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Biomedical subjects

R Osterby

Publications and source records attributed to R Osterby.

At least 55 records · Page 3Linked to original sources
PubMed1993

Early glomerulopathy is present in young, type 1 (insulin-dependent) diabetic patients with microalbuminuria.

Increased urinary albumin excretion, microalbuminuria, may be the first sign of early diabetic nephropathy. We examined glomeruli by morphometric methods in 17 patients with Type 1 (insulin-dependent) diabetes mellitus and microalbuminuria. The median age was 19 (range 18-29) years, duration of diabetes 12 (8-15) years, mean blood pressure 93 (87-115) mm Hg, glomerular filtration rate 132 (101-209) ml.min-1.1.73 m2 -2, albumin excretion rate (mean over 1 year) 32 (15-194) micrograms/min. Reference data were obtained from 11 healthy kidney donors. Mesangial volume estimates were obtained by serial sectioning in three total profiles in each of three glomeruli in diabetic patients. Basement membrane thickness and matrix volume fraction were estimated from one level per glomerulus. Two matrix parameters, matrix star volume and matrix thickness, were estimated. Interstitial volume fraction in cortex was measured by light microscopy. The morphological parameters were significantly increased in the diabetic group compared to the control group, basement membrane thickness (mean with 95% confidence intervals) was 595 nm (549-641 nm) vs 305 nm (287-325 nm), p = 0.0001; mesangial volume fraction 0.22 (0.21-0.23) vs 0.19 (0.18-0.21), p = 0.04, and matrix volume fraction 0.13 (0.12-0.13 vs 0.09 (0.08-0.10), p = 0.001. Also matrix star volume and thickness, interstitial volume fraction and mean capillary diameter were significantly increased. The intra-individual variation among glomeruli expressed as coefficient of variation was 7.4% vs 9% (basement membrane thickness) and 11.7% vs 25% (mesangial volume fraction) in the diabetic and the control group, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Renal pathology in diabetes mellitus.

The key change in diabetic glomerulopathy is accumulation of extracellular material. Basement membrane thickening and matrix expansion develop concomitantly. In insulin-dependent diabetic patients persistent microalbuminuria is associated with an early stage of glomerulopathy. Albuminuria in non-insulin-dependent patients does not always reflect glomerulopathy. Renal and glomerular hypertrophy in the early stages of insulin-dependent diabetes mellitus is unlikely to play a dominant role in the development of glomerulopathy. Loss of capillary surface, closely associated with loss of glomerular function, is only partly explained by mesangial expansion--glomerular occlusion plays an important role. Possible mechanisms of albuminuria are qualitative changes of the basement membrane, eg, loss of proteoglycans and excess glycosylation; epithelial cell changes; new vessel formation; remodeling of glomerular structures; and impeded function of juxtaglomerular arterioles. The interplay among abnormalities in individual compartments of the diabetic kidney should be explored.

Animals↗
PubMed1992

Glomerular structural changes in type 1 (insulin-dependent) diabetes mellitus: causes, consequences, and prevention.

Diabetic nephropathy is caused primarily by advanced glomerulopathy, the renal expression of diabetic microangiopathy. With stereological methods a quantitative description of the structural changes is achieved. The glomerulopathy is characterized by an increase in basement membrane material: thickening of the capillary wall and an increase in mesangial volume relative to glomerular volume, comprising increase in matrix. Among groups of patients conformity between renal function stage and structure exists. The parameters measuring glomerulopathy are normal at the onset of diabetes; patients with normoalbuminuria may show slight basement membrane thickening, or normal parameters; the microalbuminuric group shows a measurable, but moderate glomerulopathy; patients with overt nephropathy have advanced lesions; at this stage heterogeneity among glomeruli makes the estimates weaker. Recent data indicate that the changes in peripheral basement membrane and in mesangial matrix develop in concert and both contribute to the early stage of glomerulopathy in patients with microalbuminuria. As to the consequences of the structural changes the mechanism of albuminuria is not clear. It is suggested that the early glomerulopathy entails other structural modifications, including formation of new vessels which may be the site of leakage. The marked deviations in glomerular filtration rate correspond well with estimates of filtration surface area: in the early hyperfunction state it is increased; in advanced nephropathy it is decreased, due to advanced glomerulopathy in conjunction with glomerular occlusion. The diabetic state is the necessary condition for the glomerulopathy. In relating structural changes to presumed contributing causes no supporting evidence of a relationship with glomerular hyperfunction or hypertrophy was observed. The structural parameters may be useful tools in clinical trials aiming at arresting the development of glomerulopathy, and thereby providing a prevention of diabetic nephropathy.

Diabetes Mellitus, Type 1↗
PubMed1992

Glomerular structure in type-1 (insulin-dependent) diabetic patients with normo- and microalbuminuria.

Kidney biopsies from 15 type-1 (insulin-dependent) diabetic patients with a range of albumin excretion (AER) were analyzed. Nine patients had normal AER, and six had microalbuminuria. Basement membrane thickness, BMT, and mesangial matrix volume fraction, Vv(mat/glom), were obtained from at least three glomeruli per biopsy. Mesangial structures were estimated with electron microscopic analysis at three levels in each glomerulus. Glomerulopathy parameters were significantly increased in micro- versus normoalbuminuric patients with the following means and (CV): BMT 571 nm (0.12) and 442 nm (0.25), P = 0.03; Vv(mes/glom) 0.31 (0.20) and 0.22 (0.14), P = 0.002; Vv(matrix/glom) 0.17 (0.25) and 0.11 (0.28), P = 0.006; matrix star volume 56 microns 3 (0.47) and 22 microns 3 (0.43), P = 0.02. A positive correlation obtained between AER and each of the glomerulopathy parameters, BM thickness, Vv(mes/glom) and Vv(matrix/glom), as well as between AER and a structural index expressing the sum of changes in the peripheral BM and in the mesangium (r = 0.62, P = 0.01). The results indicated a parallel course of mesangial and peripheral BM changes: a positive correlation obtained between BM thickness and mesangial parameters [BMT versus Vv(matrix/glom): r = 0.82, P = 0.0001] and the ratio of the two subsets of glomerular BM material (PBM:matrix) did not show significant difference between normo- and microalbuminuric groups. The data give strong support to the contention that the transition from normo- into the microalbuminuric phase is linked to progressing glomerulopathy.

Albuminuria↗
PubMed1992

Glomerular volume in kidneys transplanted into diabetic and non-diabetic patients.

Biopsies taken at the time of renal transplantation in 12 non-diabetic and 23 diabetic patients were studied by quantitative light- and electron-microscopy. Repeat biopsies were taken at 6 months and/or after 2-3 years in patients who had acceptable graft function. All patients except two received cyclosporin as part of the immunosuppression. Glomerular volume was significantly increased, + 36(95% CI +6 to +65) % (p = 0.03), in the diabetic patients at 6 months which differed from the change of -20 (-50 to +10) % in the non-diabetic patients (p = 0.03). After 2-3 years glomerular volume was equal to the baseline value in the diabetic patients, while the change from baseline in the non-diabetic patients was -21 (-42 to -1) %. Substantial glomerular occlusion was seen in only three diabetic patients after 2-3 years. Total structural volumes per glomerulus in the 2-3-year biopsies showed an increase in basement membrane material of 0.09 x 10(6) microns 3 in the diabetic patients, significantly different from the change in non-diabetic patients (-0.10 x 10(6) microns 3, p = 0.003). No correlation was obtained between the 6-month increase in glomerular volume and the development of diabetic glomerulopathy at 2-3 years. The fact that glomerular hypertrophy was not present in the entire series may be due to the cyclosporin and to rejection. Nevertheless the diabetic group did show an early hypertrophy which did not seem to play a major role in the ensuing development of diabetic glomerulopathy.

Adult↗
PubMed1992

Kidney IGF-I and renal hypertrophy in GH-deficient diabetic dwarf rats.

Insulin-like growth factor I (IGF-I) has been proposed as a renotropic factor in initial diabetic kidney growth. To examine the effects of an isolated growth hormone (GH) and IGF-I deficiency on diabetic renal hypertrophy, dwarf rats were made diabetic and studied over a period of 7 days. Diabetic dwarf rats treated with human GH (hGH) or insulin and diabetic rats with intact pituitary were used as controls. In diabetic control animals kidney weight had increased by day 2 (P less than 0.01), and the increase amounted to 27% after 7 days, whereas untreated diabetic dwarf rats had a slower and lesser degree of kidney weight increase, reaching significance on day 7 only, amounting to 8%. hGH administration in diabetic dwarf rats increased the kidney weight on day 7 when compared with untreated diabetic dwarf rats (P less than 0.05) and was 19% over that of insulin-treated diabetic dwarf rats. The glomerular volume had increased by 43% in untreated diabetic control rats at day 7, compared with a 29% increase in untreated diabetic dwarf rats (P less than 0.05). hGH administration in diabetic dwarf rats increased the glomerular volume by 46%, comparable to the increase seen in diabetic control animals. Kidney IGF-I was increased on day 2 by 51 and 46% in saline- and hGH-injected diabetic dwarf rats, respectively, but a significantly higher increase in kidney IGF-I amounting to 96% was seen in diabetic control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Blood pressure elevation versus abnormal albuminuria in the genesis and prediction of renal disease in diabetes.

A number of risk factors associated with the development of diabetic nephropathy has been described, such as elevated blood pressure, poor metabolic control, hyperlipidemia, and smoking. Abnormal albuminuria also is associated with progression of renal disease, but has until recently been considered principally a marker of disease activity rather than a risk factor. This article discusses the role of elevated blood pressure versus abnormal albuminuria in a genesis and prediction of renal disease in diabetes. Controversy exists regarding parental disposition to hypertension and early blood pressure elevation in the course of diabetes, but all studies agree that elevated blood pressure--in the presence of abnormal albuminuria--constitutes a risk factor. Because abnormal albuminuria is associated with progression disease, it may itself be a risk factor because increased macromolecular traffic over the glomerular membrane may produce glomerulopathy. Problems related to blood pressure measurement are important, and 24-h recordings of blood pressure may be recommended in some situations. Regarding renal structure, preliminary results suggest that structural lesions precede blood pressure elevation. The solid end point for evaluation of renal disease progression is the fall rate of GFR, with abnormal albuminuria as an intermediate end point, also in drug trials. Abnormal albuminuria may constitute a new indication for antihypertensive treatment, being, as it is, a clear indicator of organ damage, whereas elevated blood pressure with normal AER may not increase risk substantially.

Albuminuria↗
PubMed1991

Kidney transplantation in type 1 (insulin-dependent) diabetic patients. Early glomerulopathy.

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-1 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Glomerular structure and function in diabetic nephropathy. Early to advanced stages.

Kidney biopsies from 14 insulin-dependent diabetes mellitus patients with persistent albuminuria were studied by light and electron microscopy. In terms of kidney function, the patients spanned stages from early to advanced nephropathy. The clinical parameters were (ranges, with medians in parentheses) urinary albumin excretion (UAE) 158-5494 micrograms/min (1153 micrograms/min), glomerular filtration rate (GFR) 30-128 ml.min-1 x 1.73 m-2 (90 ml.min-1 x 1.73 m-2) and mean arterial blood pressure (BP) 87-122 mmHg (109 mmHg). The severity of clinical nephropathy (UAE, GFR, and BP together) correlated with an index of the structural lesions (basement membrane [BM] thickness, mesangial expansion, and glomerular occlusion together; r = 0.62, 2P less than 0.05). GFR compared with remnant surface of glomerular capillaries (filtration surface; FS) gave values of r = 0.72 and 2P = 0.004, and UAE compared with the percentage of the peripheral BM surface carrying fluffy loose intrinsic fine structure gave r = 0.62 and 2P = 0.02. BP per se did not correlate with structural parameters. The area of FS per open glomerulus did not decrease with increasing mesangial volume fraction, which indicates compensatory changes of the capillaries in early and advanced stages of glomerulopathy. In 7 patients with less than 10% occluded glomeruli, correlations between glomerular volume and the parameters of diabetic glomerulopathy (i.e., BM thickness and volume fractions of mesangium and mesangial matrix) failed to reach statistical significance. The actual glomerular volume, however, is a product of the individual's original glomerular volume, probably the early diabetic hypertrophy and modifying changes consequent to the development of glomerulopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Mesangial expansion as a central mechanism for loss of kidney function in diabetic patients.

Diabetic nephropathy leading to kidney failure is a major complication of both type I (insulin-dependent) and type II (non-insulin-dependent) diabetes mellitus, and glomerular structural lesions (especially expansion of the mesangium) may constitute the principal cause of decline in kidney function experienced by a significant fraction of diabetic patients. Although the biochemical bases of these mesangial abnormalities remain unknown, an understanding of the natural history of diabetic nephropathy from a combined structural and functional approach can lead to greater pathophysiological insight. Work in animals has supported the concept that the metabolic disturbances of diabetes mellitus cause diabetic nephropathy, with structural and functional lesions prevented or reversed with improved or normalized glycemic control. Additional research must address this fundamental issue in humans, especially the response of advancing mesangial lesions to improved glycemic control. Factors not directly related to the metabolic perturbations of diabetes may serve to accelerate or diminish the pathophysiological processes of diabetic nephropathy. The elucidation and management of these factors, when coupled with improved glycemic control, may moderate the development or progression of diabetic kidney lesions in humans.

Albuminuria↗
PubMed1989

Morphology of diabetic glomerulopathy and relationship to hypertension.

The mutual relationship between elevated blood pressure and structural changes in the kidney is still an area with more open questions than clear answers. Indirect evidence is available concerning one aspect: When hypertension is present it has a significant impact on the further progression of the structural changes. This evidence is available only in terms of the effect of antihypertensive treatment on the preservation of renal function. Since it has been shown that the demise in renal function in long-term diabetics is closely related to the development of advanced diabetic glomerulopathy, it seems likely that normalization of the blood pressure leads to a slowing of this development. Structural studies to elucidate these interactions are, however, not available. An intriguing question is whether the relationship is interactive also in the other direction. Focusing on the alterations within the glomeruli, the fact is that the glomerulopathy develops over several years before it come to the stage when clinical signs appear. Thus, diabetics with "incipient nephropathy" clearly demonstrate basement membrane (BM) accumulation, showing as increased BM-thickness and increase in mesangial matrix volume. Since this is the most likely point of time for hypertension to develop the necessary condition obtains, that the development of hypertension might be triggered by structural abnormalities in the kidney. The mechanisms of action at this point of time remain speculative. The relationship between structural parameters characterizing diabetic glomerulopathy and the blood pressure level was studied in a series of 14 IDDM patients, representing a span of renal functional impairment. Mean blood pressure in the group was 117 mmHg, with a range from 87-122 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1988

A strong correlation between glomerular filtration rate and filtration surface in diabetic nephropathy.

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 mm Hg (SD = 11/9). The urinary albumin excretion rate showed a range from 100 to 5494 micrograms/min (geometric mean 688 micrograms/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 less than 10(-4). The percentage occluded glomeruli contributed significantly to the variation in glomerular filtration rate (for this relationship tested separately r = -0.78, p less than 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.

Adult↗
PubMed1988

Glomerular morphology by light microscopy in non-insulin-dependent diabetes mellitus. Lack of glomerular hypertrophy.

We quantitated glomerular structure by light microscopy in 19 subjects with non-insulin-dependent diabetes mellitus (NIDDM) and studied the possible connection between morphology and urinary albumin concentration. Autopsy material was collected retrospectively from diabetic subjects in whom urinary albumin concentration had been measured within 1.5 yr. Nineteen consecutive sex- and age-matched nondiabetic subjects were controls. A quantitative study of a random sample of glomeruli was performed blindly on periodic acid-Schiff (PAS)-stained sections. The main parameters obtained were 1) mean volume of open glomeruli, 2) frequency of glomerular occlusion, and 3) volume fraction of red-stained material (PAS-positive substance) in open glomeruli [Vv(R/G)]. There was no increase in glomerular volume in these NIDDM subjects, contrary to the glomerular hypertrophy found early as well as late in insulin-dependent diabetes mellitus. An increase in Vv(R/G) was found in diabetic subjects, demonstrating the presence of glomerulopathy as it is diagnosed by light microscopy. The frequency of glomerular occlusion was not significantly different between the groups. A high urinary albumin concentration did not necessarily reflect more advanced glomerulopathy.

Aged↗
PubMed1988

Glomerular structural quantities in baseline biopsies from cadaveric donor kidney pairs.

Glomerular structural parameters were estimated in kidney biopsies from 11 cadaveric donors at the time of transplantation. The main purpose was to compare the biopsies from the right and left kidney from each donor. Mean glomerular volume was determined by light microscopy. The ultrastructural parameters were basement membrane thickness and volume fractions of mesangial regions with either the tuft or total glomerulus, (i.e. the tuft plus the urinary space in between the capillaries) as reference spaces. Further, the mesangial composition was determined as the volume fraction of basement membrane-like material to total mesangial regions (Vv(BMLM/mes]. The structural quantities conformed with those obtained in living kidney donors. The coefficient of variation (CV) for the group of 11 cases was highest for the mean glomerular volume (0.26) and lowest for the Vv(BMLM/mes) (0.10). The coefficient of error (CE) of the two independent determinations of structural parameters in each individual was well below 5%. The findings therefore demonstrate that, with the methods used, a renal biopsy gives valid and reliable information for that particular individual - at least in cases with 'normal' structures.

Adult↗
PubMed1987

Quantitative changes of cerebral neocortical structure in insulin-treated long-term streptozocin-induced diabetes in rats.

The brains of rats with streptozocin-induced diabetes treated with a low-dose insulin regimen (1 IU/day) were studied with morphometric techniques. After 1 yr of diabetes, brain weight decreased slightly (1350 +/- 71 vs. 1521 +/- 55 mg, 2P less than .01) as did the volume of the neocortex (498 +/- 36 vs. 567 +/- 40 mm3, 2P less than .05). A significant loss of neocortical neurons occurred (38 +/- 2 X 10(6) vs. 46 +/- 3 X 10(6), 2P less than .01), and the length of the capillary network in the neocortical tissue shortened disproportionately (405 +/- 102 vs. 631 +/- 47 m, 2P less than .01), leading to increased diffusion distance. The mechanisms underlying cerebral loss in this model are unknown, but abnormalities of the vascular supply with prolongation of the route of diffusion might play a role.

Animals↗
PubMed1987

Advanced diabetic glomerulopathy. Quantitative structural characterization of nonoccluded glomeruli.

Quantitative ultrastructural data were obtained from kidney biopsy material of 12 long-term insulin-dependent diabetics. All patients had overt diabetic nephropathy with increased urinary albumin excretion and reduced glomerular filtration rate. Renal clearance of 51Cr-EDTA was in the range of 16-50 ml X min-1 X 1.73 m-2. All patients received antihypertensive treatment. A combined light- and electron-microscope study was performed. A significant proportion of the glomeruli was totally occluded (mean 36%, range 24-67%). Structural data presented relate only to the open, still-functioning glomeruli. Comparison with data previously obtained showed that the thickness of the peripheral basement membrane [647 nm, coefficient of variation (C.V.) 0.22] was more than twice the normal value (310 nm, C.V. 0.08); the width of epithelial foot processes (352 nm, C.V. 0.07) was significantly greater than in normal biopsies (224 nm, C.V. 0.06); and the mean volume of the open glomeruli was markedly increased compared with normal and clearly exceeded that in the early diabetic hypertrophy. Total mesangial volume and total basement membrane material per open glomerulus were increased by 277 and 614%, respectively. However, capillary length and surface per open glomerulus were similar to those observed in early diabetic hypertrophy. These findings suggest that a late glomerular hypertrophy with preservation of capillary surface occurs as a compensatory phenomenon, prolonging renal survival for diabetic nephropathy patients.

Adolescent↗