Subendothelial Deposits Research Articles

Glomerular lesions associated with liver cirrhosis:: An immunohistochemical and clinicopathologic analysis

Clinicopathologic and immunohistochemical analyses of the kidneys in 30 autopsy cases of liver cirrhosis of different types revealed glomerular lesions in 27 cases. Clinical nephritis was present in three cases. Characteristic diffuse mesangial proliferation with focal mesangial interposition and/or subendothelial deposits were present. Glomerular immunoglobulin deposition was observed in several cases, IgM in 23 cases, IgG in five, and IgA in 17; the latter were predominantly IgA1. Secretory component binding was found in 11 of the 17 cases with IgA deposits (65 per cent). Liver weight was related to IgA deposition (P approximately 0.05), and the volume of ascitic fluid was significantly correlated (P less than 0.05).

Glomerulonefritis Membranoproliferativa (GNMP). Correlaciones Clínico - Patológicas y Terapéuticas

Membranoprolifcrative glomcruloncpluitis is a chronic progressive entity leading to end stage renal disease greater than 50% of cases after 5 years of diagnosis. Clinically, it often presents insidiously with hcmaturia-proteinuria, hypocomplementemia, nephrotic syndrome, arterial hypertension or combinations thereof. Acute and progressive renal failure may also occur. Ultrastructurally, type 1 shows primarily intramesangial and subendothelial deposits whereas type 2 displays a partial or complete replacement of the lamina dcnsa by a denser deposit, hence, the name of dense deposit disease. Greater than 80% of MPGN 2 patients show a circulating autoantibody (an abnormal IgG, C3Nef) which blocks the €3 convertase mactivator of the alternative pathway of complement activation whereas type 1 MPGN hypocomplementemia may be mediated by activation of the classical pathway. Circulating or in situ immune complex (1C) mediation and thrombocytopathic mechanisms seem to play major roles producing, maintaining and enhancing progression of inflammation and sclerosis that leads to end stage renal disease. Thus, decreased platelet survival, platelet antigen deposition glomerular capillaries and platelet release of myointimal Mstiocyte and mesangial cell growth factors have been demonstrated. The early treatment of these abnormalities has, for the first time, demonstrated a consistent way, that the use of prednisone increases significantly the patient survival. More recently, similar results have been reported a prospective double blind placebo control study using aspirin and dipyridamolc patients with MPGN type 1 only, Prednisone. aspirin and dipyridamole are potent antiplatelet aggregatin and antiplatelet release agents. Thus, it stands to reason, and it is strongly recommended to initiate early treatment of both types of this enti ty, or for that matter of any other progressive and scleiosing glomerulopathy, with a combination of these 3 substances given for a prolonged period of time. It is these clinicians' conviction that this form of therapy is fully indicated MPGN regardless of the histopathology and that therapeutic inertia is no longer justifiable. (

Idiopathic microscopic polyarteritis nodosa: ultrastructural observations on the renal vascular and glomerular lesions.

Although the glomerulonephritis (GN) and renal vasculitis in polyarteritis nodosa (PAN) are generally considered to be immune-mediated, the pathogenesis of the renal injury and the role of immune complex (IC) deposition are unclear. To better define the nature of the glomerular and vascular injury in PAN, we performed a detailed ultrastructural study of 27 renal biopsies from 20 patients with histologically confirmed PAN of the microscopic or overlap (microscopic/macroscopic) type. A total of 48 arteries and arterioles were studied ultrastructurally, including 20 vessels with recognizable vasculitis in 1 micron-thick survey sections. By immunofluorescence, glomerular and vascular immunoglobulin deposits were generally scanty, primarily located in areas of necrosis or sclerosis. Fibrinogen, C3 and C1 were more commonly detected, often in the absence of demonstrable immunoglobulin. By electron microscopy, discrete electron-dense deposits of probable immune-type were found in the glomeruli of five initial biopsies. No electron-dense deposits were identified in any of the arteries or arterioles studied. In both glomeruli and vessels, endothelial injury and subendothelial fibrin deposition were the earliest detectable ultrastructural changes. The pathogenetic implications of these findings are discussed.

Glomerular disease in cirrhosis of the liver: low frequency of IgA deposits.

Twelve HBsAg-negative patients with histologically documented cirrhosis of the liver of either alcoholic (8 of 12) or cryptogenic (4 of 12) origin underwent renal biopsy to investigate proteinuria, hematuria and/or renal failure. Immunofluorescence was positive for IgA in 2 patients with mesangiocapillary glomerulonephritis (MCGN) and could not be performed in 2 additional patients with the same diagnosis. However, in the remaining 8 patients, immunofluorescence was negative for IgA and frequently positive for C3, IgG, IgM and/or fibrinogen. These 8 patients without IgA were classified as follows: MCGN with subendothelial electron-dense deposits (2 cases), IgM-IgG cryoglobulinemia with diffuse endocapillary glomerulonephritis (1 case), membranous nephropathy (1 case), diffuse endocapillary proliferative glomerulonephritis (1 case), vasculitis with focal segmental necrotizing glomerulitis and crescentic glomerulonephritis (2 cases). These results show that cirrhosis of the liver can be associated with a wide variety of glomerular disorders. Contrary to previous belief, IgA is absent in two thirds of patients with cirrhosis and glomerulopathy. Therefore, the pathogenetic importance of IgA in the development of glomerular disease in such patients is doubtful.

子羊の多発性結節性動脈炎の1例

A female Corriedale lamb 5 months of age manifested anorexia, pyrexia, nasal discharge and a rale in the lung. It showed leukocytosis (18, 000/mm3), an increase in GOT volume (142 KU) and decrease in total serum protein (4.4 g/dl). Yellowish white foci were disseminated in the kidney. The arcuate arteries were thickened. Dilation of the cardiac ventricles and hepatization in the lung were also seen. Polyarteritis nodosa was shown in the kidney, spleen, heart, lung, alimentary tract, and lymph nodes. Subendothelial fibrinoid deposition and infiltration of cells mainly composed of mononuclear cells in the media and adventitia were systemically observed in small to medium-sized muscular arteries. Infiltration of mononuclear cells was seen in the brain, reticulum and kidney. No cases of polyarteritis nodosa in sheep had never been reported in Japan.

Clinicopathological associations in mesangial IgA nephropathy.

On hundred and fifteen renal biopsies performed in 112 patients with mesangial IgA nephropathy were reviewed and the histological disease patterns correlated with the clinical features at the time of initial biopsy. To determine the significance of macroscopic haematuria in this disease, specific comparisons were made between patients with a history of episodes of macroscopic haematuria and those with only microscopic haematuria. The mean age at initial biopsy was 38.3 years (90 males, mean 40.3 years; 22 females, mean 30.2 years). Histological examination showed 9 patients (8%) with class I disease (mesangial matrix expansion alone); 43 patients (38%) with class II disease (diffuse mesangial proliferation); 60 patients (54%) with class III disease (focal and segmental proliferation), including subsets of 20 patients (16%) with segmental sclerosis and/or synechiae and 23 patients (21%) with crescent formation. Class III disease and crescent formation correlated with an increased frequency of capillary loop IgA and glomerular fibrin deposition and with the presence of subendothelial and subepithelial deposits. The degree of renal impairment and the incidence of hypertension were increased in class III disease. Macroscopic haematuria patients were younger (mean 31.1 vs. 43.0 years; p less than 0.001), had less severe renal impairment (mean creatinine 116.2 vs. 213.3 mumol/l; p less than 0.001) and less class III disease (48 vs. 58%; p less than 0.05). The incidence of crescentic disease was equal in macroscopic (17%) and microscopic (23%) haematuria. Eventual progression to end-stage renal failure occurred in 12 patients (11%) and correlated with crescentic disease, renal impairment, hypertension and heavy proteinuria at the time of diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Systemic proliferative vasculitis and glomerulonephritis in ICR-nude mice infected with mouse hepatitis virus.

ICR-nude mice inoculated intraperitoneally with MHV-NuU, showed progressive proteinuria and had virus in the kidney at 2 to 5 weeks postinoculation. In the renal glomeruli, mesangial and endothelial cells were enlarged and proliferated with infiltration of neutrophils, mononuclear cells and a few multinucleated giant cells. Proliferative endovasculitis was seen also in the brain, lung, liver, pancreas, omentum and mesentery. Immunofluorescence revealed MHV antigen within endothelial cells of the small veins, and multinucleated giant cells and glomerular mesangial cells. Segmental or diffuse deposition of immunogloblin as well as C3 were present in glomerular mesangial areas in association with MHV-antigen. By electron microscopy were seen degeneration of podocytes and hypertrophy of endothelial cells with subendothelial or paramesangial deposits. Virions were seen within vascular endothelial cells, macrophages and giant cells in and around the small vein but not within those in the glomeruli.

Thrombosis in Systemic Lupus Erythematosus

In an earlier report on the kidney in systemic lupus erythematosus (SLE), we described a subset of patients with circulating anticoagulants; many had glomerular and arteriolar thrombosis in the absence of necrosis and subendothelial deposits. The present study extends these observations to a larger group of patients with SLE and a circulating anticoagulant, and compares its findings with those in patients with SLE without evidence of an anticoagulant. It demonstrates (1) a higher prevalence of clinically recognizable thrombotic events in the venous and arterial circulations in patients with SLE and a detectable anticoagulant; (2) a probable shortening in life span; (3) a higher prevalence of glomerular thrombi; (4) elevated levels of factor VIII antigen and von Willebrand factor; and (5) significantly lower platelet counts and decreased in vitro platelet aggregation in response to adenosine diphosphate, epinephrine, and collagen. Since prednisone treatment often results in improvement or disappearance of a prolonged partial thromboplastin time, the test most commonly used for screening of a circulating anticoagulant, we suggest that the prevalence of this abnormality may be underestimated in patients with SLE.

Immunohistochemistry of vascular lesion in thrombotic thrombocytopenic purpura, with special reference to factor VIII related antigen

We collected 23 autopsied cases of thrombotic thrombocytopenic purpura(TTP) and examined them immunohistochemically and electronmicroscopically to elucidate the nature of thrombi and subendothelial deposits. The findings were compared with those of 10 cases of disseminated intravascular coagulation(DIC) and 3 cases of polyarteritis nodosa(PN). Intravascular thrombi and subendothelial hyaline deposits in TTP stained weakly for fibrinogen/fibrin by the PAP technique, while they stained strongly for factor VIII related antigen(FVIIIR: Ag). Electronmicroscopically, thrombi in TTP were composed of numerous, variably degranulated and altered platelets, and a small amount of amorphous materials. Thrombi in DIC were strongly positive for fibrinogen/ fibrin, while they were weakly positive for FVIIIR:Ag. Electronmicroscopically they were composed of polymerized fibrin. Fibrinoid necrotic lesions in PN were strongly positive for fibrinogen/fibrin but negative for FVIII R:Ag. Based on these findings, we concluded that thrombi in TTP are essentially platelet thrombi and that subendothelial hyaline deposits may not be a result of increased vascular permeability but may be platelet thrombi incorporated into the arterial wall and covered with newly formed endothelial cells.

Morphological Parameters in Lupus Nephritis: Their Relevance for Classification and Relationship with Clinical and Histological Findings and Outcome

One hundred and sixty-seven renal biopsies from 147 patients with lupus nephritis were studied retrospectively to assess the contribution to morphological classification by features assessed with immunofluorescence and electron microscopy, together with pathological indices obtained by scoring specific histologic changes. The prognostic relevance of the histologic scoring was also evaluated. The biopsies were assigned to the following classes: I, absence of glomerular lesions; II, mesangial proliferation; III, focal segmental proliferation; IVa, diffuse (more than 50 per cent of the glomeruli) but segmentally distributed proliferation; IVb, diffuse and generalised proliferation; IVc, extracapillary proliferation; Va, pure membranous changes; Vb, membranous changes with slight mesangial proliferation; VI, association of class V and class III or IV. The incidence and degree of some glomerular and non-glomerular 'active' and 'sclerotic' changes as assessed by light microscopy were evaluated in the different classes. Both the activity and sclerosis indices obtained by scoring these lesions were found to be significantly higher in classes with glomerular proliferative changes. Eighteen patients had a second biopsy and two of these had a third; more severe changes were observed in nine and improvement in four. In 146 biopsies light microscopy findings were compared with immunofluorescence patterns (negative, mesangial, mesangial and peripheral, peripheral, membranous). The mesangial pattern was mainly present in class II with a few examples in classes I and III; in the last two the mesangial-peripheral pattern was most common; the peripheral pattern was by far the most common in class IV (a, b and c) and frequent in class VI; a membranous pattern was the rule in class V and occasionally found in class VI. Immunoglobulins (Igs) and complement (C) fractions were simultaneously present in most cases, IgG, C3 and C1q being the commonest in all classes. Except for IgM and fibrinogen, the differences in distribution of Igs and C fractions among the various classes were statistically significant. The deposits most commonly found by electron microscopy in all biopsies were mesangial; subendothelial deposits were mainly found in classes with active glomerular changes, frequently associated with deposits at the other sites in the most severe cases. A highly significant correlation was found between the activity index and the sclerosis index and severity of the clinical picture at biopsy. An unfavourable progress was confined mainly to classes with extensive intracapillary proliferation and correlated significantly with the highest activity and sclerosis indices.(ABSTRACT TRUNCATED AT 400 WORDS)

Glomerular electron-dense deposits in childhood IgA nephropathy.

An electron-microscopic study of the glomeruli was made on 154 children with IgA nephropathy and no evidence of systemic disease, in whom immunofluorescence microscopy had shown diffuse mesangial deposition of IgA. Mesangial deposits were observed in all but eight children. Subepithelial deposits were observed in 40 children and were almost always accompanied by both mesangial and subendothelial deposits. Subepithelial deposits were significantly associated with more severe clinical presentations, a worse outcome and more severe light microscopic glomerular changes. These observations support the concept that IgA nephropathy is an immune complex disease.

Immunopathologic mechanism of glomerular injury--an overview of current concepts.

It is now firmly established that a variety of immune mechanisms are responsible for most glomerulonephritides, and that they act largely through the activation of complement, recruitment of leukocytes and macrophages, stimulation of clotting, and liberation of vasoactive kinins. The etiological factors which originate the process can be either infectious agents, endogenous antigens (DNA, tumoral antigens), or exogenous toxins. The activation of the immune system may take different forms, including: the production of anti-GBM antibodies which may at times cross-react with other tissues or organs; the formation of antigen-antibody complexes of specific solubility, molecular size, permeability, which will variously tend to localize in the mesangium, in subepithelial, or subendothelial deposits; the development of antibodies which specifically react with native antigens present in the GBM in a discontinuous manner; the trapping of antigens within the GBM, which then act as "planted" antigens. The morphologic type of glomerulonephritis and its clinical course will probably depend upon the predominant type of antigen produced, its persistence, its mode of action, and the concurrent degree of activation of complement, recruitment of PMNs and macrophages, stimulation of the clotting system, as well as upon the development of hypertension and the functional response of the kidney to reduced renal mass. Whether or not it will be possible, in the future, to relate directly each type of glomerulonephritis to specific etiologic agents, to the type of immune response, and to genetic predisposition is unclear, but this will determine whether it will be possible to devise specific treatment strategies for each condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinicopathological correlation of IgA nephropathy in children.

22 patients with IgA nephropathy aged 7-16 years, 15 of whom were found by mass urine screening of school children, were divided into three groups based on the degree of their proteinuria at admission: group A (n = 6) below 0.5 g/day of urine protein, group B (n = 7) between 0.6 and 3.0, and group C (n = 9) above 3.0 g/day of urine protein. The degree of proteinuria seemed to be related to the severity of pathological changes of the glomerular basement membrane; most severe in group C, moderate in group B, and minimal in group A. IgA deposits in the mesangial area were found in all groups of patients, but those in the capillary walls were most frequently found in group C. In addition to electron-dense deposits in the mesangial area, which was found in all groups of patients, the subendothelial and subepithelial deposits were the most remarkable changes found in group C. During the clinical observation period, which was between 2.0 and 7.1 years, no patient belonging to group A progressed to groups B or C. 4 cases in group C developed chronic renal failure, but none in the other groups did. The amount of urine protein might be used as a valuable parameter of the pathological damage of the glomerulus in children with IgA nephropathy.

Ultrastructure of the intestinal mucosa in pigs experimentally inoculated with an edema disease-producing strain of Escherichia coli (0139:K12:H1).

The intestinal tissues from 11 pigs orally inoculated with Escherichia coli (E. coli, 0139:K12:H1) were examined by transmission electron microscopy. The colonization of E. coli along the small intestinal mucosa was found in seven principals without any major changes in the enterocytes from day 2 to day 7 after inoculation when the experiment was terminated. Lesions of vessels of the intestinal mucosa could be detected as early as two days after inoculation and persisted until the experiment was terminated. Lesions consisted of endothelial swelling and vacuolation, subendothelial fibrin deposition, perivascular edema, microthrombus formation, endothelial proliferation, and necrosis of the tunica media. The possible pathogenesis of the disease is discussed.

Diffuse Proliferative Lupus Glomerulonephritis

Clinical, laboratory and pathological factors in 35 females with diffuse proliferative lupus glomerulonephritis were analyzed to determine the prognostic significance of the individual variables. The clinical and laboratory variables were age, serum creatinine (Cr), serum C3, serum C4 and proteinuria at the time of biopsy while the biopsy ones included intraglomerular monocytic infiltration (NSE index), total glomerular deposits, extent of subendothelial deposits, extent of extraglomerular deposits, tubulo-interstitial inflammation, relative tubulo-interstitial volume and total pathologic score. Standard morphometric and counting procedures were used to determine the levels of all pathologic variables but pathologic score and extra glomerular deposits where grading estimates were done. Survival curves were determined by the life table method. Logrank and chi-square tests were used to establish levels of statistical significance. Seven patients developed established renal failure (Cr greater than or equal to 2.0 on two or more occasions at least 3 months apart) and nine showed significant deterioration of renal function (decrease in CrCl of 25% or more in between biopsy and last follow-up visit or an increase in serum Cr of 0.4 mg/dl or more over the follow-up period). The 5-year renal survival rate (absence of established renal failure) for the whole group was 77%. Serum Cr (p less than .005) and extent of extraglomerular deposits (p less than .025) were shown to be significant prognostic factors for renal survival. Of the seven patients who developed renal failure none had an NSE index greater than 3.0 and one had a C3 greater than or equal to 45 mg/dl. Statistically these factors were weak prognostic indicators (0.5 less than p less than .1). Multivariate analysis demonstrated that the extraglomerular deposit factor contributed significant additional prognostic information to that provided by Cr. Although not important as a prognostic factor on its own, the NSE index significantly improved the prognostic performance of serum Cr. The product of the NSE index and serum C3 proved to be a strong prognostic factor (p less than .005).

Immunoglobulin deposits in bladder epithelium and vessels in interstitial cystitis: Possible relationship to circulating anti-intermediate filament autoantibodies

Sera from patients suffering from interstitial cystitis (IC) reacted with bright staining of the bladder epithelium and vascular endothelium when tested for autoantibodies by indirect immunofluorescence using normal bladder tissue as target antigen. When tested for autoantibodies using cultured cells as antigen the antibodies were found to be directed against cytoskeletal intermediate filaments (IMF). Sera from 43 IC patients had a high incidence and high titers of anti-IMF autoantibodies as compared to both healthy individuals and patients suffering from other urological or surgical diseases. The results suggest that anti-IMF autoantibodies may be involved in the perpetuating chronic type of tissue injury seen in these patients. The antibodies were of the IgM class. In vivo deposits of IgM in patient bladder biopsies localized similarly to the autoantibodies; epithelial tissue showed deposits in 19% and vascular tissue, deposits in more than 50% of the patients, often together with complement components C1q, C3, or C4. In addition, subendothelial deposits associated with fibrillar structures could be observed. The results suggest a possible relationship between the in vivo IgM deposits in the bladder epithelium and vascular endothelium, on one hand, and the presence of anti-IMF antibodies capable of reacting with these cell structures, on the other hand. However, as the autoantibodies have to gain access to intracellular structures in order to cause in vivo deposits, primary tissue injury has to be postulated.

Immune-mediated injury to basement membranes in mice immunized with murine laminin

Mice immunized with laminin isolated from mouse EHS sarcoma developed immunemediated pathological changes in the basement membranes of the kidneys and lungs, and in the subendothelial basement membranes of arteries in the kidney. Subendothelial and mesangial dense deposits were seen in the renal glomerulus. Thickening and splitting of both the glomerular basement membrane and the alveolar basement membrane occurred in mice immunized with laminin. Granular dense structures were present in the lamina densa of subendothelial basement membranes of renal arteries. Staining for in vivo-bound mouse IgG was observed primarily along the glomerular basement membrane and in the mesangium by the indirect peroxidase technique. Mouse IgG was also detected in the adventital connective tissue of renal arteries and was present focally along tubular basement membranes. No circulating antibody was detectable using either Western immunoblotting or microELISA techniques.

Electron microscopic studies on IgA nephropathy.

We carried out electron microscopic studies on renal tissues from 9 patients with IgA nephropathy. Electron dense deposits were present in the mesangial area in all cases, subendothelial deposits in 4, and subepithelial deposits in only one. In basement membrane, segmental swelling and rarefaction of basement membrane substance were observed. In some cases the degenerated basement membrane substance protruded through the dilated endothelial fenestration into capillary lumina. Focal splitting, attenuation, mouse eaten appearance, and herniation of basement membrane were seen in a high incidence. Mesangial cells possessed well developed rough endoplasmic reticulums and polysomes. In the peripheral areas of mesangial cell cytoplasm, there was accumulation of electron dense substance and this was occasionally continuously present in the mesangial matrix. There was segmental swelling of endothelial cell cytoplasm, resulting in loss of fenestration. Epithelial cells had well developed rough endoplasmic reticulums and polysomes. Segmental foot process fusion was seen, and these processes, regardless of fusion, became electron denser in the area close to the basement membrane. Multivesiculated bodies were present in all cases in the epithelial cells and in 7 cases in the endothelial cells. Spherical microparticles were present in 3 cases in the urinary space or between the basement membrane and the epithelial cells.

Clinical and Pathological Features of Membranous Glomerulonephritis of Systemic Lupus erythematosus

The prognostic significance of glomerular inflammation in patients with lupus membranous glomerulonephritis (MGN) was evaluated by classifying 100 renal biopsies from lupus patients according to World Health Organization (WHO) criteria and correlating the histology with clinical data. There were 22 cases of MGN: in 3 the lesion was pure MGN (Va); in the remainder, diffuse MGN was modified by superimposed mesangial proliferation in 6 (Vb), segmental glomerulonephritis (GN) or sclerosis in 10 (Vc), and diffuse GN in 3 (Vd). Patients in the four categories had similar clinical presentations. When the 4 patients with active proliferative glomerulonephritis (PGN) were grouped and compared to those without PGN, they had more active serologies. Quantitation of glomerular electrondense deposits in MGN showed variation in the percentage of basal lamina covered by subepithelial deposits, segmental subepithelial deposits in 4 cases, focal segmental subendothelial deposits in most cases and massive subendothelial deposits in 5 biopsies. 4 of the latter patients had active PGN, suggesting that only extensive subendothelial deposits are pathogenetically significant. The predicted 5-year survival for all MGN patients was 90%, and the only 2 deaths were not related to renal failure. Thus, it appears valid to include mixed lesions in the membranous category, but it is our impression that the immediate course and prognosis of SLE and associated PGN depends upon the extent and reversibility of the inflammatory lesions.

In situ formation of subepithelial immune complexes in the rabbit glomerulus: requirement of a cationic antigen.

In a previous study we examined the role of antigenic electrical charge as a factor influencing glomerular immune complex (IC) localization in the rabbit. From that study patterned after chronic serum sickness nephritis it was demonstrated that the administration of charge-modified cationic bovine serum albumin (BSA) of isoelectric point (pI) greater than or equal to 9.5 invariably resulted in heavy subepithelial deposits, whereas native BSA (anionic, pI 4.5) produced principally mesangial deposits. In order to investigate the mechanism by which the immune deposits formed, passive serum sickness was induced in New Zealand white rabbits by unilaterally perfusing kidneys of nonimmunized rabbits with five alternating cycles of saline, antigen and antibody, or immunized rabbits with saline and antigen alone. Localization of BSA and IgG along the glomerular basement membrane (GBM) occurred only after exposure to cationic BSA and antibody; nonimmunized animals perfused with cationic BSA and antibody to cationic BSA uniformly developed generalized, diffuse nearly linear deposits of IgG and BSA along the GBM. Similar deposits, which became progressively more granular after exposure to circulating antibody, were seen after the perfusion of cationic BSA alone into animals actively immunized with cationic or native BSA. Ultrastructural examination showed effacement of foot processes and isolated, irregular subepithelial and subendothelial deposits. Control perfusion employing alternating cycles of native BSA and anti-native BSA antibody, cationic BSA and normal sheep IgG, or native BSA alone in animals actively immunized with native or cationic BSA failed to develop glomerular IgG deposits. All control kidneys were normal on ultrastructural examination.(ABSTRACT TRUNCATED AT 250 WORDS)