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  • 1
    Electronic Resource
    Electronic Resource
    Glomerular size- and charge selectivity in Type 2 (non-insulin-dependent) diabetic patients with diabetic nephropathy (1994)
    Springer
    Diabetologia 37 (1994), S. 195-201 
    Details
    ISSN: 1432-0428
    Keywords: Key words Type 2 (non-insulin-dependent) diabetes mellitus, diabetic nephropathy, IgG, IgG4, IgG/albumin selectivity index, IgG/IgG4 selectivity index.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In an attempt to evaluate the mechanisms of proteinuria in diabetic kidney disease, we measured the renal clearances of albumin, total IgG, and IgG4 in 20 male Type 2 (non-insulin-dependent) diabetic patients with diabetic glomerulosclerosis (biopsy proven), in 10 male Type 2 diabetic patients without nephropathy (urinary albumin excretion rate ≤ 30 mg/24 h), and in 10 healthy male subjects. The fractional clearance of albumin was increased in patients with nephropathy: 659 (42–4355) · 10–6 (median (range)), compared to 2.6 (0.2–14.2) · 10–6 in patients without nephropathy, and 2.3 (0.4–4.2) · 10–6 in healthy subjects. The fractional clearance of total IgG (neutral) and of IgG4 (anionic) was 40–50 times higher in patients with nephropathy compared to the two other groups. The IgG/IgG4 selectivity index was not significantly different in the three groups, being: 1.12 (0.06–5.65), 1.16 (0.45–3.72) and 1.35 (0.65–3.34) in patients with nephropathy, patients without nephropathy, and healthy subjects, respectively. The IgG/albumin selectivity index was decreased in patients with nephropathy: 0.27 (0.01–1.26) compared to 1.29 (0.07–2.67) (p〈0.05) and 1.23 (0.76–7.84) (p〈0.001) in patients without nephropathy and healthy subjects, respectively. No significant change in IgG/albumin selectivity index was observed between patients without nephropathy and healthy subjects. The systolic blood pressure was elevated in the patients with nephropathy: 164±21 mm Hg (mean ± SD) compared to patients without nephropathy: 145±20 mm Hg (p〈0.05) and to healthy subjects: 133±19 mm Hg (p〈0.005). The diastolic blood pressure was higher in patients with and without nephropathy: 92±7 vs 90±10 mm Hg compared to 79±8 mm Hg (p〈0.005) in healthy subjects. Our cross-sectional study suggests that impaired barrier size selectivity, probably due to an increase in large pore area (“shunt pathway”) in the glomerular capillary wall and systemic hypertension are the major pathogenic mechanisms of proteinuria in Type 2 diabetic patients with diabetic nephropathy. [Diabetologia (1994) 37: 195–201]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050093
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  • 2
    Electronic Resource
    Electronic Resource
    Diabetes mellitus induced inhibition of glucosaminyl N-deacetylase: effect of short-term blood glucose control in diabetic rats (1993)
    Springer
    Diabetologia 36 (1993), S. 310-315 
    Details
    ISSN: 1432-0428
    Keywords: Heparan sulphate ; experimental diabetes ; BB rat ; albuminuria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Inhibition of glucosaminyl N-deacetylase activity, a key enzyme in heparan sulphate sulphation, may be involved in the development of late diabetic vascular complications. We examined the effect of short- and long-term metabolic control on N-deacetylase activity in streptozotocin diabetic H and U rats. Spontaneously diabetic BB rats were included in parts of the study. Over a 3-week period blood glucose was maintained at predetermined levels (6–10 mmol/l or 10–20 mmol/l) by insulin treatment and then during the final 2 days rapidly reversed in half of each group. In the U rats, the hepatic N-deacetylase activity significantly decreased by 10–15% following short-and long-term poor metabolic control and the inhibition was entirely reversed by short-term good control. In the H rats a similar, not significant, effect was seen. BB rats in long-term poor control showed a 10% reduction in hepatic N-deacetylase activity (p=0.003). Glomerular N-deacetylase activity was reduced in U rats after long-term poor control (p=0.004) but not in H and BB rats. There was an overall correlation between urinary albumin excretion and glomerular N-deacetylase activity (r=−0.60, p〈0.0001). We conclude that diabetes-induced inhibition of hepatic N-deacetylase is not restricted to the streptozotocin diabetic model, and that short-term blood glucose control is of major importance. Genetic factors and tissue specificity influence the vulnerability of the enzyme. Finally, the study suggests an association between N-deacetylase activity and urinary albumin excretion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400233
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  • 3
    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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  • 4
    Electronic Resource
    Electronic Resource
    Size- and charge selectivity of glomerular filtration in Type 1 (insulin-dependent) diabetic patients with and without albuminuria (1993)
    Springer
    Diabetologia 36 (1993), S. 244-251 
    Details
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; dextran clearance ; IgG4 ; IgG ; IgG/IgG4 selectivity index ; diabetic nephropathy ; tubular function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Albuminuria is the first clinical event in the development of diabetic nephropathy. We assessed glomerular charge- and size selectivity in 51 patients with Type 1 (insulin-dependent) diabetes mellitus of juvenile onset and 11 healthy individuals. Patients were allocated to five groups. The urinary albumin excretion rate was normal in group D1; 30–100 mg/24 h in group D2; 101–300 mg/24 h in group D3 and greater than 300 mg/24 h in groups D4 and D5. Group D5 had elevated serum creatinine (above 110 μmol/l). Glomerular filtration rate and renal plasma flow were determined by constant infusion techniques and tubular protein reabsorption by excretion of β2-microglobulin. Charge selectivity was estimated from the IgG/IgG4 selectivity index. Size selectivity was measured by dextran clearance. Dextran was measured by refractive index detection after fractionation (2 Å fractions in the range 26–64 Å) by size exclusion chromatography. IgG/IgG4 selectivity index was significantly decreased in patients with albuminuria (p〈0.001). The drop in IgG/IgG4 selectivity index was found in patients with minimal albuminuria (D2) and was not accompanied by any changes in tubular function or glomerular haemodynamics. Size selectivity was significantly altered only in patients with the most advanced nephropathy (D5) as reflected by an increase in the clearance of 62 Å dextran (p〈0.04). We conclude that loss of glomerular charge selectivity precedes or accompanies the formation of new glomerular macromolecular pathways in the development of diabetic nephropathy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00399958
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