Biochemical Genetics

, Volume 56, Issue 6, pp 627–638 | Cite as

Preliminary Report on the Association Between STAT3 Polymorphisms and Susceptibility to Acute Kidney Injury After Cardiopulmonary Bypass

  • Sara Aghakhani Chegeni
  • Mahsa Rahimzadeh
  • Hossein Montazerghaem
  • Mahmood Khayatian
  • Farzaneh Dasturian
  • Nadereh Naderi
Original Article


Cardiopulmonary bypass-associated acute kidney injury (CPB-AKI) is a well-recognized complication which is clearly linked to increased morbidity and mortality. Due to important role of inflammation in CPB-AKI pathogenesis, we explored the association between polymorphisms in STAT3, an inflammation-associated transcription factor, and the risk of CPB-AKI. In this study, STAT3 rs1053004 and rs744166 polymorphisms were analyzed in 129 patients undergoing coronary artery bypass grafting in Jorjani heart center, Bandar Abbas, Iran. The genotypes were determined using sequence-specific primers (PCR–SSP). Sixty-three patients met the criteria for AKI after cardiac surgery (AKI group). The remaining 66 patients did not develop AKI (non-AKI group). Rs1053004 GG genotype was significantly associated with a decreased risk (OR 0.4, 95% CI 0.17–0.9, P = 0.03) of CPB-AKI. Subgroup analyses revealed that GG genotype has also a protective effect in older patients (Age ≥ 60) (OR 0.19, 95% CI 0.04–0.8, P = 0.01). However, rs744166 did not show any difference between AKI and non-AKI groups. The result of our study for the first time provides evidence that rs1053004 polymorphism is significantly associated with a decreased risk of CPB-AKI in Iranian population, especially in older subjects.


Acute kidney injury Cardiac surgery Cardiopulmonary bypass, polymorphism, Stat3 



Cardiopulmonary bypass-associated acute kidney injury


Transducer and activator of transcription 3

NKT cells

Natural killer T cells


Toll like receptor


Non-steroidal anti-inflammatory drugs



We extend our thanks to the research council of the Hormozgan University of Medical Sciences for their financial support.

Author Contributions

NN developed the concept and prepared the manuscript; MR analyzed data, prepared manuscript, figures, and tables, and incorporated her suggestions; SA and FD performed experimentation; MK and HM performed examination on patients and handled sampling. All authors read and approved the final article.

Compliance with Ethical Standards

Conflict of interest

Authors declare that they had no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.


  1. Akcay A, Nguyen Q, Edelstein CL (2009) Mediators of inflammation in acute kidney injury. Mediators Inflamm. CrossRefPubMedGoogle Scholar
  2. Barenboim M, Zoltick BJ, Guo Y, Weinberger DR (2010) MicroSNiPer: a web tool for prediction of SNP effects on putative microRNA targets. Hum Mutat 31(11):1223–1232CrossRefGoogle Scholar
  3. Basile DP, Anderson MD, Sutton TA (2012) Pathophysiology of acute kidney injury. Compr Physiol 2(2):1303–1353PubMedPubMedCentralGoogle Scholar
  4. Boddu R, Fan C, Rangarajan S, Sunil B, Bolisetty S, Curtis LM (2017) Unique sex-and age-dependent effects in protective pathways in acute kidney injury. Am J Physiol-Ren Physiol 313(3):F740–F755CrossRefGoogle Scholar
  5. Camporeale A, Poli V (2012) IL-6, IL-17 and STAT3: a holy trinity in auto-immunity? Front Biosci (Landmark Ed) 17:2306–2326CrossRefGoogle Scholar
  6. Cao Q, Li Y-Y, He W-F, Zhang Z-Z, Zhou Q, Liu X, Shen Y, Huang T-T (2013) Interplay between microRNAs and the STAT3 signaling pathway in human cancers. Physiol Genomics 45(24):1206–1214CrossRefGoogle Scholar
  7. Chan AJ, Alikhan MA, Odobasic D, Gan PY, Khouri MB, Steinmetz OM, Mansell AS, Kitching AR, Holdsworth SR, Summers SA (2014) Innate IL-17A–producing leukocytes promote acute kidney injury via inflammasome and toll-like receptor activation. Am J Pathol 184(5):1411–1418CrossRefGoogle Scholar
  8. Cheng F, Wang H-W, Cuenca A, Huang M, Ghansah T, Brayer J, Kerr WG, Takeda K, Akira S, Schoenberger SP (2003) A critical role for Stat3 signaling in immune tolerance. Immunity 19(3):425–436CrossRefGoogle Scholar
  9. Chew S, Mar W, Ti L (2012) Association of ethnicity and acute kidney injury after cardiac surgery in a South East Asian population. Br J Anaesth 110(3):397–401CrossRefGoogle Scholar
  10. Cho JS, Shim J-K, Soh S, Kim MK, Kwak Y-L (2016) Perioperative dexmedetomidine reduces the incidence and severity of acute kidney injury following valvular heart surgery. Kidney Int 89(3):693–700CrossRefGoogle Scholar
  11. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr (2003) The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA 289(19):2560–2571CrossRefGoogle Scholar
  12. Dasta JF, Kane-Gill SL, Durtschi AJ, Pathak DS, Kellum JA (2008) Costs and outcomes of acute kidney injury (AKI) following cardiac surgery. Nephrol Dial Transplant 23(6):1970–1974CrossRefGoogle Scholar
  13. Dube S, Matam T, Yen J, Mang HE, Dagher PC, Hato T, Sutton TA (2017) Endothelial STAT3 modulates protective mechanisms in a mouse ischemia-reperfusion model of acute kidney injury. J Immunol Res. CrossRefPubMedPubMedCentralGoogle Scholar
  14. Gaudino M, Di Castelnuovo A, Zamparelli R, Andreotti F, Burzotta F, Iacoviello L, Glieca F, Alessandrini F, Nasso G, Donati MB (2003) Genetic control of postoperative systemic inflammatory reaction and pulmonary and renal complications after coronary artery surgery. J Thorac Cardiovasc Surg 126(4):1107–1112CrossRefGoogle Scholar
  15. Greenberg JH, Whitlock R, Zhang WR, Thiessen-Philbrook HR, Zappitelli M, Devarajan P, Eikelboom J, Kavsak PA, Devereaux P, Shortt C (2015) Interleukin-6 and interleukin-10 as acute kidney injury biomarkers in pediatric cardiac surgery. Pediatr Nephrol 30(9):1519–1527CrossRefGoogle Scholar
  16. Haghikia A, Hoch M, Stapel B, Hilfiker-Kleiner D (2012) STAT3 regulation of and by microRNAs in development and disease. Jak-Stat 1(3):143–150CrossRefGoogle Scholar
  17. He G, Karin M (2011) NF-κB and STAT3–key players in liver inflammation and cancer. Cell Res 21(1):159–168CrossRefGoogle Scholar
  18. Heringlake M, Schön J, Paarmann H (2013) The kidney in critical illness: how to monitor a pivotal organ system. Best Pract Res Clin Anaesthesiol 27(2):271–277CrossRefGoogle Scholar
  19. Hodge DR, Hurt EM, Farrar WL (2005) The role of IL-6 and STAT3 in inflammation and cancer. Eur J Cancer 41(16):2502–2512CrossRefGoogle Scholar
  20. Isbir SC, Tekeli A, Ergen A, Yilmaz H, Ak K, Civelek A, Zeybek U, Arsan S (2007) Genetic polymorphisms contribute to acute kidney injury after coronary artery bypass grafting. Heart Surg Forum 10(6):E439–E444CrossRefGoogle Scholar
  21. Khwaja A (2012) KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract 120(4):c179–c184PubMedPubMedCentralGoogle Scholar
  22. Kinsey GR, Okusa MD (2014) Expanding role of T cells in acute kidney injury. Curr Opin Nephrol Hypertens 23(1):9CrossRefGoogle Scholar
  23. Kinsey GR, Sharma R, Huang L, Li L, Vergis AL, Ye H, Ju S-T, Okusa MD (2009) Regulatory T cells suppress innate immunity in kidney ischemia-reperfusion injury. J Am Soc Nephrol 20(8):1744–1753CrossRefGoogle Scholar
  24. Kitching AR, Holdsworth SR (2011) The emergence of TH17 cells as effectors of renal injury. J Am Soc Nephrol 22(2):235–238CrossRefGoogle Scholar
  25. MacKensen GB, Swaminathan M, Ti LK, Grocott HP, Phillips-Bute BG, Mathew JP, Newman MF, Milano CA, Stafford-Smith M, P. O. R. Group (2004) Preliminary report on the interaction of apolipoprotein E polymorphism with aortic atherosclerosis and acute nephropathy after CABG. Ann Thorac Surg 78(2):520–526CrossRefGoogle Scholar
  26. Mao H, Katz N, Ariyanon W, Blanca-Martos L, Adýbelli Z, Giuliani A, Danesi TH, Kim JC, Nayak A, Neri M (2013) Cardiac surgery-associated acute kidney injury. Cardioren Med 3(3):178–199CrossRefGoogle Scholar
  27. Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A (2007) Acute kidney injury network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 11(2):R31CrossRefGoogle Scholar
  28. O’Neal JB, Shaw AD, Billings FT (2016) Acute kidney injury following cardiac surgery: current understanding and future directions. Crit Care 20(1):187CrossRefGoogle Scholar
  29. Rosner MH, Okusa MD (2006) Acute kidney injury associated with cardiac surgery. Clin J Am Soc Nephrol 1(1):19–32CrossRefGoogle Scholar
  30. Scrascia G, Guida P, Rotunno C, Luca Tupputi Schinosa L, Paparella D (2014) Anti-inflammatory strategies to reduce acute kidney injury in cardiac surgery patients: a meta-analysis of randomized controlled trials. Artif Organs 38(2):101–112CrossRefGoogle Scholar
  31. Vervaet BA, D’Haese PC, Verhulst A (2017) “Environmental toxin–induced acute kidney injury. Clin Kidney J 10(6):747–758CrossRefGoogle Scholar
  32. Weimbs T, Talbot JJ (2013) STAT3 signaling in polycystic kidney disease. Drug Discov Today 10(3):e113–e118CrossRefGoogle Scholar
  33. Yu H, Pardoll D, Jove R (2009) STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer 9(11):798–809CrossRefGoogle Scholar
  34. Zhu B, Zhu Y, Jiao Lou JK, Zhang Y, Li J, Gong Y, Yang Y, Tian J, Peng X, Zou D (2016) A single nucleotide polymorphism in the 3′-UTR of STAT3 regulates its expression and reduces risk of pancreatic cancer in a Chinese population. Oncotarget 7(38):62305CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Sara Aghakhani Chegeni
    • 1
    • 2
  • Mahsa Rahimzadeh
    • 1
  • Hossein Montazerghaem
    • 3
  • Mahmood Khayatian
    • 1
  • Farzaneh Dasturian
    • 1
  • Nadereh Naderi
    • 3
    • 4
  1. 1.Department of Biochemistry, Faculty of MedicineHormozgan University of Medical SciencesBandar AbbasIran
  2. 2.Food Health Research CenterHormozgan University of Medical SciencesBandar AbbasIran
  3. 3.Cardiovascular Research CenterHormozgan University of Medical SciencesBandar AbbasIran
  4. 4.Department of Immunology, Faculty of MedicineHormozgan University of Medical SciencesBandar AbbasIran

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