[Acute renal failure due to vascular disease in the adult].
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Biomedical subjects
Publications and source records attributed to C Orfila.
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Urinary sediment of 11 patients with amyloidosis and 12 without (with proteinuria or in good health) have been sutdied by different morphological techniques. By light microscopy, an amyloid-related substance was occasionally demonstrated both in patients with amyloidosis and in control subjects. Immunofluorescence (IF) showed substance A (amyloid component) to be present in some cases of amyloidosis and in controls. On electron-microscopy, fibrils with characteristic appearance of amyloid substance were found in some cases of amyloidosis (4 out of 11), but were also found in controls. It therefore seems difficult to establish the diagnosis of amyloidosis by microscopic studies of the urinary sediment.
Although the term hypertension in pregnancy is a simple and uncontroversial one, it unfortunately encompasses some ill defined clinical conditions as well as pre-eclampsia. The prime cause of pre-eclampsia is utero-placental ischaemia. Such utero-placental ischaemia is responsible for the hypothetical secretion of a vasopressor agent and for intravascular coagulation. An immunological cause should also be suspected: a study of the immune profile of the kidney has shown that the glomerular capillaries contain immunoglobulins G and M as well as the C3 fraction of complement. Renal biopsies carried out three months after delivery have shown deposits of C3 in the arteriolar walls. During normal pregnancy, there exists a state of stable equilibrium of hormonal, haemodynamic, haematological and immunological factors. It seems that all components of this equilibrium are disturbed in cases of hypertension in pregnancy.
In 18 patients who received renal allografts, tubulo-interstitial lesions were studied, according to the types of rejection or the possible recurrence of primary disease. Immunofluorescent (IF) investigation revealed tubular basement membrane (TBM) deposits of IgG and/or C3 and sometimes other components of Complement. The pattern of these deposits was: "linear" in 3 cases, "granular" in 9 cases and "atypical" with linear and granular segments in 6 cases. The IF study of own kidneys of 3 patients, before the transplantation, revealed no TBM deposits. TBM deposits were accompanied by arterial wall deposits of IgM and/or C3 and sometimes C5 in 17 cases. Electron-microscopy study of renal tubules showed thickening, lamellation and/or deposits along the tubular basement membrane. The immunopathogenesis of these deposits was discussed.
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A nephropathy affecting both tubules and glomeruli has been induced in Rabbits by the injection of an heterologous immune serum directed against Rabbit tubular basement membrane. It differs from experimental antiglomerular basement membrane nephropathy by the fixation of antibodies and C3 on tubular basement membrane and by the occurrence of glucosuria.
Correlations between immunofluorescent protein deposits in the glomeruli, urinary sediment and proteinuria selectivity pattern have been attempted in different glomerulonephritis. The overall study showed following results: a) Glomerular and urinary casts deposits of immunoglobulins, C3 and fibrin/fibrinogen are related to moderately selective proteinuria; b) IgG and IgA are most often found in urinary sediment and c) Glomerular deposits of IgG and IgA are well correlated with the presence of these immunoglobulins in urinary casts. Analysis according to different histological types of nephritis: a) In "minimal changes" nephropathy, deposits are infrequent and well correlated with urinary sediment, when they are present; b) In lupus nephritis, constant and intense glomerular deposits of immunoglobulins, fibrin/fibrinogen are correlated with the same proteins found in urinary casts; c) Inconstant correlations are found in membranous nephritis and in IgA-IgG nephropathy.
14 cases of idiopathic rapidly progressive glomerulonephritis (I. R. P. G. N.) treated by heparin between 1968 and 1974 were collected by the authors. Extra-capillary crescents (E. C. C.) occurred in 75 to 100% of glomeruli in ten patients and in 50 to 75% in four. Gross proteinuria, hematuria and renal failure were always present. 9 patients were admitted with primary oligo-anuric renal failure. 11 patients were treated by repeated hemodialysis before and during anticoagulant treatment. Heparin was given by intra-venous injection every 3 hours for one to two months with Howell times range from 150 to 200% of control. Heparin was the only treatment in 6 cases, and was given with dipyridamole in 4, with prednisone in 3 and with azathioprine in one case. 5 severe or fatal hemorragic complications were observed. The clinical course was usually unfavorable with 5 early deaths, 3 provisional steady-states with 2 late deaths. Six patients were treated by periodic hemodialysis. Repeat kidney biopsies were obtained in 8 patients. The findings suggest that heparin affects mainly the E. C. C. and fibrinoid deposits but not glomerular sclerosis. The inefficiency of all current treatments of primary oligo-anuric IRPGN is stressed. In patients with better initial renal function choice between anticoagulant and/or immuno-depressive drugs must be scrutinized in individual cases bearing in mind potential iatrogenic complications. In equivocal cases, patients should be referred to the chronic hemodialysis and/or transplantation program.
Liver biopsies of sixty patients with different forms of hepatitis and ten control subjects without hepatic disorders were examined by means of direct immunofluorescent methods for the HBsAg, immunoglobulins, fibrin and C3. The presence of fluorescent particles of HBsAg in the cytoplasm of hepatocytes were correlated with the presence of HBsAg in the serum. The fluorescence did not seem specific of histological stage of hepatitis. Immunoglobulins and fibrin were often demonstrated in hepatic sinusoids, especially in chronic aggressive hepatitis. In contrast, C3 is rarely observed.
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Ultrastructural changes in the tubular basement membrane (TBM) of 65 renal biopsy specimens from patients with nephropathies or transplant rejection were examined for their potential relationship to deposits observed along the TBM by immunofluorescence (IF). The TBM showed various alterations: irregularities with thickening, lamellation, duplication, and clear spaces. Granular vesicles or inclusions were present inside the thickened TBM. The morphologic changes of the TBM occurred regardless of the severity of rejection of transplants and the type of deposits observed on IF. Electron-dense deposits inside or along the TBM were not found in cases of linear deposits, however. Although these changes were not strictly specific to tubular immune diseases, they could reflect a reaction of the TBM to immune complexes or deposits of antibodies to TBM with degeneration of tubular epithelial cells and sometimes regeneration of a new TBM.
The effect of mercuric chloride on kallikrein content and secretion of renal cortical slices was studied. Mercuric chloride showed dose-dependent inhibition of the secretion of immunoreactive and active kallikrein in the medium associated with a relative increase in the kallikrein tissue content of slices. However the net de novo biosynthesis was also reduced. Active and inactive kallikrein exhibited the same percentage of inhibition indicating that the activation mechanism of prokallikrein was not affected. These results suggest that mercuric chloride exerts an inhibition on tubular secretion but also on the tissular biosynthesis of kallikrein in these in vitro conditions. Morphological study of slices incubated in the presence of mercury also revealed significant tissular lesions which were located on the proximal tubule, but distal tubular changes were also observed. Distal nephrons were identified by the presence of immunoreactive kallikrein with the peroxidase-antiperoxidase method. These ultrastructural alterations included an increase in number and size of lysozomes, vacuoles and lipid droplets. These lesions were associated with an increased release of the lysozomal enzyme N-acetyl-beta-D-glucosaminidase. Since these distal tubular lesions are associated with inhibition of kallikrein secretion which is specifically located in the distal tubule, these results suggest that acute exposure of kidney cortical slices to mercuric chloride causes rapid and marked ultrastructural changes not only on the proximal tubule but also induced structural and biochemical effects at the distal tubule level. As incubation of mercuric chloride did not induce any direct alterations of immunoreactive and active kallikrein, it is likely that the observed inhibition of kallikrein synthesis and secretion are secondary to the morphological lesions.
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