Metabolomic characterization of renal ischemia and reperfusion in a swine model

详细信息    查看全文

• 作者：Pamella Araujo Malagrino^a ; ^{pamalagrino@gmail.com.br" class="auth_mail" title="E-mail the corresponding author} ; ; Gabriela Venturini^a ; Patrí ; cia Schneider Yogi^a ; Rafael Dariolli^a ; Kallyandra Padilha^a ; Bianca Kiers^a ; Tamiris Carneiro Gois^a ; Joaquim Maurí ; cio Motta-Leal-Filho^b ; Celso Kiyochi Takimura^a ; Adriana Castello Costa Girardi^a ; Francisco Cé ; sar Carnevale^c ; Rafael Canevarolo^d ; Denise Maria Avancini Costa Malheiros^e ; Ana Carolina de Mattos Zeri^d ; José ; Eduardo Krieger^a ; Alexandre Costa Pereira^a
• 关键词：Acute kidney injury ; Kidney disease ; Kidney biomarkers ; Metabolomics ; Huntingtin ; Balloon-catheter
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：1 July 2016
• 年：2016
• 卷：156
• 期：Complete
• 页码：57-67
• 全文大小：2078 K

文摘

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 ¹H 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 NFκB, leptin, INF-γ 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.