Hypoxia-inducible factor 1 (HIF-1) as a biomarker of acute kidney injury in patients with acute decompensation of chronic heart failure

Actuality. Impaired kidney function adversely influences both immediate and remote prognosis for patients with chronic heart failure (CHF). However, early detection and prediction of acute kidney injury (AKI) are understudied.

The aim of study was to investigate hypoxia-inducible factor 1 (HIF-1) as a biomarker for early diagnosis of AKI and determining prognosis in patients with acute decompensated CHF (ADCHF).

Materials and methods: 84 patients admitted for ADCHF (18 women; mean age, 61.4±7.1) were evaluated. ADCHF was diagnosed in accordance with SEHF guidelines for diagnosis and treatment of chronic heart failure (RCS, 2016). AKI was diagnosed according to KDIGO criteria (2012). HIF-1, N-terminal pro B-type natriuretic peptide (NТ-proBNP), and erythropoietin were measured in blood serum. The follow-up period lasted for 12 months.

Results: AKI was diagnosed in 27 (32.1 %) patients. Level of HIF-1 was 1.27±0.63 ng / ml; NТ-proBNP – 2469.6 (interquartile range (IQR), 1312.2; 3300.0) pg / ml; eryhthropoietin – 56.0 mIU / ml (IQR, 13.2; 68.1). No correlation was found between HIF-1 and glomerular filtration rate, NТ-proBNP, or erythropoietin. Differences in biomarker levels were not observed between patients with and without AKI; however, HIF-1 was higher in the group of deceased patients than in the group of survived patients (1.64±0.9 vs. 1.17±0.44 ng / ml, р=0.004), which was not observed for NТ-proBNP and erythropoietin.

Conclusion. AKI was observed in every third patient with ADCHF. In ADCHF, HIF-1 was not correlated with the kidney function; however, a relationship was found between the HIF-1 level and prediction for patients with CHF.

1. Smirnov A. V., Rumyantsev A. Sh., Kayukov I. G., Antonova T. V., Galkina O. V., Dobronravov V. A. et al. Acute kidney injury. -M.: MIA; 488 p. [Russian: Смирнов А. В., Румянцев А. Ш., Каюков И. Г., Антонова Т. В., Галкина О. В., Добронравов В. А. и др. Острое повреждение почек. – М.: МИА, 2015. – 488с]. ISBN 978-5-9986-0228-3

2. Kobalava Zh. D., Villevalde S. V., Efremovtseva M. A. Cardiorenal interaction in decompensated chronic heart failure. Rational Pharmacotherapy in Cardiology. 2016;12(2):138–46. [Russian: Кобалава Ж. Д., Виллевальде С. В., Ефремовцева М. А. Кардиоренальные взаимодействия при декомпенсации хронической сердечной недостаточности. Рациональная фармакотерапия в кардиологии. 2016;12(2):138-46]. DOI: 10.20996/1819-6446-2016-12-2-138-146

3. Coca SG, Singanamala S, Parikh CR. Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis. Kidney International. 2012;81(5):442–8. DOI: 10.1038/ki.2011.379

4. Fomin I. V. Chronic heart failure in Russian Federation: what do we know and what to do. Russian journal of cardiology. 2016;8:7–13. [Russian: Фомин И. В. Хроническая сердечная недостаточность в Российской Федерации: что сегодня мы знаем и что должны делать. Российский кардиологический журнал. 2016;8:7-13.]. DOI: 10.15829/1560-4071-2016-8-7-13

5. Galvao M, Kalman J, Demarco T, Fonarow GC, Galvin C, Ghali JK et al. Gender Differences in In-Hospital Management and Outcomes in Patients with Decompensated Heart Failure: Analysis from the Acute Decompensated Heart Failure National Registry (ADHERE). Journal of Cardiac Failure. 2006;12(2):100–7. DOI: 10.1016/j.cardfail.2005.09.005

6. Mareev V. Yu., Danielyan M. O., Belenkov Yu. N. The first results of the national epidemiological study. Epidemiological Examination of patients with CHF in real practice (on the Marketability) EPOHA-O-CHF. Russian Heart Failure Journal. 2003;4(3):116–20. [Russian: Мареев В. Ю., Даниелян М. О., Беленков Ю. Н. Первые результаты национального эпидемиологического исследования — эпидемиологическое Обследование больныХ ХСН в реальной практике (по Обращаемости) ЭПОХА-О-ХСН. Журнал Сердечная недостаточность. 2003;4(3):116-20]

7. van Veldhuisen DJ, Ruilope LM, Maisel AS, Damman K. Biomarkers of renal injury and function: diagnostic, prognostic and therapeutic implications in heart failure. European Heart Journal. 2016;37(33):2577–85. DOI: 10.1093/eurheartj/ehv588

8. Ronco C, Rizo-Topete L, Serrano-Soto M, Kashani K. Pro: Prevention of acute kidney injury: time for teamwork and new biomarkers. Nephrology Dialysis Transplantation. 2017;32(3):408–13. DOI: 10.1093/ndt/gfx016

9. Vandenberghe W, Gevaert S, Kellum JA, Bagshaw SM, Peperstraete H, Herck I et al. Acute Kidney Injury in Cardiorenal Syndrome Type 1 Patients: A Systematic Review and Meta-Analysis. Cardiorenal Medicine. 2016;6(2):116–28. DOI: 10.1159/000442300

10. Kociol RD, Greiner MA, Hammill BG, Phatak H, Fonarow GC, Curtis LH et al. Long-Term Outcomes of Medicare Beneficiaries with Worsening Renal Function During Hospitalization for Heart Failure. The American Journal of Cardiology. 2010;105(12):1786–93. DOI: 10.1016/j.amjcard.2010.01.361

11. Makeeva E. R., Menzorov M. V., Shutov A. M., Serov V. A., Saenko Yu. V., Strakhov A. A. Effect of acute kidney injury on prognosisin patients with acute decompensation of chronic heart. Russian Heart Failure Journal. 2014;15(1):33–8. [Russian: Макеева Е. Р., Мензоров М. В., Шутов А. М., Серов В. А., Саенко Ю. В., Страхов А. А. Влияние острого повреждения почек на прогноз больных острой декомпенсацией хронической сердечной недостаточности. Журнал Сердечная Недостаточность. 2014;15(1):33-8]

12. Chawla LS, Kimmel PL. Acute kidney injury and chronic kidney disease: an integrated clinical syndrome. Kidney International. 2012;82(5):516–24. DOI: 10.1038/ki.2012.208

13. Cerda J, Lameire N, Eggers P, Pannu N, Uchino S, Wang H et al. Epidemiology of Acute Kidney Injury. Clinical Journal of the American Society of Nephrology. 2008;3(3):881–6. DOI: 10.2215/CJN.04961107

14. Van der Wel MC, Jansen RWMM, Bakx JC, Bor HHJ, OldeRikkert MGM, van Weel C. Non-cardiovascular co-morbidity in elderly patients with heart failure outnumbers cardiovascular co-morbidity. European Journal of Heart Failure. 2007;9(6–7):709–15. DOI: 10.1016/j.ejheart.2007.02.004

15. Nangaku M, Rosenberger C, Heyman SN, Eckardt K-U. Regulation of hypoxia-inducible factor in kidney disease. Clinical and Experimental Pharmacology and Physiology. 2013;40(2):148–57. DOI: 10.1111/1440-1681.12005

16. Kirova Yu. I., Germanova E. L., Lukyanova L. D. Phenotypic features of the dynamics of the content of HIF-1a in the neocortex of rats at different modes of hypoxia. Bulletin of Experimental Biology and Medicine. 2012;154(12):681–6. [Russian: Кирова Ю. И., Германова Э. Л., Лукьянова Л. Д. Фенотипические особенности динамики содержания HIF-1a в неокортексе крыс при различных режимах гипоксии. Бюллетень экспериментальной биологии и медицины. 2012;154(12):681–6]

17. Bao L, Chen Y, Lai H-T, Wu S-Y, Wang JE, Hatanpaa KJ et al. Methylation of hypoxia-inducible factor (HIF)-1α by G9a/GLP inhibits HIF- 1 transcriptional activity and cell migration. Nucleic Acids Research. 2018;46(13):6576–91. DOI: 10.1093/nar/gky449

18. Sarkar K, Cai Z, Gupta R, Parajuli N, Fox-Talbot K, Darshan MS et al. Hypoxia-inducible factor 1 transcriptional activity in endothelial cells is required for acute phase cardioprotection induced by ischemic preconditioning. Proceedings of the National Academy of Sciences. 2012;109(26):10504–9. DOI: 10.1073/pnas.1208314109

19. Gunaratnam L, Bonventre JV. HIF in Kidney Disease and Development. Journal of the American Society of Nephrology. 2009;20(9):1877–87. DOI: 10.1681/ASN.2008070804

20. Chou Y-H, Chen Y-F, Pan S-Y, Huang T-M, Yang F-J, Shen W-C et al. The role of brain natriuretic peptide in predicting renal outcome and fluid management in critically ill patients. Journal of the Formosan Medical Association. 2015;114(12):1187–96. DOI: 10.1016/j.jfma.2015.10.015

21. Steg PG, Dabbous OH, Feldman LJ, Cohen-Solal A, Aumont M-C, López-Sendón J et al. Determinants and Prognostic Impact of Heart Failure Complicating Acute Coronary Syndromes: Observations From the Global Registry of Acute Coronary Events (GRACE). Circulation. 2004;109(4):494–9. DOI: 10.1161/01.CIR.0000109691.16944.DA

22. Menzorov M. V., Shutov A. M., Larionova N. V., Strakhov A. A., Serova D. V. Prognostic Significance of Erythropoietin in Patients with Acute Coronary Syndrome. Kardiologiia. 2016;56(9):15–20. [Russian: Мензоров М. В., Шутов А. М., Ларионова Н. В., Страхов А. А., Серова Д. В. Прогностическое значение эритропоэтина у больных с острым коронарным синдромом. Кардиология. 2016;56(9):15- 20]. DOI: 10.18565/cardio.2016.9.15-20

23. Vanderheyden M, Bartunek J, Goethals M. Brain and other natriuretic peptides: molecular aspects. European Journal of Heart Failure. 2004;6(3):261–8. DOI: 10.1016/j.ejheart.2004.01.004

24. Hung T-W, Liou J-H, Yeh K-T, Tsai J-P, Wu S-W, Tai H-C et al. Renal expression of hypoxia inducible factor-1α in patients with chronic kidney disease: a clinicopathologic study from nephrectomized kidneys. The Indian Journal of Medical Research. 2013;137(1):102–10. PMID: 23481058

25. Li G, Lu W, Wu X, Cheng J, Ai R, Zhou Z et al. Admission hypoxiainducible factor 1α levels and in-hospital mortality in patients with acute decompensated heart failure. BMC Cardiovascular Disorders. 2015;15(1). DOI: 10.1186/s12872-015-0073-6