Metabolomic characterization of renal ischemia and reperfusion in a swine model

Autor(es):Mostrar menos -

Malagrino, Pamella Araujo ^[1] ; Venturini, Gabriela ^[1] ; Yogi, Patricia Schneider ^[1] ; Dariolli, Rafael ^[1] ; Padilha, Kallyandra ^[1] ; Kiers, Bianca ^[1] ; Gois, Tamiris Carneiro ^[1] ; Motta-Leal-Filho, Joaquim Mauricio ^[2] ; Takimura, Celso Kiyochi ^[1] ; Costa Girardi, Adriana Castello ^[1] ; Carnevale, Francisco Cesar ^[3] ; Canevarolo, Rafael ^[4] ; Avancini Costa Malheiros, Denise Maria ; de Mattos Zeri, Ana Carolina ^[4] ; Krieger, Jose Eduardo ^[1] ; Pereira, Alexandre Costa ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Lab Genet & Mol Cardiol, Inst Heart, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Sch Med, Intervent Radiol Unit, Dept Radiol, Heart Inst, Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Sch Med, Intervent Radiol Unit, Radiol Inst, Hosp Clin, Sao Paulo, SP - Brazil

^[4] LNBio, Biosci Natl Lab, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Life Sciences; v. 156, p. 57-67, JUL 1 2016.
• Citações Web of Science: 6

Resumo

Acute kidney injury (AKI) is a serious complication in hospitalized and transplanted patients, and is mainly caused by ischemia/reperfusion (I/R). However, the current diagnosis of AKI based on acute alterations in serum creatinine or urine output is late and unspecific. To identify new systemic biomarkers for AKI, we performed serum and urine metabolomic profile analyses during percutaneous unilateral renal I/R in a well-controlled swine model. For this, serial serum and urine samples obtained during the pre-ischemia, ischemia and reperfusion periods were analyzed by H-1 nuclear magnetic resonance at 600 MHz. Through the metabolic profiles over I/R, we identified eight serum metabolites that increased with ischemia and recovered to basal values after reperfusion, delineating the ischemic period. In addition, we identified 13 urinary metabolites that changed during the early reperfusion reflecting the ischemic kidney, being able to differentiate between pre-ischemia and post I/R periods. All selected metabolites are described in terms of disease pathophysiology (change of energetic pathway and oxidative stress), which suggest that these serum and urinary metabolites are candidate AKI biomarkers. Interestingly, the selected metabolites allowed us to identify, well described NF kappa B, leptin, INF-gamma and insulin pathways, and a new pathway (Huntingtin) that had not been previously implicated in renal I/R. Huntingtin showed different fragment patterns in ischemic versus non-ischemic kidneys. Therefore, the metabolomic profile found in renal I/R led to the identification of candidate disease biomarkers and a new pathway associated with renal injury. (C) 2016 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 12/05447-0 - Herdabilidade de fenótipos metabólicos em uma população brasileira
• Beneficiário: Kallyandra Padilha
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 13/13526-0 - Identificação de marcadores proteicos de alterações de Shear Stress
• Beneficiário: Gabriela Venturini da Silva
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 13/17368-0 - Genômica cardiovascular: mechanismos & novas terapias - CVGen mech2ther
• Beneficiário: José Eduardo Krieger
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 12/12042-7 - Herdabilidade de fenótipos metabólicos em uma população brasileira
• Beneficiário: Alexandre da Costa Pereira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/04344-0 - Identificação de proteínas nitradas com potencial diagnóstico e prognóstico em doenças renais isquêmicas
• Beneficiário: Pamella Araujo Malagrino
• Modalidade de apoio: Bolsas no Brasil - Mestrado