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  • 1
    Electronic Resource
    Electronic Resource
    Glomerular charge selectivity and the influence of improved blood glucose control in Type 1 (insulin-dependent) diabetic patients with microalbuminuria (1992)
    Springer
    Diabetologia 35 (1992), S. 1165-1169 
    Details
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes mellitus ; nephropathy ; microalbuminuria ; continuous subcutaneous insulin infusion ; metabolic control ; glomerular charge selectivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We first compared glomerular charge selectivity index in two matched groups of Type 1 (insulin-dependent) diabetic patients with micro and normoalbuminuria respectively, and secondly, investigated prospectively in a randomized clinical trial, the influence of improved metabolic control on selectivity index in diabetic patients with microalbuminuria. In Study 1, 27 patients with microalbuminuria (albumin excretion 〉-15 μg/min in at least two out of three overnight urine samples) were matched (age, diabetes duration, mean 1-year HbA1c, gender) with normoalbuminuria patients (n=24), and in Study 2, 23 microalbuminuric patients were randomly allocated to either intensive (continuous subcutaneous insulin infusion) or conventional treatment. Glomerular charge selectivity index was measured as IgG/IgG4 selectivity index, i.e. total IgG/IgG4 clearance ratio in timed overnight urine samples. The microalbuminuric patients had a significantly reduced selectivity index compared to the normoalbuminuric patients: 1.20 (0.92–1.40) vs 1.68 (1.22–2.21), median and 95% confidence interval (p〈0.01). In Study 2, the HbA1c improved in the intensive-treatment group compared to the conventional-treatment group: at 2, 6 and 12 months the difference in mean percentage HbA1c between the groups was 1.1, 1.2 and 1.4, respectively (p〈0.01). A sharp 50% increment in IgG/IgG4 selectivity index was seen in the intensive-treatment group during the first 6 months (p〈0.05 compared to the conventional group). We conclude that adolescents and young adults in an early stage of diabetic nephropathy have reduced glomerular charge selectivity, which may be improved by reducing the mean blood glucose level.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00401371
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  • 2
    Electronic Resource
    Electronic Resource
    Improvement of blood glucose control in IDDM patients retards the progression of morphological changes in early diabetic nephropathy (1994)
    Springer
    Diabetologia 37 (1994), S. 483-490 
    Details
    ISSN: 1432-0428
    Keywords: Key words Diabetic glomerulopathy, microalbuminuria, basement membrane thickness, mesangial expansion, mesangial matrix, stereology, hyperglycaemia.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We investigated in a randomized, prospective study the influence of improved blood glucose control during 2–3 years in young insulin-dependent diabetic (IDDM) patients with microalbuminuria, which is indicative of early nephropathy. Patients were randomized either to intensive treatment by continuous subcutaneous insulin infusion (CSII) (n =9) or CT (n =9). Kidney biopsies were taken at baseline and after 26–34 months. End points were structural changes in the glomeruli. Sensitive, quantitative, morphometric methods were used. The blood glucose control improved significantly (p =0.01) during the study in the CSII-group as glycated haemoglobin (HbA1 c) fell from 10.1 % ([95 % CI] 8.9–11.3) to 8.6 % (7.9–9.2), but not in the CT-group, 10.1 % (8.3–11.9) vs 9.7 % (8.7–10.8). Mean HbA1 c during the study period was significantly lower in the CSII-group than in the CT-group, 8.7 % (8.1–9.3) vs 9.9 % (8.5–11.3), p =0.04. Basement membrane thickness (BMT) increased in both groups, most (CT vs CSII, p =0.03) in the CT-group: 140 nm (50–230) vs CSII: 56 nm (27–86). In the CT-group only an increase was seen in matrix/mesangial volume fraction (p =0.006) and matrix star volume (p =0.04). Furthermore, a positive correlation between mean HbA1 c during the study and change from baseline in BMT (r =0.70, p =0.001) and matrix/glomerular volume fraction (r =0.33, p =0.09, NS) was demonstrated. Albumin excretion rate correlated significantly to BMT and most of the matrix parameters. The present study shows that during a period of only 2.5 years, a close relationship between the level of mean blood glucose and progression of glomerular morphological changes in early diabetic nephropathy can be demonstrated. [Diabetologia (1994) 37: 483–490]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050136
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  • 3
    Electronic Resource
    Electronic Resource
    A quantitative ultrastructural study of juxtaglomerular arterioles in IDDM patients with micro-and normoalbuminuria (1995)
    Springer
    Diabetologia 38 (1995), S. 1320-1327 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00401765
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  • 4
    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: Key words 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. [Diabetologia (1995) 38: 1197–1204]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00422369
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  • 5
    Electronic Resource
    Electronic Resource
    Blood glucose control and microvascular complications — what do we do now? (1994)
    Springer
    Diabetologia 37 (1994), S. 1172-1177 
    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/BF00399789
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  • 6
    Electronic Resource
    Electronic Resource
    Blood glucose control and microvascular complications – what do we do now? (1994)
    Springer
    Diabetologia 37 (1994), S. 1172-1177 
    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/BF00399789
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    Paper (German National Licenses)
    Fulltext
  • 7
    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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    Paper (German National Licenses)
    Fulltext
  • 8
    Electronic Resource
    Electronic Resource
    A quantitative ultrastructural study of juxtaglomerular arterioles in IDDM patients with micro- and normoalbuminuria (1995)
    Springer
    Diabetologia 38 (1995), S. 1320-1327 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00401765
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    Paper (German National Licenses)
    Fulltext
  • 9
    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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  • 10
    Electronic Resource
    Electronic Resource
    Urinary albumin excretion rate and puberty in non-diabetic children and adolescents (1994)
    Springer
    Pediatric nephrology 8 (1994), S. 210-210 
    Details
    ISSN: 1432-198X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00865480
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