Pronounced kidney hypoxia precedes albuminuria in type 1 diabetic mice

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 in order to be the causal mechanism. In order to establish if 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 to normoglycemic controls. On day 16, urinary albumin excretions and conscious glomerular filtration rates were determined in order to define the temporal relationship between intrarenal hypoxia and disease development. Diabetic mice developed pronounced intrarenal hypoxia three 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.
The status of this article was previous Manuscript.Funding agencies: Swedish Research Council; Swedish Heart Lung Foundation; Swedish Diabetes Foundation