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  • Review Article
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Acute kidney injury: what's the prognosis?

Abstract

Acute kidney injury (AKI) is common (especially during critical illness), increasing in incidence, and is associated with considerable morbidity and mortality. The Risk, Injury, Failure, Loss, and End-stage renal disease (RIFLE) classification currently provides a standardized estimate of incidence and outcomes from AKI. Despite advances in the understanding of the pathogenesis of human AKI, our ability to assess kidney function is limited and functional impairment poorly correlates with structural injury to the kidneys. Emerging novel biomarkers are, however, likely to further enhance risk stratification, facilitate early diagnosis, enable early enrollment in therapeutic trials, and assess prognosis. Sepsis remains the leading cause of AKI among the critically ill and over the past few years insights into the pathogenesis of AKI in sepsis are beginning to shift attention from renal blood flow to inflammation-mediated organ injury. Emerging evidence suggests that survivors of AKI incur long-term risks for developing chronic kidney disease and end-stage renal disease compared with those without AKI. Despite decades of research, no specific therapy for AKI other than supportive care currently exists and further work is required to better understand the pathogenesis of AKI during critical illness and to develop novel treatments.

Key Points

  • Acute kidney injury (AKI) is common and is associated with higher resource utilization and mortality than that of other critical care syndromes

  • Risk, Injury, Failure, Loss, and End-stage renal disease classification is a validated definition of AKI and together with the AKI Network modification is widely accepted

  • Emerging biomarkers may further aid early diagnosis and risk stratification of AKI

  • Current understanding of the pathogenesis and pathophysiology of AKI is poor and treatment is largely supportive

  • AKI increases susceptibility to chronic kidney disease and end-stage renal disease

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Figure 1: Conceptual model of AKI.
Figure 2: RIFLE criteria for diagnosing AKI.
Figure 3: Incidence of various organ failure among critically ill patients.
Figure 4: Risk of AKI varies by definition used and timing of assessment.
Figure 5: Theoretical next generation in AKI diagnosis and classification.

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References

  1. Uchino, S. et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA 294, 813–818 (2005).

    Article  CAS  Google Scholar 

  2. Hoste, E. A. et al. RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a cohort analysis. Crit. Care 10, R73 (2006).

    Article  Google Scholar 

  3. Ali, T. et al. Incidence and outcomes in acute kidney injury: a comprehensive population-based study. J. Am. Soc. Nephrol. 18, 1292–1298 (2007).

    Article  CAS  Google Scholar 

  4. Alejandro, V. et al. Mechanisms of filtration failure during postischemic injury of the human kidney. A study of the reperfused renal allograft. J. Clin. Invest. 95, 820–831 (1995).

    Article  CAS  Google Scholar 

  5. Myers, B. D. et al. Nature of the renal injury following total renal ischemia in man. J. Clin. Invest. 73, 329–341 (1984).

    Article  CAS  Google Scholar 

  6. Uchino, S., Bellomo, R., Goldsmith, D., Bates, S. & Ronco, C. An assessment of the RIFLE criteria for acute renal failure in hospitalized patients. Crit. Care Med. 34, 1913–1917 (2006).

    Article  Google Scholar 

  7. Ostermann, M. & Chang, R. W. Acute kidney injury in the intensive care unit according to RIFLE. Crit. Care Med. 35, 1837–1843 (2007).

    Article  Google Scholar 

  8. Bagshaw, S. M., George, C. & Bellomo, R. Early acute kidney injury and sepsis: a multicentre evaluation. Crit. Care 12, R47 (2008).

    Article  Google Scholar 

  9. Uchino, S., Bellomo, R., Bagshaw, S. M. & Goldsmith, D. Transient azotaemia is associated with a high risk of death in hospitalized patients. Nephrol. Dial. Transplant. 25, 1833–1839 (2010).

    Article  Google Scholar 

  10. Rosen, S. & Heyman, S. N. Difficulties in understanding human “acute tubular necrosis”: limited data and flawed animal models. Kidney Int. 60, 1220–1224 (2001).

    Article  CAS  Google Scholar 

  11. Brun, C. & Munck, O. Lesions of the kidney in acute renal failure following shock. Lancet 272, 603–607 (1957).

    Article  CAS  Google Scholar 

  12. Smith, H. W. Lectures on the Kidney 3–23 (University Extension Division, University of Kansas, Kansas City, 1943).

    Google Scholar 

  13. Natochin, Y. V. Evolutionary aspects of renal function. Kidney Int. 49, 1539–1542 (1996).

    Article  CAS  Google Scholar 

  14. Solez, K., Morel-Maroger, L. & Sraer, J. D. The morphology of “acute tubular necrosis” in man: analysis of 57 renal biopsies and a comparison with the glycerol model. Medicine (Baltimore) 58, 362–376 (1979).

    Article  CAS  Google Scholar 

  15. Racusen, L. C., Fivush, B. A., Li, Y. L., Slatnik, I. & Solez, K. Dissociation of tubular cell detachment and tubular cell death in clinical and experimental “acute tubular necrosis”. Lab. Invest. 64, 546–556 (1991).

    CAS  PubMed  Google Scholar 

  16. Dear, J. W. et al. Dendrimer-enhanced MRI as a diagnostic and prognostic biomarker of sepsis-induced acute renal failure in aged mice. Kidney Int. 67, 2159–2167 (2005).

    Article  Google Scholar 

  17. Waikar, S. S. & Bonventre, J. V. Creatinine kinetics and the definition of acute kidney injury. J. Am. Soc. Nephrol. 20, 672–679 (2009).

    Article  CAS  Google Scholar 

  18. Kellum, J. A., Levin, N., Bouman, C. & Lameire, N. Developing a consensus classification system for acute renal failure. Curr. Opin. Crit. Care 8, 509–514 (2002).

    Article  Google Scholar 

  19. Bellomo, R., Ronco, C., Kellum, J. A., Mehta, R. L. & 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 8, R204–R212 (2004).

    Article  Google Scholar 

  20. Mehta, R. L. et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit. Care 11, R31 (2007).

    Article  Google Scholar 

  21. Murugan, R. et al. Acute kidney injury in non-severe pneumonia is associated with an increased immune response and lower survival. Kidney Int. 77, 527–535 (2010).

    Article  CAS  Google Scholar 

  22. Ricci, Z., Cruz, D. & Ronco, C. The RIFLE criteria and mortality in acute kidney injury: a systematic review. Kidney Int. 73, 538–546 (2008).

    Article  CAS  Google Scholar 

  23. Bagshaw, S. M., George, C., Dinu, I. & Bellomo, R. A multi-centre evaluation of the RIFLE criteria for early acute kidney injury in critically ill patients. Nephrol. Dial. Transplant. 23, 1203–1210 (2008).

    Article  Google Scholar 

  24. Acute Kidney Injury—United States Renal Data System 2009 Annual Data Report. United States Renal Data System [online], http://www.usrds.org/2009/pdf/V1_08_09.PDF, (2009).

  25. Waikar, S. S. et al. Validity of international classification of diseases, ninth revision, clinical modification codes for acute renal failure. J. Am. Soc. Nephrol. 17, 1688–1694 (2006).

    Article  Google Scholar 

  26. Waikar, S. S., Curhan, G. C., Wald, R., McCarthy, E. P. & Chertow, G. M. Declining mortality in patients with acute renal failure, 1988 to 2002. J. Am. Soc. Nephrol. 17, 1143–1150 (2006).

    Article  Google Scholar 

  27. Fang, Y. et al. Acute kidney injury in a Chinese hospitalized population. Blood Purif. 30, 120–126 (2010).

    Article  Google Scholar 

  28. Lafrance, J. P. & Miller, D. R. Defining acute kidney injury in database studies: the effects of varying the baseline kidney function assessment period and considering CKD status. Am. J. Kidney Dis. 56, 651–660 (2010).

    Article  Google Scholar 

  29. Thakar, C. V., Christianson, A., Freyberg, R., Almenoff, P. & Render, M. L. Incidence and outcomes of acute kidney injury in intensive care units: a Veterans Administration study. Crit. Care Med. 37, 2552–2558 (2009).

    Article  Google Scholar 

  30. Hackworth, L. A., Wen, X., Clermont, G., Murugan R. & Kellum, J. A. Hospital versus community-acquired acute kidney injury in the critically Ill: differences in epidemiology. J. Am. Soc. Nephrol. 20, 355A (2009).

    Google Scholar 

  31. Centers for Disease Control and Prevention (CDC). Hospitalization discharge diagnoses for kidney disease–United States, 1980–2005. MMWR Morb. Mortal. Wkly 57, 309–312 (2005).

  32. Hsu, C. Y. et al. Nonrecovery of kidney function and death after acute on chronic renal failure. Clin. J. Am. Soc. Nephrol. 4, 891–898 (2009).

    Article  Google Scholar 

  33. Xue, J. L. et al. Incidence and mortality of acute renal failure in Medicare beneficiaries, 1992 to 2001. J. Am. Soc. Nephrol. 17, 1135–1142 (2006).

    Article  Google Scholar 

  34. Bagshaw, S. M. et al. Septic acute kidney injury in critically ill patients: clinical characteristics and outcomes. Clin. J. Am. Soc. Nephrol. 2, 431–439 (2007).

    Article  Google Scholar 

  35. de Mendonça, A. et al. Acute renal failure in the ICU: risk factors and outcome evaluated by the SOFA score. Intensive Care Med. 26, 915–921 (2000).

    Article  Google Scholar 

  36. Wan, L. et al. Pathophysiology of septic acute kidney injury: what do we really know? Crit. Care Med. 36 (Suppl. 4), S198–S203 (2008).

    Article  Google Scholar 

  37. Langenberg, C., Wan, L., Egi, M., May, C. N. & Bellomo, R. Renal blood flow in experimental septic acute renal failure. Kidney Int. 69, 1996–2002 (2006).

    Article  CAS  Google Scholar 

  38. Heyman, S. N., Rosenberger, C. & Rosen, S. Experimental ischemia-reperfusion: biases and myths–the proximal vs. distal hypoxic tubular injury debate revisited. Kidney Int. 77, 9–16 (2010).

    Article  Google Scholar 

  39. Rosen, S. & Heyman, S. N. Difficulties in understanding human “acute tubular necrosis”: limited data and flawed animal models. Kidney Int. 60, 1220–1224 (2001).

    Article  CAS  Google Scholar 

  40. Wen, X., Murugan, R., Peng, Z. & Kellum, J. A. Pathophysiology of acute kidney injury: a new perspective. Contrib. Nephrol. 165, 39–45 (2010).

    Article  Google Scholar 

  41. Humphreys, B. D. et al. Intrinsic epithelial cells repair the kidney after injury. Cell Stem Cell 2, 284–291 (2008).

    Article  CAS  Google Scholar 

  42. Zhang, X. L., Topley, N., Ito, T. & Phillips, A. Interleukin-6 regulation of transforming growth factor (TGF)-β receptor compartmentalization and turnover enhances TGF-β1 signaling. J. Biol. Chem. 280, 12239–12245 (2005).

    Article  CAS  Google Scholar 

  43. Levy, M. M. et al. Early changes in organ function predict eventual survival in severe sepsis. Crit. Care Med. 33, 2194–2201 (2005).

    Article  Google Scholar 

  44. Bellomo, R. et al. Intensity of continuous renal-replacement therapy in critically ill patients. N. Engl. J. Med. 361, 1627–1638 (2009).

    Article  Google Scholar 

  45. Palevsky, P. M. et al. Intensity of renal support in critically ill patients with acute kidney injury. N. Engl. J. Med. 359, 7–20 (2008).

    Article  CAS  Google Scholar 

  46. Kellum, J. A. & Ronco, C. Dialysis: results of RENAL—what is the optimal CRRT target dose? Nat. Rev. Nephrol. 6, 191–192 (2010).

    Article  Google Scholar 

  47. Himmelfarb, J. et al. Evaluation and initial management of acute kidney injury. Clin. J. Am. Soc. Nephrol. 3, 962–967 (2008).

    Article  Google Scholar 

  48. Hoste, E. A. & Kellum, J. A. RIFLE criteria provide robust assessment of kidney dysfunction and correlate with hospital mortality. Crit. Care Med. 34, 2016–2017 (2006).

    Article  Google Scholar 

  49. Kellum, J. A. & Angus, D. C. Patients are dying of acute renal failure. Crit. Care Med. 30, 2156–2157 (2002).

    Article  Google Scholar 

  50. Wiedemann, H. P. et al. Comparison of two fluid-management strategies in acute lung injury. N. Engl. J. Med. 354, 2564–2575 (2006).

    Article  CAS  Google Scholar 

  51. Sprung, C. L. et al. Hydrocortisone therapy for patients with septic shock. N. Engl. J. Med. 358, 111–124 (2008).

    Article  CAS  Google Scholar 

  52. Elapavaluru, S. & Kellum, J. A. Why do patients die of acute kidney injury? Acta Clin. Belg. Suppl. 326–331 (2007).

  53. Uchino, S. et al. Continuous renal replacement therapy: a worldwide practice survey. The beginning and ending supportive therapy for the kidney (B. E. S. T. kidney) investigators. Intensive Care Med. 33, 1563–1570 (2007).

    Article  Google Scholar 

  54. Vincent, J. L. et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the working group on sepsis-related problems of the European Society of Intensive Care Medicine. Intensive Care Med. 22, 707–710 (1996).

    Article  CAS  Google Scholar 

  55. Morgera, S., Kraft, A. K., Siebert, G., Luft, F. C. & Neumayer, H. H. Long-term outcomes in acute renal failure patients treated with continuous renal replacement therapies. Am. J. Kidney Dis. 40, 275–279 (2002).

    Article  Google Scholar 

  56. Liaño, F. et al. Long-term outcome of acute tubular necrosis: a contribution to its natural history. Kidney Int. 71, 679–686 (2007).

    Article  Google Scholar 

  57. Chertow, G. M., Christiansen, C. L., Cleary, P. D., Munro, C. & Lazarus, J. M. Prognostic stratification in critically ill patients with acute renal failure requiring dialysis. Arch. Intern. Med. 155, 1505–1511 (1995).

    Article  CAS  Google Scholar 

  58. Hoste, E. A. et al. Acute renal failure in patients with sepsis in a surgical ICU: predictive factors, incidence, comorbidity, and outcome. J. Am. Soc. Nephrol. 14, 1022–1030 (2003).

    Article  Google Scholar 

  59. Ishani, A. et al. Acute kidney injury increases risk of ESRD among elderly. J. Am. Soc. Nephrol. 20, 223–228 (2009).

    Article  Google Scholar 

  60. Amdur, R. L., Chawla, L. S., Amodeo, S., Kimmel, P. L. & Palant, C. E. Outcomes following diagnosis of acute renal failure in, U. S. veterans: focus on acute tubular necrosis. Kidney Int. 76, 1089–1097 (2009).

    Article  Google Scholar 

  61. Devarajan, P. Review: neutrophil gelatinase-associated lipocalin: a troponin-like biomarker for human acute kidney injury. Nephrology (Carlton) 15, 419–428 (2010).

    Article  Google Scholar 

  62. Soto, K. et al. Cystatin C as a marker of acute kidney injury in the emergency department. Clin. J. Am. Soc. Nephrol. 5, 1745–1754 (2010).

    Article  CAS  Google Scholar 

  63. Devarajan, P. Neutrophil gelatinase-associated lipocalin: a promising biomarker for human acute kidney injury. Biomark. Med. 4, 265–280 (2010).

    Article  CAS  Google Scholar 

  64. Liu, K. D. et al. Serum interleukin-6 and interleukin-8 are early biomarkers of acute kidney injury and predict prolonged mechanical ventilation in children undergoing cardiac surgery: a case-control study. Crit. Care 13, R104 (2009).

    Article  Google Scholar 

  65. Bennett, M. R. et al. Using proteomics to identify preprocedural risk factors for contrast induced nephropathy. Proteomics Clin. Appl. 2, 1058–1064 (2008).

    Article  CAS  Google Scholar 

  66. Portilla, D. et al. Liver fatty acid-binding protein as a biomarker of acute kidney injury after cardiac surgery. Kidney Int. 73, 465–472 (2008).

    Article  CAS  Google Scholar 

  67. Parikh, C. R. et al. Urinary IL-18 is an early predictive biomarker of acute kidney injury after cardiac surgery. Kidney Int. 70, 199–203 (2006).

    Article  CAS  Google Scholar 

  68. Ramesh, G., Krawczeski, C. D., Woo, J. G., Wang, Y. & Devarajan, P. Urinary netrin-1 is an early predictive biomarker of acute kidney injury after cardiac surgery. Clin. J. Am. Soc. Nephrol. 5, 395–401 (2010).

    Article  CAS  Google Scholar 

  69. Bonventre, J. V. Kidney injury molecule-1 (KIM-1): a urinary biomarker and much more. Nephrol. Dial. Transplant. 24, 3265–3268 (2009).

    Article  CAS  Google Scholar 

  70. Solomon, R. & Segal, A. Defining acute kidney injury: what is the most appropriate metric? Nat. Clin. Pract. Nephrol. 4, 208–215 (2008).

    Article  Google Scholar 

  71. Xiao, W. B., Wang, Q. D., Xu, J. J., Han, F. & Zhang, M. M. Evaluation of kidney oxygen bioavailability in acute renal failure by blood oxygen level dependent magnetic resonance imaging [Chinese]. Zhejiang. Da. Xue. Xue. Bao. Yi. Xue. Ban. 39, 157–162 (2010).

    PubMed  Google Scholar 

  72. Han, F. et al. The significance of BOLD MRI in differentiation between renal transplant rejection and acute tubular necrosis. Nephrol. Dial. Transplant. 23, 2666–2672 (2008).

    Article  Google Scholar 

  73. Molitoris, B. A. & Sandoval, R. M. Multiphoton imaging techniques in acute kidney injury. Contrib. Nephrol. 165, 46–53 (2010).

    Article  Google Scholar 

  74. Vincent, J. L. et al. Sepsis in European intensive care units: results of the SOAP study. Crit. Care Med. 34, 344–353 (2006).

    Article  Google Scholar 

  75. Turney, J. H., Marshall, D. H., Brownjohn, A. M., Ellis, C. M. & Parsons, F. M. The evolution of acute renal failure, 1956–1988. Q. J. Med. 74, 83–104 (1990).

    CAS  PubMed  Google Scholar 

  76. Brivet, F. G., Kleinknecht, D. J., Loirat, P. & Landais, P. J. Acute renal failure in intensive care units--causes, outcome, and prognostic factors of hospital mortality; a prospective, multicenter study. French study group on acute renal failure. Crit. Care Med. 24, 192–198 (1996).

    Article  CAS  Google Scholar 

  77. McCarthy, J. T. Prognosis of patients with acute renal failure in the intensive-care unit: a tale of two eras. Mayo Clin. Proc. 71, 117–126 (1996).

    Article  CAS  Google Scholar 

  78. Korkeila, M., Ruokonen, E. & Takala, J. Costs of care, long-term prognosis and quality of life in patients requiring renal replacement therapy during intensive care. Intensive Care Med. 26, 1824–1831 (2000).

    Article  CAS  Google Scholar 

  79. Liaño, F., Pascual, J. & The Madrid acute renal failure study group. Epidemiology of acute renal failure: a prospective, multicenter, community-based study. Kidney Int. 50, 811–818 (1996).

    Article  Google Scholar 

  80. Van Berendoncks, A. M., Elseviers, M. M. & Lins, R. L. Outcome of acute kidney injury with different treatment options: long-term follow-up. Clin. J. Am. Soc. Nephrol. 5, 1755–1762 (2010).

    Article  Google Scholar 

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Acknowledgements

This publication was made possible in part by funding from grants R01DK070910 and R01DK083961 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the grant KL2RR024154 from the National Center for Research Resources (NCRR), and components of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. The contents of this Review are solely the responsibility of the authors and do not necessarily represent the official view of NIDDK, NCRR or NIH.

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R. Murugan and J. A. Kellum contributed equally to the discussions, research, writing, editing, and reviewing of this manuscript.

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Correspondence to John A. Kellum.

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R. Murugan and J. A. Kellum declare an association with the following company: Baxter (consultant and grant/research support). J. A. Kellum declares associations with the following companies: Alere (consultant), Abbott Laboratories (consultant), Astute Medical (consultant, grant/research support, patent holder/applicant), Gambro (consultant and grant/research support).

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Murugan, R., Kellum, J. Acute kidney injury: what's the prognosis?. Nat Rev Nephrol 7, 209–217 (2011). https://doi.org/10.1038/nrneph.2011.13

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