Proteome analysis of acute kidney injury - Discovery of new predominantly renal candidates for biomarker of kidney disease

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Malagrino, Pamella Araujo ; Venturini, Gabriela ; Yogi, Patricia Schneider ; Dariolli, Rafael ; Padilha, Kallyandra ; Kiers, Bianca ; Gois, Tamiris Carneiro ; Morais Cardozo, Karina Helena ; Carvalho, Valdemir Melechco ; Salgueiro, Jessica Silva ; Costa Girardi, Adriana Castello ; de Oliveira Titan, Silvia Maria ; Krieger, Jose Eduardo ; Pereira, Alexandre Costa

• Document type: Journal article
• Source: JOURNAL OF PROTEOMICS; v. 151, p. 8-pg., 2017-01-16.

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 (60 min) and 4, 11 and 16 h post-reperfusion, and renal cortex samples after 24 h of reperfusion. Peptides were analyzed on the Q-Exactive (TM). 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. Biological significance: 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. (C) 2016 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 12/05447-0 - Heritability of metabolic phenotypes in a Brazilian population
• Grantee: Kallyandra Padilha
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 13/13526-0 - Identification of protein markers changed by shear stress
• Grantee: Gabriela Venturini da Silva
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 11/04344-0 - Identification of nitrated protein with disgnostic potencial and prognostic in desease ischemic kidney
• Grantee: Pamella Araujo Malagrino
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 13/17368-0 - Cardiovascular genomics: mechanisms & novel therapeutics - CVGen mech2ther
• Grantee: José Eduardo Krieger
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/12042-7 - Heritability of Metabolic Phenotypes in the Brazilian Population
• Grantee: Alexandre da Costa Pereira
• Support Opportunities: Regular Research Grants