Intramembranous Electron-dense Deposits Research Articles

Inhaled Cadmium Oxide Nanoparticles: Their in Vivo Fate and Effect on Target Organs.

The increasing amount of heavy metals used in manufacturing equivalently increases hazards of environmental pollution by industrial products such as cadmium oxide (CdO) nanoparticles. Here, we aimed to unravel the CdO nanoparticle destiny upon their entry into lungs by inhalations, with the main focus on the ultrastructural changes that the nanoparticles may cause to tissues of the primary and secondary target organs. We indeed found the CdO nanoparticles to be transported from the lungs into secondary target organs by blood. In lungs, inhaled CdO nanoparticles caused significant alterations in parenchyma tissue including hyperemia, enlarged pulmonary septa, congested capillaries, alveolar emphysema and small areas of atelectasis. Nanoparticles were observed in the cytoplasm of cells lining bronchioles, in the alveolar spaces as well as inside the membranous pneumocytes and in phagosomes of lung macrophages. Nanoparticles even penetrated through the membrane into some organelles including mitochondria and they also accumulated in the cytoplasmic vesicles. In livers, inhalation caused periportal inflammation and local hepatic necrosis. Only minor changes such as diffusely thickened filtration membrane with intramembranous electron dense deposits were observed in kidney. Taken together, inhaled CdO nanoparticles not only accumulated in lungs but they were also transported to other organs causing serious damage at tissue as well as cellular level.

C4 Glomerulopathy: A Disease Entity Associated With C4d Deposition

Complement-mediated glomerulonephritis, which includes C3 glomerulopathy, is characterized by dominant staining of C3 with minimal or no immunoglobulin deposits on immunofluorescence studies. We describe a new entity of complement-mediated glomerulonephritis that is characterized by bright C4d staining but with no or minimal C3 or immunoglobulin deposits on immunofluorescence studies. We label this entity as C4 glomerulopathy. C4 glomerulopathy includes C4 dense deposit disease and C4 glomerulonephritis. C4 dense deposit disease is characterized by bright C4d staining and dense deposits along glomerular basement membranes. C4 glomerulonephritis is characterized by bright C4d staining and many mesangial electron-dense deposits, with or without rare intramembranous electron-dense deposits. We describe clinical featuresand kidney biopsy results in a short series of 3 patients to highlight these findings. All 3 patients presentedwith proteinuria, and 2 patients also had hematuria. Kidney function was preserved in 2 patients, whereas 1 patient presented with declining kidney function. Evaluation for autoimmune disease, infection, and paraprotein yielded negative results in all patients. Complement levels were normal, although 1 patient had borderline low C4 levels. Kidney biopsy showed mesangial proliferative or membranoproliferative glomerulonephritis with bright C4d staining and absent or minimal C1q, C3, and immunoglobulin. Laser microdissection and mass spectrometry of glomeruli in all 3 patients showed large to moderate numbers of spectra matching C4. Furthermore, analysis of amino acid sequences showed that they were localized to the C4d portion of C4, consistent with immunofluorescence findings. Further studies are required to determine the underlying cause. In summary, we describe a novel complement-mediated glomerulonephritis that is characterized by bright glomerular C4d staining with minimal or absent staining for C1q, C3, and immunoglobulin.

Current approach to classification of membranoproliferative glomerulonephritis

Membranoproliferative glomerulonephritis (MPGN) is a pattern of injury, which historically has been classified using light and electron microscopic morphologic features. Primary (idiopathic) MPGN was divided into types I, II (dense deposit disease) and III, respectively defined by the presence of subendothelial deposits with capillary double contours, intramembranous electron dense material, or subepithelial and/or intramembranous deposits with or without basement membrane irregularities and subendothelial deposits. Secondary MPGN was associated with underlying diseases including infection, lymphoplasmacytic disorders, autoimmune disease, and malignancy. However, this classification encompasses entities with overlapping pathogenesis, clinical features, and treatment approaches. Therefore, classification of MPGN based on pathogenesis and associated immunofluorescence findings has been suggested. MPGN is divided into immune complex (IC)-mediated (immunoglobulin and complement deposition), complement (C)-mediated (C deposition) and non-IC, non-C-mediated forms. IC-mediated MPGN results from chronic antigenemia, including those previously designated type I, type III and secondary. C-mediated MPGN includes type II (dense deposit disease) and C3 glomerulonephritis, the latter with features of MPGN types I or III. Non-IC, non-C MPGN is secondary to few underlying causes, predominantly thrombotic microangiopathy of any cause. This classification allows for improved prognostic information and optimized approach to therapy. As pathogenesis is better understood, primary MPGN may cease to exist.

Transition from endocapillary proliferative glomerulonephritis to membranoproliferative glomerulonephritis in a patient with a prolonged human parvovirus B19 infection

We report a case in which renal biopsies were performed 4 years apart in a woman with a prolonged human parvovirus B19 (HPB19) infection. When she was 29 years old the first biopsy, performed because of microscopic hematuria and mild proteinuria, showed endocapillary and mesangial proliferative glomerulonephritis in light microscopy as well as deposits of immunoglobulins (Igs) and complement C3 on capillary walls. Mesangial, intramembranous, and subepithelial hump-like electron dense deposits were seen in electron microscopy. The principal differential diagnoses, acute poststreptococcal glomerulonephritis and lupus nephritis, were unlikely, and her serological positivity for IgM antibody for HPB19 made us diagnose acute glomerulonephritis associated with HPB19 infection. The second biopsy, performed 4 years later because of persistent proteinuria and prolonged positivity for IgM antibody for HPB19, showed membranoproliferative glomerulonephritis (MPGN) with mesangial interposition and with thickening and double contours of glomerular basement membrane. In tissues obtained in both biopsies, HPB19 DNA was detected by polymerase chain reaction. HPB19 infection has been widely known to cause various glomerular diseases. This case reveals that acute endocapillary proliferative glomerulonephritis can change into MPGN during prolonged HPB19 infection.

Dense Deposit Disease

Dense deposit disease (DDD) is a rare disorder that most commonly affects children. This study reports the largest North American series addressing clinicopathologic and outcome differences in children and adults. Thirty-two patients with DDD were analyzed from the archives of Columbia University between 1977 and 2007. Characteristic intramembranous electron-dense deposits defined all diagnoses. The cohort included 14 children (<16 yr) and 18 adults, with 39% of adults >60 yr. The female/male ratio was 1.9. At presentation, the mean 24-h urine protein was 4.6 g, nephrotic syndrome was present in 33%, renal insufficiency in 59%, and hematuria in 87% of patients. Compared with adults, children had lower incidence of renal insufficiency and were more likely to have reduced C3. Histologic pattern included membranoproliferative, mesangial, endocapillary, and crescentic glomerulonephritis. Treatment included immunosuppression (IS) alone in seven, renin angiotensin system (RAS) blockade alone in six, and combined IS/RAS blockade in 11. On follow-up (mean 63 mo) available in 27 patients, 26% had complete response, 48% had persistent renal dysfunction, and 26% had ESRD. Correlates of ESRD were older age and higher creatinine at biopsy, the absence of combined IS/RAS blockade therapy and the presence of subepithelial humps, but not histologic pattern. On multivariate analysis, age and creatinine emerged as the only independent predictors of ESRD. DDD is clinically and pathologically heterogeneous. Adults have worse outcome than children, despite similar treatment. Combined IS/RAS blockade appears superior to either agent alone.

Intramembranous electron-dense deposits in a nephrotic patient with mixed connective tissue disease: unusual response to corticosteroid therapy.

A 56-year-old female patient, who had had minor change nephrotic syndrome (MCNS), was referred to us because of a fever and a massive proteinuria. Six years before, she had first noticed leg oedema, leading to the detection of nephrotic-range proteinuria. The diagnosis of MCNS at that time was based on minor glomerular abnormality by the light microscopy examination. She had then been treated with corticosteroid, after which her proteinuria had promptly disappeared. Her corticosteroid had then been gradually withdrawn, and no relapse had occurred for 6 years. At her first visit with us, she had a fever and sclerodactylia as well as swollen hands and Raynaud’s phenomenon, and laboratory examinations showed a high titer of anti-nuclear and anti-RNP antibodies, resulting in a diagnosis of mixed connective tissue disease (MCTD). She also had a massive proteinuria (3.2 g/day), and a kidney re-biopsy was performed (Figure 1). She was treated again with corticosteroid (prednisolone 20 mg daily) and her proteinuria had completely disappeared within a week.

Membranous glomerulonephritis in the Iberian lynx ( Lynx pardinus)

The Iberian lynx is the most endangered felid species in the world, confined nowadays to two isolated metapopulations in the southwest of Spain, where less than 200 individuals survive. Little is known about the diseases that affect these animals in the wild or in captivity. Kidney samples from necropsies of 27 Iberian lynxes, wild and captive, were examined by histopathology, immunohistochemistry (IgG, IgM, IgA, laminin, type IV collagen, and fibronectin), electron microscopy ( n = 8) and immunogold labelling for IgM, IgG and IgA in one case, in order to characterize the glomerulopathy prevalent in this species. Urinalyses from records were available for 9 of the necropsied animals and blood and urine samples from 23 free ranging and captive Iberian lynxes were prospectively obtained in order to evaluate the renal function of the living population. A focal, diffuse membranous glomerulonephritis (MGN) that progressed with age was diagnosed in all but one of the animals in different stages not associated to concurrently known infectious diseases. Positive immunoexpression of IgM and IgG was observed in the glomerular capillary basement membranes and intramembranous electron-dense deposits, compatible with immune complexes (ICs) were seen with electron microscopy. The immunogold labelling was also positive for IgM and IgG in the electron-dense areas. The serum biochemistry and urinalyses also revealed signs of mild chronic kidney disease in 16 of the 23 animals evaluated. In conclusion, the membranous glomerulopathy affecting the Iberian lynx is a progressive disease of immune origin. We postulate a possible genetic predisposition towards the disease, enhanced by inbreeding and a possible connection to an immune-mediated systemic disease.

Association of glomerular podocytopathy and nephrotic proteinuria in mesangial lupus nephritis

We investigated a series of patients with systemic lupus erythematosus (SLE), who had sparse subepithelial and mesangial immune deposits. Our goal was to determine structure: function correlation. We examined whether proteinuria correlated with either capillary wall immune aggregate formation or abnormal podocyte morphology. Renal biopsies from patients with sparse (two or fewer subepithelial or intramembranous electron dense deposits per glomerular capillary loop) immune deposits and podocyte effacement were studied. Patients fulfilled criteria for the diagnosis of SLE. Cases were excluded if the biopsy showed endocapillary proliferation or necrosis. Eighteen biopsies were studied, five from patients with nephrotic range proteinuria (> or =3 g/day) and 13 from patients with non-nephrotic proteinuria (<3 g/day). The five nephrotic patients had a mean foot process effacement of 48% +/- 39% (range 10-100%). Thirteen non-nephrotic patients had a mean foot process effacement of 11.7% +/- 8% (range 0-20%). The only distinguishing morphologic finding associated with nephrotic range proteinuria was diffuse foot process effacement. No correlation between subepithelial deposits and proteinuria was observed. There were no other histologic differences between the nephrotic and non-nephrotic patients. Among these patients, the nephrotic syndrome appears best correlated with podocytopathy rather than subepithelial electron dense deposits, mesangial deposits, or mesangial hypercellularity.

Correlation of membranous glomerular ultrastructural changes with disease severity and outcome in lupus patients initiating cyclophosphamide therapy

The aim of this study was to assess the utility applying an electron microscopy (EM) scoring system used in idiopathic membranous nephritis based on the location of subepithelial and/or intramembranous electron dense deposits in interpretation of renal biopsies from patients with lupus nephritis. We selected patients with electron dense deposits traditionally associated with membranous changes on EM from 84 patients treated with bolus cyclophosphamide, with five years follow-up. An EM scoring system designed for idiopathic membranous nephritis was applied (stages I or II, mild changes; stages III or IV, advanced changes). Twenty-seven out of 84 had membranous changes by light microscopy, of whom 22 had satisfactory tissue for EM membranous analysis. Eleven out of 22 had mild EM changes (EM stage I or II); 11 had advanced disease (EM stage III). Advanced EM stage was associated with a higher serum creatinine at entry when tests were adjusted for WHO class (2.62 +/- 0.6 versus 1.31 +/- 0.28 mg/dL, P < 0.022 by ANOVA), and EM stage was independent of NIH activity or chronicity indexes or disease duration. After five years, adverse outcomes (death or dialysis) were seen in one of the 11 patients with EM stages I-II versus five of the 11 EM stage III patients (P < 0.07). Advanced membranous type electron dense deposition in lupus as assessed by EM was associated with worse renal function in patients with comparable WHO classification and NIH activity and chronicity indexes. In this group of lupus patients initiating cyclophosphamide for severe nephritis, EM stage provided important additional information regarding the extent of renal injury.

Long-term follow-up of type II membranoproliferative glomerulonephritis in two children

We report the long-term follow-up of two patients with type II membranoproliferative glomerulonephritis (MPGN). One Patients was treated with high-dose alternate-day prednisolone and the other with dipyridamole. Both had favorable clinical courses over 8.5 and 15.5 years of follow-up, respectively. One patient who showed diffuse proliferative changes lost the urinary abnormalities 2 years after starting treatment. Her follow-up renal biopsies showed histological improvement. In the other patient, a boy, renal biopsy performed 6 years after the onset showed mild mesangial proliferation and a moderate matrix increase. His urine became normal 14 years after onset. Intramembranous electron-dense deposits persisted in these patients over 7 and 6 years of observation, respectively. Patients with type II MPGN are usually difficult to treat and often progress to endstage renal failure. There is, however, a group of patients who have a favorable clinical course.

Age‐related modification of serum sickness nephritis in the rat

Summary: Serum sickness nephritis was induced in young (3 weeks old) and old (50 weeks old) Fischer rats by immunization with egg albumin, and the age‐related clinicopathological differences were analyzed. At least four differences were recognized between the young and old nephritis rats. First, the induced proteinuria was transient in the young group, but persistent in the old group and second, intramembranous electron dense deposits (IMEDD) in the thickened glomerular basement membrane were characteristic in the old group by electron microscopic observation. Third, the peripheral distribution of immune complexes in glomemlus was much more dominant in the young group. Fourth, the accumulation of monocytes was more prominent in the young group. These findings support the following suggestions: (i) in the ageing rats, there may be lowered efficiency of turnover of the extracellular matrix and the decreased ability of the mononuclear phagocyte system function; (ii) these changes may be responsible for the delayed clearance of the immune complexes from the glomerulus, and (iii) the longstanding presence of IMEDD observed in the ageing rats may play a role in persistent proteinuria.

Bull terrier hereditary nephritis: A model for autosomal dominant Alport syndrome

Bull terrier hereditary nephritis is inherited as an autosomal dominant disease and causes renal failure at variable ages in affected dogs. The aims of this study were to compare the clinical, ultrastructural and immunohistochemical features of bull terrier hereditary nephritis with the characteristics of the human forms of Alport syndrome. Many animals with bull terrier hereditary nephritis have hematuria, and some have anterior lenticonus. However, deafness is not associated with the renal disease, and affected dogs do not have the large platelets that are occasionally seen in patients with autosomal Alport syndrome. The glomerular capillary basement membrane (GCBM) in affected bull terriers has an identical ultrastructural appearance to that seen in X-linked Alport syndrome, with lamellations and intramembranous electron-dense deposits. However, both the Goodpasture and the Alport antigens, which represent parts of the alpha 3(IV) and alpha 5(IV) collagen chains, respectively, are present in the GCBM of affected dogs. Bull terrier hereditary nephritis represents an animal model for autosomal dominant Alport syndrome, and can be used to further examine how genetic mutations affect a basement membrane protein and the corresponding membrane structure.

IgA nephropathy associated with chronic hepatitis B virus infection in adults: the pathogenetic role of HBsAG.

Five adult cases of IgA nephropathy associated with chronic hepatitis B virus infection were studied. Serum HBsAg and anti-HBc were present in five patients and HBeAg in four patients. Glomerular changes were typical of primary IgA nephropathy in four patients, and a mixed picture of IgA and membranous nephropathy was demonstrated in one patient. Immunofluorescence microscopy using polyclonal and monoclonal antibodies against HBsAg, HBcAg, and HBeAg revealed mesangial deposits of HBsAg in renal biopsies from four patients. One renal biopsy showed only mesangial and capillary HBcAg by polyclonal antiserum, and virus-like particles were demonstrated in the intramembranous electron-dense deposits on ultrastructural examination. Mesangial HBeAg was not detected in the renal biopsies from these patients with IgA nephropathy. As for the single patient with a mixed picture of IgA and membranous nephropathy, granular deposits of HBeAg with a distribution similar to IgG were detected in the glomerular capillary walls in addition to the mesangial deposition of HBsAg. These findings suggest that HBsAg rather than HBeAg may play a role of the pathogenesis in some of the adult patients with IgA nephropathy associated with chronic hepatitis B virus infection.

Effects of a specific thromboxane synthetase inhibitor on development of experimental Dirofilaria immitis immune complex glomerulonephritis in the dog.

Twelve Beagle dogs were immunized with aqueous-soluble Dirofilaria immitis antigens, and subsequent to at least fivefold increases in serum antibody titer, 6 mg of homologous antigen was infused into the left renal artery. Six dogs were treated once daily starting the day of infusion with 0.75 mg/kg of 1-benzylimidazole (1-BIM) in saline. Six control dogs were given saline only. Light, immunofluorescent, and transmission electron microscopic examinations of renal tissue from control dogs, 10 days after antigen infusion, showed a mesangioproliferative glomerulonephritis in the left kidney with polymorphonuclear leukocyte (PMNL) infiltration and fibrin deposition. Immunoglobulin (Ig) G, M, C3, and Dirofilaria antigen deposits were observed in a segmental granular pattern. Mesangial, subendothelial, and intramembranous electron dense deposits were observed, and anti-Dirofilaria antibodies were demonstrated in kidney eluates from each dog. Administration of 1-BIM had no significant effect on IgG, IgM, C3, or antigen deposits, electron dense deposits, or concentration of antibody in kidney eluates. However, 1-BIM-treated dogs had less glomerular cell proliferation, periodic acid-Schiff (PAS) positive glomerular staining, PMNL infiltration, and fibrin deposition. These data suggest that thromboxane is an important mediator in the development of immune complex glomerulonephritis, and that in certain circumstances, inhibition of thromboxane synthesis may be an effective therapy for immune complex glomerulonephritis in the dog.

Autologous Immune Complex Nephritis in Streptozotocin-Induced Diabetic Rats

In order to investigate the influence of diabetes mellitus on immune complex-mediated nephritis , we produced Heymann nephritis in streptozotocin-induced diabetic rats (DM-HN group) in which the clinical course for 24 weeks and histological changes were examined. Nondiabetic rats with Heymann nephritis (HN group) and diabetic rats (DM group) were also examined as controls. The degree of proteinuria, hypoproteinemia, hyperlipidemia and anemia were more pronounced and the mortality rate was higher in the DM-HN group than in the HN group or in the DM group. Histologically, larger and more subepithelial or intramembranous electron-dense deposits as well as a more markedly thickened glomerular basement membrane (GBM) were observed in the DM-HN group than in the HN group. In conclusion, the nephrotic manifestations and histological changes in the GBM in Heymann nephritis were augmented by the association with diabetes mellitus.

Membranous and vascular choroidopathy: Two patterns of immune deposits in systemic lupus erythematosus

Two patterns of immune aggregate localization were demonstrated by immunofluorescence and electron microscopy in the choroid plexus of four young women with fatal systemic lupus erythematosus. The two patients with granular immune aggregates localized to the basement membrane of the choroid epithelium (membranous choroidopathy) had subepithelial and intramembranous electron-dense deposits and membranous glomerulopathy in their kidneys. The two patients with immune aggregates in the walls of choroidal blood vessels (vascular choroidopathy) had subendothelial electron-dense deposits and proliferative glomerulonephritis. Vascular deposits in the choroid plexus were associated with capillary thrombi and extravasation of fibrinoid material, while isolated membranous choroidopathy had no histopathologic evidence of inflammation. The clinical presentation and serological studies of blood and cerebrospinal fluid were compared in an effort to discriminate between patients with membranous and vascular choroidopathy. All patients had variable neuropsychiatric symptoms and major motor seizures. While those with vascular choroidopathy had more evidence of disease activity in their sera, both groups demonstrated elevated titers of immune-complexed antinuclear antibodies in cerebrospinal fluid. Although both patterns of choroidal localization of immune aggregates were associated with neuropsychiatric dysfunction, we were unable to identify discrete clinical-symptom complexes which differentiated patients with membranous and vascular choroidopathy. These contrasting patterns of choroid plexus immunopathology suggest that factors responsible for differential localization of immune aggregates are not restricted to the renal glomerulus.

Fatal pulmonary hypertension and resolving immune-complex glomerulonephritis in mixed connective tissue disease: A case report and review of the literature

Mixed connective tissue disease (MCTD) has been characterized as a benign rheumatic syndrome with a favorable response to immunosuppressive therapy. Serious renal and pulmonary involvement are reported to be rare in MCTD. We are describing a female adolescent with MCTD in whom fatal cor pulmonale developed due to recurrent thromboembolic primary pulmonary hypertension. Death occurred after two years of therapy with prednisone and azathioprine for an immune-complex glomerulonephritis. Paramesangial and intramembranous electron-dense deposits had been identified in several glomeruli at the start of treatment. Improved renal function and apparent histologic improvement were demonstrated four months after the institution of prednisone and azathioprine therapy, and stable renal function was maintained until death. The pulmonary hypertension was progressive and apparently not altered by either the prednisone or azathioprine. At necropsy, there was no evidence of a pulmonary arteritis or vascular immune-complex deposition to account for the recurrent thromboembolic lesions in the small pulmonary arteries and arterioles. This is a clinical course not previously described in patients with MCTD and may represent an extreme of the clinical spectrum of this syndrome.

Mesangial proliterative glomerulonephritis with irregular intramembranous deposits: Another variant of hypocomplementemic nephritis

Two patients with a persistent mesangial proliferative glomerulonephritis and reduced serum C3 levels have been followed for six and 10 years. Both have had a mild course with normal renal function and spontaneous morphologic improvement. Levels of the fourth component (C4) and second component (C2) of complement, and properdin factor B have been normal; the third component (C3) of complement nephritic factor has not been detected. Ultrastructurally, irregular intramembranous electron-dense deposits are present, primarily within the lamina densa. These deposits are separated by varying lengths of normal-appearing glomerular basement membrane. Intramembranous and subendothelial electron-lucent areas, containing vesicles, are also seen. Subendothelial deposits, mesangial interposition, splitting of the glomerular basement membrane and ribbon-like intramembranous deposits are not found. The disease in these patients was clinically indistinguishable at onset from membranoproliferative glomerulonephritis (MPGN). The possibility of a variant with mild clinical course, no progression and spontaneous morphologic improvement is important in planning and assessing treatment programs in this disease group.

Alternate C3 pathway activation in pneumococcal glomerulonephritis

Glomerulonephritis following pneumococcal infection has been observed, but possible immunopathologic mechanisms have not been adequately explored. Multiple serologic studies as well as light, immunofluorescence and electron microscopic evaluation of kidney biopsy tissue from a 4 year old girl with pneumococcal glomerulonephritis were performed. Clinical studies at the onset of disease showed normal serum C3 and C4 levels (third and fourth components of complement) with progression to selective C3 hypocomplementemia from days 2 to 58. A serum factor capable of breaking down C3 in normal human serum was present during the period of maximum C3 hypocomplementemia. Renal glomerular histology revealed a mesangial proliferative glomerulonephritis. Glomerular bound C3 and type 14 pneumococcal antigen were associated with similar, but less extensive, deposits of properdin. Minimal immunoglobulin M (IgM) and C4 were seen, but immunoglobulin G (IgG) and fibrinogen were absent. Ultra-structurally, subepithellal “humps” and intramembranous electron dense deposits were noted. It is hypothesized that the pneumococcal polysaccharide can activate the alternate complement pathway and may be responsible for a limited course of glomerulonephritis.

Immunologically-mediated renal disease in Waldenström's macroglobulinemia

A patient with Waldenström's macroglobulinemia associated with nephrotic syndrome is described. Serum cryoglobulin and rheumatoid factor were absent. Intramembranous electron-dense deposits were demonstrated in kidney biopsy material by electron microscopy. Deposits of immunoglobulin G (IgG), M (IgM) and the third component of complement (C3) were identified hi kidney biopsy tissue by immunofluorescent staining methods. The serum immunoglobulins were characterized by Chromatographic and immunochemical methods and showed a monoclonal IgM-κ, IgG-κ and γ-chain piece of undefined structure. Free κ- and γ-chains were found in the urine. The IgM was not complexed to the IgG or vice versa, but the IgG was in an aggregated form. Although it is not known which immunoglobulin initiated the tissue injury, IgG, IgM and complement deposits probably contributed to the renal dysfunction. The nephrotic syndrome diminished after treatment with chlorambucil and corticosteroids.