Munsoor A Hanifa1,2,3, Martin Skott4, Raluca G Maltesen2, Bodil S Rasmussen2,3, Søren Nielsen5, Jørgen Frøkiær6, Troels Ring7,8, Reinhard Wimmer9. 1. Department of Chemistry and Bioscience, Aalborg University, Fredrik Bajers Vej 7H, 9220, Aalborg, Denmark. 2. Department of Anaesthesia and Intensive Care Medicine, Aalborg University Hospital, 9000, Aalborg, Denmark. 3. Department of Clinical Medicine, Aalborg University, 9000, Aalborg, Denmark. 4. Department of Urology, Aarhus University Hospital, 8250, Aarhus N, Denmark. 5. Meta-IQ, Fredensgade 9, 8000, Aarhus C, Denmark. 6. Department of Clinical Medicine, Aarhus University, 8200, Aarhus N, Denmark. 7. Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark. 8. Department of Critical Care Medicine, The Center for Critical Care Nephrology, University of Pittsburgh, Pittsburg, PA, 15261, USA. 9. Department of Chemistry and Bioscience, Aalborg University, Fredrik Bajers Vej 7H, 9220, Aalborg, Denmark. rw@bio.aau.dk.
Abstract
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.
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.
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