title: Proteome analysis of acute kidney injury - Discovery of new predominantly renal candidates for biomarker of kidney disease.
abstract: The main bottleneck in studies aiming to identify novel biomarkers in acute kidney injury (AKI) has been the identification of markers that are organ and process specific. Here, we have used different tissues from a controlled porcine renal ischemia/reperfusion (I/R) model to identify new, predominantly renal biomarker candidates for kidney disease. Urine and serum samples were analyzed in pre-ischemia, ischemia (60min) and 4, 11 and 16h post-reperfusion, and renal cortex samples after 24h of reperfusion. Peptides were analyzed on the Q-Exactive™. In renal cortex proteome, we observed an increase in the synthesis of proteins in the ischemic kidney compared to the contralateral, highlighted by transcription factors and epithelial adherens junction proteins. Intersecting the set of proteins up- or down-regulated in the ischemic tissue with both serum and urine proteomes, we identified 6 proteins in the serum that may provide a set of targets for kidney injury. Additionally, we identified 49, being 4 predominantly renal, proteins in urine. As prove of concept, we validated one of the identified biomarkers, dipeptidyl peptidase IV, in a set of patients with diabetic nephropathy. In conclusion, we identified 55 systemic proteins, some of them predominantly renal, candidates for biomarkers of renal disease.
  
  
  
  The main bottleneck in studies aiming to identify novel biomarkers in acute kidney injury (AKI) has been the identification of markers that are predominantly renal. In fact, putative biomarkers for this condition have also been identified in a number of other clinical scenarios, such as cardiovascular diseases, chronic kidney failure or in patients being treated in intensive care units from a number of conditions. Here we propose a comprehensive, sequential screening procedure able to identify and validate potential biomarkers for kidney disease, using kidney ischemia/reperfusion as a paradigm for a kidney pathological event.
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of São Paulo Medical School, São Paulo, SP, Brazil. Electronic address: pamalagrino@gmail.com.
authors.forename: Pamella Araujo
authors.initials: PA
authors.lastname: Malagrino
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of São Paulo Medical School, São Paulo, SP, Brazil.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Venturini
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of São Paulo Medical School, São Paulo, SP, Brazil.
authors.forename: Patrícia Schneider
authors.initials: PS
authors.lastname: Yogi
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of São Paulo Medical School, São Paulo, SP, Brazil.
authors.forename: Rafael
authors.initials: R
authors.lastname: Dariolli
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of São Paulo Medical School, São Paulo, SP, Brazil.
authors.forename: Kallyandra
authors.initials: K
authors.lastname: Padilha
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of São Paulo Medical School, São Paulo, SP, Brazil.
authors.forename: Bianca
authors.initials: B
authors.lastname: Kiers
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of São Paulo Medical School, São Paulo, SP, Brazil.
authors.forename: Tamiris Carneiro
authors.initials: TC
authors.lastname: Gois
authors.affiliation: Grupo Fleury, São Paulo, SP, Brazil.
authors.forename: Karina Helena Morais
authors.initials: KH
authors.lastname: Cardozo
authors.affiliation: Grupo Fleury, São Paulo, SP, Brazil.
authors.forename: Valdemir Melechco
authors.initials: VM
authors.lastname: Carvalho
authors.affiliation: Grupo Fleury, São Paulo, SP, Brazil.
authors.forename: Jéssica Silva
authors.initials: JS
authors.lastname: Salgueiro
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of São Paulo Medical School, São Paulo, SP, Brazil.
authors.forename: Adriana Castello Costa
authors.initials: AC
authors.lastname: Girardi
authors.affiliation: Renal Division, Department of Clinical Medicine, Faculty of Medicine, University of São Paulo Medical School, São Paulo, SP, Brazil.
authors.forename: Silvia Maria de Oliveira
authors.initials: SM
authors.lastname: Titan
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of São Paulo Medical School, São Paulo, SP, Brazil.
authors.forename: José Eduardo
authors.initials: JE
authors.lastname: Krieger
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of São Paulo Medical School, São Paulo, SP, Brazil. Electronic address: alexander.pereira@incor.usp.br.
authors.forename: Alexandre Costa
authors.initials: AC
authors.lastname: Pereira
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000175:diagnosis*; D022005:Adherens Junctions / Q000737:chemistry; D000818:Animals; D015415:Biomarkers / Q000097:blood; D005786:Gene Expression Regulation; D007672:Kidney Cortex / Q000737:chemistry; D011506:Proteins / Q000032:analysis; D020543:Proteome / Q000032:analysis*; D015427:Reperfusion Injury / Q000097:blood / Q000175:diagnosis; D013552:Swine; D014157:Transcription Factors
chemical_list: D015415:Biomarkers; D011506:Proteins; D020543:Proteome; D014157:Transcription Factors
keywords: Acute kidney injury; Biomarkers; DPPIV; Kidney disease; Proteome; Renal ischemia