Metabolomic and biochemical characterization of a new model of the transition of acute kidney injury to chronic kidney disease induced by folic acid

Marlene Marisol Perales-Quintana, Alma L. Saucedo, Juan Ricardo Lucio-Gutiérrez, Noemí Waksman, Gabriela Alarcon-Galvan, Gustavo Govea-Torres, Concepcion Sanchez-Martinez, Edelmiro Pérez-Rodríguez, Francisco J. Guzman-De La Garza, Paula Cordero-Pérez

Research output: Contribution to journalArticle

Abstract

Background: Renal diseases represent a major public health problem. The demonstration that maladaptive repair of acute kidney injury (AKI) can lead to the development of chronic kidney disease (CKD) and end-stage renal disease has generated interest in studying the pathophysiological pathways involved. Animal models of AKI-CKD transition represent important tools to study this pathology. We hypothesized that the administration of multiple doses of folic acid (FA) would lead to a progressive loss of renal function that could be characterized through biochemical parameters, histological classification and nuclear magnetic resonance (NMR) profiling. Methods: Wistar rats were divided into groups: the control group received a daily intraperitoneal (I.P.) injection of double-distilled water, the experimental group received a daily I.P. injection of FA (250 mg kg body weight-1). Disease was classified according to blood urea nitrogen level: mild (40-80 mg dL-1), moderate (100-200 mg dL-1) and severe (>200 mg dL-1). We analyzed through biochemical parameters, histological classification and NMR profiling. Results: Biochemical markers, pro-inflammatory cytokines and kidney injury biomarkers differed significantly (P < 0.05) between control and experimental groups. Histology revealed that as damage progressed, the degree of tubular injury increased, and the inflammatory infiltrate was more evident. NMR metabolomics and chemometrics revealed differences in urinary metabolites associated with CKD progression. The main physiological pathways affected were those involved in energy production and amino-acid metabolism, together with organic osmolytes. These data suggest that multiple administrations of FA induce a reproducible model of the induction of CKD. This model could help to evaluate new strategies for nephroprotection that could be applied in the clinic.

Original languageEnglish
Article numbere7113
JournalPeerJ
Volume7
DOIs
Publication statusPublished - 2019

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Metabolomics
metabolomics
kidney diseases
Chronic Renal Insufficiency
Folic Acid
Acute Kidney Injury
folic acid
kidneys
Magnetic Resonance Spectroscopy
Intraperitoneal Injections
Kidney
nuclear magnetic resonance spectroscopy
Biomarkers
intraperitoneal injection
Nuclear magnetic resonance
Control Groups
Blood Urea Nitrogen
biomarkers
Wounds and Injuries
Chronic Kidney Failure

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Perales-Quintana, M. M., Saucedo, A. L., Lucio-Gutiérrez, J. R., Waksman, N., Alarcon-Galvan, G., Govea-Torres, G., ... Cordero-Pérez, P. (2019). Metabolomic and biochemical characterization of a new model of the transition of acute kidney injury to chronic kidney disease induced by folic acid. PeerJ, 7, [e7113]. https://doi.org/10.7717/peerj.7113
Perales-Quintana, Marlene Marisol ; Saucedo, Alma L. ; Lucio-Gutiérrez, Juan Ricardo ; Waksman, Noemí ; Alarcon-Galvan, Gabriela ; Govea-Torres, Gustavo ; Sanchez-Martinez, Concepcion ; Pérez-Rodríguez, Edelmiro ; Guzman-De La Garza, Francisco J. ; Cordero-Pérez, Paula. / Metabolomic and biochemical characterization of a new model of the transition of acute kidney injury to chronic kidney disease induced by folic acid. In: PeerJ. 2019 ; Vol. 7.
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abstract = "Background: Renal diseases represent a major public health problem. The demonstration that maladaptive repair of acute kidney injury (AKI) can lead to the development of chronic kidney disease (CKD) and end-stage renal disease has generated interest in studying the pathophysiological pathways involved. Animal models of AKI-CKD transition represent important tools to study this pathology. We hypothesized that the administration of multiple doses of folic acid (FA) would lead to a progressive loss of renal function that could be characterized through biochemical parameters, histological classification and nuclear magnetic resonance (NMR) profiling. Methods: Wistar rats were divided into groups: the control group received a daily intraperitoneal (I.P.) injection of double-distilled water, the experimental group received a daily I.P. injection of FA (250 mg kg body weight-1). Disease was classified according to blood urea nitrogen level: mild (40-80 mg dL-1), moderate (100-200 mg dL-1) and severe (>200 mg dL-1). We analyzed through biochemical parameters, histological classification and NMR profiling. Results: Biochemical markers, pro-inflammatory cytokines and kidney injury biomarkers differed significantly (P < 0.05) between control and experimental groups. Histology revealed that as damage progressed, the degree of tubular injury increased, and the inflammatory infiltrate was more evident. NMR metabolomics and chemometrics revealed differences in urinary metabolites associated with CKD progression. The main physiological pathways affected were those involved in energy production and amino-acid metabolism, together with organic osmolytes. These data suggest that multiple administrations of FA induce a reproducible model of the induction of CKD. This model could help to evaluate new strategies for nephroprotection that could be applied in the clinic.",
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Perales-Quintana, MM, Saucedo, AL, Lucio-Gutiérrez, JR, Waksman, N, Alarcon-Galvan, G, Govea-Torres, G, Sanchez-Martinez, C, Pérez-Rodríguez, E, Guzman-De La Garza, FJ & Cordero-Pérez, P 2019, 'Metabolomic and biochemical characterization of a new model of the transition of acute kidney injury to chronic kidney disease induced by folic acid', PeerJ, vol. 7, e7113. https://doi.org/10.7717/peerj.7113

Metabolomic and biochemical characterization of a new model of the transition of acute kidney injury to chronic kidney disease induced by folic acid. / Perales-Quintana, Marlene Marisol; Saucedo, Alma L.; Lucio-Gutiérrez, Juan Ricardo; Waksman, Noemí; Alarcon-Galvan, Gabriela; Govea-Torres, Gustavo; Sanchez-Martinez, Concepcion; Pérez-Rodríguez, Edelmiro; Guzman-De La Garza, Francisco J.; Cordero-Pérez, Paula.

In: PeerJ, Vol. 7, e7113, 2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Metabolomic and biochemical characterization of a new model of the transition of acute kidney injury to chronic kidney disease induced by folic acid

AU - Perales-Quintana, Marlene Marisol

AU - Saucedo, Alma L.

AU - Lucio-Gutiérrez, Juan Ricardo

AU - Waksman, Noemí

AU - Alarcon-Galvan, Gabriela

AU - Govea-Torres, Gustavo

AU - Sanchez-Martinez, Concepcion

AU - Pérez-Rodríguez, Edelmiro

AU - Guzman-De La Garza, Francisco J.

AU - Cordero-Pérez, Paula

PY - 2019

Y1 - 2019

N2 - Background: Renal diseases represent a major public health problem. The demonstration that maladaptive repair of acute kidney injury (AKI) can lead to the development of chronic kidney disease (CKD) and end-stage renal disease has generated interest in studying the pathophysiological pathways involved. Animal models of AKI-CKD transition represent important tools to study this pathology. We hypothesized that the administration of multiple doses of folic acid (FA) would lead to a progressive loss of renal function that could be characterized through biochemical parameters, histological classification and nuclear magnetic resonance (NMR) profiling. Methods: Wistar rats were divided into groups: the control group received a daily intraperitoneal (I.P.) injection of double-distilled water, the experimental group received a daily I.P. injection of FA (250 mg kg body weight-1). Disease was classified according to blood urea nitrogen level: mild (40-80 mg dL-1), moderate (100-200 mg dL-1) and severe (>200 mg dL-1). We analyzed through biochemical parameters, histological classification and NMR profiling. Results: Biochemical markers, pro-inflammatory cytokines and kidney injury biomarkers differed significantly (P < 0.05) between control and experimental groups. Histology revealed that as damage progressed, the degree of tubular injury increased, and the inflammatory infiltrate was more evident. NMR metabolomics and chemometrics revealed differences in urinary metabolites associated with CKD progression. The main physiological pathways affected were those involved in energy production and amino-acid metabolism, together with organic osmolytes. These data suggest that multiple administrations of FA induce a reproducible model of the induction of CKD. This model could help to evaluate new strategies for nephroprotection that could be applied in the clinic.

AB - Background: Renal diseases represent a major public health problem. The demonstration that maladaptive repair of acute kidney injury (AKI) can lead to the development of chronic kidney disease (CKD) and end-stage renal disease has generated interest in studying the pathophysiological pathways involved. Animal models of AKI-CKD transition represent important tools to study this pathology. We hypothesized that the administration of multiple doses of folic acid (FA) would lead to a progressive loss of renal function that could be characterized through biochemical parameters, histological classification and nuclear magnetic resonance (NMR) profiling. Methods: Wistar rats were divided into groups: the control group received a daily intraperitoneal (I.P.) injection of double-distilled water, the experimental group received a daily I.P. injection of FA (250 mg kg body weight-1). Disease was classified according to blood urea nitrogen level: mild (40-80 mg dL-1), moderate (100-200 mg dL-1) and severe (>200 mg dL-1). We analyzed through biochemical parameters, histological classification and NMR profiling. Results: Biochemical markers, pro-inflammatory cytokines and kidney injury biomarkers differed significantly (P < 0.05) between control and experimental groups. Histology revealed that as damage progressed, the degree of tubular injury increased, and the inflammatory infiltrate was more evident. NMR metabolomics and chemometrics revealed differences in urinary metabolites associated with CKD progression. The main physiological pathways affected were those involved in energy production and amino-acid metabolism, together with organic osmolytes. These data suggest that multiple administrations of FA induce a reproducible model of the induction of CKD. This model could help to evaluate new strategies for nephroprotection that could be applied in the clinic.

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