Morphometric studies of the peripheral glomerular basement membrane in early juvenile diabetes I. Development of initial basement membrane thickening

Østerby, Ruth

doi:10.1007/bf01235631

Cited by 147 publications

(58 citation statements)

References 23 publications

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“…This discrepancy could be due to the shorter duration of diabetes in the rat. On the other hand there are striking similarities, such as increase in kidney size [22,27,29], in glomerular volume [9,27,38], in glomerular basement membrane thickness [4,12,28,36], increase of mesanglum [10,14,19] and basement membrane-like material [1,35,37].…”

Section: Discussionmentioning

confidence: 99%

Prevention of diabetic glomerulopathy in streptozotocin diabetic rats by insulin treatment

Rasch

1979

Diabetologia

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Smmnm'y.A quantitative morphological study of the mesangial regions has been performed on the kidneys of two groups of insulin treated diabetic rats 6 months after the induction of diabetes. In one group reasonably good control of plasma glucose levels (182 + 20 (SD) rag/100 ml at 0800 h; 95 + 35 mg/ 100 ml at 2300 h) was achieved. This group showed no mesangial changes when compared to a nondiabetic control group. In the second diabetic group poor control was intended (plasma glucose 452 +_ 41mg/100ml and 555 _+ 86mg/100ml respectively). The following differences were noted when this group was compared to the non-diabetic controls and to the rats in which the blood glucose was wellcontrolled: 1. Increase in total mesangial volume per glomerulus by 42% and 38% (2p = 0.025 and 0.037); 2. Increase in the total amount of basement membrane-like material (BMLM) per glomerulus by 30 and 27% (2p = 0.030 and 0.046); 3. Increase in the total mesangial cell volume per glomerulus by 46 and 43% (2p = 0.033 and 0.048); 4. Increase in volume of electron dense material in the BMLM by about 200% compared to both groups (2p ---0.001 and 0.0003). The study has shown that the mesangial regions also are involved in the diabetic glomerulopathy of experimental diabetes. The morphological changes including increased amounts of basement membrane material are prevented by proper glycaemic control.Key words: Mesangial region, streptozotocin diabetes, glucose control in rats, diabetic glomerulopathy, stereology, insulin treatment.It has previously been shown that kidneys and glomeruli become enlarged over a 6 months period in rats with constant high plasma glucose levels [27].Glomerular basement membranes (GBM) were also significantly thicker than in non-diabetic control rats [28]. There is also evidence of mesangial changes in experimental diabetes in the rat [11,13,19,34,35], similar to those found in humans [21,23,24,35]. The mesangial changes due to experimental diabetes are described as an increase of the mesangium, with increased amounts of basement membrane-like material (BMLM). The mesangial regions also become strongly reactive to periodic acid-Schiff (PAS) and with the immunofluorescent technique a positive reaction to immunoglobulin and complement is seen.Consequently, the experimental diabetic rat was considered an acceptable model for studying the prevention of diabetic mesangial changes using morphometric techniques. The cationic stain Alcian Blue [31], which reveals the surface coat of the glomerular cells [2], is also bound to the mesangial regions of diabetic and non-diabetic rats [25] and this electron microscopic histochemical technique was also used in the present study. Material and MethodDetailed description of the animals, their treatment and the tissue sampling procedure has been given previously [27,28]. In summary, streptozotocin diabetes was induced by administrating 90 mg/kg intravenously. Three groups of female Wistar rats were used. In one group of 8 streptozotocin diabetic rats good diabetic control was plan...

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Section: Discussionmentioning

confidence: 99%

Prevention of diabetic glomerulopathy in streptozotocin diabetic rats by insulin treatment

Rasch

1979

Diabetologia

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“…Glomerular structure in normoalbuminuric type 1 diabetic patients. Glomerular structure is normal at onset of diabetes, and changes can be detected by morphometric measurements within 1.5-2.5 years after onset (26). However, because the normal range for glomerular structures, such as glomerular basement membrane (GBM) width or mesangial fractional volume (Vv[Mes/glom]) is quite wide, it may take some time for some individuals to progress from the normal to the abnormal range.…”

Section: Type 1 Diabetesmentioning

confidence: 99%

The need for early predictors of diabetic nephropathy risk: is albumin excretion rate sufficient?

2000

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Initial studies showing an ~80% rate of progression from microalbuminuria (MA) to proteinuria in type 1 diabetic patients led to the broad acceptance of MA as a useful clinical predictor of increased diabetic nephropathy (DN) risk. Some MA patients, however, have quite advanced renal structural changes, and MA may, in these cases, be a marker rather than a predictor of DN. More recent studies have observed only about a 30-45% risk of progression of MA to proteinuria over 10 years, while about 30% of type 1 diabetic patients with MA became normoalbuminuric and the rest remained microalbuminuric. The finding that some MA patients have only mild diabetic renal lesions is consistent with the lower than originally estimated risk of progression from MA to proteinuria and with the notion that some MA patients revert to normoalbuminuria. To increase the complexity of the scenario, some normoalbuminuric long-standing type 1 diabetic patients have well-established DN lesions and ~40% of all patients destined to progress to proteinuria are normoalbuminuric at initial screening, despite many years of diabetes. A similar picture is emerging in type 2 diabetic patients, although fewer studies have been conducted. Thus, the predictive precision for MA to progress to overt nephropathy over the subsequent decade or so is considerably less than originally described. It is unclear whether this is due to changes in the natural history of DN resulting from improved glycemia and blood pressure control, or whether there were overestimates of risk in the original studies due to the small sample sizes, post hoc analyses, and variable MA definitions. Albumin excretion rate (AER) remains the best available noninvasive predictor of DN risk and should be regularly measured according to established guidelines. However, AER may be unable to define patients who are safe from or at risk of DN with an accuracy that is adequate for optimal clinical decision making or for the design of certain clinical trials. Investigations into new risk markers or into the combined use of several currently available predictive parameters are needed.

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“…The first changes that can be measured are thickening of the GBM and tubular basement membrane (TBM) [22]. Within few years after the onset of diabetes, afferent and efferent arteriolar hyalinosis can also be noted.…”

Section: Renal Lesions In Type 1 Diabetesmentioning

confidence: 99%

The kidney in diabetes: dynamic pathways of injury and repair. The Camillo Golgi Lecture 2007

2008

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Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD). The natural history of diabetic nephropathy has changed over the last decades, as a consequence of better metabolic and blood pressure management. Thus, it may now be possible to delay or halt the progression towards ESRD in patients with overt diabetic nephropathy, and the decline of renal function is not always inexorable and unavoidable. Also, the rate of progression from microalbuminuria to overt nephropathy is much lower than originally estimated in the early 80s. Furthermore, there is now evidence that it is possible, in humans, to obtain reversal of the established lesions of diabetic nephropathy. This review focuses on the contribution of kidney biopsy studies to the understanding of the pathogenesis and natural history of diabetic nephropathy and the identification of patients at high risk of progression to ESRD. The classic lesions of diabetic nephropathy and the well-established structural-functional relationships in type 1 diabetes will be briefly summarised and the renal lesions leading to renal dysfunction in type 2 diabetes will be described. The relevance of these biopsy studies to diabetic nephropathy pathogenesis will be outlined. Finally, the evidence and the possible significance of reversibility of diabetic renal lesions will be discussed, as well as future directions for research in this field.

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Morphometric studies of the peripheral glomerular basement membrane in early juvenile diabetes I. Development of initial basement membrane thickening

Cited by 147 publications

References 23 publications

Prevention of diabetic glomerulopathy in streptozotocin diabetic rats by insulin treatment

Prevention of diabetic glomerulopathy in streptozotocin diabetic rats by insulin treatment

The need for early predictors of diabetic nephropathy risk: is albumin excretion rate sufficient?

The kidney in diabetes: dynamic pathways of injury and repair. The Camillo Golgi Lecture 2007

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