The glomerular number and size are major factors in predicting outcomes in renal disease. We have recently established synchrotron radiation microcomputed tomography (SRµCT) imaging of the glomeruli in perfused kidneys, and reported the glomerular and renal hypertrophy, but not glomerular loss in obese type 2 diabetic db/db mice. To visualize pathophysiological basis of diabetic kidney of type 1 diabetes, we here explored SRµCT imaging of the glomeruli in streptozotocin-induced type 1 diabetic male mice (STZ mice) and of control male C57BL/6J mice (control mice). STZ mice at the age of 22 weeks significantly showed hyperglycemia and elevated urinary albumin excretion, but not hypertension or body weight changes compared to control mice. There was approximately 22% loss of the total glomerular number (Nglom) of STZ mice compared to that of control mice (p<0.001). STZ mice had fewer glomerular number in all renal cortical zone of the whole kidney than control mice (p=0.003). However, type 1 diabetes had no impact on the mean glomerular volume (Vglom), coefficient of variation (CV; SD/mean) of glomerular volume, and renal volume (Vkidney) (Vglom, p=0.149; CV, p=0.591; Vkidney, p=0.093 vs. control mice, respectively). Nglom was significantly correlated with body weight (r=0.458, p=0.032), blood glucose levels (r=-0.623, p=0.002) or HbA1c (r=-0.530, p=0.011). Vglom was correlated with Vkidney (r=0.622, p=0.002) by each other. Multivariate regression analysis with the stepwise forward method identified blood glucose (β=-0.665, p<0.001) and systolic blood pressure (β=-0.499, p=0.001) as significant independent determinants of Nglom. Our study, for the first time, demonstrated a significant reduction of the total glomerular number in STZ mice, without affecting the glomerular volume or renal volume. These results indicate the glomerular pathology markedly differs between type 1 and type 2 diabetes.
Y. Takiyama: None. T. Sera: None. M. Nakamura: None. R. Bessho: None. T. Takiyama: None. T. Ota: None. M. Haneda: None.
