The effects of angiotensin converting enzyme inhibition with captopril were investigated in patients with diabetic nephropathy and hypertension. After nine days' treatment with captopril glomerular filtration rate was unchanged in 13 patients, whereas renal plasma flow had increased from 265 to 302 ml/min/173 ml body surface area (p
Glomerular ultrastructure was examined in a series of 20 Type 2 (non-insulin-dependent) diabetic patients with proteinuria. Reference was made to data previously obtained in non-diabetic kidney donors and in Type 1 (insulin-dependent) diabetic patients with similar degrees of proteinuria. The Type 2 diabetic patients demonstrated the changes which characterize the diabetic glomerulopathy seen in Type 1 diabetic patients: basement membrane thickening, and increase in the mesangium and mesangial matrix expressed as fraction of the glomerular volume. Among the Type 2 diabetic patients there was more variation than among the Type 1 diabetic patients, as this group included subjects with normal parameters. The group means and coefficients of variation (= SD/mean) of the glomerulopathy parameters combined in the glomerulopathy index = basement membrane thickness/10+ Vv(matrix/glom).100 were 81 (0.30) and 92 (0.15) in the two diabetic groups, clearly different from the non-diabetic index, 42 (0.16). All Type 2 diabetic patients who also had retinopathy had a glomerulopathy index above the normal range. Similar changes in glomerular composition were seen in the two diabetic groups: with increasing glomerulopathy the volume of matrix dominated over the peripheral basement membrane, and a shift in the ratio of interfaces was seen: mesangial surface towards capillary lumen increased relative to the urinary surface, and peripheral capillary surface comprised less of the total capillary surface. Data indicated marked glomerular hypertrophy, which correlated with the mesangial volume fraction, thus encompassing preserved filtration surface per glomerulus.(ABSTRACT TRUNCATED AT 250 WORDS)
Increased urinary albumin excretion, microalbuminuria, may be the first sign of early diabetic nephropathy. We examined glomeruli by morphometric methods in 17 patients with Type 1 (insulin-dependent) diabetes mellitus and microalbuminuria. The median age was 19 (range 18-29) years, duration of diabetes 12 (8-15) years, mean blood pressure 93 (87-115) mm Hg, glomerular filtration rate 132 (101-209) ml.min-1.1.73 m2 -2, albumin excretion rate (mean over 1 year) 32 (15-194) micrograms/min. Reference data were obtained from 11 healthy kidney donors. Mesangial volume estimates were obtained by serial sectioning in three total profiles in each of three glomeruli in diabetic patients. Basement membrane thickness and matrix volume fraction were estimated from one level per glomerulus. Two matrix parameters, matrix star volume and matrix thickness, were estimated. Interstitial volume fraction in cortex was measured by light microscopy. The morphological parameters were significantly increased in the diabetic group compared to the control group, basement membrane thickness (mean with 95% confidence intervals) was 595 nm (549-641 nm) vs 305 nm (287-325 nm), p = 0.0001; mesangial volume fraction 0.22 (0.21-0.23) vs 0.19 (0.18-0.21), p = 0.04, and matrix volume fraction 0.13 (0.12-0.13 vs 0.09 (0.08-0.10), p = 0.001. Also matrix star volume and thickness, interstitial volume fraction and mean capillary diameter were significantly increased. The intra-individual variation among glomeruli expressed as coefficient of variation was 7.4% vs 9% (basement membrane thickness) and 11.7% vs 25% (mesangial volume fraction) in the diabetic and the control group, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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