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

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  • Munsoor A. Hanifa, Aalborg University
  • ,
  • Martin Skott
  • Raluca G. Maltesen, Aalborg University
  • ,
  • Bodil S. Rasmussen, Department of Anaesthesia and Intensive Care Medicine, Aalborg University
  • ,
  • Søren Nielsen, Meta-IQ
  • ,
  • Jørgen Frøkiær
  • Troels Ring, University of Pittsburgh
  • ,
  • Reinhard Wimmer, Aalborg University

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.

Original languageEnglish
Article number112
JournalMetabolomics
Volume15
Issue8
ISSN1573-3882
DOIs
Publication statusPublished - Aug 2019

    Research areas

  • 5/6 Nephrectomy, Allantoin, Chronic kidney disease, Metabolomics, Oxidative stress

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