Advanced Diabetic Glomerulopathy: Quantitative Structural Characterization of Nonoccluded Glomeruli

Abstract

Quantitative ultrastructural data were obtained from kidney biopsy material of 12 long-term insulin-dependent diabetics. All patients had overt diabetic nephropathy with increased urinary albumin excretion and reduced glomerular filtration rate. Renal clearance of 51Cr-EDTA was in the range of 16-50 ml X min-1 X 1.73 m-2. All patients received antihypertensive treatment. A combined light- and electron-microscope study was performed. A significant proportion of the glomeruli was totally occluded (mean 36%, range 24-67%). Structural data presented relate only to the open, still-functioning glomeruli. Comparison with data previously obtained showed that the thickness of the peripheral basement membrane [647 nm, coefficient of variation (C.V.) 0.22] was more than twice the normal value (310 nm, C.V. 0.08); the width of epithelial foot processes (352 nm, C.V. 0.07) was significantly greater than in normal biopsies (224 nm, C.V. 0.06); and the mean volume of the open glomeruli was markedly increased compared with normal and clearly exceeded that in the early diabetic hypertrophy. Total mesangial volume and total basement membrane material per open glomerulus were increased by 277 and 614%, respectively. However, capillary length and surface per open glomerulus were similar to those observed in early diabetic hypertrophy. These findings suggest that a late glomerular hypertrophy with preservation of capillary surface occurs as a compensatory phenomenon, prolonging renal survival for diabetic nephropathy patients.

Are glomerular volume differences between type 1 and type 2 diabetic patients pathologically significant?

“…The glomerulus may enlarge in order to maintain filtration surface area in the face of an expanding mesangium or as a result of a reduction in glomerular number due to occlusion-the remnant glomeruli compensating for the loss [24]. We found no significant difference in the percentage of occluded glomeruli between the type 1 and type 2 diabetic patients in our series; therefore, glomerular loss due to occlusion seems unlikely to account for the differences in glomerular volume.…”

Extracellular Matrix Proteins as Early Markers in Diabetic Nephropathy

“…Diabetes induces morphological alterations in the kidney, such as glomerular basement membrane thickening and expansion of the mesangial matrix, which occurs prior to albuminuria and changes of glomerular filtration rate (2,20). Methods based on the measurement of these functional quantities, routinely used in the diagnosis of diabetic nephropathy, lack the sensitivity required for early detection of the above mentioned structural changes, because the kidney has considerable functional reserves (21).…”

The effect of intrauterine environment and low glomerular number on the histological changes in diabetic glomerulosclerosis

“…Ultrathin sections were taken from three glomeruli per animal, stained with uranyl acetate and lead citrate, and examined using a Philips CM100 electron microscope. The whole glomerular profile was photographed for the estimation of mesangial volume fraction by point counting [16], podocyte number was estimated by the method of Weibel [17,18] and surface densities were calculated using the line intercept method [19]. To obtain absolute surfaces, densities were multiplied by glomerular volume.…”