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Predictive ability of urinary biomarkers for outcome in children with acute kidney injury

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Abstract

Background

Urinary neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-beta-D-glucosaminidase (NAG), and interleukin 18 (IL-18) were found to be useful for early detection of acute kidney injury (AKI). The objective of this study was to determine the predictive ability of biomarkers for mortality and variation in levels in relation to different stages of AKI, need for dialysis, etiologies, and with duration of hospital stay.

Methods

Urinary NGAL, NAG, and IL-18 levels were measured in 50 children with AKI and 30 age- and gender-matched healthy controls. AKI was classified as per pediatric Risk, Injury, Failure, Loss, and End-stage (RIFLE) criteria.

Results

Median NGAL, NAG, and IL-18 values were significantly increased in AKI patients compared with controls (p < 0.001), with significant increase among risk, injury, and failure stages. Nonsurvivors had significantly higher median levels of NGAL (p = 0.008) and NAG (p = 0.018) than survivors. NGAL had highest area under the curve (AUC) at 0.750 [confidence interval (CI) 0.580–0.920], followed by NAG at 0.724 (CI 0.541–0.907), with sensitivity and specificity of 75 % each; and IL-18 (AUC 0.688, CI 0.511–0.864), with sensitivity 62.5 % and specificity 70.8 %, for predicting mortality. Values were significantly higher in patients who required peritoneal dialysis (PD) than in those in whom it was not indicated. Levels were comparable among different etiologies. Only NGAL level was found to be a significant risk factor associated with longer duration of hospital stay.

Conclusions

Urinary NGAL and NAG had modest predictive ability for mortality. Children requiring dialysis had significantly raised levels, and the NGAL level had significant association with duration of hospital stay.

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Abbreviations

AKI:

Acute kidney injury

IL-18:

Interleukin 18

NAG:

N-acetyl-beta-D-glucosaminidase

NAGL:

Neutrophil gelatinase-associated lipocalin

PD:

Peritoneal dialysis

References

  1. Xue JL, Daniels F, Star RA, Kimmel PL, Eggers PW, Molitoris BA, Himmelfarb J, Collins AJ (2006) Incidence and mortality of acute renal failure in Medicare beneficiaries, 1992 to 2001. J Am Soc Nephrol 17:1135–1142

    Article  PubMed  Google Scholar 

  2. Goldstein SL (2003) Overview of pediatric renal replacement therapy in acute renal failure. Artif Organs 27:781–785

    Article  PubMed  Google Scholar 

  3. Mishra OP, Gupta AK, Pooniya V, Prasad R, Tiwary NK, Schaefer F (2012) Peritoneal dialysis in children with acute kidney injury: A developing country experience. Perit Dial Int 32:431–436

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Lameire N, Van Biesen W, Vanholder R (2005) Acute renal failure. Lancet 365:417–430

    Article  CAS  PubMed  Google Scholar 

  5. Hoste EA, Lameire NH, Vanholder RC, Benoit DD, Decruyenaere JM, Colardyn FA (2003) Acute renal failure in patients with sepsis in a surgical ICU: predictive factors, incidence, comorbidity, and outcome. J Am Soc Nephrol 14:1022–1030

    Article  PubMed  Google Scholar 

  6. Mak RH (2008) Acute kidney injury in children : the dawn of a new era. Pediatr Nephrol 23:2147–2149

    Article  PubMed  Google Scholar 

  7. Devarajan P (2008) Emerging urinary biomarkers in the diagnosis of acute kidney injury. Expert Opin Med Diagn 2:387–398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Nguyen MT, Devarajan P (2008) Biomarkers for the early detection of acute kidney injury. Pediatr Nephrol 23:2151–2157

    Article  PubMed  Google Scholar 

  9. Han WK, Waikar SS, Johnson A, Betensky RA, Dent CL, Devarajan P, Bonventre JV (2008) Urinary biomarkers in the early diagnosis of acute kidney injury. Kidney Int 73:863–869

    Article  CAS  PubMed  Google Scholar 

  10. Parikh CR, Mishra J, Thiessen-Philbrook H, Dursun B, Ma Q, Kelly C, Dent C, Devarajan P, Edelstein CL (2006) Urinary IL-18 is an early predictive biomarker of acute kidney injury after cardiac surgery. Kidney Int 70:199–203

    Article  CAS  PubMed  Google Scholar 

  11. Soni SS, Cruz D, Bobek I, Chionh CY, Nalesso F, Lentini P, de Cal M, Corradi V, Virzi G, Ronco C (2010) NGAL: a biomarker of acute kidney injury and other systemic conditions. Int Urol Nephrol 42:141–150

    Article  CAS  PubMed  Google Scholar 

  12. Schmidt-Ott KM, Mori K, Li JY, Kalandadze A, Cohen DJ, Devarajan P, Barasch J (2007) Dual action of neutrophil gelatinase-associated lipocalin. J Am Soc Nephrol 18:407–413

    Article  CAS  PubMed  Google Scholar 

  13. Han WK, Wagener G, Zhu Y, Wang S, Lee HT (2009) Urinary biomarkers in the early detection of acute kidney injury after cardiac surgery. Clin J Am Soc Nephrol 4:873–882

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Parikh CR, Abraham E, Ancukiewicz M, Edelstein CL (2005) Urine IL-18 is an early diagnostic marker for acute kidney injury and predicts mortality in the intensive care unit. J Am Soc Nephrol 16:3046–3052

    Article  CAS  PubMed  Google Scholar 

  15. Liangos O, Perianayagam MC, Vaidya VS, Han WK, Wald R, Tighiouart H, MacKinnon RW, Li L, Balakrishnan VS, Pereira BJ, Bonventre JV, Jaber BL (2007) Urinary N-acetyl-beta- (D)-glucosaminidase activity and kidney injury molecule-1 level are associated with adverse outcomes in acute renal failure. J Am Soc Nephrol 18:904–912

    Article  CAS  PubMed  Google Scholar 

  16. Xin C, Yulong X, Yu C, Changchun C, Feng Z, Xinwei M (2008) Urine neutrophil gelatinase-associated lipocalin and interleukin-18 predict acute kidney injury after cardiac surgery. Ren Fail 30:904–913

    Article  PubMed  Google Scholar 

  17. Parikh CR, Devarajan P, Zappitelli M, Sint K, Thiessen-Philbrook H, Li S, Kim RW, Koyner JL, Coca SG, Edelstein CL, Shlipak MG, Garg AX, Krawczeski CD, TRIBE-AKI Consortium (2011) Postoperative biomarkers predict acute kidney injury and poor outcomes after pediatric cardiac surgery. J Am Soc Nephrol 22:1737–1347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Bennett M, Dent CL, Ma Q, Dastrala S, Grenier F, Workman R, Syed H, Ali S, Barasch J, Devarajan P (2008) Urine NGAL predicts severity of acute kidney injury after cardiac surgery: a prospective study. Clin J Am Soc Nephrol 3(3):665–673

    Article  PubMed  PubMed Central  Google Scholar 

  19. Du Y, Zappitelli M, Mian A, Bennett M, Ma Q, Devarajan P, Mehta R, Goldstein SL (2011) Urinary biomarkers to detect acute kidney injury in the pediatric emergency center. Pediatr Nephrol 26(2):267–274

    Article  PubMed  Google Scholar 

  20. Akcan-Arikan A, Zappitelli M, Loftis LL, Washburn KK, Jefferson LS, Goldstein SL (2007) Modified RIFLE criteria in critically ill children with acute kidney injury. Kidney Int 71:1028–1035

    Article  CAS  PubMed  Google Scholar 

  21. Kidney Disease Global Outcome (KDIGO) (2012) Clinical practice guideline for acute kidney injury: definition and classification of AKI. Kidney Int 2:19–36

    Article  Google Scholar 

  22. Schwartz GJ, Gauthier B (1985) A simple estimate of glomerular filtration rate in adolescent boys. J Pediatr 106(3):522–526

    Article  CAS  PubMed  Google Scholar 

  23. Pollack MM, RuttimannUE GPR (1988) Pediatric risk of mortality (PRISM) score. Crit Care 16:1110–1116

    Article  CAS  Google Scholar 

  24. Yang HT, Yim H, Cho YS, Kym D, Hur J, Kim JH, Chun W, Kim HS (2014) Assessment of biochemical markers in the early post-burn period for predicting acute kidney injury and mortality in patients with major burn injury: comparison of serum creatinine, serum cystatin-C, plasma and urine neutrophil gelatinase-associated lipocalin. Crit Care 18:R151

    Article  PubMed  PubMed Central  Google Scholar 

  25. Fan H, Zhao Y, Zhu JH, Song FC (2014) Urine neutrophil gelatinase-associated lipocalin in septic patients with without acute kidney injury. Ren Fail 36:1399–1403

    Article  CAS  PubMed  Google Scholar 

  26. Trachtman H, Christen E, Cnaan A, Patrick J, Mai V, Mishra J, Jain A, Bullington N, Devarajan P, Investigators of the HUS SYNSORBPk Multicenter Clinical Trial (2006) Urinary neutrophil gelatinase-associated lipocalcin in D + HUS: a novel marker of renal injury. Pediatr Nephrol 21:989–994

    Article  PubMed  Google Scholar 

  27. Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, Ruff SM, Zahedi K, Shao M, Bean J, Mori K, Barasch J, Devarajan P (2005) Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 365:1231–1238

    Article  CAS  PubMed  Google Scholar 

  28. Wagener G, Gubitosa G, Wang S, Borregaard N, Kim M, Lee HT (2008) Urinary neutrophil gelatinase-associated lipocalin and acute kidney injury after cardiac surgery. Am J Kidney Dis 52:425–433

    Article  CAS  PubMed  Google Scholar 

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Author’s contributions

OPM, AKR, and AA were involved in the study design, conduction, data analysis, and manuscript drafting; RP and RNM helped in data analysis and manuscript drafting; PS and KP performed estimation of urinary biomarkers; FS helped conceptualize the study and provide critical revision of the manuscript.

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Authors and Affiliations

  1. Division of Pediatric Nephrology, Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India

    Om P. Mishra, Avinash K. Rai, Abhishek Abhinay & Rajniti Prasad

  2. Division of Biostatistics, Department of Community Medicine, Institute of Medical Sciences,Banaras Hindu University, Varanasi, 221005, India

    Rabindra N Mishra

  3. Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, 221005, India

    Khushaboo Pandey

  4. School of Biochemical Engineering, Indian Institute of Technology, Banaras Hindu University, Varanasi, 221005, India

    Pradeep Srivastava

  5. Division of Pediatric Nephrology, Centre for Pediatrics and Adolescent Medicine, Heidelberg University Medical Centre, 69120, Heidelberg, Germany

    Franz Schaefer

Authors
  1. Om P. Mishra
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  2. Avinash K. Rai
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  3. Pradeep Srivastava
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  4. Khushaboo Pandey
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  5. Abhishek Abhinay
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  6. Rajniti Prasad
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  7. Rabindra N Mishra
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  8. Franz Schaefer
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Corresponding author

Correspondence to Om P. Mishra.

Ethics declarations

The study protocol was approved by the institute's Ethical Committee, and informed consent was taken from each parent.

Funding

The study was supported by the Institutional Grant of School of Biochemical Engineering, Indian Institute of Technology, Banaras Hindu University, Varanasi and University Grants Commission (Dr. D. S. Kothari Post Doctoral Fellowship- F 4-2/2006 (BSR)/13-679/2012 (BSR), New Delhi, India.

Competing interest

None

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Mishra, O.P., Rai, A.K., Srivastava, P. et al. Predictive ability of urinary biomarkers for outcome in children with acute kidney injury. Pediatr Nephrol 32, 521–527 (2017). https://doi.org/10.1007/s00467-016-3445-y

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  • DOI: https://doi.org/10.1007/s00467-016-3445-y

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