Hostname: page-component-586b7cd67f-r5fsc Total loading time: 0 Render date: 2024-11-24T00:45:33.815Z Has data issue: false hasContentIssue false
  • English
  • Français

Neutrophil gelatinase-associated lipocalin reflects inflammation and is not a reliable renal biomarker in neonates and infants after cardiopulmonary bypass: a prospective case–control study

Published online by Cambridge University Press:  11 September 2017

Karl Reiter Open the ORCID record for Karl Reiter [Opens in a new window] ,
Gunter Balling ,
Vittorio Bonelli ,
Jelena Pabst von Ohain ,
Siegmund Lorenz Braun ,
Peter Ewert  and
Bettina Ruf
Karl Reiter*
Affiliation:
Paediatric Intensive Care Unit, University Children’s Hospital, von Haunersche Kinderklinik, Ludwig-Maximilians-Universitaet, Munich, Germany
Gunter Balling
Affiliation:
Department of Pediatric Cardiology and Congenital Heart Disease, Deutsches Herzzentrum Muenchen, Technische Universitaet, Germany
Vittorio Bonelli
Affiliation:
Department of Anaesthesiology, Deutsches Herzzentrum Muenchen, Technische Universitaet, Germany
Jelena Pabst von Ohain
Affiliation:
Department of Thoracic and Cardiovascular Surgery, Deutsches Herzzentrum Muenchen, Technische Universitaet, Germany
Siegmund Lorenz Braun
Affiliation:
Institute of Laboratory Medicine, Deutsches Herzzentrum Muenchen, Technische Universitaet, Germany
Peter Ewert
Affiliation:
Department of Pediatric Cardiology and Congenital Heart Disease, Deutsches Herzzentrum Muenchen, Technische Universitaet, Germany
Bettina Ruf
Affiliation:
Department of Pediatric Cardiology and Congenital Heart Disease, Deutsches Herzzentrum Muenchen, Technische Universitaet, Germany
*
Correspondence to: K. Reiter, MD, Paediatric Intensive Care Unit, University Children’s Hospital, von Haunersche Kinderklinik, Ludwig-Maximilians-Universitaet, Munich 80337, Germany. Tel: ++49 89 44005 2811; Fax: ++49 89 44005 4499; E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Introduction

Acute kidney injury is a frequent complication after cardiac surgery with cardiopulmonary bypass in infants. Neutrophil gelatinase-associated lipocalin has been suggested to be a promising early biomarker of impending acute kidney injury. On the other hand, neutrophil gelatinase-associated lipocalin has been shown to be elevated in systemic inflammatory diseases without renal impairment. In this secondary analysis of data from our previous study on acute kidney injury after infant cardiac surgery, our hypothesis was that neutrophil gelatinase-associated lipocalin may be associated with surgery-related inflammation.

Methods

We prospectively enrolled 59 neonates and infants undergoing cardiopulmonary bypass surgery for CHD and measured neutrophil gelatinase-associated lipocalin in plasma and urine and interleukin-6 in the plasma. Values were correlated with postoperative acute kidney injury according to the paediatric Renal-Injury-Failure-Loss-Endstage classification.

Results

Overall, 48% (28/59) of patients developed acute kidney injury. Of these, 50% (14/28) were classified as injury and 11% (3/28) received renal replacement therapy. Both plasma and urinary neutrophil gelatinase-associated lipocalin values were not correlated with acute kidney injury occurrence. Plasma neutrophil gelatinase-associated lipocalin showed a strong correlation with interleukin-6. Urinary neutrophil gelatinase-associated lipocalin values correlated with cardiopulmonary bypass time.

Conclusion

Our results suggest that plasma and urinary neutrophil gelatinase-associated lipocalin values are not reliable indicators of impending acute kidney injury in neonates and infants after cardiac surgery with cardiopulmonary bypass. Inflammation may have a major impact on plasma neutrophil gelatinase-associated lipocalin values in infant cardiac surgery. Urinary neutrophil gelatinase-associated lipocalin may add little prognostic value over cardiopulmonary bypass time.

Keywords

Acute kidney injuryneutrophil gelatinase-associated lipocalininflammationinterleukin-6CHDcardiopulmonary bypass
Type
Original Articles
Information
Cardiology in the Young , Volume 28 , Issue 2 , February 2018 , pp. 243 - 251
Check for updates
Copyright
© Cambridge University Press 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

The data were presented as an abstract at the AEPC 2014 in Helsinki, Finland.

References

1. Ruf, B, Bonelli, V, Balling, G, et al. Influence of bypass time and systemic inflammatory response after cardiopulmonary bypass on the increase of neutrophil gelatinase-associated lipocalin in infants after cardiac surgery. Cardiol Young 2014; 24 (Suppl 1): S153.Google Scholar
2. Aydin, SI, Seiden, HS, Blaufox, AD, et al. Acute kidney injury after surgery for congenital heart disease. Ann Thorac Surg 2012; 94: 1589–1595.Google Scholar
3. Schneider, J, Khemani, R, Grushkin, C, Bart, R. Serum creatinine as stratified in the RIFLE score for acute kidney injury is associated with mortality and length of stay for children in the pediatric intensive care unit. Crit Care Med 2010; 38: 933–939.Google Scholar
4. Li, S, Krawczeski, CD, Zappitelli, M, et al. Incidence, risk factors, and outcomes of acute kidney injury after pediatric cardiac surgery – a prospective multicenter study. Crit Care Med 2011; 39: 1493–1499.Google Scholar
5. Zappitelli, M, Bernier, PL, Saczkowski, RS, et al. A small post-operative rise in serum creatinine predicts acute kidney injury in children undergoing cardiac surgery. Kidney Int 2009; 76: 885–892.Google Scholar
6. dos Santos, E, Halal, MG, Carvalho, PR. Acute kidney injury according to pediatric RIFLE criteria is associated with negative outcomes after heart surgery in children. Pediatr Nephrol 2013; 28: 1307–1314.Google Scholar
7. Ricci, Z, Di Nardo, M, Iacoella, C, Netto, R, Picca, S, Cogo, P. Pediatric RIFLE for acute kidney injury diagnosis and prognosis for children undergoing cardiac surgery: a single-center prospective observational study. Pediatr Cardiol 2013; 34: 1404–1408.Google Scholar
8. Tóth, R, Breuer, T, Cserép, Z, et al. Acute kidney injury is associated with higher morbidity and resource utilization in pediatric patients undergoing heart surgery. Ann Thorac Surg 2012; 93: 1984–1990.Google Scholar
9. Pedersen, K. Acute kidney injury in children undergoing surgery for congenital heart disease. Eur J Pediatr Surg 2012; 22: 426–433.Google Scholar
10. Blinder, JJ, Goldstein, SL, Lee, VV, et al. Congenital heart surgery in infants: effects of acute kidney injury on outcomes. J Thorac Cardiovasc Surg 2012; 143: 368–374.Google Scholar
11. Vanmassenhove, J, Vanholder, R, Nagler, E, Van Biesen, W. Urinary and serum biomarkers for the diagnosis of acute kidney injury: an in-depth review of the literature. Nephrol Dial Transplant 2013; 28: 254–273.Google Scholar
12. Basu, RK, Wong, HR, Krawczeski, CD, et al. Combining functional and tubular damage biomarkers improves diagnostic precision for acute kidney injury after cardiac surgery. J Am Coll Cardiol 2014; 64: 2753–2762.Google Scholar
13. Metzger, J, Mullen, W, Husi, H, et al. Acute kidney injury prediction in cardiac surgery patients by a urinary peptide pattern: a case-control validation study. Critical Care 2016; 20: 157.Google Scholar
14. Meisner, A, Kerr, KF, Thiessen-Philbrook, H, Coca, SG, Parikh, CR. Methodological issues in current practice may lead to bias in the development of biomarker combinations for predicting acute kidney injury. Kidney Int 2016; 89: 429–438.Google Scholar
15. Wheeler, DS, Devarajan, P, Ma, Q, et al. Serum neutrophil gelatinase-associated lipocalin (NGAL) as a marker of acute kidney injury in critically ill children with septic shock. Crit Care Med 2008; 36: 1297–1303.Google Scholar
16. Biezeveld, MH, van Mierlo, G, Lutter, R, et al. Sustained activation of neutrophils in the course of Kawasaki disease: an association with matrix metalloproteinases. Clin Exp Immunol 2005; 141: 183–188.Google Scholar
17. Janas, RM, Ochocińska, A, Snitko, R, et al. Neutrophil gelatinase-associated lipocalin in blood in children with inflammatory bowel disease. J Gastroenterol Hepatol 2014; 29: 1883–1889.Google Scholar
18. Kim, BK, Yim, HE, Yoo, KH. Plasma neutrophil gelatinase-associated lipocalin: a marker of acute pyelonephritis in children. Pediatr Nephrol 2017; 32: 477–484.Google Scholar
19. Tang, Y, Huang, XR, Lv, J, et al. C-reactive protein promotes acute kidney injury by impairing G1/S-dependent tubular epithelium cell regeneration. Clin Sci 2014; 126: 645–659.Google Scholar
20. Svensson, AS, Kvitting, JE, Kovesdy, CP, Cederholm, I, Szabó, Z. Changes in serum cystatin C, creatinine, and C-reactive protein after cardiopulmonary bypass in patients with normal preoperative kidney function. Nephrology (Carlton) 2014; 21: 519–525.Google Scholar
21. Ruf, B, Bonelli, V, Balling, G, et al. Intraoperative renal near-infrared spectroscopy indicates developing acute kidney injury in infants undergoing cardiac surgery with cardiopulmonary bypass: a case-control study. Crit Care 2015; 19: 27.Google Scholar
22. Liu, KD, Altmann, C, Smits, G, et al. Serum interleukin-6 and interleukin-8 are early biomarkers of acute kidney injury and predict prolonged mechanical ventilation in children undergoing cardiac surgery: a case-control study. Critical Care 2009; 13: R104.Google Scholar
23. Morgan, CJ, Gill, PJ, Lam, S, Joffe, AR. Peri-operative interventions, but not inflammatory mediators, increase risk of acute kidney injury after cardiac surgery: a prospective cohort study. Intensive Care Med 2013; 39: 934–941.Google Scholar
24. Zappitelli, M. Preoperative predictors of acute kidney injury – from clinical scores to biomarkers. Pediatr Nephrol 2013; 28: 1173–1182.Google Scholar
25. Kashani, K, Al-Khafaji, A, Ardiles, T, et al. Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Critical Care 2013; 17: R25.Google Scholar
26. Meersch, M, Schmidt, C, Van Aken, H, et al. Validation of cell-cycle arrest biomarkers for acute kidney injury after pediatric cardiac surgery. PLoS One 2014; 9: e110865.Google Scholar
27. Mishra, J, Dent, C, Tarabishi, R, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 2005; 365: 1231–1238.Google Scholar
28. Dent, CL, Ma, Q, Dastrala, S, et al. Plasma neutrophil gelatinase-associated lipocalin predicts acute kidney injury, morbidity and mortality after pediatric cardiac surgery: a prospective uncontrolled cohort study. Crit Care 2007; 11: R127.Google Scholar
29. Parikh, CR, Devarajan, P, Zappitelli, M, et al. Postoperative biomarkers predict acute kidney injury and poor outcomes after pediatric cardiac surgery. J Am Soc Nephrol 2011; 22: 1737–1747.Google Scholar
30. Alcaraz, AJ, Gil-Ruiz, MA, Castillo, A, et al. Postoperative neutrophil gelatinase–associated lipocalin predicts acute kidney injury after pediatric cardiac surgery. Pediatr Crit Care Med 2014; 15: 121–130.Google Scholar
31. Mishra, J, Ma, Q, Prada, A, et al. Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol 2003; 14: 2534–2543.Google Scholar
32. Mishra, J, Ma, Q, Kelly, C, et al. Kidney NGAL is a novel early marker of acute injury following transplantation. Pediatr Nephrol 2006; 21: 856–863.Google Scholar
33. Bennett, M, Dent, CL, Ma, Q, et al. Urine NGAL predicts severity of acute kidney injury after cardiac surgery: a prospective study. Clin J Am Soc Nephrol 2008; 3: 665–673.Google Scholar
34. Krawczeski, 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: 1009–1015.Google Scholar