Metabolomic characterization of renal ischemia and reperfusion in a swine model

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 bio...

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Bibliographic Details
Published in:Life sciences (1973) 2016-07, Vol.156, p.57-67
Main Authors: Malagrino, Pamella Araujo, Venturini, Gabriela, Yogi, Patrícia Schneider, Dariolli, Rafael, Padilha, Kallyandra, Kiers, Bianca, Gois, Tamiris Carneiro, Motta-Leal-Filho, Joaquim Maurício, Takimura, Celso Kiyochi, Girardi, Adriana Castello Costa, Carnevale, Francisco César, Canevarolo, Rafael, Malheiros, Denise Maria Avancini Costa, de Mattos Zeri, Ana Carolina, Krieger, José Eduardo, Pereira, Alexandre Costa
Format: Article
Language:English
Subjects:
Acute kidney injury
Animals
Balloon-catheter
Biomarkers - blood
Biomarkers - urine
Creatinine - blood
Disease Models, Animal
Huntingtin
Kidney - blood supply
Kidney - metabolism
Kidney - pathology
Kidney biomarkers
Kidney disease
Metabolomics
Metabolomics - methods
Reperfusion Injury - blood
Reperfusion Injury - metabolism
Reperfusion Injury - urine
Sus scrofa
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Summary: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 600MHz. 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.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2016.05.025