Phlorizin prevents glomerular hyperfiltration but not hypertrophy in diabetic rats

Slava Malatiali, Issam Francis, Mario Barac-Nieto, Slava Malatiali, Issam Francis, Mario Barac-Nieto

Abstract

The relationships of renal and glomerular hypertrophies to development of hyperfiltration and proteinuria early in streptozotocin-induced diabetes were explored. Control, diabetic, phlorizin-treated controls, and diabetic male Fischer rats were used. Phlorizin (an Na+-glucose cotransport inhibitor) was given at a dose sufficient to normalize blood glucose. Inulin clearance (C(inulin)) and protein excretion rate (PER) were measured. For morphometry, kidney sections were stained with periodic acid Schiff. At one week, diabetes PER increased 2.8-folds (P < .001), C(inulin) increased 80% (P < .01). Kidney wet and dry weights increased 10%-12% (P < .05), and glomerular tuft area increased 9.3% (P < .001). Phlorizin prevented proteinuria, hyperfiltration, and kidney hypertrophy, but not glomerular hypertrophy. Thus, hyperfiltration, proteinuria, and whole kidney hypertrophy were related to hyperglycemia but not to glomerular growth. Diabetic glomerular hypertrophy constitutes an early event in the progression of glomerular pathology which occurs in the absence of mesangial expansion and persists even after changes in protein excretion and GFR are reversed through glycemic control.

Figures

Figure 1
Figure 1
Blood glucose concentrations in phlorizin-treated diabetic rats (n = 5).
Figure 2
Figure 2
Glomerular morphological changes due to one-week diabetes in Fischer rats. Glomerular tuft area significantly increased after one week of diabetes. PAS positive area exhibited no change in one-week diabetics (D) when compared to controls (C). Phlorizin treatment (DPLZ) did not prevent glomerular growth. (4 μm, paraffin sections, periodic acid-Schiff (PAS) stain, ×400).
Figure 3
Figure 3
Correlation of protein excretion rate (PER) with inulin clearance (P < .001) in control, diabetic, and phlorizin-treated control and diabetic Fischer rats. Inulin clearance was normalized to 100 g of initial body weight.
Figure 4
Figure 4
Percent changes from control of kidney dry weight to initial body weight ratio (KDW/BW0), glomerular tuft area (GTA), protein excretion rate (PER), and glomerular filtration rate (GFR) in diabetic (D) and phlorizin-treated diabetic (DPLZ) rats. Phlorizin treatment prevented renal growth, proteinuria and hyperfiltration, but did not prevent glomerular hypertrophy in diabetic rats. Absolute values and statistics are presented in Tables 1, 2, and 3.

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