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.
Bibliographical noteFunding Information:
This work was supported by National Council on Science and Technology–Conacyt (project 2017-01-5652). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
This work was supported by National Council on Science and Technology-Conacyt (project 2017-01-5652). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Copyright © 2019 Perales-Quintana et al.
Copyright 2019 Elsevier B.V., All rights reserved.
All Science Journal Classification (ASJC) codes
- General Neuroscience
- General Biochemistry,Genetics and Molecular Biology
- General Agricultural and Biological Sciences