. Author manuscript; available in PMC: 2021 Sep 1.

Published in final edited form as: Kidney Int. 2020 Apr 26;98(3):579–589. doi: 10.1016/j.kint.2020.02.041

Table 1.

Evidence of renal hypoxia in experimental models of diabetes as shown by multiple measurement techniques

Ref.	Animal	Method	Measurement	Outcome	Observations
52	Rat T1D	Sealed chamber + oxygen probe	Reduction of O₂ percentage in a sealed chamber after a given time	Oxygen consumption (QO₂)	QO2 of renal cells of diabetic rats is higher than that of the corresponding cells of nondiabetic controls
53	Rat T1D	Sealed chamber + oxygen probe		Oxygen consumption (QO₂)

52	Rat T1D	Ouabain - inhibition	Inhibition of sodium reabsorption by blockade of the basolateral sodium extrusion by the NKA-pump	NKA (in)dependent QO₂	NKA-dependent QO2 of renal cells of diabetic rats is higher than that of healthy controls
53	Rat T1D	Ouabain - inhibition		NKA (in)dependent QO₂

53	Rat T1D	Micro-electrodes	Micro-electrodes placed at various depths of renal tissue	Tissue oxygen tension (PO₂)	PO2 of the renal parenchyma of diabetic rats is decreased in comparison with healthy control parenchyma, predominantly in the medullar region
54	Rat T1D
55	Rat T1D
49	Rat T1D
56

54	Rat T1D	BOLD-MRI	The level of deoxyhemoglobin, which affects the relaxation rate of water molecules in a magnetic field, as a measure of arterial oxygenation	Transverse relaxation rate (R2*) as an indicator of PO₂, assuming equilibrium between renal tissue and arterial oxygenation	PO2 of the renal parenchyma of diabetic rats is decreased when compared with healthy controls, as early as 2 d after the induction of diabetes
57	Rat T1D	BOLD-MRI

58	Rat T1D	HIF- Immunostaining	Antibody binding to HIF-complexes	Histological visualization of the tissue reaction to (moderate) hypoxia	HIF immunostaining increases during 30 d after diabetes induction, but is no longer present after 90 d HIFs are present more strongly in the proximal tubules of diabetic mice than in healthy controls
59	Mouse T2D	HIF- Immunostaining	Antibody binding to HIF-complexes

58	Rat T1D	PIM- immunostaining	Pimonidazole binds to and undergoes reductions in hypoxic cells with PO₂ < 10mmHg	Histological visualization of tissue experiencing severe hypoxia	PIM immunostaining increases during 30 d after diabetes induction, but is no longer present after 90 d

BOLD-MRI: blood oxygen level dependent – magnetic resonance imaging, HIF: hypoxia-inducible facto, NKA: Na⁺-K⁺-ATPase, O₂: oxygen, PIM: pimonidazole adduct, PO₂: tissue partial pressure of oxygen, T1D: type 1 diabetes, T2D: type 2 diabetes, QO₂ : oxygen consumption.