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Diagnostic Approach: Differential Diagnosis, Physical Exam, Lab Tests, Imaging, and Novel Biomarkers

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Core Concepts in Acute Kidney Injury
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Abstract

Traditionally, acute kidney injury (AKI) has been classified into prerenal, intrinsic renal/intrarenal, and post-renal categories. If diagnosed early, pre- and post-renal AKI may be readily reversible, and thus earlier diagnosis may not only mitigate the severity of the AKI but potentially the morbidity and mortality that are associated with it. A revamped classification has been proposed by some authors based upon the presence or absence of changes in functional and structural/injury biomarkers. Patients without a change in either biomarker would be classified as having no AKI, while those who have changes in both are thought to have severe intrinsic AKI (e.g., ATN). A change in functional biomarkers without change in injury biomarkers would be classified as prerenal AKI, while changes in their injury biomarkers without a concomitant change in functional biomarkers may be viewed as being “subclinical AKI.”

The approach to any patient with AKI requires detailed attention to physical exam findings (which may often be subtle), several blood and urine tests (including examination of the urinary sediment), and potentially a variety of imaging test. Urinary indices such as FENa and FEUrea may aid in the differential diagnosis but have not been validated in all settings. Ultrasound is often the first-line imaging modality in the initial evaluation of AKI given its inexpensive nature, wide availability, and absence of complications. Newer imaging modalities including the blood oxygen level-dependent magnetic resonance imaging (BOLD MRI) are emerging and may prove useful in the setting of AKI. Given that serum creatinine is an imperfect marker of renal function, various biomarkers such a NGAL and TIMP-2*IGFBP7 have been studied extensively in a variety of clinical settings (e.g., sepsis, cardiac surgery). While several of these biomarkers have become available for clinical use in the last few years, none of them have gained widespread acceptance. To date no new biomarker has been incorporated into new definitions of AKI.

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References

  1. KDIGO. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int. 2012;2:1–138.

    Article  Google Scholar 

  2. Koyner JL, Parikh CR. Clinical utility of biomarkers of AKI in cardiac surgery and critical illness. Clin J Am Soc Nephrol. 2013;8(6):1034–42.

    Article  CAS  PubMed  Google Scholar 

  3. Thadhani R, Pascual M, Bonventre JV. Acute renal failure. N Engl J Med. 1996;334(22):1448–60.

    Article  CAS  PubMed  Google Scholar 

  4. Kelleher SP, Robinette JB, Conger JD. Sympathetic nervous system in the loss of autoregulation in acute renal failure. Am J Physiol. 1984;246(4 Pt 2):F379–86.

    CAS  PubMed  Google Scholar 

  5. Nolan CR, Anderson RJ. Hospital-acquired acute renal failure. J Am Soc Nephrol. 1998;9(4):710–8.

    CAS  PubMed  Google Scholar 

  6. Sacks SH, Aparicio SA, Bevan A, Oliver DO, Will EJ, Davison AM. Late renal failure due to prostatic outflow obstruction: a preventable disease. BMJ. 1989;298(6667):156–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Humphreys BD, Soiffer RJ, Magee CC. Renal failure associated with cancer and its treatment: an update. J Am Soc Nephrol. 2005;16(1):151–61.

    Article  PubMed  Google Scholar 

  8. Thomas MH, Chisholm GD. Retroperitoneal fibrosis associated with malignant disease. Br J Cancer. 1973;28(5):453–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Liaño F, Pascual J. Epidemiology of acute renal failure: a prospective, multicenter, community-based study. Madrid Acute Renal Failure Study Group. Kidney Int. 1996;50(3):811–8.

    Article  PubMed  Google Scholar 

  10. Rosen S, Stillman IE. Acute tubular necrosis is a syndrome of physiologic and pathologic dissociation. J Am Soc Nephrol. 2008;19(5):871–5.

    Article  PubMed  Google Scholar 

  11. Perazella MA, Markowitz GS. Drug-induced acute interstitial nephritis. Nat Rev Nephrol. 2010;6(8):461–70.

    Article  CAS  PubMed  Google Scholar 

  12. Endre ZH, Kellum JA, Di Somma S, et al. Differential diagnosis of AKI in clinical practice by functional and damage biomarkers: workgroup statements from the tenth Acute Dialysis Quality Initiative Consensus Conference. Contrib Nephrol. 2013;182:30–44.

    Article  PubMed  Google Scholar 

  13. Bosch JP. Renal reserve: a functional view of glomerular filtration rate. Semin Nephrol. 1995;15(5):381–5.

    CAS  PubMed  Google Scholar 

  14. 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. J Am Coll Cardiol. 2011;57(17):1752–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. 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. J Am Coll Cardiol. 2012;59(3):246–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Bellomo R, Kellum JA, Bagshaw SM. Normotensive ischemic acute renal failure. N Engl J Med. 2007;357(21):2205; author reply 2205–6.

    CAS  PubMed  Google Scholar 

  17. Poukkanen M, Wilkman E, Vaara ST, et al. Hemodynamic variables and progression of acute kidney injury in critically ill patients with severe sepsis: data from the prospective observational FINNAKI study. Crit Care. 2013;17(6):R295.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Xue FS, Li RP, Wang SY. Association of intraoperative hypotension with postoperative acute kidney and myocardial injuries in noncardiac surgery patients. Anesthesiology. 2014;120(5):1278–80.

    Article  PubMed  Google Scholar 

  19. Walsh M, Devereaux PJ, Garg AX, et al. Relationship between intraoperative mean arterial pressure and clinical outcomes after noncardiac surgery: toward an empirical definition of hypotension. Anesthesiology. 2013;119(3):507–15.

    Article  PubMed  Google Scholar 

  20. Badin J, Boulain T, Ehrmann S, et al. Relation between mean arterial pressure and renal function in the early phase of shock: a prospective, explorative cohort study. Crit Care. 2011;15(3):R135.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Lehman LW, Saeed M, Moody G, Mark R. Hypotension as a risk factor for acute kidney injury in ICU patients. Comput Cardiol (2010). 2010;37:1095–8.

    Google Scholar 

  22. Raimundo M, Crichton S, Syed Y, et al. Low systemic oxygen delivery and BP and risk of progression of early AKI. Clin J Am Soc Nephrol. 2015;10(8):1340–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Meyer TW, Hostetter TH. Uremia. N Engl J Med. 2007;357(13):1316–25.

    Article  CAS  PubMed  Google Scholar 

  24. Clarkson MR, Giblin L, O’Connell FP, et al. Acute interstitial nephritis: clinical features and response to corticosteroid therapy. Nephrol Dial Transplant. 2004;19(11):2778–83.

    Article  CAS  PubMed  Google Scholar 

  25. Sugrue M. Abdominal compartment syndrome. Curr Opin Crit Care. 2005;11(4):333–8.

    Article  PubMed  Google Scholar 

  26. Bailey J, Shapiro MJ. Abdominal compartment syndrome. Crit Care. 2000;4(1):23–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Malbrain ML, Deeren D, De Potter TJ. Intra-abdominal hypertension in the critically ill: it is time to pay attention. Curr Opin Crit Care. 2005;11(2):156–71.

    Article  PubMed  Google Scholar 

  28. Kirkpatrick AW, Roberts DJ, De Waele J, et al. Intra-abdominal hypertension and the abdominal compartment syndrome: updated consensus definitions and clinical practice guidelines from the World Society of the Abdominal Compartment Syndrome. Intensive Care Med. 2013;39(7):1190–206.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Uchino S, Bellomo R, Goldsmith D. The meaning of the blood urea nitrogen/creatinine ratio in acute kidney injury. Clin Kidney J. 2012;5(2):187–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Adams D, de Jonge R, van der Cammen T, Zietse R, Hoorn EJ. Acute kidney injury in patients presenting with hyponatremia. J Nephrol. 2011;24(6):749–55.

    Article  CAS  PubMed  Google Scholar 

  31. Turgutalp K, Ozhan O, Gok Oguz E, et al. Clinical features, outcome and cost of hyponatremia-associated admission and hospitalization in elderly and very elderly patients: a single-center experience in Turkey. Int Urol Nephrol. 2013;45(1):265–73.

    Article  CAS  PubMed  Google Scholar 

  32. Uchino S, Bellomo R, Ronco C. Intermittent versus continuous renal replacement therapy in the ICU: impact on electrolyte and acid-base balance. Intensive Care Med. 2001;27(6):1037–43.

    Article  CAS  PubMed  Google Scholar 

  33. Funk GC, Lindner G, Druml W, et al. Incidence and prognosis of dysnatremias present on ICU admission. Intensive Care Med. 2010;36(2):304–11.

    Article  PubMed  Google Scholar 

  34. An JN, Lee JP, Jeon HJ, et al. Severe hyperkalemia requiring hospitalization: predictors of mortality. Crit Care. 2012;16(6):R225.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Libório AB, Leite TT, Neves FM, Teles F, Bezerra CT. AKI complications in critically ill patients: association with mortality rates and RRT. Clin J Am Soc Nephrol. 2015;10(1):21–8.

    Article  PubMed  Google Scholar 

  36. Vaara ST, Reinikainen M, Wald R, Bagshaw SM, Pettila V. Timing of RRT based on the presence of conventional indications. Clin J Am Soc Nephrol. 2014;9(9):1577–85.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Bellomo R, Cass A, Cole L, et al. Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med. 2009;361(17):1627–38.

    Article  PubMed  Google Scholar 

  38. Perazella MA, Coca SG, Kanbay M, Brewster UC, Parikh CR. Diagnostic value of urine microscopy for differential diagnosis of acute kidney injury in hospitalized patients. Clin J Am Soc Nephrol. 2008;3(6):1615–9.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Perazella MA. The urine sediment as a biomarker of kidney disease. Am J Kidney Dis. 2015;66(5):748–55.

    Article  CAS  PubMed  Google Scholar 

  40. Bagshaw SM, Haase M, Haase-Fielitz A, Bennett M, Devarajan P, Bellomo R. A prospective evaluation of urine microscopy in septic and non-septic acute kidney injury. Nephrol Dial Transplant. 2012;27(2):582–8.

    Article  CAS  PubMed  Google Scholar 

  41. Chawla LS, Dommu A, Berger A, Shih S, Patel SS. Urinary sediment cast scoring index for acute kidney injury: a pilot study. Nephron Clin Pract. 2008;110(3):c145–50.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Perazella MA, Coca SG, Hall IE, Iyanam U, Koraishy M, Parikh CR. Urine microscopy is associated with severity and worsening of acute kidney injury in hospitalized patients. Clin J Am Soc Nephrol. 2010;5(3):402–8.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Schinstock CA, Semret MH, Wagner SJ, et al. Urinalysis is more specific and urinary neutrophil gelatinase-associated lipocalin is more sensitive for early detection of acute kidney injury. Nephrol Dial Transplant. 2013;28(5):1175–85.

    Article  CAS  PubMed  Google Scholar 

  44. Kashani K, Al-Khafaji A, Ardiles T, et al. Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Crit Care. 2013;17(1):R25.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Endre ZH, Walker RJ, Pickering JW, et al. Early intervention with erythropoietin does not affect the outcome of acute kidney injury (the EARLYARF trial). Kidney Int. 2010;77(11):1020–30.

    Article  CAS  PubMed  Google Scholar 

  46. Ralib A, Pickering JW, Shaw GM, et al. Test characteristics of urinary biomarkers depend on quantitation method in acute kidney injury. J Am Soc Nephrol. 2012;23(2):322–33.

    Article  CAS  PubMed  Google Scholar 

  47. Parikh CR, Coca SG, Thiessen-Philbrook H, et al. Postoperative biomarkers predict acute kidney injury and poor outcomes after adult cardiac surgery. J Am Soc Nephrol. 2011;22(9):1748–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Parikh CR, Devarajan P, Zappitelli M, et al. Postoperative biomarkers predict acute kidney injury and poor outcomes after pediatric cardiac surgery. J Am Soc Nephrol. 2011;22(9):1737–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Parikh CR, Thiessen-Philbrook H, Garg AX, et al. Performance of kidney injury molecule-1 and liver fatty acid-binding protein and combined biomarkers of AKI after cardiac surgery. Clin J Am Soc Nephrol. 2013;8(7):1079–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Muriithi AK, Nasr SH, Leung N. Utility of urine eosinophils in the diagnosis of acute interstitial nephritis. Clin J Am Soc Nephrol. 2013;8(11):1857–62.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Espinel CH, Gregory AW. Differential diagnosis of acute renal failure. Clin Nephrol. 1980;13(2):73–7.

    CAS  PubMed  Google Scholar 

  52. Miller TR, Anderson RJ, Linas SL, et al. Urinary diagnostic indices in acute renal failure: a prospective study. Ann Intern Med. 1978;89(1):47–50.

    Article  CAS  PubMed  Google Scholar 

  53. Espinel CH. The FENa test. Use in the differential diagnosis of acute renal failure. JAMA. 1976;236(6):579–81.

    Article  CAS  PubMed  Google Scholar 

  54. Bagshaw SM, Langenberg C, Bellomo R. Urinary biochemistry and microscopy in septic acute renal failure: a systematic review. Am J Kidney Dis. 2006;48(5):695–705.

    Article  CAS  PubMed  Google Scholar 

  55. Pru C, Kjellstrand CM. The FENa test is of no prognostic value in acute renal failure. Nephron. 1984;36(1):20–3.

    Article  CAS  PubMed  Google Scholar 

  56. Jones LW, Weil MH. Water, creatinine and sodium excretion following circulatory shock with renal failure. Am J Med. 1971;51(3):314–8.

    Article  CAS  PubMed  Google Scholar 

  57. Vaz AJ. Low fractional excretion of urine sodium in acute renal failure due to sepsis. Arch Intern Med. 1983;143(4):738–9.

    Article  CAS  PubMed  Google Scholar 

  58. Langenberg C, Wan L, Bagshaw SM, Egi M, May CN, Bellomo R. Urinary biochemistry in experimental septic acute renal failure. Nephrol Dial Transplant. 2006;21(12):3389–97.

    Article  CAS  PubMed  Google Scholar 

  59. Fang LS, Sirota RA, Ebert TH, Lichtenstein NS. Low fractional excretion of sodium with contrast media-induced acute renal failure. Arch Intern Med. 1980;140(4):531–3.

    Article  CAS  PubMed  Google Scholar 

  60. Van Biesen W, Yegenaga I, Vanholder R, et al. Relationship between fluid status and its management on acute renal failure (ARF) in intensive care unit (ICU) patients with sepsis: a prospective analysis. J Nephrol. 2005;18(1):54–60.

    PubMed  Google Scholar 

  61. Koyner JL, Bennett MR, Worcester EM, et al. Urinary cystatin C as an early biomarker of acute kidney injury following adult cardiothoracic surgery. Kidney Int. 2008;23:23.

    Google Scholar 

  62. Koyner JL, Davison DL, Brasha-Mitchell E, et al. Furosemide stress test and biomarkers for the prediction of AKI severity. J Am Soc Nephrol. 2015;26(8):2023–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Koyner JL, Vaidya VS, Bennett MR, et al. Urinary biomarkers in the clinical prognosis and early detection of acute kidney injury. Clin J Am Soc Nephrol. 2010;5(12):2154–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Belcher JM, Sanyal AJ, Peixoto AJ, et al. Kidney biomarkers and differential diagnosis of patients with cirrhosis and acute kidney injury. Hepatology (Baltimore, Md). 2014;60(2):622–32.

    Article  CAS  Google Scholar 

  65. Belcher JM, Garcia-Tsao G, Sanyal AJ, et al. Urinary biomarkers and progression of AKI in patients with cirrhosis. Clin J Am Soc Nephrol. 2014;9(11):1857–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Kaplan AA, Kohn OF. Fractional excretion of urea as a guide to renal dysfunction. Am J Nephrol. 1992;12(1–2):49–54.

    Article  CAS  PubMed  Google Scholar 

  67. Carvounis CP, Nisar S, Guro-Razuman S. Significance of the fractional excretion of urea in the differential diagnosis of acute renal failure. Kidney Int. 2002;62(6):2223–9.

    Article  CAS  PubMed  Google Scholar 

  68. Kalantarinia K. Novel imaging techniques in acute kidney injury. Curr Drug Targets. 2009;10(12):1184–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Gottlieb RH, Voci SL, Cholewinski SP, et al. Sonography: a useful tool to detect the mechanical causes of renal transplant dysfunction. J Clin Ultrasound. 1999;27(6):325–33.

    Article  CAS  PubMed  Google Scholar 

  70. Smith-Bindman R, Aubin C, Bailitz J, et al. Ultrasonography versus computed tomography for suspected nephrolithiasis. N Engl J Med. 2014;371(12):1100–10.

    Article  CAS  PubMed  Google Scholar 

  71. Anderson IH, Jones GR, Standen JR. Ultrasonographic assessment of hydronephrosis of pregnancy. J Can Assoc Radiol. 1983;34(1):29–31.

    CAS  PubMed  Google Scholar 

  72. Stevens S, Brown BD, McGahan JP. Nephrogenic diabetes insipidus: a cause of severe nonobstructive urinary tract dilatation. J Ultrasound Med. 1995;14(7):543–5.

    Article  CAS  PubMed  Google Scholar 

  73. Pozzi Mucelli R, Bertolotto M, Quaia E. Imaging techniques in acute renal failure. Contrib Nephrol. 2001;132:76–91.

    Article  Google Scholar 

  74. Platt JF, Ellis JH, Rubin JM, DiPietro MA, Sedman AB. Intrarenal arterial Doppler sonography in patients with nonobstructive renal disease: correlation of resistive index with biopsy findings. AJR Am J Roentgenol. 1990;154(6):1223–7.

    Article  CAS  PubMed  Google Scholar 

  75. Abu-Alfa AK. Nephrogenic systemic fibrosis and gadolinium-based contrast agents. Adv Chronic Kidney Dis. 2011;18(3):188–98.

    Article  PubMed  Google Scholar 

  76. Choyke PL, Kobayashi H. Functional magnetic resonance imaging of the kidney using macromolecular contrast agents. Abdom Imaging. 2006;31(2):224–31.

    Article  CAS  PubMed  Google Scholar 

  77. Juillard L, Lerman LO, Kruger DG, et al. Blood oxygen level-dependent measurement of acute intra-renal ischemia. Kidney Int. 2004;65(3):944–50.

    Article  PubMed  Google Scholar 

  78. Pedersen M, Dissing TH, Mørkenborg J, et al. Validation of quantitative BOLD MRI measurements in kidney: application to unilateral ureteral obstruction. Kidney Int. 2005;67(6):2305–12.

    Article  PubMed  Google Scholar 

  79. Zhang JL, Morrell G, Rusinek H, et al. Measurement of renal tissue oxygenation with blood oxygen level-dependent MRI and oxygen transit modeling. Am J Physiol Renal Physiol. 2014;306(6):F579–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Li LP, Ji L, Santos E, Dunkle E, Pierchala L, Prasad P. Effect of nitric oxide synthase inhibition on intrarenal oxygenation as evaluated by blood oxygenation level-dependent magnetic resonance imaging. Invest Radiol. 2009;44(2):67–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Arakelyan K, Cantow K, Hentschel J, et al. Early effects of an x-ray contrast medium on renal T(2) */T(2) MRI as compared to short-term hyperoxia, hypoxia and aortic occlusion in rats. Acta Physiol (Oxf). 2013;208(2):202–13.

    Article  CAS  Google Scholar 

  82. Alford SK, Sadowski EA, Unal O, et al. Detection of acute renal ischemia in swine using blood oxygen level-dependent magnetic resonance imaging. J Magn Reson Imaging. 2005;22(3):347–53.

    Article  PubMed  Google Scholar 

  83. Han F, Xiao W, Xu Y, et al. The significance of BOLD MRI in differentiation between renal transplant rejection and acute tubular necrosis. Nephrol Dial Transplant. 2008;23(8):2666–72.

    Article  PubMed  Google Scholar 

  84. Zhou HY, Chen TW, Zhang XM. Functional magnetic resonance imaging in acute kidney injury: present status. Biomed Res Int. 2016;2016:2027370.

    PubMed  PubMed Central  Google Scholar 

  85. Fischer K, Meral FC, Zhang Y, et al. High-resolution renal perfusion mapping using contrast-enhanced ultrasonography in ischemia-reperfusion injury monitors changes in renal microperfusion. Kidney Int. 2016;89(6):1388–98.

    Article  PubMed  PubMed Central  Google Scholar 

  86. Schneider AG, Schelleman A, Goodwin MD, Bailey M, Eastwood GM, Bellomo R. Contrast-enhanced ultrasound evaluation of the renal microcirculation response to terlipressin in hepato-renal syndrome: a preliminary report. Ren Fail. 2015;37(1):175–9.

    Article  PubMed  Google Scholar 

  87. Schneider AG, Goodwin MD, Schelleman A, Bailey M, Johnson L, Bellomo R. Contrast-enhanced ultrasound to evaluate changes in renal cortical perfusion around cardiac surgery: a pilot study. Crit Care. 2013;17(4):R138.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Schneider AG, Calzavacca P, Schelleman A, et al. Contrast-enhanced ultrasound evaluation of renal microcirculation in sheep. Intensive Care Med Exp. 2014;2(1):33.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Okusa MD, Jaber BL, Doran P, et al. Physiological biomarkers of acute kidney injury: a conceptual approach to improving outcomes. Contrib Nephrol. 2013;182:65–81.

    Article  PubMed  Google Scholar 

  90. 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. 2004;8(4):R204–12.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Mehta RL, Kellum JA, Shah SV, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11(2):R31.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Baum N, Dichoso CC, Carlton CE. Blood urea nitrogen and serum creatinine. Physiology and interpretations. Urology. 1975;5(5):583–8.

    Article  CAS  PubMed  Google Scholar 

  93. Ducharme MP, Smythe M, Strohs G. Drug-induced alterations in serum creatinine concentrations. Ann Pharmacother. 1993;27(5):622–33.

    Article  CAS  PubMed  Google Scholar 

  94. Charlton JR, Portilla D, Okusa MD. A basic science view of acute kidney injury biomarkers. Nephrol Dial Transplant. 2014;29(7):1301–11.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Chen LX, Koyner JL. Biomarkers in acute kidney injury. Crit Care Clin. 2015;31(4):633–48.

    Article  CAS  PubMed  Google Scholar 

  96. Vanmassenhove J, Vanholder R, Nagler E, Van Biesen W. Urinary and serum biomarkers for the diagnosis of acute kidney injury: an in-depth review of the literature. Nephrol Dial Transplant. 2013;28(2):254–73.

    Article  CAS  PubMed  Google Scholar 

  97. Ostermann M, Philips BJ, Forni LG. Clinical review: biomarkers of acute kidney injury: where are we now? Crit Care. 2012;16(5):233.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Chawla LS, Davison DL, Brasha-Mitchell E, et al. Development and standardization of a furosemide stress test to predict the severity of acute kidney injury. Crit Care. 2013;17(5):R207.

    Article  PubMed  PubMed Central  Google Scholar 

  99. 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(9466):1231–8.

    Article  CAS  PubMed  Google Scholar 

  100. Coca SG, Garg AX, Thiessen-Philbrook H, et al. Urinary biomarkers of AKI and mortality 3 years after cardiac surgery. J Am Soc Nephrol. 2014;25(5):1063–71.

    Article  CAS  PubMed  Google Scholar 

  101. Koyner JL, Garg AX, Coca SG, et al. Biomarkers predict progression of acute kidney injury after cardiac surgery. J Am Soc Nephrol. 2012;23(5):905–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Zappitelli M, Coca SG, Garg AX, et al. The association of albumin/creatinine ratio with postoperative AKI in children undergoing cardiac surgery. Clin J Am Soc Nephrol. 2012;7(11):1761–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Ho J, Tangri N, Komenda P, 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(6):993–1005.

    Article  CAS  PubMed  Google Scholar 

  104. Pilarczyk K, Edayadiyil-Dudasova M, Wendt D, et al. Urinary [TIMP-2]*[IGFBP7] for early prediction of acute kidney injury after coronary artery bypass surgery. Ann Intensive Care. 2015;5(1):50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Meersch M, Schmidt C, Van Aken H, et al. Validation of cell-cycle arrest biomarkers for acute kidney injury after pediatric cardiac surgery. PLoS One. 2014;9(10):e110865.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Meersch M, Schmidt C, Van Aken H, et al. Urinary TIMP-2 and IGFBP7 as early biomarkers of acute kidney injury and renal recovery following cardiac surgery. PLoS One. 2014;9(3):e93460.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Bihorac A, Chawla LS, Shaw AD, et al. Validation of cell-cycle arrest biomarkers for acute kidney injury using clinical adjudication. Am J Respir Crit Care Med. 2014;189(8):932–9.

    Article  CAS  PubMed  Google Scholar 

  108. Hoste EA, McCullough PA, Kashani K, et al. Derivation and validation of cutoffs for clinical use of cell cycle arrest biomarkers. Nephrol Dial Transplant. 2014;29(11):2054–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Koyner JL, Shaw AD, Chawla LS, 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(7):1747–54.

    Article  CAS  PubMed  Google Scholar 

  110. Endre ZH, Pickering JW, Walker RJ, et al. Improved performance of urinary biomarkers of acute kidney injury in the critically ill by stratification for injury duration and baseline renal function. Kidney Int. 2011;79(10):1119–30.

    Article  CAS  PubMed  Google Scholar 

  111. Koyner JL, Coca SG, Thiessen-Philbrook H, et al. Urine biomarkers and perioperative acute kidney injury: the impact of preoperative estimated GFR. Am J Kidney Dis. 2015;66(6):1006–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Chou KM, Lee CC, Chen CH, Sun CY. Clinical value of NGAL, L-FABP and albuminuria in predicting GFR decline in type 2 diabetes mellitus patients. PLoS One. 2013;8(1):e54863.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Conway BR, Manoharan D, Manoharan D, et al. Measuring urinary tubular biomarkers in type 2 diabetes does not add prognostic value beyond established risk factors. Kidney Int. 2012;82(7):812–8.

    Article  CAS  PubMed  Google Scholar 

  114. Bagshaw SM, Langenberg C, Haase M, Wan L, May CN, Bellomo R. Urinary biomarkers in septic acute kidney injury. Intensive Care Med. 2007;9:9.

    Google Scholar 

  115. 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(10):3046–52.

    Article  CAS  PubMed  Google Scholar 

  116. Go AS, Parikh CR, Ikizler TA, et al. The assessment, serial evaluation, and subsequent sequelae of acute kidney injury (ASSESS-AKI) study: design and methods. BMC Nephrol. 2010;11:22.

    Article  PubMed  PubMed Central  Google Scholar 

  117. Basu RK, Wong HR, Krawczeski CD, et al. Combining functional and tubular damage biomarkers improves diagnostic precision for acute kidney injury after cardiac surgery. J Am Coll Cardiol. 2014;64(25):2753–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Krawczeski CD, Goldstein SL, Woo JG, et al. Temporal relationship and predictive value of urinary acute kidney injury biomarkers after pediatric cardiopulmonary bypass. J Am Coll Cardiol. 2011;58(22):2301–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Katagiri D, Doi K, Honda K, et al. Combination of two urinary biomarkers predicts acute kidney injury after adult cardiac surgery. Ann Thorac Surg. 2012;93(2):577–83.

    Article  PubMed  Google Scholar 

  120. Katagiri D, Doi K, Matsubara T, et al. New biomarker panel of plasma neutrophil gelatinase-associated lipocalin and endotoxin activity assay for detecting sepsis in acute kidney injury. J Crit Care. 2013;28(5):564–70.

    Article  CAS  PubMed  Google Scholar 

  121. Kolhe NV, Reilly T, Leung J, et al. A simple care bundle for use in acute kidney injury: a propensity score matched cohort study. Nephrol Dial Transplant. 2016;31(11):1846–54.

    Article  PubMed  Google Scholar 

  122. Kolhe NV, Staples D, Reilly T, et al. Impact of compliance with a care bundle on acute kidney injury outcomes: a prospective observational study. PLoS One. 2015;10(7):e0132279.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Meersch M, Schmidt C, Hoffmeier A, et al. Prevention of cardiac surgery-associated AKI by implementing the KDIGO guidelines in high risk patients identified by biomarkers: the PrevAKI randomized controlled trial. Intensive Care Med. 2017;43(11):1551–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Zhang Z, Lu B, Sheng X, Jin N. Cystatin C in prediction of acute kidney injury: a systemic review and meta-analysis. Am J Kidney Dis. 2011;58(3):356–65.

    Article  CAS  PubMed  Google Scholar 

  125. Herget-Rosenthal S, Bökenkamp A, Hofmann W. How to estimate GFR-serum creatinine, serum cystatin C or equations? Clin Biochem. 2007;40(3–4):153–61.

    Article  CAS  PubMed  Google Scholar 

  126. Séronie-Vivien S, Delanaye P, Piéroni L, Mariat C, Froissart M, Cristol J-P. Cystatin C: current position and future prospects. Clin Chem Lab Med. 2008;46:1664.

    PubMed  Google Scholar 

  127. Nejat M, Hill JV, Pickering JW, Edelstein CL, Devarajan P, Endre ZH. Albuminuria increases cystatin C excretion: implications for urinary biomarkers. Nephrol Dial Transplant. 2012;27(Suppl 3):iii96–iii103.

    Article  CAS  PubMed  Google Scholar 

  128. Dinarello CA, Novick D, Kim S, Kaplanski G. Interleukin-18 and IL-18 binding protein. Front Immunol. 2013;4:289.

    PubMed  PubMed Central  Google Scholar 

  129. Parikh CR, Jani A, Melnikov VY, Faubel S, Edelstein CL. Urinary interleukin-18 is a marker of human acute tubular necrosis1. Am J Kidney Dis. 2004;43(3):405–14.

    Article  CAS  PubMed  Google Scholar 

  130. Ichimura T, Bonventre JV, Bailly V, 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(7):4135–42.

    Article  CAS  PubMed  Google Scholar 

  131. Bonventre JV. Kidney injury molecule-1: a translational journey. Trans Am Clin Climatol Assoc. 2014;125:293–9.

    PubMed  PubMed Central  Google Scholar 

  132. Ichimura T, Brooks CR, Bonventre JV. Kim-1/Tim-1 and immune cells: shifting Sands. Kidney Int. 2012;81(9):809–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Maatman RG, van de Westerlo EM, van Kuppevelt TH, Veerkamp JH. Molecular identification of the liver- and the heart-type fatty acid-binding proteins in human and rat kidney. Use of the reverse transcriptase polymerase chain reaction. Biochem J. 1992;288(Pt 1):285–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Yamamoto T, Noiri E, Ono Y, et al. Renal L-type fatty acid–binding protein in acute ischemic injury. J Am Soc Nephrol. 2007;18(11):2894–902.

    Article  CAS  PubMed  Google Scholar 

  135. Tanaka T, Noiri E, Yamamoto T, et al. Urinary human L-FABP is a potential biomarker to predict COX-inhibitor-induced renal injury. Nephron Exp Nephrol. 2008;108(1):e19–26.

    Article  CAS  PubMed  Google Scholar 

  136. Negishi K, Noiri E, Sugaya T, et al. A role of liver fatty acid-binding protein in cisplatin-induced acute renal failure. Kidney Int. 2007;72(3):348–58.

    Article  CAS  PubMed  Google Scholar 

  137. Yamashita T, Doi K, Hamasaki Y, Matsubara T, et al. Evaluation of urinary tissue inhibitor of metalloproteinase-2 in acute kidney injury: a prospective observational study. Crit Care. 2014;18(6):716. https://www.ncbi.nlm.nih.gov/pubmed/25524453

  138. Kjeldsen L, Johnsen A, Sengelov H, Borregaard N. Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase. J Biol Chem. 1993;268(0021–9258 (Print)):10425–32.

    CAS  PubMed  Google Scholar 

  139. Haase-Fielitz A, Haase M, Devarajan P. Neutrophil gelatinase-associated lipocalin as a biomarker of acute kidney injury: a critical evaluation of current status. Ann Clin Biochem. 2014;51(Pt 3):335–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Singer E, Markó L, Paragas N, et al. Neutrophil gelatinase-associated lipocalin: pathophysiology and clinical applications. Acta Physiol (Oxf). 2013;207(4):663–72.

    Article  CAS  Google Scholar 

  141. Martensson J, Bellomo R. The rise and fall of NGAL in acute kidney injury. Blood Purif. 2014;37:304–10.

    Article  CAS  PubMed  Google Scholar 

  142. Chang C, Werb Z. The many faces of metalloproteases: cell growth, invasion, angiogenesis and metastasis. Trends Cell Biol. 2001;11(11):S37–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Tamura K, Hashimoto K, Suzuki K, Yoshie M, Kutsukake M, Sakurai T. Insulin-like growth factor binding protein-7 (IGFBP7) blocks vascular endothelial cell growth factor (VEGF)-induced angiogenesis in human vascular endothelial cells. Eur J Pharmacol. 2009;610(1–3):61–7.

    Article  CAS  PubMed  Google Scholar 

  144. Mazanowska O, Żabińska M, Kościelska-Kasprzak K, et al. Increased plasma matrix metalloproteinase-2 (MMP-2), tissue inhibitor of proteinase-1 (TIMP-1), TIMP-2, and urine MMP-2 concentrations correlate with proteinuria in renal transplant recipients. Transplant Proc. 2014;46(8):2636–9.

    Article  CAS  PubMed  Google Scholar 

  145. Seo D-W, Li H, Qu C-K, et al. Shp-1 mediates the antiproliferative activity of tissue inhibitor of metalloproteinase-2 in human microvascular endothelial cells. J Biol Chem. 2006;281(6):3711–21.

    Article  CAS  PubMed  Google Scholar 

  146. Hwa V, Oh Y, Rosenfeld RG. The insulin-like growth factor-binding protein (IGFBP) superfamily. Endocr Rev. 1999;20(6):761–87.

    CAS  PubMed  Google Scholar 

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Sharma, A., Koyner, J.L. (2018). Diagnostic Approach: Differential Diagnosis, Physical Exam, Lab Tests, Imaging, and Novel Biomarkers. In: Waikar, S., Murray, P., Singh, A. (eds) Core Concepts in Acute Kidney Injury. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-8628-6_3

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