Oral Adsorbent Prevents Reduction of Anionic Sites of the Glomerular Basement Membrane in Diabetic Nephropathy

Abstract

Background: AST-120, an oral adsorbent, inhibits progression of diabetic nephropathy by reducing albuminuria. The purpose of the present study was to explore the mechanism underlying the protective effect of AST-120 against albuminuria. Methods: Twenty-four male Sprague-Dawley rats underwent intravenous injection of streptozotocin and subsequent uninephrectomy. Half of the rats were fed standard rat chow, and the other half were fed rat chow containing AST-120. All rats were killed at week 6 after a clearance study. Results: There were no significant differences in body weight, kidney weight, urinary volume, blood pressure, blood glucose or inulin clearance between the two groups at week 6. However, urinary albumin excretion at week 6 was significantly lower in the AST-120 group than in the control group (p < 0.05). Light microscopic observation showed that the planar area of glomeruli was significantly smaller in the AST-120 group than in the control group (p < 0.01), and the shortest diameter of proximal tubules was less in the AST-120 group than in the control group (p < 0.01). Electron microscopic observation showed a significantly greater number of anionic sites on the lamina rara externa of the glomerular basement membrane in the AST-120 group than in the control group (p < 0.01). Conclusion: We conclude that AST-120 reduces albuminuria by preventing the decrease in the number of anionic sites in the glomerular basement membrane in rats with diabetic nephropathy. In addition, AST-120 inhibits the appearance of glomerular and tubular hypertrophy.

The Convoluted Tubules of the Nephron Must Be Considered Elliptical, and Not Circular, in Stereological Studies of the Kidney

“…PCT, proximal convoluted tubule; DCT, distal convoluted tubule; SCA, small circular area; LCA, large circular area; EA, elliptical area; PA, program area. DOI: 10.1159/000515051 short axis (short diameter) of the ellipse [12][13][14][16][17][18][19], while others report the value of both axes (short and long diameters) of the ellipse [11,15,20]. Furthermore, care should be taken to always measure tubules as ellipses and not some tubules as ellipses and other tubules as circles in the same sample [21,22].…”

“…It is noteworthy that in the literature, some authors do not specify the total number of tubules examined per subject [5, 6, 8, 9, 11, 20]. When specified, most authors report measurements in 100 tubules or fewer [3, 4, 10, 12-18, 21, 22]. Only transverse tubules with complete basement membrane (BM) were evaluated; longitudinal tubules were not considered.…”

“…The tubular area, defined as the space bounded by the BM (blue line), was measured in 4 ways. The SCA was calculated by using the formula for the area of a circle, A = π•r 2 , where r is one-half of d. The LCA was calculated by using the same formula, but replacing the d value by D. The EA was obtained by using the formula for the area of an ellipse, phometrically fixed the kidneys by perfusion before inclusion in paraffin [4,11,22], most used the immersion method for this purpose [6,[8][9][10][12][13][14][15][16][17][18][19][20][21]. Then, 5-μm thick sections were cut, deparaffinized in xylene, hydrated in a graded series of alcohol, and stained with hematoxylin and eosin (H&E) according to standard techniques.…”

“…Several authors measure only one diameter, as if the tubules were circular [3][4][5][6][7][8][9][10]. On the contrary, other authors consider that the tubules have an elliptical shape and report the short diameter (minimum, proximal), sometimes along with the large diameter (maximum, distal) [11][12][13][14][15][16][17][18][19][20]. Even more, other authors measure in the same sample some tubules as circles and others as ellipses [21,22].…”