title: High altitude may alter oxygen availability and renal metabolism in diabetics as measured by hyperpolarized [1-(13)C]pyruvate magnetic resonance imaging.
abstract: The kidneys account for about 10% of the whole body oxygen consumption, whereas only 0.5% of the total body mass. It is known that intrarenal hypoxia is present in several diseases associated with development of kidney disease, including diabetes, and when renal blood flow is unaffected. The importance of deranged oxygen metabolism is further supported by deterioration of kidney function in patients with diabetes living at high altitude. Thus, we argue that reduced oxygen availability alters renal energy metabolism. Here, we introduce a novel magnetic resonance imaging (MRI) approach to monitor metabolic changes associated with diabetes and oxygen availability. Streptozotocin diabetic and control rats were given reduced, normal, or increased inspired oxygen in order to alter tissue oxygenation. The effects on kidney oxygen metabolism were studied using hyperpolarized [1-(13)C]pyruvate MRI. Reduced inspired oxygen did not alter renal metabolism in the control group. Reduced oxygen availability in the diabetic kidney altered energy metabolism by increasing lactate and alanine formation by 23% and 34%, respectively, whereas the bicarbonate flux was unchanged. Thus, the increased prevalence and severity of nephropathy in patients with diabetes at high altitudes may originate from the increased sensitivity toward inspired oxygen. This increased lactate production shifts the metabolic routs toward hypoxic pathways.
authors.affiliation: 1] MR Research Centre, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark [2] Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
authors.forename: Christoffer
authors.initials: C
authors.lastname: Laustsen
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Lycke
authors.affiliation: 1] Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden [2] Division of Drug Research, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden [3] Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Palm
authors.affiliation: 1] Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark [2] Department of Clinical Medicine, Aarhus University, Aarhus, Denmark [3] Danish Diabetes Academy, Aarhus University, Aarhus, Denmark.
authors.forename: Jakob A
authors.initials: JA
authors.lastname: Østergaard
authors.affiliation: Department of Biostatistics, Aarhus University, Aarhus, Denmark.
authors.forename: Bo M
authors.initials: BM
authors.lastname: Bibby
authors.affiliation: Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Rikke
authors.initials: R
authors.lastname: Nørregaard
authors.affiliation: 1] Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark [2] Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Allan
authors.initials: A
authors.lastname: Flyvbjerg
authors.affiliation: 1] MR Research Centre, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark [2] Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Pedersen
authors.affiliation: 1] Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark [2] GE Healthcare, Copenhagen, Denmark [3] Department of Electrical Engineering, Technical University of Denmark, Kgs Lyngby, Denmark.
authors.forename: Jan H
authors.initials: JH
authors.lastname: Ardenkjaer-Larsen
mesh_terms: D000409:Alanine / Q000378:metabolism; D000531:Altitude; D000532:Altitude Sickness / Q000150:complications / Q000378:metabolism; D000818:Animals; D001274:Atmospheric Pressure; D001639:Bicarbonates / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000150:complications / Q000378:metabolism; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D019344:Lactic Acid / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001639:Bicarbonates; D001786:Blood Glucose; D019344:Lactic Acid; D019289:Pyruvic Acid; D000409:Alanine; D010100:Oxygen