani, S., Mori, K., Shoji, T., et al. (2021) Association of Zinc Deficiency with Development of CVD Events in Patients with CKD. Nu-trients, 13, Article No. 1680. [Google Scholar] [CrossRef] [PubMed]
[68] Nardinocchi, L., Pantisano, V., Puca, R., et al. (2010) Zinc Downregulates HIF-1α and Inhibits Its Activity in Tumor Cells in Vitro and in Vivo. PLOS ONE, 5, e15048. [Google Scholar] [CrossRef] [PubMed]
[69] Rao, K., Sethi, K., Ischia, J., et al. (2017) Protective Effect of Zinc Preconditioning against Renal Ischemia Reperfusion Injury Is Dose Dependent. PLOS ONE, 12, e0180028. [Google Scholar] [CrossRef] [PubMed]
[70] Meng, X.M., Nikolic-Paterson, D.J. and Lan, H.Y. (2014) In-flammatory Processes in Renal Fibrosis. Nature Reviews. Nephrology, 10, 493-503. [Google Scholar] [CrossRef] [PubMed]
[71] Hodgkins, K.S. and Schnaper, H.W. (2012) Tubulointerstitial Injury and the Progression of Chronic Kidney Disease. Pediatric Nephrology (Berlin, Germany), 27, 901-909. [Google Scholar] [CrossRef] [PubMed]
[72] Ruiz-Ortega, M., Rayego-Mateos, S., Lamas, S., et al. (2020) Targeting the Progression of Chronic Kidney Disease. Nature Reviews Nephrology, 16, 269-288. [Google Scholar] [CrossRef] [PubMed]
[73] Biernacka, A. and Frangogiannis, N.G. (2011) Aging and Cardiac Fibrosis. Aging and Disease, 2, 158-173.
[74] Lawson, J., Elliott, J., Wheeler-Jones, C., et al. (2015) Renal Fibrosis in Feline Chronic Kidney Disease: Known Mediators and Mechanisms of Injury. The Veterinary Journal, 203, 18-26. [Google Scholar] [CrossRef] [PubMed]
[75] Lim, J.H., Kim, E.N., Kim, M.Y., et al. (2012) Age-Associated Molecular Changes in the Kidney in Aged Mice. Oxidative Medicine and Cellular Longevity, 2012, Article ID: 171383. [Google Scholar] [CrossRef] [PubMed]
[76] Gagliano, N., Arosio, B., Santambrogio, D., et al. (2000) Age-Dependent Expression of Fibrosis-Related Genes and Collagen Deposition in Rat Kidney Cortex. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 55, B365-B372. [Google Scholar] [CrossRef
[77] Denic, A., Glassock, R.J. and Rule, A.D. (2016) Structural and Functional Changes with the Aging Kidney. Advances in Chronic Kidney Disease, 23, 19-28. [Google Scholar] [CrossRef] [PubMed]
[78] Maric, C., Sandberg, K. and Hinojosa-Laborde, C. (2004) Glomer-ulosclerosis and Tubulointerstitial Fibrosis Are Attenuated with 17beta-Estradiol in the Aging Dahl Salt Sensitive Rat. Journal of the American Society of Nephrology: JASN, 15, 1546-1556. [Google Scholar] [CrossRef
[79] Mehta, R., Cai, X., Lee, J., et al. (2016) Association of Fibroblast Growth Factor 23 with Atrial Fibrillation in Chronic Kidney Disease, from the Chronic Renal Insufficiency Cohort Study. JAMA Cardiology, 1, 548-556. [Google Scholar] [CrossRef] [PubMed]
[80] Seiler, S., Reichart, B., Roth, D., et al. (2011) FGF-23 Associ-ates with Death, Cardiovascular Events, and Initiation of Chronic Dialysis. Journal of the American Society of Nephrolo-gy: JASN, 22, 1913-1922. [Google Scholar] [CrossRef
[81] Gutiérrez, O.M., Januzzi, J.L., Isakova, T., et al. (2009) Fibroblast Growth Factor 23 and Left Ventricular Hypertrophy in Chronic Kidney Disease. Circulation, 119, 2545-2552. [Google Scholar] [CrossRef
[82] Gutiérrez, O.M., Mannstadt, M., Isakova, T., et al. (2008) Fibroblast Growth Factor 23 and Mortality among Patients Undergoing Hemodialysis. The New England Journal of Medicine, 359, 584-592. [Google Scholar] [CrossRef
[83] Isakova, T., Xie, H., Yang, W., et al. (2011) Fibroblast Growth Factor 23 and Risks of Mortality and End-Stage Renal Disease in Patients with Chronic Kidney Disease. JAMA, 305, 2432-2439. [Google Scholar] [CrossRef] [PubMed]
[84] Scialla, J.J., Xie, H., Rahman, M., et al. (2014) Fibroblast Growth Factor-23 and Cardiovascular Events in CKD. Journal of the American Society of Nephrology: JASN, 25, 349-360. [Google Scholar] [CrossRef
[85] Scialla, J.J., Astor, B.C., Isakova, T., et al. (2013) Miner-al Metabolites and CKD Progression in African Americans. Journal of the American Society of Nephrology: JASN, 24, 125-135. [Google Scholar] [CrossRef