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R Osterby

Publications and source records attributed to R Osterby.

At least 37 records · Page 2Linked to original sources
PubMed1998

Renal structural changes in insulin-dependent diabetic patients with albuminuria. Comparison of cases with onset of albuminuria after short or long duration.

The large interindividual variation in diabetes duration until the onset of nephropathy is partly unexplained. This study was performed to compare renal structure in insulin-dependent (IDDM) patients who had developed signs of nephropathy after a short or long duration of diabetes. Renal biopsies were obtained from 17 IDDM patients, with albumin excretion rate 20-300 microg/min and normal blood pressure. Six patients had <25 years duration ("short-term", early onset of microalbuminuria) and eight patients had duration >30 years ("long-term", late onset of microalbuminuria). Biopsies were obtained 18 months after entry into a study testing the effect of low-dose antihypertensives. Parameters characterizing diabetic glomerulopathy were significantly increased in IDDM patients compared with those in 17 living donors: Basement membrane thickness, mean and (CV): 591 nm (0.17) vs 320 nm (0.12), mesangial volume fraction per glomerulus 0.27 (0.19) vs 0.19 (0.10), matrix volume fraction per glomerulus 0.16 (0.20) vs 0.097 (0.22), matrix star volume 38.5 microm3 (0.43) vs 13.9 microm3 (0.31), (p<10(-4) for each). Comparison of short vs long-term patients showed no significant differences in glomerulopathy parameters, glomerular volume or extracellular material per glomerulus, whereas the fraction of occluded glomeruli was significantly increased in long-term patients. A close correlation obtained between fraction of occluded glomeruli and glomerular filtration rate (r=0.72, p= 0.001). Glomerular occlusion occurred unrelated to the severity of diabetic glomerulopathy. It is suggested that diabetic macroangiopathy and arteriolar hyalinization may play an important role in the renal function of patients with slow development of nephropathy.

Adult↗
PubMed1998

Diabetic glomerulopathy in young IDDM patients. Preventive and diagnostic aspects.

The clinical course of diabetic nephropathy may be described in stages; the normo-, micro- and macroalbuminuric stage. The basis for its development is the diabetic glomerulopathy in which accumulation of basement membrane (BM) material is pivotal. Normoalbuminuric patients have normal or slightly increased BM thickness; microalbuminuric patients show further BM thickening and mesangial expansion, formation of new capillaries, arteriolar and interstitial changes. The degree of diabetic glomerulopathy may be predicted by long-term glycemic control, diabetes duration and glomerular filtration rate (GFR). A slight decline in GFR in microalbuminuric patients is associated with increases in BM thickness, capillary diameter and interstitial volume fraction. In turn, the degree of early diabetic glomerulopathy may predict the level of microalbuminuria several years later. Improved metabolic control, even to not normal levels, retards the increase of BM thickness and matrix volume in microalbuminuric adolescents. If matrix accumulation may be prevented diabetic nephropathy will not develop. Morphometric analyses may thus be useful in evaluating the effect of intervention, also during shorter periods and at early stages.

Adolescent↗
PubMed1997

Glomerular volume and the glomerular vascular pole area in patients with insulin-dependent diabetes mellitus.

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 micrograms/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 approximately 10 microns, 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) microns2 in ND, 3555 (34) micron2 in IDDM group 1, and 3528 (48) microns2 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.

Adolescent↗
PubMed1997

Advanced glycation end products in serum predict changes in the kidney morphology of patients with insulin-dependent diabetes mellitus.

The biochemical mechanisms that cause the development and progression of diabetic nephropathy are unknown. Advanced glycation end products (AGEs) might play a role, as shown by increased levels of tissue-bound and circulating AGEs that correlate with the severity of diabetic nephropathy. The aim of the present study was to investigate if circulating AGEs predict the progression of morphological pathology in patients with diabetic nephropathy. We have developed an immunoassay to determine serum levels of AGEs. In a prospective clinical trial of young insulin-dependent diabetes mellitus (IDDM) patients with microalbuminuria, kidney biopsies were taken at baseline and after 24 to 36 months. The biopsies were analyzed for structural changes in the glomeruli by quantitative morphometry (electron microscopy). We have retrospectively analyzed serum AGEs. The mean serum level of AGEs at the start of the study was 18.7 U/mL (95% confidence interval [CI], 16.9 to 20.5). A positive correlation between serum AGE levels at the start of study and changes from baseline to follow-up study in basement membrane thickness (r = .56, P < .02) and matrix/glomerular volume fraction (r = .57, P < .02) was demonstrated. In a stepwise regression analysis with changes in the matrix/glomerular volume fraction as the dependent variable, serum AGE levels at the start of the study proved to be a significant independent variable (P < .02), whereas the mean hemoglobin A1c (HbA1c) or HbA1c at the start was not. This study shows that serum AGEs predict the progression of early morphological kidney damage during 2.5 years in patients with IDDM.

Adolescent↗
PubMed1997

Decreasing glomerular filtration rate--an indicator of more advanced diabetic glomerulopathy in the early course of microalbuminuria in IDDM adolescents?

BACKGROUND: Overt diabetic nephropathy is accompanied by a progressive decline in glomerular filtration rate (GFR). In this study we have investigated if a reduction of GFR already during the transition from normo- to microalbuminuria is associated with glomerular structural changes. METHODS: Seventeen adolescents (11 girls/6 boys) with 10.5 (3.3) (mean, SD) years of IDDM were studied. GFR was previously measured in the normoalbuminuric stage 2-5 years prior to the renal biopsy, and measured again at the time for the biopsy, after in mean 1.8 years of microalbuminuria (15-200 micrograms/min). HbAlc and albumin excretion rate were measured 3 or 4 times yearly and blood pressure 1-4 times yearly between the GFR examinations. The associations between the yearly rate of fall in GFR and basement membrane (BM) thickness, mesangial and matrix volume fractions, matrix star volume, mean capillary diameter (CAPD), area of filtration surface (peripheral BM) per glomerulus, total capillary length per glomerulus, the ratio of peripheral BM to capillary surface, glomerular volume, and interstitial volume fraction were analysed. RESULTS: BM thickness and matrix star volume were increased in patients with, as compared to those without, a decline in GFR > or = 6 ml/min per year (P < 0.005 respectively). Patients with previous glomerular hyperfiltration (> or = 135 ml/min per 1.73 m2) showed the steepest decline in GFR; 11 ml/min per year versus -0.8 ml/min per year in previously normofiltering patients, P < 0.001. The rate of fall in GFR was positively correlated to BM thickness (P < 0.001), interstitial volume fraction (P = 0.02) and CAPD (P = 0.04), mean HbAlc (P = 0.01), but not to the change in HbAlc between GFR examinations. CONCLUSION: A decreasing glomerular filtration rate in the early stage of microalbuminuria may be due to more advanced diabetic glomerulopathy than in IDDM patients with stable GFR.

Adolescent↗
PubMed1997

Effect of GH/IGF-I deficiency on long-term renal changes and urinary albumin excretion in diabetic dwarf rats.

Growth hormone (GH) and insulin-like growth factor I (IGF-I) may play a role in early diabetic renal and glomerular growth and in the later development of experimental diabetic kidney disease. Rats from a genetic GH/IGF-I-deficient dwarf rat strain were made streptozotocin diabetic and were compared with nondiabetic dwarf rats. GH/IGF-I-intact rats with and without diabetes served as controls. After 6 mo of diabetes, kidney weight and total glomerular volume increased significantly in GH/IGF-I-intact diabetic rats compared with the nondiabetic GH/IGF-I-intact rats (P < 0.05), whereas the diabetic dwarf rats had insignificant changes compared with dwarf control rats. By the end of the study, urinary albumin excretion (UAE) increased from similar base levels of approximately 15-20 micrograms/24 h to 473 +/- 52 (SE) micrograms/24 h in GH/IGF-I-intact diabetic rats compared with 151 +/- 32 micrograms/24 h in diabetic dwarf rats (P < 0.01). In conclusion, isolated GH/IGF-I deficiency reduces the degree of renal and glomerular hypertrophy and the increase in UAE after 6 mo of experimental diabetes in GH/IGF-I-deficient rats.

Albuminuria↗
PubMed1997

Predictors of renal morphological changes in the early stage of microalbuminuria in adolescents with IDDM.

OBJECTIVE: To evaluate the impact of glycemic control, blood pressure, lipid levels, glomerular filtration rate (GFR), age, and duration of IDDM on the degree of structural glomerular changes in the transitional stage of microalbuminuria. RESEARCH DESIGN AND METHODS: Fifteen adolescents (seven boys and eight girls) with > 5 years of duration of IDDM and with low-grade microalbuminuria (15-30 micrograms/min) participated. Seventeen living kidney donors served as healthy control subjects. Five-year mean HbA1c; 5-year mean systolic and diastolic blood pressure; GFR, cholesterol, and triglycerides 2-5 years before renal biopsy; age; and duration of IDDM were investigated and related to basement membrane thickness (BMT), mesangial and matrix volume fractions, and the overall glomerulopathy index [(BMT/10 + mat/glom, %) + matrix star volume]. RESULTS: BMT and the overall diabetic glomerulopathy were increased in diabetic patients as compared with control subjects (P < 0.001), whereas matrix volume fraction, but not mesangial volume fraction, tended to be increased (P = 0.11). In multivariate analysis, BMT was predicted by 5-year mean HbA1c, diabetes duration, and previous GFR (R2 = 0.71, P = 0.003). With matrix volume fraction as the dependent variable, BMT and diabetes duration were the only significant determinants (R2 = 0.63, P = 0.003). Diabetes duration, 5-year mean HbA1c, and GFR were the variables with an independent influence on the overall diabetic glomerulopathy index (R2 = 0.72, P = 0.003). Preceding blood pressure and lipid levels or age had no significant independent influence on these morphometric measures. CONCLUSIONS: In the very early stage of microalbuminuria in IDDM adolescents, a high percentage of the variation in BMT and overall severity of glomerulopathy is explained by prolonged hyperglycemia and diabetes duration. Previous glomerular hyperfiltration may also add to the prediction of these morphological changes.

Adolescent↗
PubMed1996

Effects of heparin on renal morphology and albuminuria in experimental diabetes.

Female nondiabetic and streptozotocin diabetic Wistar rats received 200 units heparin two times daily by subcutaneous injection for 6 mo. Mesangial volume fraction was reduced in heparin-treated control (CH) compared with untreated control (C) animals (CH 0.18 +/- 0.02 vs. C 0.24 +/- 0.02, P < 0.05), but other histological parameters were similar. In the heparin-treated diabetic (DH) group, wet kidney weight was increased compared with the untreated diabetic (D) group (DH 1,156 +/- 39 vs. D 1,050 +/- 30 mg, P < 0.05), as were absolute, but not fractional, glomerular volume (P < 0.05) and capillary volume (P < 0.05). Basement membrane thickness (DH 193 +/- 3 vs. D 231 +/- 9 nm, P < 0.01) and mesangial/glomerular volume fraction (P < 0.001) were decreased. Urinary albumin excretion was increased in the heparin-treated control animals compared with control animals [CH 980 (range 150-4,448) vs. C 221 (range 86-654) micrograms/24 h, P < 0.001] and in the heparin-treated diabetic animals compared with the diabetic animals [DH 12,785 (range 4,495-29,520) vs. D 899 (range 450-1,335) micrograms/24 h, P < 0.001]. Thus the possibly deleterious increases in glomerular capillary volume and albumin excretion may negate the beneficial effects of heparin on mesangial and basement membrane structures.

Albuminuria↗
PubMed1996

Glomerular ultrastructure in kidneys transplanted simultaneously with a segmental pancreas to patients with type 1 diabetes.

BACKGROUND: Pancreas transplantation has been reported to prevent development and progression of diabetic glomerulopathy. STUDY DESIGN: Kidneys transplanted to type 1 diabetic patients were investigated for signs of diabetic glomerulopathy. Biopsies were obtained from 11 patients 2-4 years after simultaneous pancreas and kidney transplantation and from six patients 2-6 years after kidney transplantation alone. During follow-up, glycaemic control was monitored as glycated haemoglobin and, in the pancreas transplant patients, as i.v. glucose tolerance. RESULTS: Measures of glycaemic control were consistently normal in only two pancreas transplant patients. Four had mean k values <1.0. In kidney biopsies from the pancreas transplant patients, thickness of the glomerular basement membrane was 395 (0.13) nm (mean, coefficient of variation), which is higher than normal (324 (0.13) nm, P=0.01) and not different from diabetic patients with kidney transplants alone, 418 (0.15) nm. The mean calculated annual increase in thickness did not differ between patients with and without a pancreas transplant, 26 (0.77) versus 29 (0.54) nm/year. Estimates of the mesangium and mesangial matrix were in the normal range in both groups while the interstitial volume fraction was increased and to a similar extent. CONCLUSION: The increase in thickness of the glomerular basement membrane in kidneys transplanted simultaneously with a segmental pancreas is probably an expression of diabetic glomerulopathy caused by the modest impairment in glucose metabolism present in most patients.

Adult↗
PubMed1995

Effect of octreotide and insulin on manifest renal and glomerular hypertrophy and urinary albumin excretion in long-term experimental diabetes in rats.

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 placebo-treated 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.

Albuminuria↗
PubMed1995

A quantitative ultrastructural study of juxtaglomerular arterioles in IDDM patients with micro- and normoalbuminuria.

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 micrograms/min) and 16 with microalbuminuria (15-200 micrograms/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-micron thick sections for light microscopy at 10-micron intervals, and thin sections for electron microscopy taken at 60-micron intervals. The arterioles were identified as afferent or efferent, and total profiles were photographed (magnification 7500x), 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 (co-efficient 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) micron vs 1.44 (0.30) micron (p = 0.004), and 1.62 (0.28) micron 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.

Adolescent↗
PubMed1995

Glomerular epithelial foot processes and filtration slits in IDDM patients.

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.

Adolescent↗
PubMed1994

Improvement of blood glucose control in IDDM patients retards the progression of morphological changes in early diabetic nephropathy.

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 (HbA1c) 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 HbA1c 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 HbA1c 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Glomerular structure and function in proteinuric type 2 (non-insulin-dependent) diabetic patients.

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)

Adult↗