Tissue, urine and blood metabolite signatures of chronic kidney disease in the 5/6 nephrectomy rat model

Introduction Progressive chronic kidney disease (CKD) is an important cause of morbidity and mortality. It has a long asymptomatic phase, where routine blood tests cannot identify early functional losses, and therefore identifying common mechanisms across the many etiologies is an important goal. Ob...

Full description

Saved in:
Bibliographic Details
Published in:Metabolomics 2019-08, Vol.15 (8), p.112-16, Article 112
Main Authors: Hanifa, Munsoor A., Skott, Martin, Maltesen, Raluca G., Rasmussen, Bodil S., Nielsen, Søren, Frøkiær, Jørgen, Ring, Troels, Wimmer, Reinhard
Format: Article
Language:English
Subjects:
Allantoin
Asparagine
Biochemistry
Biomedical and Life Sciences
Biomedicine
Blood
Cell Biology
Citric acid
Creatine
Developmental Biology
Dimethylglycine
Energy metabolism
Inositol
Kidney diseases
Life Sciences
Magnetic resonance spectroscopy
Metabolites
Metabolomics
Molecular Medicine
Morbidity
Nephrectomy
NMR
Nuclear magnetic resonance
Original Article
Oxidative stress
Rodents
Spleen
Statistical analysis
Trimethylamine
Urine
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Introduction Progressive chronic kidney disease (CKD) is an important cause of morbidity and mortality. It has a long asymptomatic phase, where routine blood tests cannot identify early functional losses, and therefore identifying common mechanisms across the many etiologies is an important goal. Objectives Our aim was to characterize serum, urine and tissue (kidney, lung, heart, spleen and liver) metabolomics changes in a rat model of CKD. Methods A total of 17 male Wistar rats underwent 5/6 nephrectomy, whilst 13 rats underwent sham operation. Urine samples were collected weekly, for 6 weeks; blood was collected at weeks 0, 3 and 6; and tissue samples were collected at week 6. Samples were analyzed on a nuclear magnetic resonance spectroscopy platform with multivariate and univariate data analysis. Results Changes in several metabolites were statistically significant. Allantoin was affected in all compartments. Renal asparagine, creatine, hippurate and trimethylamine were significantly different; in other tissues creatine, dimethylamine, dimethylglycine, trigonelline and trimethylamine were significant. Benzoate, citrate, dimethylglycine, fumarate, guanidinoacetate, malate, myo-inositol and oxoglutarate were altered in urine or serum. Conclusion Although the metabolic picture is complex, we suggest oxidative stress, the gut-kidney axis, acid–base balance, and energy metabolism as promising areas for future investigation.
ISSN:1573-3882
1573-3890
DOI:10.1007/s11306-019-1569-3