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" 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Biomarkers in Acute Kidney Injury

Abstract Full-Text HTML XML Download Download as PDF (Size:362KB) PP. 51-60
DOI: 10.4236/ojneph.2013.31009    5,565 Downloads   9,181 Views   Citations

ABSTRACT

Acute kidney injury (AKI) is one of the popular topics of discussions due to increasing development of biomarkers recently. The disease progression and prognosis may be determined by these biomarkers detected in blood and urine specimens. Since acute kidney injury is associated with a broad spectrum of disease conditions, prevention and early detection of AKI becomes very important in those clinical settings. Early measurements of AKI biomarkers predict subsequent development of intrinsic AKI, dialysis requirement, duration of intensive care unit stay and finally affect mortality. We, here, discuss the acute kidney injury in different clinical situations and associated natures of biomarkers, which may help us guide to prevent and treat AKI more effectively.

Cite this paper

Zheng, C. , Liao, M. , Lin, M. , Lo, L. , Wu, C. , Hsu, Y. , Lin, Y. and Lu, K. (2013) Biomarkers in Acute Kidney Injury. Open Journal of Nephrology, 3, 51-60. doi: 10.4236/ojneph.2013.31009.

Conflicts of Interest

The authors declare no conflicts of interest.

References

Biomarkers in Acute Kidney Injury [22]
[1] R. Bellomo, C. Ronco, J. A. Kellum, R. L. Mehta and P. Palevsky, “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,” Critical Care, Vol. 8, No. 4, 2004, pp. R204-R212. doi:10.1186/cc2872
[2] J. A. Kellum, N. Levin, C. Bouman and N. Lameire, “Developing a Consensus Classification System for Acute Renal Failure,” Current Opinion in Critical Care, Vol. 8, No. 6, 2002, pp. 509-514. doi:10.1097/00075198-200212000-00005
[3] G. M. Chertow, E. Burdick, M. Honour, J. V. Bonventre and D. W. Bates, “Acute Kidney Injury, Mortality, Length of Stay, and Costs in Hospitalized Patients,” Journal of the American Society of Nephrology, Vol. 16, No. 11, 2005, pp. 3365-3370. doi:10.1681/ASN.2004090740
[4] R. L. Mehta, J. A. Kellum, S. V. Shah, B. A. Molitoris, C. Ronco, D. G. Warnock and A. Levin, “Acute Kidney Injury Network: Report of an Initiative to Improve Outcomes in Acute Kidney Injury,” Critical Care, Vol. 11, No. 2, 2007, p. R31. doi:10.1186/cc5713
[5] J. Kaufman, M. Dhakal, B. Patel and R. Hamburger, “Community-Acquired Acute Renal Failure,” American Journal of Kidney Diseases, Vol. 17, No. 2, 1991, pp. 191-198.
[6] K. Nash, A. Hafeez and S. Hou, “Hospital-Acquired Renal Insufficiency,” American Journal of Kidney Diseases, Vol. 39, No. 5, 2002, pp. 930-936. doi:10.1053/ajkd.2002.32766
[7] R. L. Mehta, M. T. Pascual, S. Soroko, et al., “Spectrum of Acute Renal Failure in the Intensive Care Unit: The PICARD Experience,” Kidney International, Vol. 66, No. 4, 2004, pp. 1613-1621. doi:10.1111/j.1523-1755.2004.00927.x
[8] M. Ostermann and R.W. Chang, “Acute Kidney Injury in the Intensive Care Unit According to RIFLE,” Critical Care Medicine, Vol. 35, No. 8, 2007, pp. 1837-1843. doi:10.1097/01.CCM.0000277041.13090.0A
[9] F. Liano, C. Felipe, M. T. Tenorio, M. Rivera, V. Abraira, J. M. Saezde-Urturi, J. Ocana, C. Fuentes and S. Severiano, “Long-Term Outcome of Acute Tubular Necrosis: A Contribution to Its Natural History,” Kidney International, Vol. 71, No. 7, 2007, pp. 679-686. doi:10.1038/sj.ki.5002086
[10] S. M. Bagshaw, K. B. Laupland, C. J. Doig, G. Mortis, G. H. Fick, M. Mucenski, T. Godinez-Luna, L. W. Svenson and T. Rosenal, “Prognosis for Long-Term Survival and Renal Recovery in Critically Ill Patients with Severe Acute Renal Failure: A Population-Based Study,” Critical Care, Vol. 9, No. 6, 2005, pp. R700-R709. doi:10.1186/cc3879
[11] E. A. Hoste, G. Clermont, A. Kersten, R. Venkataraman, D. C. Angus, D. De Bacquer and J. A. Kellum, “RIFLE Criteria for Acute Kidney Injury Are Associated with Hospital Mortality in Critically Ill Patients: A Cohort Analysis,” Critical Care, Vol. 10, No. 3, 2006, p. R73. doi:10.1186/cc4915
[12] J. V. Bonventre and J. M. Weinberg, “Recent Advances in the Pathophysiology of Ischemic Acute Renal Failure,” Journal of the American Society of Nephrology, Vol. 14, No. 8, 2003, pp. 2199-2210. doi:10.1097/01.ASN.0000079785.13922.F6
[13] R. W. Schrier, W. Wang, B. Poole and A. Mitra, “Acute Renal Failure: Definitions, Diagnosis, Pathogenesis, and Therapy,” The Journal of Clinical Investigation, Vol. 114, No. 1, 2004, pp. 5-14.
[14] M. S. Rangel-Frausto, D. Pittet, M. Costigan, T. Hwang, C. S. Davis and R. P. Wenzel, “The Natural History of the Systemic Inflammatory Response Syndrome (SIRS). A Prospective Study,” Journal of the American Medical Association, Vol. 273, No. 2, 1995, pp. 117-123. doi:10.1001/jama.1995.03520260039030
[15] G. Van den Berghe, A. Wilmer, G. Hermans, et al., “Intensive Insulin Therapy in the Medical ICU,” The New England Journal of Medicine, Vol. 354, No. 5, 2006, pp. 449-461. doi:10.1056/NEJMoa052521
[16] J. Himmelfarb, E. McMonagle, S. Freedman, et al., “Oxidative Stress Is Increased in Critically Ill Patients with Acute Renal Failure,” Journal of the American Society of Nephrology, Vol. 15, No. 9, 2004, pp. 2449-2456. doi:10.1097/01.ASN.0000138232.68452.3B
[17] G. H. Metnitz, M. Fischer, C. Bartens, H. Steltzer, T. Lang and W. Druml, “Impact of Acute Renal Failure on Antioxidant Status in Multiple Organ Failure,” Acta Anaesthesiologica Scandinavica, Vol. 44, No. 3, 2000, pp. 236-240. doi:10.1034/j.1399-6576.2000.440304.x
[18] P. Devarajan, “Emerging Biomarkers of Acute Kidney Injury,” Contributions to Nephrology, Vol. 156, 2007, pp. 203-212. doi:10.1159/000102085
[19] P. Devarajan, “Emerging Urinary Biomarkers in the Diagnosis of Acute Kidney Injury,” Expert Opinion on Medical Diagnostics, Vol. 2, No. 4, 2008, pp. 387-398.
[20] N. E. Tolkoff-Rubin, R. H. Rubin and J. V. Bonventre, “Non-invasive Renal Diagnostic Studies,” Clinics in Laboratory Medicine, Vol. 8, No. 3, 1988, pp. 507-526.
[21] C. Bazzi, C. Petrini, V. Rizza, et al., “Urinary Excretion of IgG and Alpha(1)-Microglobulin Predicts Clinical Course Better than Extent of Proteinuria in Membranous Nephropathy,” American Journal of Kidney Diseases, Vol. 38, No. 2, 2001, pp. 240-248. doi:10.1053/ajkd.2001.26080
N. Taniguchi, M. Tanaka, C. Kishihara, et al., “Determination of Carbonic Anhydrase C and Beta 2-Microglobulin by Radioimmunoassay in Urine of Heavy-Metal- Exposed Subjects and Patients with Renal Tubular Acidosis,” Environmental Research, Vol. 20, No. 1, 1979, pp. 154-161. doi:10.1016/0013-9351(79)90094-X
[23] A. Mutti, S. Lucertini, P. Valcavi, et al., “Urinary Excretion of Brush-Border Antigen Revealed by Monoclonal Antibody: Early Indicator of Toxic Nephropathy,” Lancet, Vol. 2, No. 8461, 1985, pp. 914-917. doi:10.1016/S0140-6736(85)90850-5
[24] J. Boldt, T. Brenner, J. Lang, B. Kumle and F. Isgro, “Kidney-Specific Proteins in Elderly Patients Undergoing Cardiac Surgery with Cardiopulmonary Bypass,” Anesthesia and Analgesia, Vol. 97, No. 6, 2003, pp. 1582-1589. doi:10.1213/01.ANE.0000090146.02929.2E
[25] K. Sugimura, T. Goto, K. Tsuchida, Y. Takemoto, T. Kim and T. Kishimoto, “Production and Activation of Hepa- tocyte Growth Factor in Acute Renal Failure,” Renal Failure, Vol. 23, No. 3-4, 2001, pp. 597-603. doi:10.1081/JDI-100104741
[26] F. Mariano, G. Guida, D. Donati, et al., “Production of Platelet-Activating Factor in Patients with Sepsis-Associated Acute Renal Failure,” Nephrology, Dialysis, Transplantation, Vol. 14, No. 5, 1999, pp. 1150-1157. doi:10.1093/ndt/14.5.1150
[27] H. Zhou, T. Pisitkun, A. Aponte, et al., “Exosomal Fetuin-A Identified by Proteomics: A Novel Urinary Biomarker for Detecting Acute Kidney Injury,” Kidney International, Vol. 70, No. 10, 2006, pp. 1847-1857. doi:10.1038/sj.ki.5001874
[28] Y. Muramatsu, M. Tsujie, Y. Kohda, et al., “Early Detection of Cysteine Rich Protein 61 (CYR61, CCN1) in Urine Following Renal Ischemic Reperfusion Injury,” Kidney International, Vol. 62, No. 5, 2002, pp. 1601-1610. doi:10.1046/j.1523-1755.2002.00633.x
[29] J. Mishra, Q. Ma, A. Prada, et al., “Identification of Neutrophil Gelatinase-Associated Lipocalin as a Novel Early Urinary Biomarker for Ischemic Renal Injury,” Journal of the American Society of Nephrology, Vol. 14, No. 10, 2003, pp. 2534-2543. doi:10.1097/01.ASN.0000088027.54400.C6
[30] J. Mishra, C. Dent, R. Tarabishi, et al., “Neutrophil Gelatinase-Associated Lipocalin (NGAL) as a Biomarker for Acute Renal Injury after Cardiac Surgery,” Lancet, Vol. 365, No. 9466, 2005, pp. 1231-1238. doi:10.1016/S0140-6736(05)74811-X
[31] G. Wagener, M. Jan, M. Kim, et al., “Association between Increases in Urinary Neutrophil Gelatinase-Associated Lipocalin and Acute Renal Dysfunction after Adult cardiac Surgery,” Anesthesiology, Vol. 105, No. 3, 2006, pp. 485-491. doi:10.1097/00000542-200609000-00011
[32] C. L. Dent, Q. Ma, S. Dastrala, et al., “Plasma Neutrophil Gelatinase-Associated Lipocalin Predicts Acute Kidney Injury, Morbidity and Mortality after Pediatric Cardiac Surgery: A Prospective Uncontrolled Cohort Study,” Critical Care, Vol. 11, No. 6, 2007, p. R127. doi:10.1186/cc6192
[33] C. R. Parikh, A. Jani, J. Mishra, et al., “Urine NGAL and IL-18 Are Predictive Biomarkers for Delayed Graft Function Following Kidney Transplantation,” American Journal of Transplantation, Vol. 6, No. 7, 2006, pp. 1639-1645. doi:10.1111/j.1600-6143.2006.01352.x
[34] T. L. Nickolas, M. J. O’Rourke, J. Yang, et al., “Sensitivity and Specificity of a Single Emergency Department Measurement of Urinary Neutrophil Gelatinase-Associated Lipocalin for Diagnosing Acute Kidney Injury,” Annals of Internal Medicine, Vol. 148, No. 11, 2008, pp. 810-819.
[35] T. Ichimura, J. V. Bonventre, V. Bailly, 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,” The Journal of Biological Chemistry, Vol. 273, No. 7, 1998, pp. 4135-4142. doi:10.1074/jbc.273.7.4135
[36] T. Ichimura, C. C. Hung, S. A. Yang, J. L. Stevens and J. V. Bonventre, “Kidney Injury Molecule-1: A Tissue and Urinary Biomarker for Nephrotoxicant-Induced Renal Injury,” American Journal of Physiology Renal Physiology, Vol. 286, No. 3, 2004, pp. F552-F563. doi:10.1152/ajprenal.00285.2002
[37] W. K. Han, A. Alinani, C. L. Wu, et al., “Human Kidney Injury Molecule-1 Is a Tissue and Urinary Tumor Marker of Renal Cell Carcinoma,” Journal of the American Society of Nephrology, Vol. 16, No. 4, 2005, pp. 1126-1134.
[38] W. K. Han, V. Bailly, R. Abichandani, R. Thadhani and J. V. Bonventre, “Kidney Injury Molecule-1 (KIM-1): A Novel Biomarker for Human Renal Proximal Tubule Injury,” Kidney International, Vol. 62, No. 1, 2002, pp. 237-244. doi:10.1046/j.1523-1755.2002.00433.x
[39] W. K. Han, S. S. Waikar, A. Johnson, et al., “Urinary Biomarkers in the Early Diagnosis of Acute Kidney Injury,” Kidney International, Vol. 73, No. 7, 2008, pp. 863-869. doi:10.1038/sj.ki.5002715
[40] M. M. van Timmeren, V. S. Vaidya, R. M. van Ree, et al., “High Urinary Excretion of Kidney Injury Molecule-1 Is an Independent Predictor of Graft Loss in Renal Transplant Recipients,” Transplantation, Vol. 84, No. 12, 2007, pp. 1625-1630. doi:10.1097/01.tp.0000295982.78039.ef
[41] W. K. Han, V. Bailly, R. Abichandani, R. Thadhani and J. V. Bonventre, “Kidney Injury Molecule-1 (KIM-1): A Novel Biomarker for Human Renal Proximal Tubule Injury,” Kidney International, Vol. 62, No. 1, 2002, pp. 237-244. doi:10.1046/j.1523-1755.2002.00433.x
[42] M. H. Rosner, “Urinary Biomarkers for the Detection of Renal Injury,” Advances in Clinical Chemistry, Vol. 49, 2009, pp. 73-97. doi:10.1016/S0065-2423(09)49004-8
[43] C. R. Parikh, A. Jani, V. Y. Melnikov, S. Faubel and C. L. Edelstein, “Urinary Interleukin-18 Is a Marker of Human Acute Tubular Necrosis,” American Journal of Kidney Diseases, Vol. 43, No. 3, 2004, pp. 405-414. doi:10.1053/j.ajkd.2003.10.040
[44] C. R. Parikh, E. Abraham, M. Ancukiewicz and C. L. Edelstein, “Urine IL-18 Is an Early Diagnostic Marker for Acute Kidney Injury and Predicts Mortality in the Intensive Care Unit,” Journal of the American Society of Nephrology, Vol. 16, No. 10, 2005, pp. 3046-3052. doi:10.1681/ASN.2005030236
[45] C. R. Parikh, J. Mishra, H. Thiessen-Philbrook, et al., “Urinary IL-18 Is an Early Predictive Biomarker of Acute Kidney Injury after Cardiac Surgery,” Kidney Interna- tional, Vol. 70, No. 1, 2006, pp. 199-203. doi:10.1038/sj.ki.5001527
[46] E. Coll, A. Botey, L. Alvarez, et al., “Serum Cystatin C as a New Marker for Noninvasive Estimation of Glomerular Filtration Rate and as a Marker for Early Renal Impairment,” American Journal of Kidney Diseases, Vol. 36, No. 1, 2000, pp. 29-34. doi:10.1053/ajkd.2000.8237
[47] V. R. Dharnidharka, C. Kwon and G. Stevens, “Serum Cystatin C Is Superior to Serum Creatinine as a Marker of Kidney Function: A Meta-Analysis,” American Journal of Kidney Diseases, Vol. 40, No. 2, 2002, pp. 221-226. doi:10.1053/ajkd.2002.34487
[48] S. Song, M. Meyer, T. R. Turk, et al., “Serum Cystatin C in Mouse Models: A Reliable and Precise Marker for Renal Function and Superior to Serum Creatinine,” Nephrology, Dialysis, Transplantation, Vol. 24, No. 4, 2009, pp. 1157-1161. doi:10.1093/ndt/gfn626
[49] S. Herget-Rosenthal, G. Marggraf, J. Husing, et al., “Early Detection of Acute Renal Failure by Serum Cystatin C,” Kidney International, Vol. 66, No. 3, 2004, pp. 1115-1122. doi:10.1111/j.1523-1755.2004.00861.x
[50] M. G. Shlipak, M. J. Sarnak, R. Katz, et al., “Cystatin C and the Risk of Death and Cardiovascular Events among Elderly Persons,” The New England Journal of Medicine, Vol. 352, No. 20, 2005, pp. 2049-2060. doi:10.1056/NEJMoa043161
[51] M. J. Sarnak, R. Katz, C. O. Stehman-Breen, et al., “Cystatin C Concentration as a Risk Factor for Heart Failure in Older Adults,” Annals of Internal Medicine, Vol. 142, No. 7, 2005, pp. 497-505.
[52] M. G. Shlipak, L. F. Fried, C. Crump, et al., “Cardiovascular Disease Risk Status in Elderly Persons with Renal Insufficiency,” Kidney International, Vol. 62, No. 3, 2002, pp. 997-1004. doi:10.1046/j.1523-1755.2002.00522.x
[53] M. G. Shlipak, R. Katz, M. J. Sarnak, et al., “Cystatin C and Prognosis for Cardiovascular and Kidney Outcomes in Elderly Persons without Chronic Kidney Disease,” Annals of Internal Medicine, Vol. 145, No. 4, 2006, pp. 237-246.
[54] J. L. Koyner, M. R. Bennett, E. M. Worcester, et al., “Urinary Cystatin C as an Early Biomarker of Acute Kidney Injury Following Adult Cardiothoracic Surgery,” Kidney International, Vol. 74, No. 8, 2008, pp. 1059-1069. doi:10.1038/ki.2008.341
[55] S. Herget-Rosenthal, D. Poppen, J. Husing, et al., “Prognostic Value of Tubular Proteinuria and Enzymuria in Nonoliguric Acute Tubular Necrosis,” Clinical Chemistry, Vol. 50, No. 3, 2004, pp. 552-558. doi:10.1373/clinchem.2003.027763
[56] S. Herget-Rosenthal, S. Trabold, F. Pietruck, M. Holt- mann, T. Philipp and A. Kribben, “Cystatin C: Efficacy as Screening Test for Reduced Glomerular Filtration Rate,” American Journal of Nephrology, Vol. 20, No. 2, 2000, pp. 97-102. doi:10.1159/000013564
[57] L. A. Inker, C. H. Schmid, H. Tighiouart, et al., “Estimating Glomerular Filtration Rate from Serum Creatinine and Cystatin C,” The New England Journal of Medicine, Vol. 367, No. 1, 2012, pp. 20-29. doi:10.1056/NEJMoa1114248
[58] C. R. Parikh, J. Mishra, H. Thiessen-Philbrook, et al., “Urinary IL-18 Is an Early Predictive Biomarker of Acute Kidney Injury after Cardiac Surgery,” Kidney International, Vol. 70, No. 1, 2006, pp. 199-203. doi:10.1038/sj.ki.5001527
[59] D. R. McIlroy, G. Wagener and H. T. Lee, “Biomarkers of Acute Kidney Injury: An Evolving Domain,” Anesthesiology, Vol. 112, No. 4, 2010, pp. 998-1004. doi:10.1097/ALN.0b013e3181cded3f
[60] S. M. Bagshaw, D. N. Cruz, R. T. Gibney and C. Ronco, “A Proposed Algorithm for Initiation of Renal Replacement Therapy in Adult Critically Ill Patients,” Critical Care, Vol. 13, No. 6, 2009, p. 317. doi:10.1186/cc8037
[61] N. Lameire, “Pathophysiology of Acute Renal Failure in Sepsis,” Acta Clinica Belgica, Vol. 59, No. 4, 2004, pp. 199-208.
[62] N. Lameire, W. Van Biesen and R. Vanholder, “Acute Renal Failure,” Lancet, Vol. 380, No. 9857, 2012, p. 1904.
[63] J. A. Foland, J. D. Fortenberry, B. L. Warshaw, et al., “Fluid Overload before Con-tinuous Hemofiltration and Survival in Critically Ill Children: A Retrospective Analysis,” Critical Care Medicine, Vol. 32, No. 8, 2004, pp. 1771-1776. doi:10.1097/01.CCM.0000132897.52737.49
[64] P. Bent, H. K. Tan, R. Bellomo, et al., “Early and Intensive Continuous Hemofiltration for Severe Renal Failure after Cardiac Surgery,” The Annals of Thoracic Surgery, Vol. 71, No. 3, 2001, pp. 832-837. doi:10.1016/S0003-4975(00)02177-9
[65] R. P. Dellinger, J. M. Carlet, H. Masur, et al., “Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,” Critical Care Medicine, Vol. 32, No. 3, 2004, pp. 858-873. doi:10.1097/01.CCM.0000117317.18092.E4
[66] M. Bell, E. Liljestam, F. Granath, J. Fryckstedt, A. Ekbom and C. R. Martling, “Optimal Follow-Up Time after Continuous Renal Replacement Therapy in Actual Renal Failure Patients Stratified with the RIFLE Criteria,” Nephrology, Dialysis, Transplantation, Vol. 20, No. 2, 2005, pp. 354-360. doi:10.1093/ndt/gfh581
[67] C. C. Shiao, V. C. Wu, W. Y. Li, et al., “Late Initiation of Renal Replacement Therapy Is Associated with Worse Outcomes in Acute Kidney Injury after Major Abdominal Surgery,” Critical Care, Vol. 13, No. 5, 2009, p. R171. doi:10.1186/cc8147
[68] V. S. Vaidya, S. S. Waikar, M. A. Ferguson, et al., “Urinary Biomarkers for Sensitive and Specific Detection of Acute Kidney Injury in Humans,” Clinical and Translational Science, Vol. 1, No. 3, 2008, pp. 200-208. doi:10.1111/j.1752-8062.2008.00053.x
[69] D. N. Cruz, H. R. de Geus and S. M. Bagshaw, “Biomarker Strategies to Predict Need for Renal Replacement Therapy in Acute Kidney Injury,” Seminars in Dialysis, Vol. 24, No. 2, 2011, pp. 124-131. doi:10.1111/j.1525-139X.2011.00830.x

  
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