title: Pronounced kidney hypoxia precedes albuminuria in type 1 diabetic mice.
abstract: Intrarenal tissue hypoxia has been proposed as a unifying mechanism for the development of chronic kidney disease, including diabetic nephropathy. However, hypoxia has to be present before the onset of kidney disease to be the causal mechanism. To establish whether hypoxia precedes the onset of diabetic nephropathy, we implemented a minimally invasive electron paramagnetic resonance oximetry technique using implanted oxygen sensing probes for repetitive measurements of in vivo kidney tissue oxygen tensions in mice. Kidney cortex oxygen tensions were measured before and up to 15 days after the induction of insulinopenic diabetes in male mice and compared with normoglycemic controls. On day 16, urinary albumin excretions and conscious glomerular filtration rates were determined to define the temporal relationship between intrarenal hypoxia and disease development. Diabetic mice developed pronounced intrarenal hypoxia 3 days after the induction of diabetes, which persisted throughout the study period. On day 16, diabetic mice had glomerular hyperfiltration, but normal urinary albumin excretion. In conclusion, intrarenal tissue hypoxia in diabetes precedes albuminuria thereby being a plausible cause for the onset and progression of diabetic nephropathy.
authors.affiliation: Department of Medical and Health Sciences, Linköping University, Linköping, Sweden; Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden; stephanie.franzen@liu.se.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Franzén
authors.affiliation: Department of Medical and Health Sciences, Linköping University, Linköping, Sweden;
authors.forename: Liselotte
authors.initials: L
authors.lastname: Pihl
authors.affiliation: EPR Center for the Study of Viable Systems, Department of Radiology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire;
authors.forename: Nadeem
authors.initials: N
authors.lastname: Khan
authors.affiliation: Department of Medical and Health Sciences, Linköping University, Linköping, Sweden; Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden; Department of Radiology Norrköping, Linköping University, Linköping, Sweden; and.
authors.forename: Håkan
authors.initials: H
authors.lastname: Gustafsson
authors.affiliation: Department of Medical and Health Sciences, Linköping University, Linköping, Sweden; Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden; Department of Medical Cell Biology, Integrative Physiology, Uppsala University, Uppsala, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Palm
mesh_terms: D000419:Albuminuria / Q000209:etiology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000209:etiology*; D018450:Disease Progression; D004578:Electron Spin Resonance Spectroscopy; D005919:Glomerular Filtration Rate; D000860:Hypoxia / Q000150:complications*; D007672:Kidney Cortex / Q000378:metabolism; D008297:Male; D051379:Mice; D010092:Oximetry
keywords: diabetic nephropathy; intrarenal hypoxia; kidney tissue oxygen tensions