Publication
Tissue, urine and blood metabolite signatures of chronic kidney disease in the 5/6 nephrectomy rat model.
Publisher:
Springer Science and Business Media LLC
Date:
08-2019
DOI:
10.1007/S11306-019-1569-3
Abstract: 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. Our aim was to characterize serum, urine and tissue (kidney, lung, heart, spleen and liver) metabolomics changes in a rat model of CKD. A total of 17 male Wistar rats underwent 5/6 nephrectomy, whilst 13 rats underwent sham operation. Urine s les were collected weekly, for 6 weeks blood was collected at weeks 0, 3 and 6 and tissue s les were collected at week 6. S les were analyzed on a nuclear magnetic resonance spectroscopy platform with multivariate and univariate data analysis. 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. 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.