Sodium Magnetic Resonance Imaging Shows Impairment of the Counter-current Multiplication System in Diabetic Mice Kidney

KEY POINTS: (23)Na MRI allows us to noninvasively assess sodium distribution. We propose the utility of (23)Na MRI for evaluating functional changes in diabetic kidney disease and not as a marker reflecting structural damage. (23)Na MRI may be an early marker for structures beyond the glomeruli, enabling prompt intervention with novel efficacious tubule-targeting therapies. BACKGROUND: Sodium magnetic resonance imaging can noninvasively assess sodium distribution, specifically sodium concentration in the countercurrent multiplication system in the kidney, which forms a sodium concentration gradient from the cortex to the medulla, enabling efficient water reabsorption. This study aimed to investigate whether sodium magnetic resonance imaging can detect changes in sodium concentrations under normal conditions in mice and in disease models, such as a mouse model with diabetes mellitus. METHODS: We performed sodium and proton nuclear magnetic resonance imaging using a 9.4-T vertical standard-bore superconducting magnet. RESULTS: A condition of deep anesthesia, with widened breath intervals, or furosemide administration in 6-week-old C57BL/6JJcl mice showed a decrease in both tissue sodium concentrations in the medulla and sodium concentration gradients from the cortex to the medulla. Furthermore, sodium magnetic resonance imaging revealed reductions in the sodium concentration in the medulla and in the gradient from the cortex to the medulla in BKS.Cg-Lepr(db)+/+ Lepr(db)/Jcl mice at very early type 2 diabetes mellitus stages compared with corresponding control BKS.Cg-m+/m+/Jcl mice. CONCLUSIONS: The kidneys of BKS.Cg-Lepr(db)+/+ Lepr(db)/Jcl mice aged 6 weeks showed impairments in the countercurrent multiplication system. We propose the utility of (23)Na MRI for evaluating functional changes in diabetic kidney disease and not as a marker that reflects structural damage. Thus, (23)Na MRI may be a potentially very early marker for structures beyond the glomerulus; this may prompt intervention with novel efficacious tubule-targeting therapies.