Acute kidney injury and macrophages of the heart-kidney axis in patients with fatal myocardial infarction


DOI: https://dx.doi.org/10.18565/therapy.2022.9.44-52

Kercheva M.A., Ryabov V.V., Gombozhapova A.E., Stepanov I.V.

1) Siberian State Medical University of the Ministry of Healthcare of Russia, Tomsk; 2) Research institute of Cardiology of Tomsk National Research Medical Center of the Russian Academy of Sciences; 3) National Research Tomsk State University
Abstract. Experiments have shown that innate immune cells are involved in the development of acute kidney injury (AKI) during myocardial ischemia. However, it is not clear how the development of AKI affects the changes in the macrophage composition of the kidneys and myocardium and, ultimately, the processes of cardiorenal correlations and subsequent regeneration of the heart muscle in patients with myocardial infarction (MI).
The aim of the study is to evaluate the peculiarities of macrophage composition of kidneys and myocardium tissues, their relationship with the development of an unfavorable outcome of the disease in patients with fatal MI and AKI presence.
Material and methods. We analyzed histological sections of the kidneys and myocardium (from the infarct zone) obtained at autopsy in patients (n=28) who died from type I MI (age 74,8±9,3 years). The macrophage composition of the kidneys and myocardium was assessed by means of immunohistochemical studies using antibodies (CD68, CD163, CD206, stabilin-1). Depending on the presence of AKI, patients were divided into two groups: group 1 – AKI+ (n=10); and 2nd – AKI- (n=18).
Results. The main disease of the majority of patients included in the study is MI with ST-segment elevation, the cause of death is cardiogenic shock. Among all the cells of the macrophage series studied by us, the predominance of CD163+ cells was revealed both in the kidneys and in the myocardium. In the kidneys, the number of these cells was 30 (8; 108) in the total sample, 25 (8; 53) in the AKI- group, 30 (13; 108) in the AKI+ group; in the myocardium, similar indicators were 500 (21; 1729), 484 (21; 1729) and 598 (26; 1504) cells, respectively. The groups differed from each other only by the number of CD206+ cells in the kidneys: 2 (2; 3) in AKI+ versus 5 (2; 6) in AKI- (p=0.0004). Correlations were found between the time of death (r=-0,7, p <0,05), as well as between the number of CD206+ cells in the kidneys (r=-0,5, p <0,05) and the presence of AKI.
Conclusion. The macrophage composition of kidney and myocardial tissue in patients with fatal MI, regardless of the degree of kidney damage, was characterized by the predominance of CD163+ cells. AKI in individuals with fatal MI was associated with lower levels of CD206+ cells in the kidneys and a faster onset of death.
Keywords: macrophages, myocardial infarction, acute kidney injury, inflammation
Read entire article

Literature

1. Wang C., Pei Y.Y., Ma Y.H. et al. Risk factors for acute kidney injury in patients with acute myocardial infarction. Chin Med J (Engl). 2019; 132(14): 1660–65. https://dx.doi.org/10.1097/ CM9.0000000000000293.


2. Межонов Е. М., Вялкина Ю.А., Шалаев С.В. Прогностическое значение острого кардиоренального синдрома у пациентов с острой кардиальной патологией. Кардиология. 2019; 59(8S): 44–55. [Mezhonov E.M., Vyalkina Yu.A., Shalaev S.V. Prognostic value of acute cardiorenal syndrome in patients with acute cardiac pathology. Kardiologiya = Cardiology. 2019; 59(8S): 44–55 (In Russ.)]. https://dx.doi.org/10.18087/cardio.2678. EDN: JIUMER.


3. Рябова Т.Р., Рябов В.В., Соколов А.А. с соавт. Динамика структурно-геометрических и функциональных показателей левого желудочка в ранние и поздние сроки инфаркта миокарда. Ультразвуковая и функциональная диагностика. 2001; 3: 54–60. [Ryabova T.R., Ryabov V.V., Sokolov A.A. Dynamics of structural-geometric and functional parameters of the left ventricle in the early and late stages of myocardial infarction. Ul’trazvukovaya i funktsional’naya diagnostika = Ultrasonic and Functional Diagnostics. 2001; 3:54-60 (In Russ.)]. EDN: VWTHHX.


4. Kofman N., Margolis G., Gal-Oz A. et al. Long-term renal outcomes and mortality following renal injury among myocardial infarction patients treated by primary percutaneous intervention. Coron Artery Dis. 2019; 30(2): 87–92.https://dx.doi.org/10.1097/MCA.0000000000000678.


5. Gameiro J., Fonseca J.A., Outerelo C., Lopes J.A. Acute kidney injury: From diagnosis to prevention and treatment strategies. J Clin Med. 2020; 9(6): 1704. https://dx.doi.org/10.3390/jcm9061704.


6. Ridker P.M., Devalaraja M., Baeres F.M.M. et al. IL-6 inhibition with ziltivekimab in patients at high atherosclerotic risk (RESCUE): A double-blind, randomised, placebo-controlled, phase 2 trial. Lancet. 2021; 397(10289): 2060–69.https://dx.doi.org/10.1016/S0140-6736(21)00520-1.


7. Cantero-Navarro E., Rayego-Mateos S., Orejudo M. et al. Role of macrophages and related cytokines in kidney disease. Front Med (Lausanne). 2021; 8: 688060. https://dx.doi.org/10.3389/fmed.2021.688060


8. Fujiu K., Shibata M., Nakayama Y. et al. A heart-brain-kidney network controls adaptation to cardiac stress through tissue macrophage activation. Nat Med. 2017; 23(5): 611–22. https://dx.doi.org/10.1038/nm.4326.


9. Silljу H., de Boer R. Heart failure: Macrophages take center stage in the heart-brain kidney axis. Nat Rev Nephrol. 2017; 13(7): 388–90. https://dx.doi.org/10.1038/nrneph.2017.73.


10. Kercheva M., Ryabov V., Gombozhapova A. et al. Macrophages of the «heart-kidney» axis: Their dynamics and correlations with clinical data and outcomes in patients with myocardial infarction. J Pers Med. 2022; 12(2): 127. https://dx.doi.org/10.3390/jpm12020127.


11. Керчева М.А., Рябов В.В. Роль макрофагов в формировании кардиоренального синдрома при инфаркте миокарда. Российский кардиологический журнал. 2021; 26(4): 143–148. [Kercheva M., Ryabov V. Role of macrophages in cardiorenal syndrome development in patients with myocardial infarction. Rossiyskiy kardiologicheskiy zhurnal = Russian Journal of Cardiology. 2021; 26(4): 143–148 (In Russ.)]. https://dx.doi.org/10.15829/1560-4071-2021-4309. EDN: KMBDDD.


12. Ryabov V., Gombozhapova A., Rogovskaya Y. et al. Cardiac CD68+ and stabilin-1+ macrophages in wound healing following myocardial infarction: From experiment to clinic. Immunobiology. 2018; 223(4–5): 413–21. https://dx.doi.org/10.1016/j.imbio.2017.11.006.


13. Gaut J.P., Liapis H. Acute kidney injury pathology and pathophysiology: a retrospective review. Clin Kidney J. 2021; 14(2): 526–36. https://dx.doi.org/10.1093/ckj/sfaa142.


14. Baylis R., Gomez D., Mallat Z. et al. The CANTOS trial: One important step for clinical cardiology but a giant leap for vascular biology. Arterioscler Thromb Vasc Biol. 2017; 37(11): e174–e177. https://dx.doi.org/10.1161/ATVBAHA.117.310097.


15. Гомбожапова А.Э., Роговская Ю.В., Ребенкова М.С. с соавт. Фенотипическая гетерогенность сердечных макрофагов в постинфарктной регенерации миокарда: перспективы клинических исследований. Сибирский журнал клинической и экспериментальной медицины. 2018; 33(2): 70–76. [Gombozhapova A.E., Rogovskaya Yu.V., Rebenkova M.S. et al. Phenotypic heterogeneity of cardiac macrophages during wound healing following myocardial infarction: perspectives in clinical research. Sibirskiy zhurnal klinicheskoy i eksperimental’noy meditsiny = The Siberian Journal of Clinical and Experimental Medicine. 2018; 33(2): 70–76 (In Russ.)]. https://dx.doi.org/10.29001/2073-8552-2018-33-2-70-76. EDN: XTXQDJ.


16. Evans B., Haskard D., Sempowksi G. et al. Evolution of the macrophage CD163 phenotype and cytokine profiles in a human model of resolving inflammation. Int J Inflamm. 2013; 2013: 780502. https://dx.doi.org/10.1155/2013/780502.


17. Olmes G., Buttner-Herold M., Ferrazzi F. et al. CD163+ M2c-like macrophages predominate in renal biopsies from patients with lupus nephritis. Arthritis Res Ther. 2016; 18: 90. https://dx.doi.org/10.1186/s13075-016-0989-y.


18. Etzerodt A., Moestrup S. CD163 and inflammation: biological, diagnostic, and therapeutic aspects. Antioxidants & Redox Signaling. 2013; 18(17): 2352–63. https://dx.doi.org/10.1089/ars.2012.4834.


19. Li J., Liu C., Gao B. et al. Clinical-pathologic significance of CD163 positive macrophage in IgA nephropathy patients with crescents. Int J Clin Exp Med. 2015; 8(6): 9299–305.


20. Guillen-Gomez E., Guirado L., Belmonte X. et al. Monocyte implication in renal allograft dysfunction. Clin Exp Immunol. 2014; 175(2): 323–33. https://dx.doi.org/10.1111/cei.12228.


21. Guiteras R., Flaquer M., Cruzado J. Macrophage in chronic kidney disease. Clin Kidney J. 2016; 9(6): 765–71.https://dx.doi.org/10.1093/ckj/sfw096


22. Chistiakov D., Killingsworth M., Myasoedova V. et al. CD68/macrosialin: Not just a histochemical marker. Lab Invest. 2017; 97(1): 4–13. https://dx.doi.org/10.1038/labinvest.2016.116.


23. Marks S., Williams S., Tullus K., Sebire N.J. Glomerular expression of monocyte chemoattractant protein-1 is predictive of poor renal prognosis in pediatric lupus nephritis. Nephrol Dial Transplant. 2008; 23(11): 3521–26. https://dx.doi.org/10.1093/ndt/gfn270.


24. Dias C., Malafronte P., Lee J. et al. Role of renal expression of CD68 in the long-term prognosis of proliferative lupus nephritis. J Nephrol. 2017; 30(1): 87–94. https://dx.doi.org/10.1007/s40620-015-0252-7.


25. Kzhyshkowska J. Multifunctional receptor stabilin-1 in homeostasis and disease. Scientific World Journal. 2010; 10: 2039–53.https://dx.doi.org/10.1100/tsw.2010.189.


About the Autors

Maria A. Kercheva, PhD in Medicine, junior researcher at the Central Research Laboratory of Siberian State Medical University of the Ministry of Healthcare of Russia, researcher at the Department of emergency cardiology of the Research Institute of Cardiology, Tomsk National Research Medical Center of the Russian Academy of Sciences. Address: 634050, Tomsk, 2 build. 18 Moskovsky Tract. E-mail: mariiakercheva@mail.ru. ORCID: https://orcid.org/0000-0003-1444-1037
Vyacheslav V. Ryabov, Dr. med. habil., professor, head of the Department of cardiology, Siberian State Medical University of the Ministry of Healthcare of Russia, deputy director for scientific and medical work, acting head of the Department of emergency cardiology, leading researcher at the Laboratory of translational cellular and molecular biomedicine of the Research Institute of Cardiology of Tomsk National Research Medical Center of the Russian Academy of Sciences. Address: 634009. Tomsk, 5 Kooperativny Lane. E-mail: rvvt@cardio-tomsk.ru.
ORCID: https://orcid.org/0000-0002-4358-7329
Alexandra E. Gombozhapova, PhD in Medicine, researcher, cardiologist at the Department of emergency cardiology, Research Institute of Cardiology of Tomsk National Research Medical Center of the Russian Academy of Sciences, assistant at the Department of cardiology of the Advanced Training Faculty and University Staff Faculty of Siberian State Medical University of the Ministry of Healthcare of Russia, junior researcher at the Laboratory of translational cellular and molecular biomedicine National Research Tomsk State University. Address: 634009. Tomsk, 5 Kooperativny Lane. E-mail: gombozhapova@gmail.com. ORCID: https://orcid.org/0000-0003-1281-3714
Ivan V. Stepanov, PhD in Medicine, pathologist, head of еру Department ща pathological anatomy, Research Institute of Cardiology of Tomsk National Research Medical Center of the Russian Academy of Sciences. Address: 634009. Tomsk, 5 Kooperativny Lane. Email: i_v_stepanov@mail.ru. ORCID: https://orcid.org/0000-0002-8543-6027


Similar Articles

Back to Content

Бионика Медиа