Skip to main content

Advertisement

Log in

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

  • Original Article
  • Published:
Biochemical Genetics Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

Abbreviations

CPB-AKI:

Cardiopulmonary bypass-associated acute kidney injury

STAT3:

Transducer and activator of transcription 3

NKT cells:

Natural killer T cells

TLR:

Toll like receptor

NSAID:

Non-steroidal anti-inflammatory drugs

References

  • Akcay A, Nguyen Q, Edelstein CL (2009) Mediators of inflammation in acute kidney injury. Mediators Inflamm. https://doi.org/10.1155/2009/137072

    Article  PubMed  Google Scholar 

  • 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):1223–1232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Basile DP, Anderson MD, Sutton TA (2012) Pathophysiology of acute kidney injury. Compr Physiol 2(2):1303–1353

    PubMed  PubMed Central  Google Scholar 

  • 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–F755

    Article  CAS  Google Scholar 

  • Camporeale A, Poli V (2012) IL-6, IL-17 and STAT3: a holy trinity in auto-immunity? Front Biosci (Landmark Ed) 17:2306–2326

    Article  Google Scholar 

  • 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):1206–1214

    Article  CAS  PubMed  Google Scholar 

  • 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):1411–1418

    Article  CAS  PubMed  Google Scholar 

  • 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):425–436

    Article  CAS  PubMed  Google Scholar 

  • 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):397–401

    Article  PubMed  Google Scholar 

  • 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):693–700

    Article  CAS  PubMed  Google Scholar 

  • 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):2560–2571

    Article  CAS  PubMed  Google Scholar 

  • 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):1970–1974

    Article  PubMed  Google Scholar 

  • 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. https://doi.org/10.1155/2017/4609502

    Article  PubMed  PubMed Central  Google Scholar 

  • 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):1107–1112

    Article  CAS  PubMed  Google Scholar 

  • 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):1519–1527

    Article  PubMed  PubMed Central  Google Scholar 

  • Haghikia A, Hoch M, Stapel B, Hilfiker-Kleiner D (2012) STAT3 regulation of and by microRNAs in development and disease. Jak-Stat 1(3):143–150

    Article  PubMed  PubMed Central  Google Scholar 

  • He G, Karin M (2011) NF-κB and STAT3–key players in liver inflammation and cancer. Cell Res 21(1):159–168

    Article  CAS  PubMed  Google Scholar 

  • 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):271–277

    Article  PubMed  Google Scholar 

  • Hodge DR, Hurt EM, Farrar WL (2005) The role of IL-6 and STAT3 in inflammation and cancer. Eur J Cancer 41(16):2502–2512

    Article  CAS  PubMed  Google Scholar 

  • 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–E444

    Article  PubMed  Google Scholar 

  • Khwaja A (2012) KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract 120(4):c179–c184

    PubMed  Google Scholar 

  • Kinsey GR, Okusa MD (2014) Expanding role of T cells in acute kidney injury. Curr Opin Nephrol Hypertens 23(1):9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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):1744–1753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kitching AR, Holdsworth SR (2011) The emergence of TH17 cells as effectors of renal injury. J Am Soc Nephrol 22(2):235–238

    Article  CAS  PubMed  Google Scholar 

  • 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):520–526

    Article  PubMed  Google Scholar 

  • 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):178–199

    Article  Google Scholar 

  • 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):R31

    Article  PubMed  PubMed Central  Google Scholar 

  • O’Neal JB, Shaw AD, Billings FT (2016) Acute kidney injury following cardiac surgery: current understanding and future directions. Crit Care 20(1):187

    Article  PubMed  PubMed Central  Google Scholar 

  • Rosner MH, Okusa MD (2006) Acute kidney injury associated with cardiac surgery. Clin J Am Soc Nephrol 1(1):19–32

    Article  PubMed  Google Scholar 

  • 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):101–112

    Article  CAS  PubMed  Google Scholar 

  • Vervaet BA, D’Haese PC, Verhulst A (2017) “Environmental toxin–induced acute kidney injury. Clin Kidney J 10(6):747–758

    Article  PubMed  PubMed Central  Google Scholar 

  • Weimbs T, Talbot JJ (2013) STAT3 signaling in polycystic kidney disease. Drug Discov Today 10(3):e113–e118

    Article  Google Scholar 

  • Yu H, Pardoll D, Jove R (2009) STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer 9(11):798–809

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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):62305

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

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

Author information

Authors and Affiliations

Authors

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.

Corresponding author

Correspondence to Nadereh Naderi.

Ethics declarations

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.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aghakhani Chegeni, S., Rahimzadeh, M., Montazerghaem, H. et al. Preliminary Report on the Association Between STAT3 Polymorphisms and Susceptibility to Acute Kidney Injury After Cardiopulmonary Bypass. Biochem Genet 56, 627–638 (2018). https://doi.org/10.1007/s10528-018-9865-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10528-018-9865-6

Keywords

Navigation