Abstract: FR-PO637

GFR Correlates with the Homogeneity of Glomerular Capillary Blood Velocity in Diabetic Rats

Session Information

Category: Diabetes

  • 501 Diabetes Mellitus and Obesity: Basic - Experimental

Authors

  • Engbjerg, Jacob Schade, University of Aarhus, Aarhus, Denmark
  • Frische, Sebastian, University of Aarhus, Aarhus, Denmark
  • Sardella, Donato, University of Camerino, Corridonia, Italy
  • Bordoni, Luca, University of Aarhus, Aarhus, Denmark
  • Trepiccione, Francesco, Second University of Naples, Naples, Italy
  • Rhodes, George, Indiana University School of Medicine Division of Nephrology, Indianapolis, Indiana, United States
  • Sandoval, Ruben M., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Østergaard, Leif, University of Aarhus, Aarhus, Denmark
  • Capasso, Giovambattista, University of Campania Luigi Vanvitelli, Napoli, Italy
  • Molitoris, Bruce A., Indiana University School of Medicine, Indianapolis, Indiana, United States
Background

Hyperfiltration is common in early diabetes, but the mechanisms behind the rise in GFR are not well understood. Theory predicts that glomerular capillary blood flow dynamics can influence GFR. We therefore aim to investigate if the heterogeneity of glomerular capilary blood velocity influence GFR in experimental diabetic rats.

Methods

3 groups of male Munich Wistar Frömter rats were studied: Control (C) (n=8), Diabetic (D) (7 days after STZ-injection (40 mg/kg)) (n=10) and acutely hyperglycemic (H) (i.v glucose injections to reach blood glucose (BG) > 20 mM) (n=7). Rats were anesthetized with Inactin and prepared for 2-photon in vivo microscopy (2PM) by externalization of the left kidney. BP and HR were monitored. Blood plasma was labelled by injection of Setau-647-coupled 500kD dextran. Blood flow velocity was measured in ≧6 glomerular capillaries in each glomerulus using longitudinal linescans at >1.3 kHz in the capillary lumen. GFR was measured by fitting a double-exponential decay function to the FITC signal in the plasma recorded by 2PM during 30 min after a bolus of FITC-3kD-dextran. Blood samples were obtained before and after microscopy.

Results

A significant correlation between the homogeneity of glomerular capillary blood flow velocity and GFR was found in the D-rats (p = 0.028), but not in C- or H-rats. In C-rats GFR correlated significantly with BP (p=0.0047), age (p=0.026) and plasma osmolality (p=0.011). GFR did not correlate with these parameters in D-rats (p =0.08, p=0.84 and p=0.45 ) or H-rats (p=0.15, p=0.22, and p=0.68).

Conclusion

Homogenization of blood flow velocities in the glomerular capillaries seems a new powerful mechanism, which may underlie hyperfiltration in diabetic rats. Mechanistically, it may result from mesangial cell dysfunctionality and it appears to override the influence of parameters influencing GFR in control rats.

Group means of the parameters investigated
 Mean and SDp-value
 CDHC vs DC vs HD vs H
Age(days)110 ±19118 ±15114 ±170.66
0.910.9
BG (mM)5.4 ± 0.8619.1 ± 4.524 ± 14.9<0.01<0.010.44
BP(mmHg)135 ±17.5130 ±7.3152 ±9.60.630.060.01
Plasma osmolality (mOsm/kg)314±17331 ±7.6328±8.80.040.130.89
GFR(ml/min)2.73 ±0.863.72±1.835.08 ±2.330.470.040.28

Funding

  • Government Support - Non-U.S.