Neutrophil gelatinase-associated lipocalin as a biomarker for acute kidney injury in children after cardiac surgery

  • Meta Herdiana Hanindita Department of Child Health, Airlangga University Medical School/Dr. Soetomo General Hospital, Surabaya, East Java
  • Riskky Vitria Prasetyo Department of Child Health, Airlangga University Medical School/Dr. Soetomo General Hospital, Surabaya, East Java
  • Ninik Asmaningsih Soemyarso Department of Child Health, Airlangga University Medical School/Dr. Soetomo General Hospital, Surabaya, East Java
  • I Ketut Alit Utamayasa Department of Child Health, Airlangga University Medical School/Dr. Soetomo General Hospital, Surabaya, East Java
  • Paul Tahalele Department of Surgery, Airlangga University Medical School/Dr. Soetomo General Hospital, Surabaya, East Java
DOI: https://doi.org/10.14238/pi56.4.2016.230-7
Keywords: NGAL, biomarker, acute kidney injury, validity, pRIFLE

Abstract

Background Acute kidney injury (AKI) is still diagnosed by measuring the estimated creatinine clearance (eCCl), despite the fact that it may not change until 50% or more of kidney function has been lost. AKI after cardiac surgery is related to prolonged intensive care, decreased quality of life, and increased long term mortality. Neutrophil gelatinase-associated lipocalin (NGAL) represents an early biomarker of AKI, which may be useful for assessing AKI in cardiac patients.


Objective To determine the validity of urinary and plasma NGAL as biomarkers for AKI in children after cardiac surgery.


Methods Subjects were children who underwent cardiac surgery in Dr. Soetomo Hospital, Surabaya, Indonesia from August 2013 to January 2014. Serial urine and blood samples were analyzed for NGAL before surgery, as well as at 2h, 4h, 12h, and 24h after surgery. The AKI was established based on pRIFLE criteria. Estimated creatinine clearance (eCCl) was calculated from the estimated glomerular filtration rate (eGFR), according to age by the traditional Schwartz formula. Serum creatinine was assayed by the Jaffe method before surgery, as well as at 12h, 24h, 48h, and 72h after surgery.


Results Of 20 subjects, 5 developed AKI. Urinary and plasma NGAL increased markedly at 2h postoperatively, as compared to eGFR which showed a rise at 12-48 h after cardiac surgery. Analysis of 2h post-operative urinary NGAL at a cut off value of 11.270ng/mL yielded an area under the curve (AUC) of 1.00 (95%CI 2.63 to 12.13), with sensitivity and specificity of 100% each for AKI. In addition, 2h post-operative plasma NGAL at a cut off value of 8.385 ng/mL yielded an AUC of 1.00 (95%CI 3.71 to 12.15) with sensitivity and specificity of 100% each for AKI.


Conclusion Urinary and plasma NGAL are valid as early biomarkers for AKI in children after cardiac surgery.

References

1. Thadhani R, Pascual M, Bonventre JV. Acute renal failure. N Engl J Med.1996;334:1448-60.
2. Parikh CR, Devarajan P, Zappitelli M, Sint K, Thiessen-Philbrook H, Li S, et al. Postoperative biomarkers predict acute kidney injury and poor outcomes after pediatric cardiac surgery. J Am Soc Nephrol. 2011;22:1737-47.
3. Devarajan P. Proteomics for biomarker discovery in acute kidney injury. Semin Nephrol.2007;27:637–51.
4. Lok CE, Austin PC, Wanh H, Tu JV. Impact of renal insufficiency on short- and long-term outcomes after cardiac surgery. Am Heart J. 2004;148:430-8.
5. Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet.2005;365:1231-8.
6. Dent CL, Ma Q. Dastrala S, Bennet M, Mitsnefes MM, Barasch J, 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;11:127.
7. 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.
8. Mori K, Lee HT, Rapoport D, Drexler IR, Foster K, Yang J, et al. Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury. J Clin Invest.2005;115:610-21.
9. Askenazi DJ, Ambalavanan N, Goldstein SL. Acute kidney injury in critically ill newborns: what do we know? What do we need to learn? Pediatr Nephrol. 2009;24:265–74.
10. Wennas, Supriyo AR, Prasetyo RV, Sumyarso NA, Noer MS. Mortality of acute kidney injury in children at nephrology ward Dr.Soetomo Hospital, Surabaya. Paediatr Indones. 2011;51:235.
11. Toth R, Breuer T, Cserep Z, Lex D, Fazekas L, Sapi 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.
12. Devarajan P. Novel biomarkers for the early prediction of acute kidney injury. Cancer Therapy.2005;3:477-88.
13. Thermo Fisher Scientific [homepage on the internet]. NGAL Rapid ELISA Kit Product Information. [cited 2016 January 1]. Available from: https://www.thermofisher.com/order/catalog/product/KIT037.
14. Peake M, Whiting M. Measurement of serum creatinine – current status and future goals. Clin Biochem Rev. 2006;27:173–84.
15. Akcan-Arikan A, Zappitelli M, Loftis LL, Washburn KK, Jefferson LS, Goldstein SL. Modified RIFLE criteria in critically ill children with acute kidney injury. Kidney Int. 2007;71:1028-35.
16. Alatas H. Pemeriksaan laboratorium pada penyakit ginjal. Dalam: Alatas H, Tambunan T, Trihono PP, Pardede SO, editors. 2nd edition. Jakarta: Balai Penerbit IDAI; 2002. p.51-72.
17. Dahlan MS. Penelitian diagnostik: dasar-dasar teoretis dan aplikasi dengan program SPSS dan Stata. Jakarta: Salemba Medika; 2009. p.23.
18. Munir MU, Khan DA, Khan FA, Shahab Naqvi SM. Rapid detection of acute kidney injury by urinary neutrophil gelatinase-associated lipocalin after cardiopulmonary bypass surgery. J Coll Phy Surg Pak.2013;23:103-6.
19. Fadel F, Abdel Rahman AM, Mohamed MF, Habib SA, Ibrahim MH, Sleem ZS, et al. Plasma neutrophil gelatinase-associated lipocalin as an early biomarker for prediction of acute kidney injury after cardio-pulmonary bypass in pediatric cardiac surgery. Arch Med Sci. 2012;8:250-5.
20. Zheng J, Xian Y, Yao Y, Xu G, Li C, Zhang Q, et al. Comparison of urinary biomarkers for early detection of acute kidney injury after cardiopulmonary bypass surgery in infants and young children. Pediatr Cardiol.2013;34:880-6.
21. Boldt J, Brenner T, Lehmann A, Suttner SW, Kumle B, Isgro F. Is kidney function altered by the duration of cardiopulmonary bypass? Ann Thorac Surg.2003;75:906–12.
22. Chiravuri SD, Riegger LQ, Christensen R, Butler RR, Malviya S, Tait AR, et al. Factors associated with acute kidney injury or failure in children undergoing cardiopulmonary bypass: a case-controlled study. Paediatr Anaesth.2011;21:880-6.
23. Alcaraz AJ, Gil-Ruiz M, Castillo A, López J, Romero C, Fernández S, et al. Postoperative neutrophil gelatinase-associated lipocalin predicts acute kidney injury after pediatric cardiac surgery. Pediatr Crit Care Med. 2014;15:121-30.
24. Sethi SK, Goyal D, Yadav DK, Shukla U, Kajala PL, Gupta VK, et al. Predictors of acute kidney injury post-cardiopulmonary bypass in children. Clin Exp Nephrol. 2011;15:529-34.
25. Conlon PJ, Stafford-Smith M, White WD, Newman MF, King S, Winn MP, et al. Acute renal failure following cardiac surgery. Nephrol Dial Transplant.1999;14:1158–62.
26. Shiekh IA, Bhat MA, Bhat AW, Ommid M, Gani T, Nisa G. Renal function in patients undergoing cardiopulmonary bypass for open cardiac surgical procedures. Sri Lankan J Anaesthesiol.2013;21:20-26.
27. Durandy YD. Pediatric cardiac surgery: effect of a miniaturized bypass circuit in reducing homologous blood transfusion. J Thorac Cardiovasc Surg.2009;138:1454-5.
28. Nagelhout JJ, Plaus KL. Vascular surgery. In: Nagelhout JJ, Plaus KL, editors. Nurse Anesthesia. 5th ed. Maryland: Elsevier;2010.p. 568-70.
29. Dittrich S, Kurschat K, Dahnert I, Vogel M, Muller C, Alexi-Meskishvili V, et al. Renal function after cardiopulmonary bypass surgery in cyanotic congenital heart disease. Int J Cardiol.2000;28:173-9.
30. Bellomo R, Auriemma S, Fabbri A, D’Onofrio A, Katz N, McCullough PA, et al. The pathophysiology of cardiac surgery-associated acute kidney injury. Int J Artif Organs. 2008;31:166-78.
Published
2016-08-31
How to Cite
1.
Hanindita M, Prasetyo R, Soemyarso N, Utamayasa IK, Tahalele P. Neutrophil gelatinase-associated lipocalin as a biomarker for acute kidney injury in children after cardiac surgery. PI [Internet]. 31Aug.2016 [cited 24Nov.2024];56(4):230-. Available from: https://paediatricaindonesiana.org/index.php/paediatrica-indonesiana/article/view/771
Issue
Vol 56 No 4 (2016): July 2016
Section
Articles

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Received 2016-10-03
Accepted 2016-10-03
Published 2016-08-31