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  • 1
    ISSN: 1432-2307
    Keywords: Key words Diabetic glomerulopathy ; Glomerular hypertrophy ; Glomerular vascular pole ; Insulin-dependent diabetes mellitus (IDDM) ; Stereology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The vascular pole area (VPA) and glomerular volume were measured in renal biopsies from 9 insulin-dependent diabetes mellitus (IDDM) patients with normal albumin excretion rate (IDDM group 1), 38 IDDM patients with albumin excretion rate 〉15 μg/min (IDDM group 2) and 10 living kidney donors (ND). The volume of individual glomeruli was estimated as the sum of profile areas factored by the measured distance between levels, t∼ 10 μm, and VPA as the sum of chords multiplied by t. Mean glomerular volume was increased in IDDM patients but reached statistical significance only in IDDM group 2 (P = 0.002 vs ND). VPA was significantly different among the groups, mean (CV%) was 2036 (29) μm2 in ND, 3555 (34) μm2 in IDDM group 1, and 3528 (48) μm2 in IDDM group 2, p = 0.004 and 0.001, IDDM versus ND. VPA calculated as a percentage of the surface area of the corresponding glomerulus was 2.4 (23)% in ND, 3.4 (27)% in IDDM group 1, and 3.3 (42)% in IDDM group 2; P = 0.007 and 0.01, IDDM versus ND. The intra-biopsy coefficient of variation was high (20–35%) and of the same order in all groups for all three measurements. Glomerular volume and absolute as well as relative size of VPA showed a positive correlation with estimates of mesangial expansion in IDDM group 2 and the VPA showed a negative correlation with GFR. Thus, part of the enlargement may represent a compensatory phenomenon triggered by the development of structural and functional abnormalities in the diabetic kidney.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 15 (1978), S. 361-363 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Diabetes ; growth hormone ; hypertrophy ; kidney ; rat ; streptozotocin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Normal and diabetic rats were given daily injections of human growth hormone for four days (5 mg per rat per day). Injected rats showed no differences from uninjected controls with respect to kidney weight or renal content of protein, RNA or DNA. Kidney weight increased by 7% after two days of diabetes and by 20% after four days, but growth hormone caused no augmentation of the hypertrophy. It is concluded that growth hormone plays no role in the initiation of diabetic renal hypertrophy.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 29 (1986), S. 146-150 
    ISSN: 1432-0428
    Keywords: Diabetic nephropathy ; diabetic glomerulopathy ; long-term diabetes ; glomerular distribution ; glomerular occlusion ; morphometry ; pattern analysis ; pattern distribution ; point patterns
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In advanced diabetic nephropathy, all nephrons are affected. However, glomerulopathy shows some variation in severity. The aim of this study was to see whether the distribution of glomerular lesions bears any relationship to known renal anatomical/functional organization. Autopsy material from 12 long-term Type 1 (insulin-dependent) diabetic patients was collected retrospectively. Sections presenting the whole depth of cortex were subdivided into 3 zones of equal width. Two parameters were estimated in the deep and the superficial zones separately: (1) in open glomeruli, the volume of red-stained (PAS-positive) material as a fraction of the total glomerular volume, and (2) the number of occluded glomeruli as a fraction of the total number. The results show that the volume fraction of red-stained (PAS-positive) material, as well as the frequency of occluded glomeruli, are similar in the superficial and the deep zone. In addition, the spatial distribution of occluded glomeruli was tested for randomness. The occluded glomeruli are not randomly distributed, but show clustering. Furthermore, they tend to be located in columns perpendicular to the kidney surface, a tendency which cannot be explained by the general tendency for glomeruli to show such an arrangement. We conclude that it is unlikely that the combined structural and functional differences that exist between the superficial and deep glomeruli play a major role in the development of diabetic glomerulopathy. The kidney topology influences the process of glomerular occlusion. Several a priori, plausible mechanisms for the process are discussed.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin-dependent) diabetes mellitus ; diabetic nephropathy ; diabetic glomerulopathy ; basement membrane ; mesangium ; mesangial matrix ; glomerular hypertrophy ; glomerular occlusion ; stereology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 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 (insulindependent) 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 then 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. An inverse correlation obtained between the index of glomerulopathy and current glomerular filtration rate, as well as the ensuing rate of decline in glomerular filtration rate, as well as the ensuing rate of decline in glomerular filtration rate: (index (glomerulopathy) vs rate of decline in glomerular filtration rater=0.84,p〈0.0001). No correlation was found between glomerular volume and the ensuing rate of decline in glomerular filtration rate.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Key words Diabetic nephropathy ; diabetic glomerulopathy ; arteriolar hyalinosis ; juxtaglomerular arterioles ; extracellular matrix ; microalbuminuria ; stereology.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Hyalinization of juxtaglomerular arterioles is prominent in advanced diabetic nephropathy and may have important functional consequences. We studied the early stages of diabetic renal disease using kidney biopsy material from insulin-dependent diabetic patients, 8 with normal albumin excretion rate ( 〈 15 μg/min) and 16 with microalbuminuria (15–200 μg/min). Ten living non-diabetic kidney donors served as a control group. Median duration of diabetes was 9.5 years (range 5–31) in patients with normoalbuminuria, and 12 years (7–22) in patients with microalbuminuria (p = 0.27). The tissue was sectioned systematically, 1-μm thick sections for light microscopy at 10-μm intervals, and thin sections for electron microscopy taken at 60-μm intervals. The arterioles were identified as afferent or efferent, and total profiles were photographed (magnification 7500 × ), providing a systematic independent sample for measurements using standard stereological methods. Patients with microalbuminuria had significantly increased arteriole parameters compared with the control group: for afferent and efferent arterioles the volume fraction of matrix/media, means and (coefficient of variation, CV), was 0.47 (0.16) vs 0.33 (0.19) (p = 0.0009), and 0.62 (0.14) vs 0.45 (0.23) (p = 0.0004) and matrix-T , expressing amount of matrix per unit arteriolar surface, 2.38 (0.38) μm vs 1.44 (0.30) μm (p = 0.004), and 1.62 (0.28) μm vs 1.03 (0.34) (p = 0.0009). Patients with normoalbuminuria showed no significant differences from the control group, and had lower values than microalbuminuric patients for all parameters except the afferent matrix-T . In the normoalbuminuric group a correlation was found between parameters for afferent arterioles and those for glomerular structure. In conclusion there is arteriolar accumulation of extracellular material in the early phase of diabetic nephropathy, concomitant with early glomerulopathy. [Diabetologia (1995) 38: 1320–1327]
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 9 (1973), S. 108-114 
    ISSN: 1432-0428
    Keywords: Diabetic glomerulosclerosis ; diabetic microangiopaty ; glomerular ultrastructure ; basement membrane ; quantitative stereology ; early diabetes ; kidney ; kidney biopsy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glomerular basement membrane thickness has been estimated by quantitative electron-microscopic study in control subjects and in juvenile diabetics at onset and with short-term diabetes. — The juxta-mesangial part of the basement membrane as well as basement membranes located close to the vascular pole were considered separately and their thickness compared with the remainder of the basement membrane of the same cross section. — It was found that basement membrane, both close to mesangial regions and to the vascular pole, showed greater variation in thickness than the remainder of the glomerular basement membrane. The deviations were, however, small. — The initial thickening occurring in diabetic patients after a few years of the disease was shown to take place as a generalized phenomenon over the entire cross section and did not primarily affect the basement membrane close to mesangial regions or the vascular pole.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 13 (1977), S. 43-48 
    ISSN: 1432-0428
    Keywords: Long-term diabetes ; diabetic glomerulosclerosis ; diabetic renal disease ; glomerular size ; compensatory glomerular hypertrophy ; kidney function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A study of autopsy kidney material from six long-term diabetics and four controls was performed in order to elucidate the mechanism of the glomerular enlargement in long-term diabetics. The volume and the severity of the glomerular lesion were measured in each of a number of randomly selected, open glomeruli. The relative amount of solid material was taken as an expression of the severity of the glomerular lesion. In the long-term diabetics the volume of open glomeruli was almost doubled compared to that of controls and in the individual subject the enlargement was found to be inversely related to the relative amount of solid material in the glomeruli. This indicates that the enlargement of open glomeruli in long-term diabetics is due to a compensatory hypertrophy rather than to the excessive deposition of basement membrane material. The number of nuclei per open glomerulus was increased in long-term diabetics, but nuclear size was unchanged. Most of the long-term diabetics had a large number of occluded glomeruli, and the individual, relative number of such glomeruli correlated closely both with the duration of diabetes above 15 years and the concentration of creatinine in serum. It is concluded that the destruction of glomeruli due to diabetic microangiopathy is compensated for some years by hypertrophy of the least affected glomeruli. This compensatory hypertrophy of glomeruli might well account for the preservation of renal function in long-term diabetics for a number of years despite the progressive basement membrane lesions of diabetic microangiopathy.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; octreotide ; urinary albumin excretion ; renal hypertrophy ; kidney morphology ; IGF-I ; IGFBPs ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Treatment of diabetic rats with octreotide can inhibit early diabetic renal hypertrophy. Octreotide administration for 6 months from the day of diabetes induction inhibits renal hypertrophy and diminishes increase in urinary albumin excretion. To investigate the effect of octreotide on manifest diabetic renal changes, octreotide treatment was given for 3 weeks after an untreated diabetic period of 3 or 6 months. In addition, following 6 months of diabetes, a group of diabetic rats was treated with insulin for 3 weeks. Renal and glomerular hypertrophy, and increased urinary albumin excretion were observed in diabetic rats compared to non-diabetic control rats from 3 months and throughout the study period. Octreotide treatment did not affect body weight, food intake, blood glucose or serum fructosamine levels. We observed no effect of octreotide treatment on renal and glomerular hypertrophy or urinary albumin excretion compared to placebotreated diabetic rats. Insulin treatment for 3 weeks after 6 months of untreated diabetes normalized blood glucose and serum fructosamine levels, and furthermore renal hypertrophy was significantly diminished compared to the placebo-treated diabetic rats. However, insulin treatment had no effect on glomerular hypertrophy or urinary albumin excretion. In conclusion, octreotide treatment for 3 weeks following an untreated diabetic period of 3 or 6 months is unable to reduce the increased renal and glomerular volume or urinary albumin excretion. However, insulin treatment for 3 weeks with induction of euglycaemia diminishes the renal hypertrophy but has no effect on glomerular volume or urinary albumin excretion.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: Diabetic nephropathy ; diabetic glomerulopathy ; arteriolar hyalinosis ; juxtaglomerular arterioles ; extracellular matrix ; microalbuminuria ; stereology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Hyalinization of juxtaglomerular arterioles is prominent in advanced diabetic nephropathy and may have important functional consequences. We studied the early stages of diabetic renal disease using kidney biopsy material from insulin-dependent diabetic patients, 8 with normal albumin excretion rate (〈15 Μ/min) and 16 with microalbuminuria (15–200 Μg/min). Ten living non-diabetic kidney donors served as a control group. Median duration of diabetes was 9.5 years (range 5–31) in patients with normoalbuminuria, and 12 years (7–22) in patients with microalbuminuria (p=0.27). The tissue was sectioned systematically, 1-Μm thick sections for light microscopy at 10-Μm intervals, and thin sections for electron microscopy taken at 60-Μm intervals. The arterioles were identified as afferent or efferent, and total profiles were photographed (magnification 7500×), providing a systematic independent sample for measurements using standard stereological methods. Patients with microalbuminuria had significantly increased arteriole parameters compared with the control group: for afferent and efferent arterioles the volume fraction of matrix/media, means and (coefficient of variation, CV), was 0.47 (0.16) vs 0.33 (0.19) (p=0.0009), and 0.62 (0.14) vs 0.45 (0.23) (p=0.0004) and matrix-T, expressing amount of matrix per unit arteriolar surface, 2.38 (0.38) Μm vs 1.44 (0.30) Μm (p=0.004), and 1.62 (0.28) Μm vs 1.03 (0.34) (p=0.0009). Patients with normoalbuminuria showed no significant differences from the control group, and had lower values than microalbuminuric patients for all parameters except the afferent matrix-T. In the normoalbuminuric group a correlation was found between parameters for afferent arterioles and those for glomerular structure. In conclusion there is arteriolar accumulation of extracellular material in the early phase of diabetic nephropathy, concomitant with early glomerulopathy.
    Type of Medium: Electronic Resource
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