Kidney Week

Abstract: SA-PO396

Hyperfiltration in Obese Diabetic BTBRob/ob Mice Can Be Measured Transcutaneously

Session Information

• Diabetic Kidney Disease: Basic - II
  November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 701 Diabetic Kidney Disease: Basic

Authors

• Hettler, Steffen Andreas, Universitat Heidelberg, Mannheim, Baden-Württemberg, Germany

Steffen Andreas Hettler,

• Pastene, Diego O., Universitat Heidelberg, Mannheim, Baden-Württemberg, Germany

Diego O. Pastene,

• Yard, Benito, Universitat Heidelberg, Mannheim, Baden-Württemberg, Germany

Benito Yard,

• Krämer, Bernhard K., Universitat Heidelberg, Mannheim, Baden-Württemberg, Germany

Bernhard K. Krämer,

Background

Transcutaneous assessment of glomerular filtration rate (tGFR) has only been validated in lean mice. At 24 weeks obese diabetic mice display vasodilation of the afferent glomerular arteriole and increased glomerular size, yet do not differ in tGFR values from lean mice. Hence, we questioned if hyperfiltration can be assessed transcutaneously in obese diabetic mice.

Methods

We measured tGFR and FITC-sinistrin plasma clearance simultaneously in obese diabetic BTBR^ob/ob and lean non-diabetic BTBR^wt/- mice at week 12. At week 24 we assessed tGFR again and used tissue clearing and light sheet microscopy to assess glomerular size and vasodilation of the afferent arteriole in mice that were perfused with an infrared fluorescent dye.

Results

While at week 12 tGFR significantly differed between the groups with a faster clearance in the diabetic BTBR^ob/ob mice (both t_1/2 of FITC-sinistrin (p=0.0081) and calculated GFR (p=0.0069)), no difference was found between diabetic and non-diabetic mice in tGFR at 24 weeks. In line with the increased tGFR, also FITC-sinistrin plasma clearance was significantly increased at week 12 in BTBR^ob/ob mice (p=0.0140). At week 24 the diameter of afferent arterioles were significantly larger in BTBR^ob/ob vs. BTBR^wt/- mice (p=0.0007) and associated with increased glomerular size (p=0.0136).

Conclusion

The results indicate that hyperfiltration can be detected in diabetic mice by tGFR early in the course of disease. In keeping with the findings that no difference in tGFR was found at 24 weeks despite morphological parameters that indicate hyperfiltration, our data might be explained by progressive loss of functional nephrons later in the disease. Accordingly, this will reduce total glomerular filtration while increased glomerular pressure and dilation of the afferent glomerular arterioles (and presumably single nephron glomerular hyperfiltration) remain in nonsclerotic nephrons.

Funding

• Government Support – Non-U.S.