Proteomics for biomarker discovery in acute kidney injury.
Acute kidney injury (AKI), previously referred to as acute renal failure, represents a common and devastating problem in clinical medicine. Despite significant improvements in therapeutics, the mortality and morbidity associated with AKI remain high. A major reason for this is the lack of early markers for AKI, and hence an unacceptable delay in initiating therapy. Fortunately, the application of innovative technologies such as functional genomics and proteomics to human and animal models of AKI has uncovered several novel biomarkers and therapeutic targets. The most promising of these are chronicled in this review. These include the identification of biomarker panels in plasma (neutrophil gelatinase-associated lipocalin and cystatin C) and urine (neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, interleukin-18, cystatin C, alpha1-microglobulin, Fetuin-A, Gro-alpha, and meprin). It is likely that the AKI panels will be useful for timing the initial insult, and assessing the duration and severity of AKI. It is also probable that the AKI panels will distinguish between the various etiologies of AKI and predict clinical outcomes. It will be important in future studies to validate the sensitivity and specificity of these biomarker panels in clinical samples from large cohorts and from multiple clinical situations. Such studies will be facilitated markedly by the development of commercial tools for the reproducible measurement of biomarkers across different laboratories.
Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA. prasad.devarajan@cchmc.org
Prasad
P
Devarajan
D058186:Acute Kidney Injury / Q000175:diagnosis* / Q000378:metabolism; D000209:Acute-Phase Proteins / Q000032:analysis; D015415:Biomarkers / Q000032:analysis*; D020869:Gene Expression Profiling; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000032:analysis; D008562:Membrane Glycoproteins / Q000032:analysis; D040901:Proteomics / Q000379:methods*; D011518:Proto-Oncogene Proteins / Q000032:analysis; D011991:Receptors, Virus / Q000032:analysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000209:Acute-Phase Proteins; D015415:Biomarkers; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D011991:Receptors, Virus