Single article

Borisov A., Raskina T.

Early diagnosis of acute kidney injury

Keywords: acute kidney injury, biomarkers of acute kidney injury

The aim of this work was to make a literature review of acute kidney injury (OPP). The current classification of acute renal failure RIFLE has a number of small flaws. The main one is the delay in diagnosis PPOs, because it is based on the levels of creatinine in the blood serum of the patient and his GFR. These indicators often do not exceed normal values within the first day of onset. Study level biomarkers of acute kidney damage allows it to neutralize a significant disadvantage classification RIFLE, which in turn makes it possible to promptly begin therapy OPP and reduce mortality.


  1. Parikh С.R., Mishra J., Thiessen-Philbrook H. et al. Urinary IL-18 is an early predictive biomarker of acute kidney injury after cardiac surgery. Kidney Int., 2006, vol. 70, pp. R199–203.
  2. Parikh С.R., Abraham E., Ancukiewicz M., Edelstein C.L. Urine IL-18 is an early diagnostic marker for acute kidney injury and predicts mortality in the intensive care unit. Am. Soc. Nephrol., 2005, vol. 16, pp. 3046–3052.
  3. Parikh C.R., Jani A., Melnikov V.Y. et al. Urinary interleukin-18 is a marker of human acute tubular necrosis. J. Kidney Dis., 2004, vol. 43, pp. 405–414.
  4. Melnikov V.Y., Ecder Т., Fantuzzi G. al. Impaired IL-18 processing protects caspase-1-deficient mice from ischemic acute renal failure. J. Clin. Invest., 2001, vol. 107, pp. 1145–1152.
  5. Wagener G., Gubitosa G., Wang S. et al. Increased incidence of acute kidney injury with aprotinin use during cardiac surgery detected with urinary NGAL. J. Nephrol., 2008, vol. 28, pp. 576–582.
  6. Boldt J., Brosch С.В., Rohm К. et al. Comparison of the effects of gelatin and a modern hydroxyethylstarch solution on renal function and inflammatory response in elderly cardiac surgery patients. J. Anaesth., 2008, vol. 100, pp. 457–464.
  7. Boldt, Brosch C., Ducke M. et al. Influence of volume therapy with a modern hydroxyethylstarch preparation on kidney function in cardiac surgery patients with compromised renal function: A compar­ison with human albumin. Crit. Care Med., 2007, vol. 35, pp. 2740–2746.
  8. Xin C., Yulong X., Yu et al. Urine neutrophil gelatinase-associated lipocalin and interleukin-18 predict acute kidney injury after cardiac surgery. Ren. Fail., 2008, vol. 30, pp. 904–913.
  9. Wegener G., Gubitosa G., Wang S. et al. Urinary neutrophil gelatinase-associated lipocalin and acute kid­ney injury after cardiac surgery. J. Kidney Dis., 2008, vol. 52, pp. 425–433.
  10. Dent С.L., Ma Q., Dastrala S. et al. Plasma neutrophil gelatinase-associated lipocalin predicts acute kid­ney injury, morbidity and mortality after pediatric cardiac surgery: A prospective, uncontrolled cohort study. Care, 2007, vol. 11, p. R127.
  11. Koyner J.L., Bennett M.R., Worcester E.M. et al. Urinary cystatin С as an early biomarker of acute kid­ney injury following adult cardiothoracic surgery. Kidney Int., 2008, vol. 74, pp. 1059–1069.
  12. Haase-Fielitz A., Bellomo R., Devarajan P. et al. Novel and conventional serum biomarkers predicting acute kidney injury in adult cardiac surgery – a prospective cohort study. Crit Care Med., 2009, vol. 37, pp. 553–560.
  13. Bennett M., Dent С.L., Ma Q. et al. Urine NGAL predicts severity of acute kidney injury after cardiac surgery: A prospective study. J. Am. Soc. Nephrol., 2008, vol. 3, pp. 665–673.
  14. Wagener G., Jan M., Kim M. et al. Association between increases in urinary neutrophil gelatinase-asso­ciated lipocalin and acute renal dysfunction after adult cardiac surgery. Anesthesiology, 2006, vol. 105, pp. 485–491.
  15. Portilla D., Dent C., Sugaya T. et al. Liver fatty acid-binding protein as a biomarker of acute kidney injury after cardiac surgery. Kidney Int., 2008, vol. 73, pp. 465–472.
  16. Parikh C.R., Mishra J., Thiessen-Philbrook H. et al. Urinary IL-18 is an early predictive biomarker of acute kidney injury after cardiac surgery. Kidney Int., 2006, vol. 70, pp. 199–203.
  17. Supavekin S., Zhang W., Kucherlapati R. et al. Differential gene expression following early renal ischemia/reperfusion. Kidney Int., 2003, vol. 63, pp. 1714–1724.
  18. Devarajan P., Mishra J., Supavekin S. et al. Gene expression in early ischemic renal injury: Clues towards pathogenesis, biomarker discovery, and novel therapeutics. Genet. Metab., 2003, vol. 80, pp. 365–376.
  19. Devarajan P., Parikh C, Barasch J. Case 31-2007: A man with abdominal pain and elevated creatinine. Engl. J. Med., 2008, vol. 358, p. 312.
  20. Devarajan P. Neutrophil gelatinase-associated lipocalin — an emerging troponin for kidney injury. Dial. Transplant., 2008, vol. 23, pp. 3737–3743.
  21. Devarajan P. Neutrophil gelatinase-associated lipocaline (NGAL): A new marker of kidney disease. J. Clin. Lab. Invest., 2008, vol. 241, pp. 89–94.
  22. Devarajan P. NGAL in acute kidney injury: From serendipity to utility. J. Kidney Dis., 2008, vol. 52, pp. 395–399.
  23. Nguyen M.T., Devarajan P. Biomarkers for the early detection of acute kidney injury. Nephrol., 2008, vol. 23, pp. 2151–2157.
  24. Devarajan P. Emerging biomarkers of acute kidney ingury. Nephrol., 2007, vol. 156, pp. 203–212.
  25. Parikh C.R., Devarajan P. New biomarkers of acute kidney injury. Care Med., 2008, vol. 36, pp. S159–S165.
  26. Bonventre J.V. Diagnosis of acute kidney injuri: From classic parameters to new biomarkers. Nephrol., 2007, vol. 156, pp. 213–219.
  27. Edelstein C.L., Ling H., Schrier R. The nature of renal cell injury. Kidney Int., 1997, vol. 51, pp. 1341–1351.
  28. Jo S.K., Rosner M.H., Okusa Doctor of Medical Sciences Pharmacologic treatment of acute kidney injury: Why drugs haven’t worked and what is on the horizon. J. Am. Soc. Nephrol., 2007, vol. 2, pp. 356–365.
  29. Thadhani R., Bonventre J.V. Acute renal failure. Engl. J. Med., 1996, vol. 334, pp. 1448–1460.
  30. Brady H., Singer G. Acute renal failure. Lancet, 1995, vol. 346, pp. 1533–1540.
  31. Star R.A. Treatment of acute renal failure. Kidney Int., 1998, vol. 54, pp. 1817–1831.
  32. Bagshaw S.M., Uchino S., Cruz D. et al. A comparison of observed versus estimated baseline creatinine for determination of RIFLE class in patients with acute kidney injury. Dial. Transplant, 2009, Apr. 6.
  33. Bellomo R., Ronco C., Kellum J.A. et al. 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. Care., 2004, vol. 8, pp. R204–R212.
  34. Di Giantomasso D., Monmatsu H., May C.N., Bellomo R. Intra-renal Blood Flow Distribution in Hyperdinamic Septic Shock: Effect of Norepinephrine. Care Med., 2003, vol. 31, pp. 2509–2513.
  35. DiGiantomasso D., Bellomo R., May C.N. The hemodynamic and metabolic effects of epinephrine in experimental hyperdinamic septic shock. Care Med., 2005, vol. 31, pp. 454–462.
  36. May С., Wan L., Williams et al. A technique for the simultaneous measurement of renal ATP, blood flow and pH in a large animal model of septic shock. Crit. Care Resusc., 2007, vol. 9, pp. 30–33.
  37. May , Wan L., Williams J. et al. A technique for the measurements of renal ATP in a large animal model of sepsis. In. J. Artif. Organs., 2005, vol. 28, pp. 16–21.
  38. Wan L., Bellomo R., May С. The effect of normal saline resuscitation on vital organ blood flow in septic sheep. Care Med., 2006, vol. 32, pp. 1238–1242.
  39. DiGiantomasso D., May , Bellomo R. Norepinephrine and organ blood flow in sepsis. Intens. Care Med., 2003, vol. 29, pp. R 1774–1781.
  40. Di Giantomasso D., May C., Bellomo R. Vital organ blood flow in hyperdynamic sepsis. Chest., 2003, vol. 124, pp. 1053–1059.
  41. Brenner M., Schaer L., Mallory D.L. et al. Detection of renal blood flow abnormalities in septic and critically ill patients using a newly designed indwelling thermodilution renal vein catheter. Chest., 1990, vol. 98, pp. 170–179.
  42. Kikeri D., Pennell J.P., Hwang K.H. et al. Endotoxemic acute renal failure in awake rats. J. Physiol., 1986, vol. 250, pp. F1098–F1106.
  43. Badr K.F., Kelley V.E., Rennke H.G., Brenner B.M. Roles for thromboxane A2 and leukotrienes in endotoxin-induced acute renal failure. Kidney Int., 1986, vol. 30, pp. 474–480.
  44. Bonomini V., Stefoni S., Vangelista A. Long-term patient and renal prognosis in acute renal failure. Nephron., 1984, vol. 36, no. 3, pp. 169–172.
  45. Liano F., Pascual J. Epidemiology of acute renal failure: A prospective multicenter, community-based studv. Kidnev Int., 1996, vol. 50, pp. 811–818.
  46. Thadhani R., Pascual J., Bonventre J.V. Acute renal failure. Engl. J. Med., 1996, vol. 334, pp. 1448–1460.
  47. Liebethal W. Renal ischemia and reperfusion impair endothelium-dependet vascular relaxion. J. Physiol., 1989, vol. 256, pp. F894–F900.
  48. Conger J. NO in acute renal failure. Nitric Oxide and the Kidney (Ed. M. Goligorsky, S. Gross). N.Y., Chapman and Hall, 1997.
  49. Kon V., Yoshioka T., Fogo A., Ichikawa I. Glomerular actions of endothelin in vivo. Clin. Invest., 1989, vol. 83, pp. 1762–1767.
  50. Ossvald H., Hermes H., Nabakowski G. Role of adenosine in signal transmission of TGF. Kidnei Int., 1982, vol. 22(12), pp. S136–S142.
  51. Goligorsky M., Iigima K., Krivenko Y. et al. Role of mesangial cells in macula densato-afferent arteriole information treansfer. Exp. Pharm. Physiol., 1997, vol. 24, pp. 527–531.
  52. Gurevich K.Ya., Kostyuchenko A.L., Sokolov A.A. The syndrome of renal failure. In: Nefrologiya – 2001. The present state of the problem. Petersburg, Renkor Publ., 2002, pp. 163–196.
  53. Munoz A., Katerndahl D.A. Diagnosis and management of acute pancreatitis. American Family Physican, 2000, July, vol. 1, pp. 1–18.
  54. Uchino S., Kellum J. A., Belbmo R. et al. Acute renal failure in critically ill patients: a multinational, mul­ticenter study. JAMA, 2005, vol. 294, pp. 813–818.
  55. Hou S.H., Bushinsky D.A., Wish J.B. et al. Hospital-acquired renal insufficiency: a prospective study. J. Med., 1983, vol. 74, pp. 243–248.
  56. Liangos O., Wald R., O’Bell J.W. et al. Epidemiology and outcomes of acute renal failure in hospitalized patients: A national survey. J. Am. Soc. Nephrol., 2006, vol. 1, pp. 43–51.
  57. Xue J.L., Daniels F., Star R.A. et al. Incidence and mortality of acute renal failure in Medicare benefi­ciaries, 1992 to 2001. Am. Soc. Nephrol., 2006, vol. 17, pp. 1135–1142.
  58. Waikar S.S., Curhan G.C, Wald R. et al. Declining mortality in patients with acute renal failure, 1988 to 2002. Am. Soc. Nephrol., 2006, vol. 17, pp. 1143–1150.
  59. Hoste E.A.J., Schurgers M. Epidemiology of acute kidney injury: How big is the problem? Care Med., 2008, vol. 36, no. 4, pp. 146–151.
  60. Bywaters E.G., Beall D. Crush injuries with impairment of renal function. Br. Med. J., 1941, vol. 1, pp. 427–432.
  61. Davies F., Weldon R. A contribution to the study of «war nephritis». Lancet, 1917, vol. 2, pp. 118–120.
  62. Eknoyan G. Emergence of the concept of acute renal failure. J. Nephrol., 2002, vol. 22, pp. 225–230.
  63. Parikh С.R., Jani A., Mishra J. et al. Urine NGAL and IL-18 are predictive biomarkers for delayed graft function following kidney transplantation. J. Transplant., 2006, vol. 6, pp. 1639–1645.
  64. Washburn K.K., Zappitelli M., Arikan A.A. et al. Urinary interleukin-18 is an acute kidney injury biomarker in critically ill children. Dial. Transplant., 2008, vol. 23, pp. 566–572.
  65. Ichimura Т., Bonventre J.V., 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. Biol. Chem., 1998, vol. 273, pp. 4135–4142.
  66. Han W.K., Bailly V., Abichandani R. et al. Kidney Injury Molecule-1 (KIM-1): A novel biomarkerfor human renal proximal tubule injury. Kidney Int., 2002, vol. 62, pp. 237–244.
  67. Ichimura Т., Hung С.С., Yang S.A. et al. Kidney injury molecule-1: A tissue and urinary bio­mar­ker for nephrotoxicant-induced renal injury. J. Physiol. Renal. Physiol., 2004, vol. 286, pp. F552–F63.
  68. Vaidya V.S., Ramirez V., Khimura T. et al. Urinary kidney injury molecule-1: A sensitive quantita­tive biomarker for early detectin of kidney tubular injury. J. Physiol. Renal. Physiol., 2006, vol. 290, pp. F517–F29.
  69. Maatman R.G., van de Westerlo E.M., van Kuppevelt T.H., Veerkamp J.H. 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. J., 1992, vol. 288, pp. 285–290.
  70. Portilla D., Dent C., Sugaya T. et al. Liver fatty acid-binding protein as a biomarker of acute kidney injury after cardiac surgery. Kidney Int., 2008, vol. 73, pp. 465–472.
  71. Kamijo-Ikemori A., Sugaya Т., Kimura K. Urinary fatty acid binding protein in renal disease. Chim. Acta, 2006, vol. 374, pp. 1–7.
  72. Kamijo A., Sugaya Т., Hikawa A. et al. Clinical evaluation of urinary excretion of liver-type fatty acid-binding protein as a marker for the monitoring of chronic kidney disease: A multicenter trial. Lab. Clin. Med., 2005, vol. 145, pp. 125–133.
  73. Nakamura K, Sugaya Т., Kawagoe Y. et al. Effect of pravastatin on urinary liver-type fatty-acid-binding protein in patients with nondiabetic mild chronic kidney disease. J. Nephrol., 2006, vol. 26, pp. 82–86.
  74. Nakamura K, Sugaya Т., Kawagoe Y. et al. Urinary liver-type fatty acid-binding protein levels for dif­ferential diagnosis of idiopathic focal glomerulosclerosis and minor glomerular abnormalities and effect of low-density lipoprotein apheresis. Nephrol., 2006, vol. 65, pp. 1–6.
  75. Nakamura K, Sugaya Т., Kawagoe Y. et al. Candesartan reduces urinary fatty acid-binding protein excretion in patients with autosomal dominant polycystic kidney disease. J. Med. Sci., 2005, vol. 330, pp. 161–165.
  76. Oyama Y., Takeda T., Hama H. et al. Evidence for megalin-mediated proximal tubular uptake of L-FABP, a carrier of potentially nephrotoxic molecules. Invest., 2005, vol. 85, pp. 522–531.
  77. Kamijo A., Sugaya T., Hikawa A. et al. Urinary liver-type fatty acid binding protein as a useful biomarker in chronic kidney disease. Cell. Biochem., 2006, vol. 284, pp. 175–182.
  78. Milovanov Yu.S., Nikolaev A.Yu., Lifshits N.L. Diagnostics and principles of treatment of chronic renal failure. Med. Zh., 1997, no. 23, pp. 7–11.
  79. Nikolaev A.Yu., Milovanov Yu.S. Treatment of renal failure: A Guide for Physicians. Moscow, MIA Publ., 1999, 362 p.
  80. Mucelli R.P., Bertolotto M. Imaging techniques in acute renal failure. Kidney Int., 1998,66, pp. S102–S105.
  81. Talner L.B. Urinary obstruction. In: Pollack H.M., ed. Clinical Urology. Philadelphia, Saunders, 1990, pp. 1535–1628.
  82. Zoran L., Barbarich M.I. Renal failure. In: Principles of Genitourinary Radiology. 2nd N.Y., Thieme Medical, 1994, pp. 251–278.
  83. Piatt J.F, Rubin J.M., Ellis J.H. Acute renal failure: Possible role of duplex Doppler US in distinction between acute prerenal failure and acute tubular necrosis. Radiology, 1991, vol. 179, pp. 419–423.
  84. Izumi M., Sugiura T., Nakamura H. et al. Differential diagnosis of prerenal azotemia from acute tubu­lar necrosis and prediction of recovery by Doppler ultrasound. J. Kidney Dis., 2000, vol. 35, pp. 713–719.
  85. Yoon D.Y, Kim S.H., Kim H.D. et al. Doppler sonography in experimentally induced acute renal failure in rabbits. Resistive index versus serum creatinine Invest. Radiol., 1995, vol. 30, pp. 168–172.
  86. Stevens P.E., Gwyther S.J., Hanson M.E. et al. Noninvasive monitoring of renal blood flow character­istics during acute renal failure in man. Care Med., 1990, vol. 16, pp. 153–158.
  87. Radermacher J., Chavan A., Schaffer J. et al. Detection of significant renal artery stenosis with color Doppler sonography: Combining extrarenal and intrarenal approaches to minimize technical failure. Nephrol., 2000, vol. 53, pp. R 333–343.
  88. Johansson M., Jensen G., Aurell M. et al. Evaluation of duplex ultrasound and captopril renography for detection of renovascular hypertension. Kidney Int., 2000, vol. 58, pp. 774–782.
  89. Bertolotto M., Quaia E., Galli G. et al. Color Doppler sonographic appearance of renal perforating ves­sels in subjects with normal and impaired renal function. Clin. Ultrasound., 2000, vol. 28, pp. 267–276.

About authors

Raskina Tatiana Valerievna
laboratory doctor of clinical diagnostic laboratory, City Clinical Hospital № 1, Russia, Cheboksary )
Borisov Alexander Yurievich
surgical diseases department graduate student, Chuvash State University, Russia, Cheboksary (; )

Article link

Borisov A., Raskina T. Early diagnosis of acute kidney injury [Electronic resource] // Acta medica Eurasica. – 2016. – №1. P. 1-13. – URL: