Biomarkers of acute kidney injury: The pathway from discovery to clinical adoption

Clinical Chemistry and Laboratory Medicine

Volumn 55, Issue 8, 2017, Pages 1074-1089

  Kashani, Kianoush ^b   Cheungpasitporn, Wisit ^b   Ronco, Claudio ^a  

^a SAN BORTOLO HOSPITAL   (Italy)

^b MAYO CLINIC   (United States)

Author keywords

acute kidney injury; angiotensinogen (AGT); biomarkers; calprotectin; insulin like growth factor binding protein 7 (IGFBP7); kidney injury molecule 1 (KIM 1); microRNA; neutrophil gelatinase associated lipocalin (NGAL); tissue inhibitor of metalloproteinase 2 (TIMP 2)

Indexed keywords

ANGIOTENSINOGEN; BIOLOGICAL MARKER; CALGRANULIN; FATTY ACID BINDING PROTEIN; INSULIN LIKE GROWTH FACTOR BINDING PROTEIN 7; INTERLEUKIN 18; KIDNEY INJURY MOLECULE 1; LIVER TYPE FATTY ACID-BINDING PROTEIN; MICRORNA; NEUTROPHIL GELATINASE ASSOCIATED LIPOCALIN; SOMATOMEDIN BINDING PROTEIN; TISSUE INHIBITOR OF METALLOPROTEINASE 2; UNCLASSIFIED DRUG;

ACUTE KIDNEY FAILURE; CLINICAL OUTCOME; CLINICAL PRACTICE; CLINICAL TRIAL (TOPIC); HUMAN; MEDICAL LITERATURE; META ANALYSIS (TOPIC); MOLECULAR DIAGNOSIS; OUTCOME ASSESSMENT; PRIORITY JOURNAL; PROGNOSIS; PROGNOSTIC ASSESSMENT; REVIEW; URINARY TRACT DISEASE ASSESSMENT; URINE LEVEL; ACUTE KIDNEY INJURY; ANIMAL; METABOLISM;

ACUTE KIDNEY INJURY; ANIMALS; BIOMARKERS; HUMANS; PROGNOSIS;

EID: 85018263728     PISSN: 14346621     EISSN: 14374331     Source Type: Journal    
DOI: 10.1515/cclm-2016-0973     Document Type: Review

References (190)

1. Bellomo R, Kellum JA, Ronco C. Acute kidney injury. Lancet (London, England). 2012;380:756-66.
2. Kellum JA, Bellomo R, Ronco C. Kidney attack. J Am Med Assoc 2012;307:2265-6.
3. Chawla LS, Eggers PW, Star RA, Kimmel PL. Acute kidney injury and chronic kidney disease as interconnected syndromes. N Engl J Med 2014;371:58-66.
4. Chawla LS, Amdur RL, Shaw AD, Faselis C, Palant CE, Kimmel PL. Association between AKI and long-term renal and cardiovascular outcomes in United States veterans. Clin J Am Soc Nephrol 2014;9:448-56.
5. Wu VC, Wu CH, Huang TM, Wang CY, Lai CF, Shiao CC, et al. Long-term risk of coronary events after AKI. J Am Soc Nephrol 2014;25:595-605.
6. Odutayo A, Wong CX, Farkouh M, Altman DG, Hopewell S, Emdin CA, et al. AKI and long-term risk for cardiovascular events and mortality. J Am Soc Nephrol 2016; pii: ASN. 2016010105. [Epub ahead of print].
7. Siew ED, Davenport A. The growth of acute kidney injury: A rising tide or just closer attention to detail Kidney Int 2015;87:46-61.
8. Cruz DN, Bagshaw SM, Maisel A, Lewington A, Thadhani R, Chakravarthi R, et al. Use of biomarkers to assess prognosis and guide management of patients with acute kidney injury. Contrib Nephrol 2013;182:45-64.
9. Sakhuja A, Kumar G, Gupta S, Mittal T, Taneja A, Nanchal RS. Acute kidney injury requiring dialysis in severe sepsis. Am J Respir Crit Care Med 2015;192:951-7.
10. Schrezenmeier EV, Barasch J, Budde K, Westhoff T, Schmidt-Ott KM. Biomarkers in acute kidney injury-pathophysiological basis and clinical performance. Acta Physiol (Oxf) 2016. doi: 10. 1111/apha. 12764. [Epub ahead of print].
11. Waikar SS, Betensky RA, Bonventre JV. Creatinine as the gold standard for kidney injury biomarker studies Nephrol Dial Transplant 2009;24:3263-5.
12. Au V, Feit J, Barasch J, Sladen RN, Wagener G. Urinary neutrophil gelatinase-associated lipocalin (NGAL) distinguishes sustained from transient acute kidney injury after general surgery. Kidney Int Rep 2016;1:3-9.
13. Wagener G, Minhaz M, Mattis FA, Kim M, Emond JC, Lee HT. Urinary neutrophil gelatinase-associated lipocalin as a marker of acute kidney injury after orthotopic liver transplantation. Nephrol Dial Transplant 2011;26:1717-23.
14. Thongprayoon C, Cheungpasitporn W, Kashani K. Serum creatinine level, a surrogate of muscle mass, predicts mortality in critically ill patients. J Thorac Dis 2016;8:E305-11.
15. Medic B, Rovcanin B, Vujovic KS, Obradovic D, Duric D, Prostran M. Evaluation of novel biomarkers of acute kidney injury: The possibilities and limitations. Curr Med Chem 2016;23:1981-97.
16. Szerlip HM, Chawla LS. Predicting acute kidney injury prognosis. Curr Opin Nephrol Hypertens 2016;25:226-31.
17. Singer E, Elger A, Elitok S, Kettritz R, Nickolas TL, Barasch J, et al. Urinary neutrophil gelatinase-associated lipocalin distinguishes pre-renal from intrinsic renal failure and predicts outcomes. Kidney Int 2011;80:405-14.
18. Devarajan P. Emerging biomarkers of acute kidney injury. Contrib Nephrol 2007;156:203-12.
19. Schmidt-Ott KM. Neutrophil gelatinase-associated lipocalin as a biomarker of acute kidney injury-where do we stand today Nephrol Dial Transplant 2011;26:762-4.
20. Nickolas TL, Schmidt-Ott KM, Canetta P, Forster C, Singer E, Sise M, et al. Diagnostic and prognostic stratification in the emergency department using urinary biomarkers of nephron damage: A multicenter prospective cohort study. J Am Coll Cardiol 2012;59:246-55.
21. Nickolas TL, O'Rourke MJ, Yang J, Sise ME, Canetta PA, Barasch N, et al. Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury. Ann Intern Med 2008;148:810-9.
22. Dent CL, Ma Q, Dastrala S, Bennett 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 (London, England) 2007;11:R127.
23. Ho J, Tangri N, Komenda P, Kaushal A, Sood M, Brar R, et al. Urinary, plasma, and serum biomarkers' utility for predicting acute kidney injury associated with cardiac surgery in adults: A Meta-analysis. Am J Kidney Dis 2015;66:993-1005.
24. 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. Am J Respir Crit Care Med 2011;183:907-14.
25. Moyake N, Buchmann E, Crowther NJ. Neutrophil gelatinaseassociated lipocalin as a diagnostic marker of acute kidney injury in pre-eclampsia. J Obstet Gynaecol Res 2016;42:1483-8.
26. Smith GL, Lichtman JH, Bracken MB, Shlipak MG, Phillips CO, DiCapua P, et al. Renal impairment and outcomes in heart failure: systematic review and meta-analysis. J Am Coll Cardiol 2006;47:1987-96.
27. Shao X, Tian L, Xu W, Zhang Z, Wang C, Qi C, et al. Diagnostic value of urinary kidney injury molecule 1 for acute kidney injury: A meta-analysis. PLoS One 2014;9:e84131.
28. Xie Y, Wang Q, Wang C, Qi C, Ni Z, Mou S. High urinary excretion of kidney injury molecule-1 predicts adverse outcomes in acute kidney injury: A case control study. Crit Care (London, England) 2016;20:286.
29. Imai N, Yasuda T, Kamijo-Ikemori A, Shibagaki Y, Kimura K. Distinct roles of urinary liver-type fatty acid-binding protein in non-diabetic patients with anemia. PLoS One 2015;10:e0126990.
30. Doi K, Negishi K, Ishizu T, Katagiri D, Fujita T, Matsubara T, et al. Evaluation of new acute kidney injury biomarkers in a mixed intensive care unit. Crit Care Med 2011;39:2464-9.
31. Krawczeski CD, Goldstein SL, Woo JG, Wang Y, Piyaphanee N, Ma Q, et al. Temporal relationship and predictive value of urinary acute kidney injury biomarkers after pediatric cardiopulmonary bypass. J Am Coll Cardiol 2011;58:2301-9.
32. Nisula S, Yang R, Poukkanen M, Vaara ST, Kaukonen KM, Tallgren M, et al. Predictive value of urine interleukin-18 in the evolution and outcome of acute kidney injury in critically ill adult patients. Br J Anaesth 2015;114:460-8.
33. Kashani K, Al-Khafaji A, Ardiles T, Artigas A, Bagshaw SM, Bell M, et al. Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Crit Care (London, England) 2013;17:R25.
34. Bell M, Larsson A, Venge P, Bellomo R, Martensson J. Assessment of cell-cycle arrest biomarkers to predict early and delayed acute kidney injury. Dis Markers 2015;2015:158658.
35. Bihorac A, Chawla LS, Shaw AD, Al-Khafaji A, Davison DL, Demuth GE, et al. Validation of cell-cycle arrest biomarkers for acute kidney injury using clinical adjudication. Am J Respir Crit Care Med 2014;189:932-9.
36. Hoste EA, McCullough PA, Kashani K, Chawla LS, Joannidis M, Shaw AD, et al. Derivation and validation of cutoffs for clinical use of cell cycle arrest biomarkers. Nephrol Dial Transplant 2014;29:2054-61.
37. Meersch M, Schmidt C, Van Aken H, Martens S, Rossaint J, Singbartl K, et al. Urinary TIMP-2 and IGFBP7 as early biomarkers of acute kidney injury and renal recovery following cardiac surgery. PLoS One 2014;9:e93460.
38. Pilarczyk K, Edayadiyil-Dudasova M, Wendt D, Demircioglu E, Benedik J, Dohle DS, et al. Urinary [TIMP-2][IGFBP7] for early prediction of acute kidney injury after coronary artery bypass surgery. Ann Intensive Care 2015;5:50.
39. Wetz AJ, Richardt EM, Wand S, Kunze N, Schotola H, Quintel M, et al. Quantification of urinary TIMP-2 and IGFBP-7: An adequate diagnostic test to predict acute kidney injury after cardiac surgery Crit Care (London, England) 2015;19:3.
40. Gunnerson KJ, Shaw AD, Chawla LS, Bihorac A, Al-Khafaji A, Kashani K, et al. TIMP2IGFBP7 biomarker panel accurately predicts acute kidney injury in high-risk surgical patients. J Trauma Acute Care Surg 2016;80:243-9.
41. Gocze I, Koch M, Renner P, Zeman F, Graf BM, Dahlke MH, et al. Urinary biomarkers TIMP-2 and IGFBP7 early predict acute kidney injury after major surgery. PLoS One 2015;10:e0120863.
42. Heller F, Frischmann S, Grunbaum M, Zidek W, Westhoff TH. Urinary calprotectin and the distinction between prerenal and intrinsic acute kidney injury. Clin J Am Soc Nephrol 2011;6:2347-55.
43. Ebbing J, Mathia S, Seibert FS, Pagonas N, Bauer F, Erber B, et al. Urinary calprotectin: A new diagnostic marker in urothelial carcinoma of the bladder. World J Urol 2014;32:1485-92.
44. Seibert FS, Pagonas N, Arndt R, Heller F, Dragun D, Persson P, et al. Calprotectin and neutrophil gelatinase-associated lipocalin in the differentiation of pre-renal and intrinsic acute kidney injury. Acta Physiol (Oxford, England). 2013;207:700-8.
45. Chang CH, Yang CH, Yang HY, Chen TH, Lin CY, Chang SW, et al. urinary biomarkers improve the diagnosis of intrinsic acute kidney injury in coronary care units. Medicine 2015;94:e1703.
46. Yang X, Chen C, Tian J, Zha Y, Xiong Y, Sun Z, et al. Urinary angiotensinogen level predicts aki in acute decompensated heart failure: A prospective, two-stage study. J Am Soc Nephrol 2015;26:2032-41.
47. Du J, Cao X, Zou L, Chen Y, Guo J, Chen Z, et al. MicroRNA-21 and risk of severe acute kidney injury and poor outcomes after adult cardiac surgery. PLoS one 2013;8:e63390.
48. Aguado-Fraile E, Ramos E, Conde E, Rodriguez M, Martin-Gomez L, Lietor A, et al. A pilot study identifying a set of micrornas as precise diagnostic biomarkers of acute kidney injury. PLoS One 2015;10:e0127175.
49. Coca SG, Yalavarthy R, Concato J, Parikh CR. Biomarkers for the diagnosis and risk stratification of acute kidney injury: A systematic review. Kidney Int 2008;73:1008-16.
50. Singer E, Marko L, Paragas N, Barasch J, Dragun D, Muller DN, et al. Neutrophil gelatinase-associated lipocalin: pathophysiology and clinical applications. Acta Physiol (Oxford, England) 2013;207:663-72.
51. Zhou F, Luo Q, Wang L, Han L. Diagnostic value of neutrophil gelatinase-associated lipocalin for early diagnosis of cardiac surgery-associated acute kidney injury: A meta-analysis. Eur J Cardiothorac Surg 2016;49:746-55.
52. Medic B, Rovcanin B, Basta Jovanovic G, Radojevic-Skodric S, Prostran M. Kidney injury molecule-1 and cardiovascular diseases: from basic science to clinical practice. BioMed Res Int 2015;2015:854070.
53. Lin X, Yuan J, Zhao Y, Zha Y. Urine interleukin-18 in prediction of acute kidney injury: A systemic review and meta-analysis. J Nephrol 2015;28:7-16.
54. Xu Y, Xie Y, Shao X, Ni Z, Mou S. L-FABP: A novel biomarker of kidney disease. Clin Chim Acta 2015;445:85-90.
55. Chen C, Yang X, Lei Y, Zha Y, Liu H, Ma C, et al. Urinary biomarkers at the time of aki diagnosis as predictors of progression of aki among patients with acute cardiorenal syndrome. Clin J Am Soc Nephrol 2016;11:1536-44.
56. Lorenzen JM, Kielstein JT, Hafer C, Gupta SK, Kumpers P, Faulhaber-Walter R, et al. Circulating miR-210 predicts survival in critically ill patients with acute kidney injury. Clin J Am Soc Nephrol 2011;6:1540-6.
57. Wheeler DS, Devarajan P, Ma Q, Harmon K, Monaco M, Cvijanovich N, 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;36:1297-303.
58. Zappitelli M, Washburn KK, Arikan AA, Loftis L, Ma Q, Devarajan P, et al. Urine neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in critically ill children: A prospective cohort study. Crit Care (London, England) 2007;11:R84.
59. Cullen MR, Murray PT, Fitzgibbon MC. Establishment of a reference interval for urinary neutrophil gelatinase-associated lipocalin. Ann. Clin. Biochem 2012;49(Pt 2):190-3.
60. Pennemans V, Rigo JM, Faes C, Reynders C, Penders J, Swennen Q. Establishment of reference values for novel urinary biomarkers for renal damage in the healthy population: Are age and gender an issue Clin Chem Lab Med 2013;51:1795-802.
61. Goetz DH, Holmes MA, Borregaard N, Bluhm ME, Raymond KN, Strong RK. The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol Cell 2002;10:1033-43.
62. Flo TH, Smith KD, Sato S, Rodriguez DJ, Holmes MA, Strong RK, et al. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature 2004;432:917-21.
63. Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, et al. Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol 2003;14:2534-43.
64. Paragas N, Kulkarni R, Werth M, Schmidt-Ott KM, Forster C, Deng R, et al. Alpha-Intercalated cells defend the urinary system from bacterial infection. J Clin Invest 2014;124:2963-76.
65. Mishra J, Mori K, Ma Q, Kelly C, Barasch J, Devarajan P. Neutrophil gelatinase-associated lipocalin: A novel early urinary biomarker for cisplatin nephrotoxicity. Am J Nephrol 2004;24:307-15.
66. Supavekin S, Zhang W, Kucherlapati R, Kaskel FJ, Moore LC, Devarajan P. Differential gene expression following early renal ischemia/reperfusion. Kidney Int 2003;63:1714-24.
67. Schmidt-Ott KM, Mori K, Li JY, Kalandadze A, Cohen DJ, Devarajan P, et al. Dual action of neutrophil gelatinase-associated lipocalin. J Am Soc Nephrol 2007;18:407-13.
68. Charlton JR, Portilla D, Okusa MD. A basic science view of acute kidney injury biomarkers. Nephrol Dial Transplant 2014;29: 1301-11.
69. Hvidberg V, Jacobsen C, Strong RK, Cowland JB, Moestrup SK, Borregaard N. The endocytic receptor megalin binds the iron transporting neutrophil-gelatinase-associated lipocalin with high affinity and mediates its cellular uptake. FEBS Lett 2005;579:773-7.
70. Devarajan P. Review: neutrophil gelatinase-associated lipocalin: A troponin-like biomarker for human acute kidney injury. Nephrology (Carlton, Vic) 2010;15:419-28.
71. 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 (London, England) 2005;365:1231-8.
72. Parikh CR, Coca SG, Thiessen-Philbrook H, Shlipak MG, Koyner JL, Wang Z, et al. Postoperative biomarkers predict acute kidney injury and poor outcomes after adult cardiac surgery. J Am Soc Nephrol 2011;22:1748-57.
73. Haase M, Devarajan P, Haase-Fielitz A, Bellomo R, Cruz DN, Wagener G, et al. The outcome of neutrophil gelatinaseassociated lipocalin-positive subclinical acute kidney injury: A multicenter pooled analysis of prospective studies. J. Am. Coll. Cardiol 2011;57:1752-61.
74. Haase-Fielitz A, Bellomo R, Devarajan P, Bennett M, Story D, Matalanis G, et al. The predictive performance of plasma neutrophil gelatinase-associated lipocalin (NGAL) increases with grade of acute kidney injury. Nephrol Dial Transplant 2009;24:3349-54.
75. 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;52:425-33.
76. Prowle JR, Calzavacca P, Licari E, Ligabo EV, Echeverri JE, Bagshaw SM, et al. Combination of biomarkers for diagnosis of acute kidney injury after cardiopulmonary bypass. Ren Fail 2015;37:408-16.
77. Pajek J, Skoberne A, Sosteric K, Adlesic B, Leskosek B, Bucar Pajek M, et al. Non-inferiority of creatinine excretion rate to urinary L-FABP and NGAL as predictors of early renal allograft function. BMC Nephrol 2014;15:117.
78. Pianta TJ, Peake PW, Pickering JW, Kelleher M, Buckley NA, Endre ZH. Clusterin in kidney transplantation: novel biomarkers versus serum creatinine for early prediction of delayed graft function. Transplantation 2015;99:171-9.
79. Ramirez-Sandoval JC, Herrington W, Morales-Buenrostro LE. Neutrophil gelatinase-associated lipocalin in kidney transplantation: A review. Transplant Rev (Orlando, Fla) 2015;29:139-44.
80. Ichimura T, Bonventre JV, Bailly V, Wei H, Hession CA, Cate RL, et al. Kidney injury molecule-1 (KIM-1), a putative epithelial cell adhesion molecule containing a novel immunoglobulin domain, is up-regulated in renal cells after injury. J Biol Chem 1998;273:4135-42.
81. Bailly V, Zhang Z, Meier W, Cate R, Sanicola M, Bonventre JV. Shedding of kidney injury molecule-1, a putative adhesion protein involved in renal regeneration. J Biol Chem 2002;277:39739-48.
82. Amin RP, Vickers AE, Sistare F, Thompson KL, Roman RJ, Lawton M, et al. Identification of putative gene based markers of renal toxicity. Environ Health Perspect 2004;112:465-79.
83. Prozialeck WC, Vaidya VS, Liu J, Waalkes MP, Edwards JR, Lamar PC, et al. Kidney injury molecule-1 is an early biomarker of cadmium nephrotoxicity. Kidney Int 2007;72:985-93.
84. Ichimura T, Hung CC, Yang SA, Stevens JL, Bonventre JV. Kidney injury molecule-1: A tissue and urinary biomarker for nephrotoxicant-induced renal injury. Am J Physiol Renal Physiol 2004;286:F552-63.
85. 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;62:237-44.
86. Ichimura T, Brooks CR, Bonventre JV. Kim-1/Tim-1 and immune cells: shifting sands. Kidney Int 2012;81:809-11.
87. Bonventre JV. Kidney injury molecule-1 (KIM-1): A urinary biomarker and much more. Nephrol Dial Transplant 2009;24:3265-8.
88. Ichimura T, Asseldonk EJ, Humphreys BD, Gunaratnam L, Duffield JS, Bonventre JV. Kidney injury molecule-1 is a phosphatidylserine receptor that confers a phagocytic phenotype on epithelial cells. J Clin Invest 2008;118:1657-68.
89. Ismail O, Zhang X, Bonventre JV, Gunaratnam L. G protein, 12 (Galpha12) is a negative regulator of kidney injury molecule-1-mediated efferocytosis. Am J Physiol Renal Physiol 2015:ajprenal. 00169. 2015.
90. Ismail OZ, Zhang X, Wei J, Haig A, Denker BM, Suri RS, et al. Kidney injury molecule-1 protects against Galpha12 activation and tissue damage in renal ischemia-reperfusion injury. Am J Pathol 2015;185:1207-15.
91. van Timmeren MM, van den Heuvel MC, Bailly V, Bakker SJ, van Goor H, Stegeman CA. Tubular kidney injury molecule-1 (KIM-1) in human renal disease. J Pathol 2007;212:209-17.
92. Liangos O, Perianayagam MC, Vaidya VS, Han WK, Wald R, Tighiouart H, et al. 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 2007;18:904-12.
93. Han WK, Waikar SS, Johnson A, Betensky RA, Dent CL, Devarajan P, et al. Urinary biomarkers in the early diagnosis of acute kidney injury. Kidney Int 2008;73:863-9.
94. Dieterle F, Sistare F, Goodsaid F, Papaluca M, Ozer JS, Webb CP, et al. Renal biomarker qualification submission: A dialog between the FDA-EMEA and Predictive Safety Testing Consortium. Nat Biotechnol 2010;28:455-62.
95. Vaidya VS, Ozer JS, Dieterle F, Collings FB, Ramirez V, Troth S, et al. Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies. Nat Biotechnol 2010;28:478-85.
96. Fuchs TC, Frick K, Emde B, Czasch S, von Landenberg F, Hewitt P. Evaluation of novel acute urinary rat kidney toxicity biomarker for subacute toxicity studies in preclinical trials. Toxicol Pathol 2012;40:1031-48.
97. Vaidya VS, Ford GM, Waikar SS, Wang Y, Clement MB, Ramirez V, et al. A rapid urine test for early detection of kidney injury. Kidney Int 2009;76:108-14.
98. Hall IE, Coca SG, Perazella MA, Eko UU, Luciano RL, Peter PR, et al. Risk of poor outcomes with novel and traditional biomarkers at clinical AKI diagnosis. Clin J Am Soc Nephrol 2011;6: 2740-9.
99. Arthur JM, Hill EG, Alge JL, Lewis EC, Neely BA, Janech MG, et al. Evaluation of 32 urine biomarkers to predict the progression of acute kidney injury after cardiac surgery. Kidney Int 2014;85:431-8.
100. Damman K, Masson S, Hillege HL, Maggioni AP, Voors AA, Opasich C, et al. Clinical outcome of renal tubular damage in chronic heart failure. Eur Heart J 2011;32:2705-12.
101. Ghatanatti R, Teli A, Tirkey SS, Bhattacharya S, Sengupta G, Mondal A. Role of renal biomarkers as predictors of acute kidney injury in cardiac surgery. Asian Cardiovasc Thorac Ann 2014;22:234-41.
102. Hazle MA, Gajarski RJ, Aiyagari R, Yu S, Abraham A, Donohue J, et al. Urinary biomarkers and renal near-infrared spectroscopy predict intensive care unit outcomes after cardiac surgery ininfants younger than 6 months of age. J Thorac Cardiovasc Surg 2013;146:861-7. e1.
103. Tan NS, Shaw NS, Vinckenbosch N, Liu P, Yasmin R, Desvergne B, et al. Selective cooperation between fatty acid binding proteins and peroxisome proliferator-activated receptors in regulating transcription. Mol Cell Biol 2002;22:5114-27.
104. Massolini G, Calleri E. Survey of binding properties of fatty acid-binding proteins. Chromatographic methods. J Chromatogr B Analyt Technol Biomed Life Sci 2003;797:255-68.
105. Chmurzynska A. The multigene family of fatty acid-binding proteins (FABPs): function, structure and polymorphism. J Appl Genet 2006;47:39-48.
106. Smathers RL, Petersen DR. The human fatty acid-binding protein family: evolutionary divergences and functions. Hum Genomics 2011;5:170-91.
107. Sweetser DA, Heuckeroth RO, Gordon JI. The metabolic significance of mammalian fatty-acid-binding proteins: Abundant proteins in search of a function. Annu Rev Nutr 1987;7:337-59.
108. Wang G, Gong Y, Anderson J, Sun D, Minuk G, Roberts MS, et al. Antioxidative function of L-FABP in L-FABP stably transfected Chang liver cells. Hepatology (Baltimore, Md) 2005;42:871-9.
109. Maatman RG, Van Kuppevelt TH, Veerkamp JH. Two types of fatty acid-binding protein in human kidney. Isolation, characterization and localization. Biochem J 1991;273 (Pt 3):759-66.
110. Yamamoto T, Noiri E, Ono Y, Doi K, Negishi K, Kamijo A, et al. Renal L-type fatty acid-binding protein in acute ischemic injury. J Am Soc Nephrol 2007;18:2894-902.
111. Yokoyama T, Kamijo-Ikemori A, Sugaya T, Hoshino S, Yasuda T, Kimura K. Urinary excretion of liver type fatty acid binding protein accurately reflects the degree of tubulointerstitial damage. Am J Pathol 2009;174:2096-106.
112. Noiri E, Doi K, Negishi K, Tanaka T, Hamasaki Y, Fujita T, et al. Urinary fatty acid-binding protein 1: An early predictive biomarker of kidney injury. Am J Physiol Renal Physiol 2009;296:F669-79.
113. Portilla D, Dent C, Sugaya T, Nagothu KK, Kundi I, Moore P, et al. Liver fatty acid-binding protein as a biomarker of acute kidney injury after cardiac surgery. Kidney Int 2008;73:465-72.
114. Ferguson MA, Vaidya VS, Waikar SS, Collings FB, Sunderland KE, Gioules CJ, et al. Urinary liver-type fatty acid-binding protein predicts adverse outcomes in acute kidney injury. Kidney Int 2010;77:708-14.
115. Susantitaphong P, Siribamrungwong M, Doi K, Noiri E, Terrin N, Jaber BL. Performance of urinary liver-type fatty acid-binding protein in acute kidney injury: A meta-analysis. Am J Kidney Dis 2013;61:430-9.
116. Parr SK, Clark AJ, Bian A, Shintani AK, Wickersham NE, Ware LB, et al. Urinary L-FABP predicts poor outcomes in critically ill patients with early acute kidney injury. Kidney Int 2015;87:640-8.
117. Zeng XF, Li JM, Tan Y, Wang ZF, He Y, Chang J, et al. Performance of urinary NGAL and L-FABP in predicting acute kidney injury and subsequent renal recovery: A cohort study based on major surgeries. Clin Chem Lab Med 2014;52:671-8.
118. Cho E, Yang HN, Jo SK, Cho WY, Kim HK. The role of urinary livertype fatty acid-binding protein in critically ill patients. J Korean Med Sci 2013;28:100-5.
119. Gracie JA, Robertson SE, McInnes IB. Interleukin-18. J Leukoc Biol 2003;73:213-24.
120. Novick D, Kim S, Kaplanski G, Dinarello CA. Interleukin-18, more than a Th1 cytokine. Semin Immunol 2013;25:439-48.
121. Gauer S, Sichler O, Obermuller N, Holzmann Y, Kiss E, Sobkowiak E, et al. IL-18 is expressed in the intercalated cell of human kidney. Kidney Int 2007;72:1081-7.
122. Dinarello CA. Interleukin-18 and the pathogenesis of inflammatory diseases. Semin Nephrol 2007;27:98-114.
123. Cheung H, Chen NJ, Cao Z, Ono N, Ohashi PS, Yeh WC. Accessory protein-like is essential for IL-18-mediated signaling. J Immunol (Baltimore, Md : 1950) 2005;174:5351-7.
124. Lochner M, Forster I. Anti-interleukin-18 therapy in murine models of inflammatory bowel disease. Pathobiology : journal of immunopathology, Mol Cell Biol 2002;70:164-9.
125. Gonzalez F, Vincent F. Biomarkers for acute kidney injury in critically ill patients. Minerva Anestesiol 2012;78:1394-403.
126. Wu H, Craft ML, Wang P, Wyburn KR, Chen G, Ma J, et al. IL-18 contributes to renal damage after ischemia-reperfusion. J Am Soc Nephrol 2008;19:2331-41.
127. Melnikov VY, Ecder T, Fantuzzi G, Siegmund B, Lucia MS, Dinarello CA, et al. Impaired IL-18 processing protects caspase-1-deficient mice from ischemic acute renal failure. J Clin Invest 2001;107:1145-52.
128. Homsi E, Janino P, de Faria JB. Role of caspases on cell death, inflammation, and cell cycle in glycerol-induced acute renal failure. Kidney Int 2006;69:1385-92.
129. Zheng J, Xiao 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.
130. Rodier F, Campisi J, Bhaumik D. Two faces of p53: Aging and tumor suppression. Nucleic Acids Res 2007;35:7475-84.
131. Witzgall R, Brown D, Schwarz C, Bonventre JV. Localization of proliferating cell nuclear antigen, vimentin, c-Fos, and clusterin in the postischemic kidney. Evidence for a heterogenous genetic response among nephron segments, and a large pool of mitotically active and dedifferentiated cells. J Clin Invest 1994;93:2175-88.
132. Yang QH, Liu DW, Long Y, Liu HZ, Chai WZ, Wang XT. Acute renal failure during sepsis: potential role of cell cycle regulation. J Infect 2009;58:459-64.
133. Megyesi J, Safirstein RL, Price PM. Induction of p21WAF1/CIP1/ SDI1 in kidney tubule cells affects the course of cisplatininduced acute renal failure. J Clin Invest 1998;101:777-82.
134. Chindarkar NS, Chawla LS, Straseski JA, Jortani SA, Uettwiller-Geiger D, Orr RR, et al. Reference intervals of urinary acute kidney injury (AKI) markers [IGFBP7][TIMP2] in apparently healthy subjects and chronic comorbid subjects without AKI. Clin Chim Acta 2016;452:32-7.
135. Koyner JL, Shaw AD, Chawla LS, Hoste EA, Bihorac A, Kashani K, et al. Tissue inhibitor metalloproteinase-2 (TIMP-2) IGF binding protein-7 (IGFBP7) levels are associated with adverse long-term outcomes in patients with AKI. J Am Soc Nephrol 2015;26:1747-54.
136. Striz I, Trebichavsky I. Calprotectin-a pleiotropic molecule in acute and chronic inflammation. Physiol Res 2004;53:245-53.
137. Ehrchen JM, Sunderkotter C, Foell D, Vogl T, Roth J. The endogenous Toll-like receptor 4 agonist S100A8/S100A9 (calprotectin) as innate amplifier of infection, autoimmunity, and cancer. J Leukoc Biol 2009;86:557-66.
138. Vogl T, Tenbrock K, Ludwig S, Leukert N, Ehrhardt C, van Zoelen MA, et al. Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock. Nat Med 2007;13:1042-9.
139. Fujiu K, Manabe I, Nagai R. Renal collecting duct epithelial cells regulate inflammation in tubulointerstitial damage in mice. J Clin Invest 2011;121:3425-41.
140. Dessing MC, Tammaro A, Pulskens WP, Teske GJ, Butter LM, Claessen N, et al. The calcium-binding protein complex S100A8/A9 has a crucial role in controlling macrophage-mediated renal repair following ischemia/reperfusion. Kidney Int 2015;87:85-94.
141. Hammer HB, Odegard S, Fagerhol MK, Landewe R, van der Heijde D, Uhlig T, et al. Calprotectin (a major leucocyte protein) is strongly and independently correlated with joint inflammation and damage in rheumatoid arthritis. Ann Rheum Dis 2007;66:1093-7.
142. Foell D, Wittkowski H, Ren Z, Turton J, Pang G, Daebritz J, et al. Phagocyte-specific S100 proteins are released from affected mucosa and promote immune responses during inflammatory bowel disease. J Pathol 2008;216:183-92.
143. Altwegg LA, Neidhart M, Hersberger M, Muller S, Eberli FR, Corti R, et al. Myeloid-related protein 8/14 complex is released by monocytes and granulocytes at the site of coronary occlusion: A novel, early, and sensitive marker of acute coronary syndromes. Eur Heart J 2007;28:941-8.
144. Muller H, Haug U, Rothenbacher D, Stegmaier C, Brenner H. Evaluation of serum and urinary myeloid related protein-14 as a marker for early detection of prostate cancer. J Urol 2008;180:1309-12; discussion 12-3.
145. Seeliger S, Vogl T, Engels IH, Schroder JM, Sorg C, Sunderkotter C, et al. Expression of calcium-binding proteins MRP8 and MRP14 in inflammatory muscle diseases. Am J Pathol 2003;163:947-56.
146. Brun JG, Madland TM, Gran JT, Myklebust G. A longitudinal study of calprotectin in patients with polymyalgia rheumatica or temporal arteritis: relation to disease activity. Scand J Rheumatol 2005;34:125-8.
147. Payen D, Lukaszewicz AC, Belikova I, Faivre V, Gelin C, Russwurm S, et al. Gene profiling in human blood leucocytes during recovery from septic shock. Intensive Care Med 2008;34:1371-6.
148. Seibert FS, Rosenberger C, Mathia S, Arndt R, Arns W, Andrea H, et al. Urinary calprotectin differentiates between prerenal and intrinsic acute renal allograft failure. Transplantation 2016. [Epub ahead of print].
149. Wysocki J, Batlle D. Urinary angiotensinogen: A promising biomarker of AKI progression in acute decompensated heart failure: what does it mean Clin J Am Soc Nephrol 2016;11:1515-7.
150. Molinas SM, Cortes-Gonzalez C, Gonzalez-Bobadilla Y, Monasterolo LA, Cruz C, Elias MM, et al. Effects of losartan pretreatment in an experimental model of ischemic acute kidney injury. Nephron Exp Nephrol 2009;112:e10-9.
151. Barrilli A, Molinas S, Petrini G, Menacho M, Elias MM. Losartan reverses fibrotic changes in cortical renal tissue induced by ischemia or ischemia-reperfusion without changes in renal function. Mol Cell Biochem 2004;260:161-70.
152. Kankuri E, Mervaala EE, Storvik M, Ahola AM, Levijoki J, Muller DN, et al. Exacerbation of acute kidney injury by bone marrow stromal cells from rats with persistent renin-angiotensin system activation. Clin Sci (London, England : 1979) 2015;128:735-47.
153. Zhang J, Rudemiller NP, Patel MB, Wei Q, Karlovich NS, Jeffs AD, et al. Competing Actions of Type 1 Angiotensin II Receptors Expressed on T Lymphocytes and Kidney Epithelium during Cisplatin-Induced AKI. J Am Soc Nephrol 2016;27:2257-64.
154. Alge JL, Karakala N, Neely BA, Janech MG, Tumlin JA, Chawla LS, et al. Association of elevated urinary concentration of reninangiotensin system components and severe AKI. Clin J Am Soc Nephrol 2013;8:2043-52.
155. Alge JL, Karakala N, Neely BA, Janech MG, Tumlin JA, Chawla LS, et al. Urinary angiotensinogen and risk of severe AKI. Clin J Am Soc Nephrol 2013;8:184-93.
156. Wysocki J, Ye M, Rodriguez E, Gonzalez-Pacheco FR, Barrios C, Evora K, et al. Targeting the degradation of angiotensin II with recombinant angiotensin-converting enzyme 2: prevention of angiotensin II-dependent hypertension. Hypertension (Dallas, Tex : 1979) 2010;55:90-8.
157. Kobori H, Harrison-Bernard LM, Navar LG. Urinary excretion of angiotensinogen reflects intrarenal angiotensinogen production. Kidney Int 2002;61:579-85.
158. Kobori H, Nangaku M, Navar LG, Nishiyama A. The intrarenal renin-angiotensin system: from physiology to the pathobiology of hypertension and kidney disease. Pharmacol Rev 2007;59:251-87.
159. Nakano D, Kobori H, Burford JL, Gevorgyan H, Seidel S, Hitomi H, et al. Multiphoton imaging of the glomerular permeability of angiotensinogen. J Am Soc Nephrol 2012;23:1847-56.
160. Ingelfinger JR, Zuo WM, Fon EA, Ellison KE, Dzau VJ. In situ hybridization evidence for angiotensinogen messenger RNA in the rat proximal tubule. An hypothesis for the intrarenal renin angiotensin system. J Clin Invest 1990;85:417-23.
161. Matsusaka T, Niimura F, Shimizu A, Pastan I, Saito A, Kobori H, et al. Liver angiotensinogen is the primary source of renal angiotensin II. J Am Soc Nephrol 2012;23:1181-9.
162. Moriyama T, Hagihara S, Shiramomo T, Nagaoka M, Iwakawa S, Kanmura Y. Comparison of three early biomarkers for acute kidney injury after cardiac surgery under cardiopulmonary bypass. J Intensive Care 2016;4:41.
163. Godwin JG, Ge X, Stephan K, Jurisch A, Tullius SG, Iacomini J. Identification of a microRNA signature of renal ischemia reperfusion injury. Proc Natl Acad Sci USA 2010;107:14339-44.
164. Koyner JL, Garg AX, Coca SG, Sint K, Thiessen-Philbrook H, Patel UD, et al. Biomarkers predict progression of acute kidney injury after cardiac surgery. J Am Soc Nephrol 2012;23:905-14.
165. Parikh CR, Abraham E, Ancukiewicz M, Edelstein CL. Urine IL-18 is an early diagnostic marker for acute kidney injury and predicts mortality in the intensive care unit. J Am Soc Nephrol 2005;16:3046-52.
166. Belcher JM, Garcia-Tsao G, Sanyal AJ, Thiessen-Philbrook H, Peixoto AJ, Perazella MA, et al. Urinary biomarkers and progression of AKI in patients with cirrhosis. Clin J Am Soc Nephrol 2014;9:1857-67.
167. Murugan R, Wen X, Shah N, Lee M, Kong L, Pike F, et al. Plasma inflammatory and apoptosis markers are associated with dialysis dependence and death among critically ill patients receiving renal replacement therapy. Nephrol Dial Transplant 2014;29:1854-64.
168. Administration UFaD. Letter to Astute Medical 2014. Available from: http://www. Accessdata. fda. gov/cdrh-docs/pdf13/ den130031. pdf. Accessed October 30, 2016.
169. Pike F, Murugan R, Keener C, Palevsky PM, Vijayan A, Unruh M, et al. biomarker enhanced risk prediction for adverse outcomes in critically ill patients receiving RRT. Clin J Am Soc Nephrol 2015;10:1332-9.
170. Koyner JL, Davison DL, Brasha-Mitchell E, Chalikonda DM, Arthur JM, Shaw AD, et al. furosemide stress test and biomarkers for the prediction of aki severity. J Am Soc Nephrol 2015;26:2023-31.
171. Parikh CR, Moledina DG, Coca SG, Thiessen-Philbrook HR, Garg AX. Application of new acute kidney injury biomarkers in human randomized controlled trials. Kidney Int 2016;89: 1372-9.
172. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. 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 (London, England) 2004;8:R204-12.
173. Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, et al. Acute kidney injury network: report of an initiative to improve outcomes in acute kidney injury. Crit Care (London, England) 2007;11:R31.
174. Section 2: AKI definition. Kidney Int 2012;2:19-36.
175. Ronco C. Acute kidney injury: from clinical to molecular diagnosis. Crit Care 2016;20:1-4.
176. Katz N, Ronco C. Acute kidney stress-a useful term based on evolution in the understanding of acute kidney injury. Crit Care 2016;20:1-3.
177. Ronco C. Kidney attack: overdiagnosis of acute kidney injury or comprehensive definition of acute kidney syndromes Blood Purif 2013;36:65-8.
178. Ronco C, Kellum JA, Haase M. Subclinical AKI is still AKI. Crit Care 2012;16:1-4.
179. Kellum JA, Bellomo R, Ronco C. Kidney attack. J Am Med Assoc 2012;307:2265-6.
180. Sharma A, Mucino MJ, Ronco C. Renal functional reserve and renal recovery after acute kidney injury. Nephron Clin Pract 2014;127:94-100.
181. Murray PT, Devarajan P, Levey AS, Eckardt KU, Bonventre JV, Lombardi R, et al. A Framework and key research questions in aki diagnosis and staging in different environments. Clin J Am Soc Nephrol 2008;3:864-8.
182. Schrier RW. Early intervention in acute kidney injury. Nat Rev Nephrol 2009;6:56-9.
183. Bagshaw SM, Bellomo R. Early diagnosis of acute kidney injury. Curr Opin Crit Care 2007;13:638-44.
184. Coburn S, Mitchell SA. Acute renal failure: early detection and prompt intervention can improve outcomes. Am J Nurs 2002;102(Suppl 4):6-12.
185. Hoste EAJ, Kashani K, Gibney N, Wilson FP, Ronco C, Goldstein SL, et al. Impact of electronic-alerting of acute kidney injury: workgroup statements from the 15th ADQI Consensus Conference. Can J Kidney Health Dis 2016;3:1-9.
186. James MT, Hobson CE, Darmon M, Mohan S, Hudson D, Goldstein SL, et al. Applications for detection of acute kidney injury using electronic medical records and clinical information systems: workgroup statements from the 15(th) ADQI Consensus Conference. Can J Kidney Health Dis 2016;3:9.
187. Mehta R, Bihorac A, Selby NM, Quan H, Goldstein SL, Kellum JA, et al. Establishing a continuum of acute kidney injury-tracing AKI using data source linkage and long-term follow-up: Workgroup Statements from the 15th ADQI Consensus Conference. Can J Kidney Health Dis 2016;3:13.
188. Levante C, Ronco C. The imperative for health economics assessment in acute kidney injury. Blood Purif 2016;42:I-VI.
189. Molitoris BA. Measuring glomerular filtration rate in the intensive care unit: no substitutesplease. Crit Care 2013;17:1-3.
190. Pickering JW, Endre ZH. Bench to bedside: The next steps for biomarkers in acute kidney injury. Am J Physiol Renal Physiol 2016:ajprenal. 00268. 2016.