HHS Public Access Author manuscript Author Manuscript
KI Rep. Author manuscript; available in PMC 2016 September 06. Published in final edited form as: KI Rep. 2016 May ; 1(1): 3–9. doi:10.1016/j.ekir.2016.04.003.
Urinary neutrophil gelatinase-associated lipocalin (NGAL) distinguishes sustained from transient acute kidney injury after general surgery Valerie Au, MD1, Justin Feit, BS1, Jonathan Barasch, MD, PhD2, Robert N. Sladen, MBChB, MRCP(UK), FRCPC, FCCM1, and Gebhard Wagener, MD1,*
Author Manuscript
Valerie Au: [email protected]; Justin Feit: [email protected]; Jonathan Barasch: [email protected]; Robert N. Sladen: [email protected] 1Department
of Anesthesiology, Columbia University College of Physicians and Surgeons, New York, New York
2Department
of Medicine, Columbia University College of Physicians and Surgeons, New York,
New York
Abstract Background—This prospective study tests the hypothesis that after general surgery urinary NGAL can distinguish between sustained acute kidney injury (AKI), typical of nephron damage, from transient AKI, commonly seen with hemodynamic variation and prerenal azotemia.
Author Manuscript
Methods—Urine was collected in 510 patients within 2-3 hr after general surgery and urinary NGAL was determined using ELISA. Patients who met AKIN Stage 1 criteria of AKI were subclassified into those with sustained AKI (serum creatinine elevation for more than 3 days), and those with transient AKI (serum creatinine elevation for less 3 days). Results—Seventeen of 510 patients (3.3%) met the Stage 1 AKIN criteria within 48 hrs of surgery. Elevations in serum creatinine were sustained in 9 and transient in 8 patients. Urinary NGAL was significantly elevated only in patients with sustained AKI (204.8+/-411.9 ng/dL); patients with transient AKI had urinary NGAL that was indistinguishable from patients who did not meet AKIN criteria at all (30.8 ±36.5 ng/dL vs. 31.9 ±113 ng/dL). The area under the curve (AUC) of the receiver operating characteristic (ROC) curve of urinary NGAL to predict sustained AKI was 0.85 [CI (95%): 0.773 to 0.929, p 0.93,16,26-28; but this has not been sustained in some recent studies in adult patients for example undergoing cardiac surgery, critically ill patients in the ICU, and after contrast exposure in coronary angiography12,17,29-32. NGAL's lower discriminatory power in adults (0.85 for sustained AKI in this study) is likely attributable most critically to variables such the prevalence of transient prerenal azotemia and pre-existing kidney disease and other co-morbidities resulting in a more heterogeneous study group10,33 and potentially contributions from different NGAL molecular species, which older assays failed to differentiate.
Author Manuscript
A limitation of our study is that the timing of urinary sampling for NGAL in the PACU was rather loosely defined as within a few hours after admission. In contrast, most studies on renal biomarkers sample at specific time points after surgery or potential renal insults so as to capture the optimum timing to utilize NGAL2,14,16,32. NGAL levels do change with time after surgery15, but most diagnostic tests of organ injury – troponin being the most obvious example - are performed at varying time points after the insult. In our study we tried to replicate the potential clinical use of measuring NGAL in the PACU, and a specific time point for sampling is not practical in normal clinical practice. Our study was designed to most realistically simulate diagnostic testing in a typical clinical setting while sampling fell within the window of peak performance of urinary NGAL (3-12 hours after renal injury). A further limitation of our study is the low rate of events. This incidence of AKI that we observed is similar to previously reported frequency of AKI in patients undergoing general, non-cardiac surgery5. Even with this low event rate our results are robust and comparable to similar the study of NGAL in patients admitted to the emergency department19. Studying higher risk patients will likely observed increase the incidence of AKI and therefore the statistical power but results of such studies may be less generalizable.
Author Manuscript
In conclusion, we have demonstrated that in patients undergoing general surgery, the incidence of SCr elevation is low, less than 4%. Nonetheless, postoperative urinary NGAL concentrations predicted the subsequent development of sustained AKI in a subset of those patients. Our study confirms the observations of Nikolas et al3,19, and other investigators20,21,24 that transient elevations in SCr seen with prerenal azotemia are not associated with NGAL expression outside of the normal range, and therefore likely do not represent tubular injury. Urinary NGAL measurements may therefore facilitate the rapid diagnosis of true intrinsic AKI and distinguishes it from transient SCr elevation due to hemodynamic variations, volume depletion previously called prerenal azotemia.
KI Rep. Author manuscript; available in PMC 2016 September 06.
Au et al.
Page 8
Author Manuscript
Acknowledgments Financial Statement: This publication was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant Number UL1 TR000040. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
References
Author Manuscript Author Manuscript Author Manuscript
1. Khwaja A. KDIGO Clinical Practice Guidelines for Acute Kidney Injury. Nephron Clinical practice. 2012; 120:179–84. 2. Wagener G, Minhaz M, Mattis FA, Kim M, Emond JC, Lee HT. Urinary neutrophil gelatinaseassociated lipocalin as a marker of acute kidney injury after orthotopic liver transplantation. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2011; 26:1717–23. 3. Nickolas TL, O'Rourke MJ, Yang J, et al. Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury. Annals of internal medicine. 2008; 148:810–9. [PubMed: 18519927] 4. Brown JR, Kramer RS, Coca SG, Parikh CR. Duration of acute kidney injury impacts long-term survival after cardiac surgery. The Annals of thoracic surgery. 2010; 90:1142–8. [PubMed: 20868804] 5. Kheterpal S, Tremper KK, Heung M, et al. Development and validation of an acute kidney injury risk index for patients undergoing general surgery: results from a national data set. Anesthesiology. 2009; 110:505–15. [PubMed: 19212261] 6. Legrand M, Payen D. Case scenario: Hemodynamic management of postoperative acute kidney injury. Anesthesiology. 2013; 118:1446–54. [PubMed: 23558177] 7. Kheterpal S, Tremper KK, Englesbe MJ, et al. Predictors of postoperative acute renal failure after noncardiac surgery in patients with previously normal renal function. Anesthesiology. 2007; 107:892–902. [PubMed: 18043057] 8. Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. Journal of the American Society of Nephrology : JASN. 2005; 16:3365–70. [PubMed: 16177006] 9. Borthwick E, Ferguson A. Perioperative acute kidney injury: risk factors, recognition, management, and outcomes. Bmj. 2010; 341:c3365. [PubMed: 20603317] 10. Devarajan P. Review: neutrophil gelatinase-associated lipocalin: a troponin-like biomarker for human acute kidney injury. Nephrology. 2010; 15:419–28. [PubMed: 20609093] 11. Mishra J, Ma Q, Prada A, et al. Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. Journal of the American Society of Nephrology : JASN. 2003; 14:2534–43. [PubMed: 14514731] 12. Haase M, Devarajan P, Haase-Fielitz A, et al. The outcome of neutrophil gelatinase-associated lipocalin-positive subclinical acute kidney injury: a multicenter pooled analysis of prospective studies. Journal of the American College of Cardiology. 2011; 57:1752–61. [PubMed: 21511111] 13. Haase-Fielitz A, Bellomo R, Devarajan P, et al. The predictive performance of plasma neutrophil gelatinase-associated lipocalin (NGAL) increases with grade of acute kidney injury. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2009; 24:3349–54. 14. Wagener G, Gubitosa G, Wang S, Borregaard N, Kim M, Lee HT. Urinary neutrophil gelatinaseassociated lipocalin and acute kidney injury after cardiac surgery. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2008; 52:425–33. [PubMed: 18649981] 15. Bachorzewska-Gajewska H, Malyszko J, Sitniewska E, Malyszko JS, Dobrzycki S. Neutrophilgelatinase-associated lipocalin and renal function after percutaneous coronary interventions. American journal of nephrology. 2006; 26:287–92. [PubMed: 16772710]
KI Rep. Author manuscript; available in PMC 2016 September 06.
Au et al.
Page 9
Author Manuscript Author Manuscript Author Manuscript Author Manuscript
16. 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; 365:1231–8. [PubMed: 15811456] 17. Siew ED, Ware LB, Gebretsadik T, et al. Urine neutrophil gelatinase-associated lipocalin moderately predicts acute kidney injury in critically ill adults. Journal of the American Society of Nephrology : JASN. 2009; 20:1823–32. [PubMed: 19628673] 18. Zappitelli M, Washburn KK, Arikan AA, et al. Urine neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in critically ill children: a prospective cohort study. Critical care. 2007; 11:R84. [PubMed: 17678545] 19. Nickolas TL, Schmidt-Ott KM, Canetta P, et al. Diagnostic and prognostic stratification in the emergency department using urinary biomarkers of nephron damage: a multicenter prospective cohort study. Journal of the American College of Cardiology. 2012; 59:246–55. [PubMed: 22240130] 20. Belcher JM, Sanyal AJ, Peixoto AJ, et al. Kidney biomarkers and differential diagnosis of patients with cirrhosis and acute kidney injury. Hepatology. 2014; 60:622–32. [PubMed: 24375576] 21. Nejat M, Pickering JW, Devarajan P, et al. Some biomarkers of acute kidney injury are increased in pre-renal acute injury. Kidney international. 2012; 81:1254–62. [PubMed: 22418979] 22. Paragas N, Qiu A, Zhang Q, et al. The Ngal reporter mouse detects the response of the kidney to injury in real time. Nature medicine. 2011; 17:216–22. 23. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976; 16:31–41. [PubMed: 1244564] 24. Singer E, Elger A, Elitok S, et al. Urinary neutrophil gelatinase-associated lipocalin distinguishes pre-renal from intrinsic renal failure and predicts outcomes. Kidney international. 2011; 80:405– 14. [PubMed: 21412214] 25. Lin J, Fernandez H, Shashaty MG, et al. False-Positive Rate of AKI Using Consensus CreatinineBased Criteria. Clinical journal of the American Society of Nephrology : CJASN. 2015; 10:1723– 31. [PubMed: 26336912] 26. Hirsch R, Dent C, Pfriem H, et al. NGAL is an early predictive biomarker of contrast-induced nephropathy in children. Pediatric nephrology. 2007; 22:2089–95. [PubMed: 17874137] 27. Makris K, Markou N, Evodia E, et al. Urinary neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of acute kidney injury in critically ill multiple trauma patients. Clinical chemistry and laboratory medicine : CCLM / FESCC. 2009; 47:79–82. 28. Portilla D, Dent C, Sugaya T, et al. Liver fatty acid-binding protein as a biomarker of acute kidney injury after cardiac surgery. Kidney international. 2008; 73:465–72. [PubMed: 18094680] 29. de Geus HR, Bakker J, Lesaffre EM, le Noble JL. Neutrophil gelatinase-associated lipocalin at ICU admission predicts for acute kidney injury in adult patients. American journal of respiratory and critical care medicine. 2011; 183:907–14. [PubMed: 20935115] 30. Koyner JL, Bennett MR, Worcester EM, et al. Urinary cystatin C as an early biomarker of acute kidney injury following adult cardiothoracic surgery. Kidney international. 2008; 74:1059–69. [PubMed: 18650797] 31. Ling W, Zhaohui N, Ben H, et al. Urinary IL-18 and NGAL as early predictive biomarkers in contrast-induced nephropathy after coronary angiography. Nephron Clinical practice. 2008; 108:c176–81. [PubMed: 18287807] 32. Wagener G, Jan M, Kim M, et al. Association between increases in urinary neutrophil gelatinaseassociated lipocalin and acute renal dysfunction after adult cardiac surgery. Anesthesiology. 2006; 105:485–91. [PubMed: 16931980] 33. McIlroy DR, Wagener G, Lee HT. Biomarkers of acute kidney injury: an evolving domain. Anesthesiology. 2010; 112:998–1004. [PubMed: 20216399]
KI Rep. Author manuscript; available in PMC 2016 September 06.
Au et al.
Page 10
Author Manuscript Author Manuscript
Figure 1.
Perioperative changes in SCr in patients with sustained (> 3 days) or transient (< 3 days) AKI or no AKI; mean ± SEM, p 3 days) by AKIN criteria; p values derived from ANOVA with Tukey post-hoc tests.
Author Manuscript Author Manuscript KI Rep. Author manuscript; available in PMC 2016 September 06.
Au et al.
Page 12
Table 1
Patient demographics
Author Manuscript
510 Patients Patient Characteristics Age
60.7 (±15.5)
Height (cm)
166.7 (±12.6)
Weight (kg)
82.5 (±24.5)
BMI
30.5 (±20.8)
Female
303 (59.4%) Surgical Procedures
Author Manuscript
Major Abdominal
113 (22.2%)
Minor Abdominal
9 (1.8%)
Gynecological
46 (9.0%)
CNS Neurosurgery
24 (4.7%)
Neuro
24 (4.7%)
Orthopedics
95 (18.6%)
Spine
48 (9.4%)
Thoracic
55 (10.8%)
Vascular major
19 (3.7%)
Vascular minor
5 (1.0%)
Author Manuscript
Angiogram
7 (1.4%)
Urology major
32 (6.3%)
Urology minor
19 (3.7%)
Other
14 (2.7%)
Data are reported as mean and standard deviation or number and percentage, as appropriate. BMI = Body mass index; CNS = Central Nervous System
Author Manuscript KI Rep. Author manuscript; available in PMC 2016 September 06.
Au et al.
Page 13
Table 2
Author Manuscript
Urine sodium, urine creatinine, fractional excretion of sodium and urinary NGAL comparing patients with sustained and transient acute kidney injury (AKI) and normal postoperative serum creatinine: one-way analysis of variance (ANOVA) and Tukey's post hoc multiple comparison test to compare mean values across the groups
Author Manuscript Author Manuscript Author Manuscript KI Rep. Author manuscript; available in PMC 2016 September 06.
KI Rep. Author manuscript; available in PMC 2016 September 06. Published in final edited form as: KI Rep. 2016 May ; 1(1): 3–9. doi:10.1016/j.ekir.2016.04.003.
Urinary neutrophil gelatinase-associated lipocalin (NGAL) distinguishes sustained from transient acute kidney injury after general surgery Valerie Au, MD1, Justin Feit, BS1, Jonathan Barasch, MD, PhD2, Robert N. Sladen, MBChB, MRCP(UK), FRCPC, FCCM1, and Gebhard Wagener, MD1,*
Author Manuscript
Valerie Au: [email protected]; Justin Feit: [email protected]; Jonathan Barasch: [email protected]; Robert N. Sladen: [email protected] 1Department
of Anesthesiology, Columbia University College of Physicians and Surgeons, New York, New York
2Department
of Medicine, Columbia University College of Physicians and Surgeons, New York,
New York
Abstract Background—This prospective study tests the hypothesis that after general surgery urinary NGAL can distinguish between sustained acute kidney injury (AKI), typical of nephron damage, from transient AKI, commonly seen with hemodynamic variation and prerenal azotemia.
Author Manuscript
Methods—Urine was collected in 510 patients within 2-3 hr after general surgery and urinary NGAL was determined using ELISA. Patients who met AKIN Stage 1 criteria of AKI were subclassified into those with sustained AKI (serum creatinine elevation for more than 3 days), and those with transient AKI (serum creatinine elevation for less 3 days). Results—Seventeen of 510 patients (3.3%) met the Stage 1 AKIN criteria within 48 hrs of surgery. Elevations in serum creatinine were sustained in 9 and transient in 8 patients. Urinary NGAL was significantly elevated only in patients with sustained AKI (204.8+/-411.9 ng/dL); patients with transient AKI had urinary NGAL that was indistinguishable from patients who did not meet AKIN criteria at all (30.8 ±36.5 ng/dL vs. 31.9 ±113 ng/dL). The area under the curve (AUC) of the receiver operating characteristic (ROC) curve of urinary NGAL to predict sustained AKI was 0.85 [CI (95%): 0.773 to 0.929, p 0.93,16,26-28; but this has not been sustained in some recent studies in adult patients for example undergoing cardiac surgery, critically ill patients in the ICU, and after contrast exposure in coronary angiography12,17,29-32. NGAL's lower discriminatory power in adults (0.85 for sustained AKI in this study) is likely attributable most critically to variables such the prevalence of transient prerenal azotemia and pre-existing kidney disease and other co-morbidities resulting in a more heterogeneous study group10,33 and potentially contributions from different NGAL molecular species, which older assays failed to differentiate.
Author Manuscript
A limitation of our study is that the timing of urinary sampling for NGAL in the PACU was rather loosely defined as within a few hours after admission. In contrast, most studies on renal biomarkers sample at specific time points after surgery or potential renal insults so as to capture the optimum timing to utilize NGAL2,14,16,32. NGAL levels do change with time after surgery15, but most diagnostic tests of organ injury – troponin being the most obvious example - are performed at varying time points after the insult. In our study we tried to replicate the potential clinical use of measuring NGAL in the PACU, and a specific time point for sampling is not practical in normal clinical practice. Our study was designed to most realistically simulate diagnostic testing in a typical clinical setting while sampling fell within the window of peak performance of urinary NGAL (3-12 hours after renal injury). A further limitation of our study is the low rate of events. This incidence of AKI that we observed is similar to previously reported frequency of AKI in patients undergoing general, non-cardiac surgery5. Even with this low event rate our results are robust and comparable to similar the study of NGAL in patients admitted to the emergency department19. Studying higher risk patients will likely observed increase the incidence of AKI and therefore the statistical power but results of such studies may be less generalizable.
Author Manuscript
In conclusion, we have demonstrated that in patients undergoing general surgery, the incidence of SCr elevation is low, less than 4%. Nonetheless, postoperative urinary NGAL concentrations predicted the subsequent development of sustained AKI in a subset of those patients. Our study confirms the observations of Nikolas et al3,19, and other investigators20,21,24 that transient elevations in SCr seen with prerenal azotemia are not associated with NGAL expression outside of the normal range, and therefore likely do not represent tubular injury. Urinary NGAL measurements may therefore facilitate the rapid diagnosis of true intrinsic AKI and distinguishes it from transient SCr elevation due to hemodynamic variations, volume depletion previously called prerenal azotemia.
KI Rep. Author manuscript; available in PMC 2016 September 06.
Au et al.
Page 8
Author Manuscript
Acknowledgments Financial Statement: This publication was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant Number UL1 TR000040. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
References
Author Manuscript Author Manuscript Author Manuscript
1. Khwaja A. KDIGO Clinical Practice Guidelines for Acute Kidney Injury. Nephron Clinical practice. 2012; 120:179–84. 2. Wagener G, Minhaz M, Mattis FA, Kim M, Emond JC, Lee HT. Urinary neutrophil gelatinaseassociated lipocalin as a marker of acute kidney injury after orthotopic liver transplantation. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2011; 26:1717–23. 3. Nickolas TL, O'Rourke MJ, Yang J, et al. Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury. Annals of internal medicine. 2008; 148:810–9. [PubMed: 18519927] 4. Brown JR, Kramer RS, Coca SG, Parikh CR. Duration of acute kidney injury impacts long-term survival after cardiac surgery. The Annals of thoracic surgery. 2010; 90:1142–8. [PubMed: 20868804] 5. Kheterpal S, Tremper KK, Heung M, et al. Development and validation of an acute kidney injury risk index for patients undergoing general surgery: results from a national data set. Anesthesiology. 2009; 110:505–15. [PubMed: 19212261] 6. Legrand M, Payen D. Case scenario: Hemodynamic management of postoperative acute kidney injury. Anesthesiology. 2013; 118:1446–54. [PubMed: 23558177] 7. Kheterpal S, Tremper KK, Englesbe MJ, et al. Predictors of postoperative acute renal failure after noncardiac surgery in patients with previously normal renal function. Anesthesiology. 2007; 107:892–902. [PubMed: 18043057] 8. Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. Journal of the American Society of Nephrology : JASN. 2005; 16:3365–70. [PubMed: 16177006] 9. Borthwick E, Ferguson A. Perioperative acute kidney injury: risk factors, recognition, management, and outcomes. Bmj. 2010; 341:c3365. [PubMed: 20603317] 10. Devarajan P. Review: neutrophil gelatinase-associated lipocalin: a troponin-like biomarker for human acute kidney injury. Nephrology. 2010; 15:419–28. [PubMed: 20609093] 11. Mishra J, Ma Q, Prada A, et al. Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. Journal of the American Society of Nephrology : JASN. 2003; 14:2534–43. [PubMed: 14514731] 12. Haase M, Devarajan P, Haase-Fielitz A, et al. The outcome of neutrophil gelatinase-associated lipocalin-positive subclinical acute kidney injury: a multicenter pooled analysis of prospective studies. Journal of the American College of Cardiology. 2011; 57:1752–61. [PubMed: 21511111] 13. Haase-Fielitz A, Bellomo R, Devarajan P, et al. The predictive performance of plasma neutrophil gelatinase-associated lipocalin (NGAL) increases with grade of acute kidney injury. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2009; 24:3349–54. 14. Wagener G, Gubitosa G, Wang S, Borregaard N, Kim M, Lee HT. Urinary neutrophil gelatinaseassociated lipocalin and acute kidney injury after cardiac surgery. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2008; 52:425–33. [PubMed: 18649981] 15. Bachorzewska-Gajewska H, Malyszko J, Sitniewska E, Malyszko JS, Dobrzycki S. Neutrophilgelatinase-associated lipocalin and renal function after percutaneous coronary interventions. American journal of nephrology. 2006; 26:287–92. [PubMed: 16772710]
KI Rep. Author manuscript; available in PMC 2016 September 06.
Au et al.
Page 9
Author Manuscript Author Manuscript Author Manuscript Author Manuscript
16. 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; 365:1231–8. [PubMed: 15811456] 17. Siew ED, Ware LB, Gebretsadik T, et al. Urine neutrophil gelatinase-associated lipocalin moderately predicts acute kidney injury in critically ill adults. Journal of the American Society of Nephrology : JASN. 2009; 20:1823–32. [PubMed: 19628673] 18. Zappitelli M, Washburn KK, Arikan AA, et al. Urine neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in critically ill children: a prospective cohort study. Critical care. 2007; 11:R84. [PubMed: 17678545] 19. Nickolas TL, Schmidt-Ott KM, Canetta P, et al. Diagnostic and prognostic stratification in the emergency department using urinary biomarkers of nephron damage: a multicenter prospective cohort study. Journal of the American College of Cardiology. 2012; 59:246–55. [PubMed: 22240130] 20. Belcher JM, Sanyal AJ, Peixoto AJ, et al. Kidney biomarkers and differential diagnosis of patients with cirrhosis and acute kidney injury. Hepatology. 2014; 60:622–32. [PubMed: 24375576] 21. Nejat M, Pickering JW, Devarajan P, et al. Some biomarkers of acute kidney injury are increased in pre-renal acute injury. Kidney international. 2012; 81:1254–62. [PubMed: 22418979] 22. Paragas N, Qiu A, Zhang Q, et al. The Ngal reporter mouse detects the response of the kidney to injury in real time. Nature medicine. 2011; 17:216–22. 23. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976; 16:31–41. [PubMed: 1244564] 24. Singer E, Elger A, Elitok S, et al. Urinary neutrophil gelatinase-associated lipocalin distinguishes pre-renal from intrinsic renal failure and predicts outcomes. Kidney international. 2011; 80:405– 14. [PubMed: 21412214] 25. Lin J, Fernandez H, Shashaty MG, et al. False-Positive Rate of AKI Using Consensus CreatinineBased Criteria. Clinical journal of the American Society of Nephrology : CJASN. 2015; 10:1723– 31. [PubMed: 26336912] 26. Hirsch R, Dent C, Pfriem H, et al. NGAL is an early predictive biomarker of contrast-induced nephropathy in children. Pediatric nephrology. 2007; 22:2089–95. [PubMed: 17874137] 27. Makris K, Markou N, Evodia E, et al. Urinary neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of acute kidney injury in critically ill multiple trauma patients. Clinical chemistry and laboratory medicine : CCLM / FESCC. 2009; 47:79–82. 28. Portilla D, Dent C, Sugaya T, et al. Liver fatty acid-binding protein as a biomarker of acute kidney injury after cardiac surgery. Kidney international. 2008; 73:465–72. [PubMed: 18094680] 29. de Geus HR, Bakker J, Lesaffre EM, le Noble JL. Neutrophil gelatinase-associated lipocalin at ICU admission predicts for acute kidney injury in adult patients. American journal of respiratory and critical care medicine. 2011; 183:907–14. [PubMed: 20935115] 30. Koyner JL, Bennett MR, Worcester EM, et al. Urinary cystatin C as an early biomarker of acute kidney injury following adult cardiothoracic surgery. Kidney international. 2008; 74:1059–69. [PubMed: 18650797] 31. Ling W, Zhaohui N, Ben H, et al. Urinary IL-18 and NGAL as early predictive biomarkers in contrast-induced nephropathy after coronary angiography. Nephron Clinical practice. 2008; 108:c176–81. [PubMed: 18287807] 32. Wagener G, Jan M, Kim M, et al. Association between increases in urinary neutrophil gelatinaseassociated lipocalin and acute renal dysfunction after adult cardiac surgery. Anesthesiology. 2006; 105:485–91. [PubMed: 16931980] 33. McIlroy DR, Wagener G, Lee HT. Biomarkers of acute kidney injury: an evolving domain. Anesthesiology. 2010; 112:998–1004. [PubMed: 20216399]
KI Rep. Author manuscript; available in PMC 2016 September 06.
Au et al.
Page 10
Author Manuscript Author Manuscript
Figure 1.
Perioperative changes in SCr in patients with sustained (> 3 days) or transient (< 3 days) AKI or no AKI; mean ± SEM, p 3 days) by AKIN criteria; p values derived from ANOVA with Tukey post-hoc tests.
Author Manuscript Author Manuscript KI Rep. Author manuscript; available in PMC 2016 September 06.
Au et al.
Page 12
Table 1
Patient demographics
Author Manuscript
510 Patients Patient Characteristics Age
60.7 (±15.5)
Height (cm)
166.7 (±12.6)
Weight (kg)
82.5 (±24.5)
BMI
30.5 (±20.8)
Female
303 (59.4%) Surgical Procedures
Author Manuscript
Major Abdominal
113 (22.2%)
Minor Abdominal
9 (1.8%)
Gynecological
46 (9.0%)
CNS Neurosurgery
24 (4.7%)
Neuro
24 (4.7%)
Orthopedics
95 (18.6%)
Spine
48 (9.4%)
Thoracic
55 (10.8%)
Vascular major
19 (3.7%)
Vascular minor
5 (1.0%)
Author Manuscript
Angiogram
7 (1.4%)
Urology major
32 (6.3%)
Urology minor
19 (3.7%)
Other
14 (2.7%)
Data are reported as mean and standard deviation or number and percentage, as appropriate. BMI = Body mass index; CNS = Central Nervous System
Author Manuscript KI Rep. Author manuscript; available in PMC 2016 September 06.
Au et al.
Page 13
Table 2
Author Manuscript
Urine sodium, urine creatinine, fractional excretion of sodium and urinary NGAL comparing patients with sustained and transient acute kidney injury (AKI) and normal postoperative serum creatinine: one-way analysis of variance (ANOVA) and Tukey's post hoc multiple comparison test to compare mean values across the groups
Author Manuscript Author Manuscript Author Manuscript KI Rep. Author manuscript; available in PMC 2016 September 06.
