J Korean Med Sci.  2013 Aug;28(8):1181-1186. 10.3346/jkms.2013.28.8.1181.

Urinary Biomarkers for Early Detection of Recovery in Patients with Acute Kidney Injury

Affiliations
  • 1Department of Internal Medicine, College of Medicine, Kwandong University, Gangneung, Korea. sunnylsc@hanafos.com
  • 2Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Abstract

Urinary biomarkers of acute kidney injury (AKI) have been revealed recently to be useful for prior prediction of AKI. However, it is unclear whether these urinary biomarkers can also detect recovery from established AKI. Urinary biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C, were measured every 2 days for 8 days in 66 patients with AKI. At day 0, there were no significant differences in plasma creatinine, BUN, and urine cystatin C between AKI patients in the recovery (n = 33) and non-recovery (n = 33) groups. Plasma creatinine concentrations were significantly lower in the recovery group (3.0 +/- 2.0 mg/dL) than in the non-recovery group (5.4 +/- 1.9 mg/dL) on day 4 after AKI diagnosis (P < 0.001). In contrast, there were significant differences in urine NGAL between the two groups starting on day 0 (297.2 +/- 201.4 vs 407.6 +/- 190.4 ng/mL, P = 0.025) through the end of the study (123.7 +/- 119.0 vs 434.3 +/- 121.5 ng/mL, P < 0.001). The multiple logistic regression analysis showed that urine NGAL could independently predict recovery from AKI. Conclusively, this prospective observational study demonstrates that urine NGAL can be a highly versatile marker for early detection of the recovery phase in established AKI patients.

Keyword

Acute Kidney Injury; Biological Markers; Neutrophil Gelatinase-Associated Lipocalin; Cystatin C

MeSH Terms

Acute Kidney Injury/*diagnosis/pathology
Acute-Phase Proteins/urine
Adolescent
Adult
Aged
Biological Markers/*urine
Creatinine/blood
Cystatin C/urine
Female
Humans
Lipocalins/urine
Logistic Models
Male
Middle Aged
Prospective Studies
Proto-Oncogene Proteins/urine
ROC Curve
Recovery of Function
Young Adult
Acute-Phase Proteins
Biological Markers
Creatinine
Cystatin C
Lipocalins
Proto-Oncogene Proteins

Figure

  • Fig. 1 BUN (A), plasma Cr (B), urine NGAL (C), urine NGAL/Cr (D), urine cystatin C (E), urine cystatin C/Cr (F) levels every 2 days for 8 day period stratified by recovery and non-recovery from AKI. Urine NGAL level shows statistically significant difference between groups since day 0 preceding the difference in plasma Cr level.*P < 0.01 comparing recovery group vs non-recovery group; †P < 0.05 comparing recovery group vs non-recovery group. BUN, blood urea nitrogen; Cr, creatinine; NGAL, Neutrophil gelatinase-associated lipocalin; AKI, acute kidney injury.

  • Fig. 2 ROC curve for the detection of AKI recovery using urine NGAL at day 0 after AKI diagnosis. ROC curve demonstrates the prognostic sensitivity and specificity of urine NGAL in the prediction of AKI recovery (AUC = 0.78; 95% CI 0.64-0.90). AUC, Area under the curve; ROC, Receiver operating characteristic; AKI, Acute kidney injury; NGAL, Neutrophil gelatinase-associated lipocalin.


Reference

1. Thadhani R, Pascual M, Bonventre JV. Acute renal failure. N Engl J Med. 1996; 334:1448–1460.
2. Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol. 2005; 16:3365–3370.
3. Koyner JL, Bennett MR, Worcester EM, Ma Q, Raman J, Jeevanandam V, Kasza KE, O'Connor MF, Konczal DJ, Trevino S, et al. Urinary cystatin C as an early biomarker of acute kidney injury following adult cardiothoracic surgery. Kidney Int. 2008; 74:1059–1069.
4. Schrier RW. Early intervention in acute kidney injury. Nat Rev Nephrol. 2010; 6:56–59.
5. Wald R, Quinn RR, Luo J, Li P, Scales DC, Mamdani MM, Ray JG. University of Toronto Acute Kidney Injury Research Group. Chronic dialysis and death among survivors of acute kidney injury requiring dialysis. JAMA. 2009; 302:1179–1185.
6. Price PM, Safirstein RL, Megyesi J. The cell cycle and acute kidney injury. Kidney Int. 2009; 76:604–613.
7. Okusa MD. The inflammatory cascade in acute ischemic renal failure. Nephron. 2002; 90:133–138.
8. Day YJ, Huang L, Ye H, Li L, Linden J, Okusa MD. Renal ischemia-reperfusion injury and adenosine 2A receptor-mediated tissue protection: the role of CD4+ T cells and IFN-gamma. J Immunol. 2006; 176:3108–3114.
9. Del Rio M, Imam A, DeLeon M, Gomez G, Mishra J, Ma Q, Parikh S, Devarajan P. The death domain of kidney ankyrin interacts with Fas and promotes Fas-mediated cell death in renal epithelia. J Am Soc Nephrol. 2004; 15:41–51.
10. Devarajan P. Update on mechanisms of ischemic acute kidney injury. J Am Soc Nephrol. 2006; 17:1503–1520.
11. Haase M, Bellomo R, Devarajan P, Schlattmann P, Haase-Fielitz A. NGAL Meta-analysis Investigator Group. Accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in diagnosis and prognosis in acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis. 2009; 54:1012–1024.
12. Vaidya VS, Waikar SS, Ferguson MA, Collings FB, Sunderland K, Gioules C, Bradwin G, Matsouaka R, Betensky RA, Curhan GC, et al. Urinary biomarkers for sensitive and specific detection of acute kidney injury in humans. Clin Transl Sci. 2008; 1:200–208.
13. Waikar SS, Liu KD, Chertow GM. Diagnosis, epidemiology and outcomes of acute kidney injury. Clin J Am Soc Nephrol. 2008; 3:844–861.
14. Goldstein SL, Chawla LS. Renal angina. Clin J Am Soc Nephrol. 2010; 5:943–949.
15. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. Acute Dialysis Quality Initiative workgroup. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004; 8:R204–R212.
16. Soni SS, Ronco C, Katz N, Cruz DN. Early diagnosis of acute kidney injury: the promise of novel biomarkers. Blood Purif. 2009; 28:165–174.
17. Han WK, Waikar SS, Johnson A, Betensky RA, Dent CL, Devarajan P, Bonventre JV. Urinary biomarkers in the early diagnosis of acute kidney injury. Kidney Int. 2008; 73:863–869.
18. Han WK, Bailly V, Abichandani R, Thadhani R, Bonventre JV. Kidney Injury Molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury. Kidney Int. 2002; 62:237–244.
19. Lebkowska U, Malyszko J, Lebkowska A, Koc-Zorawska E, Lebkowski W, Malyszko JS, Kowalewski R, Gacko M. Neutrophil gelatinase-associated lipocalin and cystatin C could predict renal outcome in patients undergoing kidney allograft transplantation: a prospective study. Transplant Proc. 2009; 41:154–157.
20. Bolignano D, Donato V, Coppolino G, Campo S, Buemi A, Lacquaniti A, Buemi M. Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney damage. Am J Kidney Dis. 2008; 52:595–605.
21. Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, Ruff SM, Zahedi K, Shao M, Bean J, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet. 2005; 365:1231–1238.
22. Wagener G, Gubitosa G, Wang S, Borregaard N, Kim M, Lee HT. Urinary neutrophil gelatinase-associated lipocalin and acute kidney injury after cardiac surgery. Am J Kidney Dis. 2008; 52:425–433.
23. Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, Barasch J, Devarajan P. Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol. 2003; 14:2534–2543.
24. Cruz DN, de Cal M, Garzotto F, Perazella MA, Lentini P, Corradi V, Piccinni P, Ronco C. Plasma neutrophil gelatinase-associated lipocalin is an early biomarker for acute kidney injury in an adult ICU population. Intensive Care Med. 2010; 36:444–451.
25. Kümpers P, Hafer C, Lukasz A, Lichtinghagen R, Brand K, Fliser D, Faulhaber-Walter R, Kielstein JT. Serum neutrophil gelatinase-associated lipocalin at inception of renal replacement therapy predicts survival in critically ill patients with acute kidney injury. Crit Care. 2010; 14:R9.
26. Bennett M, Dent CL, Ma Q, Dastrala S, Grenier F, Workman R, Syed H, Ali S, Barasch J, Devarajan P. Urine NGAL predicts severity of acute kidney injury after cardiac surgery: a prospective study. Clin J Am Soc Nephrol. 2008; 3:665–673.
27. Herget-Rosenthal S, Marggraf G, Hüsing J, Göring F, Pietruck F, Janssen O, Philipp T, Kribben A. Early detection of acute renal failure by serum cystatin C. Kidney Int. 2004; 66:1115–1122.
28. Villa P, Jiménez M, Soriano MC, Manzanares J, Casasnovas P. Serum cystatin C concentration as a marker of acute renal dysfunction in critically ill patients. Crit Care. 2005; 9:R139–R143.
29. Srisawat N, Murugan R, Wen X, Singbartl K, Clermont G, Eiam-Ong S, Kellum JA. Recovery from acute kidney injury: determinants and predictors. Contrib Nephrol. 2010; 165:284–291.
30. Srisawat N, Murugan R, Lee M, Kong L, Carter M, Angus DC, Kellum JA. Genetic and Inflammatory Markers of Sepsis (GenIMS) Study Investigators. Plasma neutrophil gelatinase-associated lipocalin predicts recovery from acute kidney injury following community-acquired pneumonia. Kidney Int. 2011; 80:545–552.
31. Srisawat N, Wen X, Lee M, Kong L, Elder M, Carter M, Unruh M, Finkel K, Vijayan A, Ramkumar M, et al. Urinary biomarkers and renal recovery in critically ill patients with renal support. Clin J Am Soc Nephrol. 2011; 6:1815–1823.
32. Hollmen ME, Kyllönen LE, Inkinen KA, Lalla ML, Salmela KT. Urine neutrophil gelatinase-associated lipocalin is a marker of graft recovery after kidney transplantation. Kidney Int. 2011; 79:89–98.
33. Yang HN, Boo CS, Kim MG, Jo SK, Cho WY, Kim HK. Urine neutrophil gelatinase-associated lipocalin: an independent predictor of adverse outcomes in acute kidney injury. Am J Nephrol. 2010; 31:501–509.
34. Singbartl K, Kellum JA. AKI in the ICU: definition, epidemiology, risk stratification, and outcomes. Kidney Int. 2012; 81:819–825.
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