Plasma gelsolin level predicts acute kidney injury after cardiopulmonary bypass in infants and young children

  • Shan-Shan Shi
  • Xiao-Jie Yue
  • Dong-Yan Zhao
  • Jia-Jie Fan
  • Jian-Guo Xu
  • Xi-Wang Liu
  • Bao-Li Cheng
  • Xiang-Ming Fang
  • Jie Fan
  • Qiang Shu
Original Article
  • 23 Downloads

Abstract

Background

Acute kidney injury (AKI) after cardiopulmonary bypass (CPB) is a common complication especially in pediatric population. Plasma gelsolin (pGSN) is an anti-inflammatory factor through binding with actin and pro-inflammatory cytokines in circulation. Decrease in pGSN has been reported in some pathologic conditions. The purpose of the study was to determine the alterations of pGSN level in infants and young children after CPB and the role of pGSN as a predictor for the morbidity and severity of post-CPB AKI.

Methods

Sixty-seven infants and young children at age ≤ 3 years old undergoing CPB were prospectively enrolled. PGSN levels were measured during peri-operative period with enzyme-linked immuno-sorbent assay and normalized with plasma total protein concentration. Other clinical characteristics of the patients were also recorded.

Results

In patients developing AKI, the normalized pGSN (pGSNN) levels significantly decreased at 6 h post-operation and remained low for 24 h post-operation as compared to the patients with non-AKI. PGSNN at 6 h post-operation combining with CPB time presents an excellent predictive value for AKI.

Conclusions

Decreased pGSNN identifies post-CPB AKI in the patients ≤ 3 years old, and is associated with adverse clinical outcomes. The findings suggest that circulating GSN in post-CPB patients may have beneficial effects on diminishing inflammatory responses.

Keywords

Acute kidney injury Cardiopulmonary bypass Infants Plasma gelsolin Young children 

Notes

Acknowledgements

We appreciated sincerely the families and patients who participated in the study, and the physicians, nurses who cared for the study patients. We also grateful to the staffs of the Key Laboratory for Diagnosis and Therapy of Neonatal Diseases, the Children’s Hospital of Zhejiang University School of Medicine serving as scientific advisers.

Author contributions

SSS and XJY participated in the design of the study and drafted the manuscript. JJF and DYZ collected the clinical data and blood samples. XWL carried out the statistical analysis. BLC carried out the ELISA test. JGX and JF helped to draft the manuscript. QS and XMF participated in the design of the study and critical revision of the article for the important content. All authors had read and approved the final manuscript.

Compliance with ethical standards

Ethical approval

Informed content was obtained from the study patients’ parents, and the study was approved by the Ethics Committee of Children’s Hospital of Zhejiang University School of Medicine.

Conflict of interest

No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article.

References

  1. 1.
    Rosner MH, Okusa MD. Acute kidney injury associated with cardiac surgery. Clin J Am Soc Nephrol. 2006;1:19–32.CrossRefPubMedGoogle Scholar
  2. 2.
    Parolari A, Pesce LL, Pacini D, Mazzanti V, Salis S, Sciacovelli C, et al. Risk factors for perioperative acute kidney injury after adult cardiac surgery: role of perioperative management. Ann Thorac Surg. 2012;93:584–91.CrossRefPubMedGoogle Scholar
  3. 3.
    Legrand M, Pirracchio R, Rosa A, Petersen ML, Van der Laan M, Fabiani JN, et al. Incidence, risk factors and prediction of post-operative acute kidney injury following cardiac surgery for active infective endocarditis: an observational study. Crit Care. 2013;17:R220.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Baskin E, Saygili A, Harmanci K, Agras PI, Ozdemir FN, Mercan S, et al. Acute renal failure and mortality after open-heart surgery in infants. Ren Fail. 2005;27:557–60.CrossRefPubMedGoogle Scholar
  5. 5.
    Skippen PW, Krahn GE. Acute renal failure in children undergoing cardiopulmonary bypass. Crit Care Resusc. 2005;7:286–91.PubMedGoogle Scholar
  6. 6.
    Yang ZH, Ning BT, Zhang CM, Lin R, Ye S, Liu T. Clinical application of extracorporeal membrane oxygenation in children with refractory cardiopulmonary failure. World J Pediatr. 2016;12:364–7.CrossRefPubMedGoogle Scholar
  7. 7.
    Ye LF, Fan Y, Tan LH, Shi LP, Zhang ZW, Du LZ, et al. Extracorporeal membrane oxygenation for the treatment of children with severe hemodynamic alteration in perioperative cardiovascular surgery. World J Pediatr. 2010;6:85–8.CrossRefPubMedGoogle Scholar
  8. 8.
    Sun HQ, Yamamoto M, Mejillano M, Yin HL. Gelsolin, multifunctional actin regulatory protein. J Biol Chem. 1999;274:33179–82.CrossRefPubMedGoogle Scholar
  9. 9.
    Silacci P, Mazzolai L, Gauci C, Stergiopulos N, Yin HL, Hayoz D. Gelsolin superfamily proteins: key regulators of cellular functions. Cell Mol Life Sci. 2004;61:2614–23.CrossRefPubMedGoogle Scholar
  10. 10.
    Bucki R, Byfield FJ, Kulakowska A, McCormick ME, Drozdowski W, Namiot Z, et al. Extracellular gelsolin binds lipoteichoic acid and modulates cellular response to proinflammatory bacterial wall components. J Immunol. 2008;181:4936–44.CrossRefPubMedGoogle Scholar
  11. 11.
    Lee PS, Drager LR, Stossel TP, Moore FD, Rogers SO. Relationship of plasma gelsolin levels to outcomes in critically ill surgical patients. Ann Surg. 2006;243:399–403.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Bucki R, Levental I, Kulakowska A, Janmey PA. Plasma gelsolin: function, prognostic value, and potential therapeutic use. Curr Protein Pept Sci. 2008;9:541–51.CrossRefPubMedGoogle Scholar
  13. 13.
    Yang Z, Chiou TT, Stossel TP, Kobzik L. Plasma gelsolin improves lung host defense against pneumonia by enhancing macrophage NOS3 function. Am J Physiol Lung Cell Mol Physiol. 2015;309:L11–6.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Wang H, Cheng B, Chen Q, Wu S, Lv C, Xie G, et al. Time course of plasma gelsolin concentrations during severe sepsis in critically ill surgical patients. Crit Care. 2008;12:R106.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Rothenbach PA, Dahl B, Schwartz JJ, O’Keefe GE, Yamamoto M, Lee WM, et al. Recombinant plasma gelsolin infusion attenuates burn-induced pulmonary microvascular dysfunction. J Appl Physiol (1985). 2004;96:25–31.Google Scholar
  16. 16.
    Suhler E, Lin W, Yin HL, Lee WM. Decreased plasma gelsolin concentrations in acute liver failure, myocardial infarction, septic shock, and myonecrosis. Crit Care Med. 1997;25:594–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Argun M, Baykan A, Narin F, Özyurt A, Pamukçu Ö, Elmalı F, et al. Plasma gelsolin as a biomarker of acute rheumatic carditis. Cardiol Young. 2015;25:1276–80.CrossRefPubMedGoogle Scholar
  18. 18.
    Pan JW, He LN, Xiao F, Shen J, Zhan RY. Plasma gelsolin level and outcomes after aneurismal subarachnoid hemorrhage. Crit Care. 2013;17:R149.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Ji L, Zhao X, Hua Z. Potential therapeutic implications of gelsolin in Alzheimer’s disease. J Alzheimers Dis. 2015;44:13–25.PubMedGoogle Scholar
  20. 20.
    Maniatis NA, Harokopos V, Thanassopoulou A, Oikonomou N, Mersinias V, Witke W, et al. A critical role for gelsolin in ventilator-induced lung injury. Am J Respir Cell Mol Biol. 2009;41:426–32.CrossRefPubMedGoogle Scholar
  21. 21.
    Oikonomou N, Thanasopoulou A, Tzouvelekis A, Harokopos V, Paparountas T, Nikitopoulou I, et al. Gelsolin expression is necessary for the development of modelled pulmonary inflammation and fibrosis. Thorax. 2009;64:467–75.CrossRefPubMedGoogle Scholar
  22. 22.
    Selewski DT, Cornell TT, Heung M, Troost JP, Ehrmann BJ, Lombel RM, et al. Validation of the KDIGO acute kidney injury criteria in a pediatric critical care population. Intensive Care Med. 2014;40:1481–8.CrossRefPubMedGoogle Scholar
  23. 23.
    Sutton TA, Fisher CJ, Molitoris BA. Microvascular endothelial injury and dysfunction during ischemic acute renal failure. Kidney Int. 2002;62:1539–49.CrossRefPubMedGoogle Scholar
  24. 24.
    Abuelo JG. Normotensive ischemic acute renal failure. N Engl J Med. 2007;357:797–805.CrossRefPubMedGoogle Scholar
  25. 25.
    Laffey JG, Boylan JF, Cheng DC. The systemic inflammatory response to cardiac surgery: implications for the anesthesiologist. Anesthesiology. 2002;97:215–52.CrossRefPubMedGoogle Scholar
  26. 26.
    Peddada N, Sagar A, Ashish P, Garg R. Plasma gelsolin: a general prognostic marker of health. Med Hypotheses. 2012;78:203–10.CrossRefPubMedGoogle Scholar
  27. 27.
    Stenvikel P, Lindholm B, Heimburger O. Novel approaches in an integrated therapy of inflammatory-associated wasting in end-stage renal disease. Semin Dial. 2004;17:505–15.CrossRefGoogle Scholar
  28. 28.
    Lee PS, Sampath K, Karumanchi SA, Tamez H, Bhan I, Isakova T, et al. Plasma gelsolin and circulating actin correlate with hemodialysis mortality. J Am Soc Nephrol. 2009;20:1140–8.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Li S, Krawczeski CD, Zappitelli M, Devarajan P, Thiessen-Philbrook H, Coca SG, et al. Incidence, risk factors, and outcomes of acute kidney injury after pediatric cardiac surgery: a prospective multicenter study. Crit Care Med. 2011;39:1493–9.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Tóth R, Breuer T, Cserép Z, Lex D, Fazekas L, Sápi E, et al. Acute kidney injury is associated with higher morbidity and resource utilization in pediatric patients undergoing heart surgery. Ann Thorac Surg. 2012;93:1984–90.CrossRefPubMedGoogle Scholar
  31. 31.
    Schwartz GJ, Furth SL. Glomerular filtration rate measurement and estimation in chronic kidney disease. Pediatr Nephrol. 2007;22:1839–48.CrossRefPubMedGoogle Scholar
  32. 32.
    Krawsczeski CD, Woo JG, Wang Y, Bennett MR, Ma Q, Devarajan P. Neutrophil gelatinase-associated lipocalin concentrations predict development of acute kidney injury in neonates and children after cardiopulmonary bypass. J Pediatr. 2011;158:1009–15.e1.CrossRefGoogle Scholar
  33. 33.
    Bennett M, Dent CL, Ma Q, Dastrala S, Grenier F, Workman R, et al. Urine NGAL predicts severity of acute kidney injury after cardiac surgery: a prospective study. Clin J Am Soc Nephrol. 2008;3:665–73.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Children's Hospital, Zhejiang University School of Medicine 2018

Authors and Affiliations

  • Shan-Shan Shi
    • 1
  • Xiao-Jie Yue
    • 2
  • Dong-Yan Zhao
    • 2
  • Jia-Jie Fan
    • 1
  • Jian-Guo Xu
    • 4
  • Xi-Wang Liu
    • 3
  • Bao-Li Cheng
    • 4
  • Xiang-Ming Fang
    • 4
  • Jie Fan
    • 5
  • Qiang Shu
    • 3
  1. 1.Cardiac Intensive Care UnitThe Children’s Hospital of Zhejiang University School of MedicineHangzhouChina
  2. 2.The Key Laboratory for Diagnosis and Therapy of Neonatal DiseasesThe Children’s Hospital of Zhejiang University School of MedicineHangzhouChina
  3. 3.Department of Thoracic and Cardiovascular SurgeryThe Children’s Hospital of Zhejiang University School of MedicineHangzhouChina
  4. 4.Department of AnesthesiologyThe First Affiliated Hospital of Zhejiang University School of MedicineHangzhouChina
  5. 5.Department of SurgeryUniversity of Pittsburgh School of MedicinePittsburghUSA

Personalised recommendations