A multivariate morphometric analysis of the glomeruli in the normal and pathologically changed human kidney.
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Publications and source records attributed to H Wehner.
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To detect structural glomerular alterations in the early stages of diabetes mellitus glomeruli from young streptozotocin diabetic rats were studied by light microscopy with morphometric methods 2, 8, 12 and 24 weeks after induction of diabetes. It was found that there is a marked increase in the percentage mesangial surface as compared with the control animals already two weeks after induction of diabetes. The relative mesangial surface fraction was greater in the diabetic animals than in the controls at all test times. It was also demonstrated that the endothelial cell count was reduced in the diabetic animals in the first few weeks of the study. High-grade glycosuria and proteinuria were likewise observed in the diabetic animals. Hence the mesangium appears to be one of the glomerular structures which shows the first changes in the initial stages of diabetes mellitus. Possibly the most likely cause of the changes based on the present study is the diabetic metabolic state (or the insulin deficiency).
To investigate whether glomerulosclerotic changes can be transmitted by spleen cells, two-month-old diabetic KK-mice received a spleen homogenate transplanted subcutaneously. the donors were two-year-old diabetic KK-mice. Control animals received physiological saline. Kidneys and pancreas were removed four or ten months after the transplantation. Apart from histological and partly immunohistological studies the kidneys (glomeruli) were also evaluated morphometrically on a blind basis. Blood sugar levels were determined together with serum insulin concentrations in some animals. Marked widening of the mesangium and an increase in mesangial cells was found in the transplanted animals four months after the transplantation when compared with the control animals, a finding that was confirmed by morphometric studies. All transplanted animals exhibited a lymphoplasmocytic periductulitis and some showed insulitis in the pancreas. Degranulation of beta-cells was observed in some animals. Serum insulin was significantly reduced one month after the transplantation and blood sugar levels in the transplanted animals were continuously higher after three month than the values in the control animals. The investigations show that transplantation of spleen cells induces progression of diabetic glomerulosclerotic renal alterations and also causes periductulitis and in isolated cases insulitis.
One hundred and eleven cases of diabetic glomerulosclerosis (biopsies n=106, autopsies n=5) are divided into three groups: Diffuse diabetic glomerulosclerosis (n=74), mixed diffuse-nodular glomerulosclerosis (n=14) and nodular diabetic glomerulosclerosis (n=23). The clinical parameters, data concerning duration of diabetes and of renal disease, as well as types of therapy, were correlated with the different morphologic groups. The following results could be observed: nodular glomerulosclerosis very frequently occurs in women, often accompanied by a diabetes-manifestation beyond the fourth decade of life. This correlated with the longest duration of diabetes and frequently showed a greatly increased serum-creatinine level. Proteinuria of about 90% is the most frequent and first symptom of diabetic glomerulosclerosis. Therapy with insulin apparently shows an advantageous influence on proteinuria. In summary, however, the variability of clinical symptoms and signs should be emphasised, preventing in some cases a diagnosis being made on clinical findings alone.
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Glomerular changes develop in rats with streptozotocin diabetes. The structure of these lesions (nodular and diffuse glomerulosclerosis, mesangial cell proliferation, basement membrane thickening, glomerular aneurysms, fibrinoid caps, glomerular adhesions) is described in the present paper and the effect of normalization of metabolism by islet transplantation on the glomerular changes is studied with histological, immunohistological and morphometric methods. Isogenous islets were transplanted into the portal vein of streptozotocin-diabetic rats after diabetes of 7 months' duration. The kidneys of normal, diabetic and transplanted animals of the same age were studied 2.5 months later. Studies of the kinetics of immunocomplexes in the mesangium were also performed. The renal changes (glomerulosclerosis, mesangial cell proliferation) were largely reversible after islet transplantation and the blood glucose level and glucose tolerance were normalized. In the diabetic animals the delayed uptake and elimination of immunocomplexes in the mesangium was normalized after the transplantation. It is possible, that the cause of the lesions is a functional disturbance of the mesangium induced by insulin deficiency and/or hyperglycaemia.
Weak nonspecific immunological stimuli can irritate the glomerular mesangium as observed following administration of insulin preparations of varying degrees of purity. In the present study further substances were investigated with regard to this effect. We wished to examine which substances obtained during purification of insulin are mainly responsible for the antigenicity, and whether porcine and bovine MC insulin have the same antigenic properties. Rabbits were treated for up to 90 days with bovine MC insulin, bovine proinsulin, bovine a + b-component, porcine a-component and porcine b-component. The kidneys were analysed morphometrically and antibody titers to bovine insulin, a-component, porcine PP and proinsulin were determined in the various test groups. It was found that bovine MC insulin and porcine MC insulin possess the same immunological activity, i.e. no antibody formation to either of the two insulins was demonstrable. Similarly, there were no differences in the morphometric findings; slight transient mesangial changes were demonstrable after both insulins. However a-component and b-component showed a pronounced immunogenic potency with antibody formation. Marked and partly persisting mesangial alterations were demonstrable, with the antigenicity of the a-component being particularly marked. The implication of the study is that a "pure" or optimally purified insulin should be used in the therapy of diabetes mellitus.
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Minimal changes in the glomerular structure and definitively provable only by the aid of morphometric methods. This is of value especially for the minimal proliferative intercapillary glomerulonephritis with and without nephrotic syndrome where, because of the different clinical symptomatology, changes in the morphology may be expected too which however, usually are not recognizable with the methods of light-microscopy. That is why morphometric analyses of kidney tissues of ever ten patients of both groups of the disease were made and the results compared with each after and against normal kidneys. It could be shown that the minimal proliferative intercapillary glomerulonephritis with nephrotic syndrome (minimal changes, lipoid-nephrosis) is accompanied by an increase of local cells, especially the mesangial cells, just as the same disease without nephrotic syndrome. Besides that there exists a clear increase of the mesangiummatrix in the minimal proliferative intercapillary glomerulonephritis without nephrotic syndrome. Because of the morphometric findings it is justified to make a demarcation of both groups of the disease as well as against the mesangioproliferative glomerulonephritis.
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A cavernous hemangioma of the renal pelvis preoperatively diagnosed by angiography is reported. The pathologic-anatomical findings are included.
Immunohistological study of 123 kidney biopsies of non-glomerulonephritic kidney diseases showed that deposits of immunoglobulins are found more often in cases of malignant than in cases of benign nephrosclerosis. Primary malignant nephrosclerosis is mostly associated with glomerular deposits of immunoglobulins. Positive immunohistological findings are frequent in cases of diabetic glomerulosclerosis, mainly within glomeruli, but also in tubular basement membranes and Bowman's capsule. In cases of glomerular amyloidosis we see cloudy-bandlike deposits, but are unable to differentiate cases with or without the nephrotic syndrome. If we consider an immunopathogenetic mechanism for the diseases discussed in terms of the present findings, it seems possible for primary malignant nephrosclerosis as well as for certain glomerular changes associated with acute renal failure or rejection of transplants. In diabetic glomerulosclerosis (apart from special forms with perimembranous lesions) and glomerular amyloidosis, we consider such a mechanism to be unlikely. By separating the non-glomerulonephritic diseases into different types of deposits we found pictures that correspond with immunocomplex diseases. Pictures resembling anti-basement membrane diseases have not been seen. Characteristic patterns of deposits were not found, thus immunohistology is without additional diagnostic value in the field of non-glomerulonephritis disease.
Thirty rabbits were immunized with MC insulin and high-molecular impurities of commercial insulin preparations (a+b component) over 30, 60 and 90 days. The serum insulin antibody titer was determined in animals as the insulin binding capacity. Further, a quantitative morphological analysis of the various types of glomerular cells and of the mesangium was performed on the glomeruli as a blind study. Significant mesangial cell proliferation and an increase in mesangial matrix were found on treatment with the a+b component whereas the animals treated with MC insulin exhibited only a transient and slight mesangial activation after 30 days. There was a positive correlation between the magnitude of the insulin binding capacity and the mesangial activation. Hence, the glomerular changes which are observed after treatment with insulin which is not highly purified must be attributed to the high treatment with insulin which is not highly purified must be attributed to the high molecular weight contaminants. Heterologous pure insulin must be regarded as having virtually no immunological effect.
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Renal complications occur frequently in diabetics. Glomerular lesions exist in basal membrane thickening, diffuse and nodular glomerulosclerosis, exudative lesions and glomerular aneurysms. Tubular and interstitial changes are characterized by Armanni-Ebstein cells, by pyelonephritis and papillary necroses. Vascular changes occur in the form of arteriosclerosis and arteriolosclerosis. Nodular glomerulosclerosis is characteristic of diabetic renal damage, all other changes only occur more frequently in diabetics. Recently, studies deserve attention which suggest a regression of glomerular lesions if the diabetic metabolism is normalized.
By means of a computer program the frequencies of the strongly fluorescent polymorphous chromosomal segments on chromosomes Nos. 3, 4, 13, 14, 15, 21, and 22 among 89 random normal persons and 247 persons suspected of having various chromosome aberrations were determined. It was discovered that: 1. In none of the 13 diagnosis categories are divergencies in frequency of autosomal fluorescence polymorphism, as compared to the normal group, statistically determinable. 2. A worthwhile comparison of the various frequencies of fluorescence polymorphism as recorded by the various investigators in not possible at present, since the applied methods of assessment differ too widely. 3. Standardization of the criteria of assessment and of the nomenclature for the polymorphous chromosomal segment would seem to be a matter of urgent necessity.