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Hypoxia precedes proteinuria in mice with diabetic nephropathy
Author(s) -
Franzen Stephanie,
Pihl Liselotte,
Gustafsson Håkan,
Palm Fredrik
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1218.5
Subject(s) - proteinuria , diabetic nephropathy , renal function , hypoxia (environmental) , kidney , diabetes mellitus , medicine , kidney disease , endocrinology , nephropathy , chemistry , oxygen , organic chemistry
Kidney hypoxia has been suggested to be a unifying mechanism for the progression of diabetic nephropathy and chronic kidney disease. Though, for hypoxia to be the actual causing mechanism it needs to be present before other functional alterations. Proteinuria is a commonly used biomarker for kidney damage and therefore, we investigated if hypoxia can be seen as early as proteinuria in mice with diabetic nephropathy. Kidney cortex oxygen tensions were analyzed using a minimally invasive electron paramagnetic resonance oximetry technique with implanted oxygen sensing probes. Measurements were made before and up to 15 days after the induction of type‐1 diabetes in male mice and compared to corresponding controls. After 16 days, proteinuria and conscious glomerular filtration rates were analyzed in order to investigate the progressive relationship between kidney hypoxia and disease progression. Diabetic mice developed pronounced intrarenal hypoxia three days after the induction of diabetes, which maintained throughout the study. On day 16, diabetic mice had increased glomerular filtration rate but normal proteinuria. In conclusion, kidney hypoxia precedes proteinuria and could therefore be considered a promising biomarker for the progression if kidney damage. Support or Funding Information All experiments was conducted according to the FASEB Statement of Principles. The study was supported and funded by the Swedish Research Council, the Swedish Diabetes Foundation and the Swedish Heart Lung Foundation.