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  • 1
    Electronic Resource
    Electronic Resource
    Reduced glomerular filtration rate and cardiovascular damage in diabetes: a key role for abnormal albuminuria (1992)
    Springer
    Acta diabetologica 29 (1992), S. 201-213 
    Details
    ISSN: 1432-5233
    Keywords: Abnormal albuminuria ; ACE-inhibition ; Hypertension ; Microalbuminuria ; Diabetic nephropathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There is general agreement that a fall rate in glomerular filtration rate (GFR) is the principal endpoint in diabetics with renal disease, and that abnormal albuminuria (including microalbuminuria) is an important intermediate end-point. The relative roles of blood pressure (BP) elevation and abnormal albuminuria in the prediction and genesis of renal disease are a matter of debate, and are further analysed in this paper. New studies show that neither genetic predisposition to hypertension (parental BP) nor parental abnormal albuminuria can be used to predict renal disease in patients with type 1 (insulin-dependent) diabetes. However, parental predisposition to proteinuria seems to be important to certain types of patients with type 2 (non-insulin-dependent) diabetes. Cross-sectional as well as follow-up studies document that GFR is generally well preserved in microalbuminuria (in both type 1 and type 2 patients), while the transition to clinical proteinuria is associated with a decline in GFR. Thus, prevention of overt proteinuria is important in clinical trials in microalbuminuric patients. In type 1 diabetes clear ultrastructural changes have been documented with microalbuminuria and a good correlation between abnormal albuminuria and structural damage is seen. Structural damage in normo- and microalbuminuric patients correlates poorly with BP. New studies in type 1 diabetes document that microalbuminuria (but not elevated BP) predicts not only clinical diabetic nephropathy but also end-stage renal failure and mortality. In type 2 diabetes microalbuminuria is the strongest predictor of mortality, whereas BP elevation is not a predictor. Several studies now document that antihypertensive treatment, especially with inhibitors of angiotensin converting enzyme, is able to reverse or reduce abnormal albuminuria, even in non-hypertensive type 1 patients, and possibly preserve GFR. Therefore, microalbuminuria may be the main indicator for starting antihypertensive treatment in these patients. With respect to organ damage in the retina, abnormal albuminuria is an important indicator of the risk of severe diabetic retinopathy. BP elevation seems not to be an initiating factor, but rather aggravates established retinopathy. Left ventricular hypertrophy has a stronger correlation with BP elevation than normoalbuminuria, suggesting that left ventricular hypertrophy is at least partially a phenomenon secondary to elevated BP in diabetic patients with abnormal albuminuria. Generally, abnormal albuminuria is a strong indicator of cardiovascular renal damage in diabetic patients and in most organs is a stronger factor than elevated BP.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00573489
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  • 2
    Electronic Resource
    Electronic Resource
    Glomerular volume and the glomerular vascular pole area in patients with insulin-dependent diabetes mellitus (1997)
    Springer
    Virchows Archiv 431 (1997), S. 351-357 
    Details
    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
    URL: http://dx.doi.org/10.1007/s004280050110
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  • 3
    Electronic Resource
    Electronic Resource
    The basement membrane controversy (1978)
    Springer
    Diabetologia 15 (1978), S. 361-363 
    Details
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01219643
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  • 4
    Electronic Resource
    Electronic Resource
    The cortical distribution pattern of diabetic glomerulopathy (1986)
    Springer
    Diabetologia 29 (1986), S. 146-150 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF02427084
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  • 5
    Electronic Resource
    Electronic Resource
    A strong correlation between glomerular filtration rate and filtration surface in diabetic nephropathy (1988)
    Springer
    Diabetologia 31 (1988), S. 265-270 
    Details
    ISSN: 1432-0428
    Keywords: Diabetic glomerulopathy ; diabetic nephropathy ; glomerular ultrastructure ; glomerular filtration rate ; stereology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Quantitative structural studies were performed in kidney biopsy specimens from 24 long-term Type 1 (insulin-dependent) diabetic patients with persistent albuminuria due to diabetic glomerulopathy. Ten patients were receiving antihypertensive treatment, and among the remaining patients the mean blood pressure was 142/91 mmHg (SD = 11/9). The urinary albumin excretion rate showed a range from 100 to 5494 μg/min (geometric mean 688 μg/min.) Glomerular filtration rate also showed a wide range, from supranormal to markedly decreased values (128 to 28 ml·min−1· (1.73 m2)−1, mean 75). The filtration surface (interface between capillary and urinary space) per total number of nephrons (open+occluded) was estimated by combined light- and electron microscopy. The percentage occluded glomeruli as well as structural quantities in the open glomeruli were taken into account in this estimate. A highly significant correlation was seen between glomerular filtration rate and filtration surface per nephron (r=0.77, p〈10−4). The percentage occluded glomeruli contributed significantly to the variation in glomerular filtration rate (for this relationship tested separately r=-0.78, p〈10−5). The volume of open glomeruli was even larger than that seen in early diabetic glomerular hypertrophy and tended to increase with the percentage of glomerular closure, indicating that a compensatory hypertrophy might have taken place. In the open glomeruli the filtration surface constituted a smaller percent of total capillary surface (the remaining part facing the mesangial regions) than in early diabetic patients and control subjects. Our study has demonstrated that reduced glomerular filtration surface is closely associated with reduced glomerular filtration rate in Type 1 diabetic patients with diabetic nephropathy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00277406
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  • 6
    Electronic Resource
    Electronic Resource
    Effect of angiotensin converting enzyme inhibitor or beta blocker on glomerular structural changes in young microalbuminuric patients with Type I (insulin-dependent) diabetes mellitus (1999)
    Springer
    Diabetologia 42 (1999), S. 589-595 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Type I diabetes ; microalbuminuria ; diabetic glomerulopathy ; angiotensin converting enzyme inhibitor ; beta-receptor blocker.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. To investigate the influence of angiotensin converting enzyme inhibitors and beta blockers on the progression of early diabetic glomerulopathy. Methods. Thirteen patients with Type I (insulin-dependent) diabetes mellitus (mean age 18.8 years) with microalbuminuria 31 (19–160) μg/min were randomised to treatment with enalapril (group 1, n = 7) or metoprolol (group 2, n = 6). Renal biopsies were taken before and after 38 (36–48) months of treatment. Albumin excretion rate, blood pressure and HbA1 c were measured every third month. A reference group without antihypertensive treatment (group 3, n = 9), with similar age, diabetes duration and degree of microalbuminuria as group 1 and 2, had baseline and follow-up renal biopsies taken previously with an interval of 26–34 months, analysed at the same laboratory. Glomerular structures were measured by stereological methods. Results. Measurements of basement membrane thickness, mesangial and matrix volume fractions were similar among groups at baseline. Structural variables were only increased in group 3 at follow-up. Delta values in basement membrane thickness and diabetic glomerulopathy index per 24 months were lower in group 1 and 2 than in group 3 (p 〈 0.05). Microalbuminuria returned to normal in group 1 and 2 only. Decreased albumin excretion rate tended to inversely correlate with increased basement membrane thickness (p = 0.08) and diabetic glomerulopathy index (p = 0.05). Mean HbA1 c was similar between groups. Mean diastolic blood pressure was lower in group 1 and 2 than in group 3 (p 〈 0.01). Mean HbA1 c and mean diastolic blood pressure correlated to changes in basement membrane thickness, mesangial volume fraction and diabetic glomerulopathy index (p 〈 0.05). Conclusion/interpretation. Contrary to findings in the group without antihypertensive treatment, no progression of glomerulopathy was seen in those treated with enalapril or metoprolol. [Diabetologia (1999) 42: 589–595]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051199
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  • 7
    Electronic Resource
    Electronic Resource
    Kidney transplantation in Type 1 (insulin-dependent) diabetic patients (1991)
    Springer
    Diabetologia 34 (1991), S. 668-674 
    Details
    ISSN: 1432-0428
    Keywords: Kidney transplants ; diabetic glomerulopathy ; basement membrane thickness ; mesangial volume fraction ; interstitial fibrosis ; cyclosporine ; stereology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The development of diabetic glomerulopathy in kidneys transplanted to diabetic patients was estimated in transplant biopsies and evaluated in relation to suspected clinical risk factors for diabetic nephropathy. Surgical biopsies were taken at baseline and at 24–36 months post-transplantation in 16 Type 1 (insulin-dependent) diabetic patients and 8 non-diabetic control subjects with a glomerular filtration rate more than 30 ml·min− at follow-up. Immunosuppressive therapy included cyclosporine in all but one case. Stereological methods were used to assess basement membrane thickness, volume fraction of mesangium per glomerulus, and volume fraction of matrix per mesangium. The volume fraction of interstitial tissue per cortex was estimated by light microscopy. After 2 years the basement membrane thickness had increased by 55 nm (SD 58 nm) in the diabetic group. This change was significantly different from that of 2 nm (SD 37 nm) in control subjects (p=0.02). Mesangial volume fraction increased significantly by 0.04 (SD 0.03) in diabetic patients, and this change was significantly different from that of -0.01 (SD 0.04) in non-diabetic patients (p=0.009). No change was detectable in the matrix expressed as fraction of mesangial volume. An increase in interstitial volume fraction from baseline to 2 years was observed, but was significant only in the diabetic group (p=0.04). The changes in structural parameters did not correlate with mean values during follow-up of glycated haemoglobin or estimated protein intake, nor was any pattern discernible in the relationship to graft tissue types. The observed increase in basement membrane thickness corresponds to that observed in native kidneys during the first years of diabetes, whereas an increase in mesangial volume fraction — using a different protocol — was not observed in the early phase of the natural development. Absence of correlation with the various risk factors may reflect an irrelevance of these variables within the current range, or their influence may be offset by stronger mechanisms in the transplant situation, and therefore does not appear in this relatively small series.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400997
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  • 8
    Electronic Resource
    Electronic Resource
    Glomerular epithelial foot processes and filtration slits in IDDM patients (1995)
    Springer
    Diabetologia 38 (1995), S. 1197-1204 
    Details
    ISSN: 1432-0428
    Keywords: Albuminuria ; diabetic glomerulopathy ; diabetic nephropathy ; filtration slits ; glomerular epithelial cells ; stereology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Diabetic nephropathy is associated with functional changes in the glomerular filtration barrier but the structural counterpart remains unknown. Width of glomerular epithelial cell foot processes and of filtration slits were determined by morphometric methods in 11 non-diabetic kidney donors and in 28 diabetic patients with albumin excretion rates ranging from normal to proteinuria. Foot process width was estimated from the ratio of tuft surface density to length density of slits. At high magnification independently sampled, perpendicularly cut slits were classified. Foot process width on peripheral basement membrane was increased in microalbuminuric compared to normoalbuminuric diabetic patients (p〈0.05) but showed no significant correlation with the level of albumin excretion when patients with increased barrier permeability were considered. Width of filtration slits in normo- and microalbuminuric diabetic patients exceeded that in non-diabetic control subjects (p〈0.05). Filtration slits were narrower in patients with overt proteinuria than in patients with microalbuminuria (p〈0.05) and correlated with glomerular filtration rate in all of the diabetic patients (r=0.65, p〈0.005). The results show that insulin-dependent diabetic patients with nephropathy present changes of epithelial cells and filtration slits, demonstrable already in the stage of microalbuminuria. The mechanism of albumin leakage is not achieved by these measures. The dimension of filtration slits may play a contributing role in the level of glomerular filtration rate in diabetic patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00422369
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  • 9
    Electronic Resource
    Electronic Resource
    Effect of octreotide and insulin on manifest renal and glomerular hypertrophy and urinary albumin excretion in long-term experimental diabetes in rats (1995)
    Springer
    Diabetologia 38 (1995), S. 135-144 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00400087
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  • 10
    Electronic Resource
    Electronic Resource
    Morphometric studies of the peripheral glomerular basement membrane (1973)
    Springer
    Diabetologia 9 (1973), S. 108-114 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF01230689
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