Immunotactoid (microtubular) glomerulopathy: an entity distinct from fibrillary glomerulonephritis?

Immunotactoid glomerulopathy (IT), or alternatively, microtubular glomerulopathy, is a term that has been used by some investigators to encompass those glomerulopathies characterized by the presence of fibrillar or microtubular deposits which are distinguished from amyloid principally by their larger size and lack of reactivity with the Congo red reagent. A case is presented here of IT as it was initially described. The present case, and a review of the literature, suggest that the diagnosis of IT be restricted to those glomerulopathies associated with large, at times organized, microtubular deposits. Terms such as fibrillary glomerulonephritis, or alternatively Congo red-negative amyloidosis-like glomerulopathy, could then be used to describe those patients with smaller, fibrillar glomerular deposits having an appearance closely resembling amyloid. We believe it is possible to separate the entities fibrillary glomerulonephritis and IT on morphological grounds. This is a potentially useful distinction that identifies patients who are likely to have or develop clinical evidence of a lymphoplasmacytic disorder or dysproteinemia, which are associated with deposits of IT, and distinguishes them from patients with fibrillary glomerulonephritis, of whom only a single case has been linked to such clinical findings.     

Immunotactoid glomerulopathy in a child with Down syndrome

A 9-year-old girl with Down (21-trisomy) syndrome was found to have proteinuria and microscopic haematuria at age 6 years. Proteinuria gradually increased during the next 3 years, although blood pressure and renal function remained normal. The patient exhibited no underlying systemic diseases, monoclonal gammopathy, cryoglobulinaemia or histological evidence of plasmacytoma. A percutaneous renal biopsy revealed immunotactoid glomerulopathy (fibrillary glomerulonephritis) characterized by thickening of the glomerular basement membrane, diffuse mesangial expansion and various-sized acid-Schiff-positive nodules that were intensely positive for IgG, light chains ( and ) and complement components (C3, C4, C1q) along the glomerular capillaries in the mesangium. Congo red dye and amyloid thioflavine T staining were negative. Fibrils (15–17 nm in diameter — larger than amyloid fibrils) were present in the mesangial area and within the glomerular basement membrane. We are not aware of a previous report of immunotactoid glomerulopathy and a patient with chromosomal abnormalities.     

Immunotactoid glomerulopathy is a rare entity with monoclonal and polyclonal variants

1. Download : Download high-res image (379KB)
2. Download : Download full-size image

     

Immunotactoid glomerulopathy with leucocytoclastic skin vasculitis and hypocomplementemia: a case report

Immunotactoid glomerulopathy is a recently described entity characterized clinically by proteinuria, hematuria and hypertension, and on renal biopsy by various glomerular lesions including extracellular microtubules composed of immune reactants. Furthermore a defined immunological disease or cryoglobulinemia are absent. We report the case of a patient with immunotactoid glomerulopathy and hypocomplementemia (low C3 level) who developed several episodes of leucocytoclastic skin vasculitis with large immune deposits in and around small vessels. It is suggested that skin and renal involvement are part of the same systemic disease.     

Monoclonal gammopathy and glomerulonephritis with organized microtubular deposits

We report a case with IgG-kappa monoclonal gammopathy of unidentified significance (MGUS) and glomerulonephritis (GN) with organized microtubular deposits on electron microscopy (EM). Light microscopy (LM) examination showed exudative features and moderate extracapillary proliferation. An acute nephritic syndrome with a rapidly progressive renal failure was clinically manifest at the onset and during each relapse. The patient was treated with methylprednisolone pulses followed by oral prednisone, cyclophosphamide, plasmapheresis, and maintenance courses of chemotherapy. The response to treatment was good, with a temporary improvement of renal function and control of the downhill course over a 3-year follow-up.     

Fibrillary glomerulonephritis and immunotactoid (microtubular) glomerulopathy are associated with distinct immunologic features

BACKGROUND: The clinical relevance of distinguishing two types of glomerulonephritis (GN) with non-amyloid organized immunoglobulin (Ig) deposits-fibrillary GN (FGN) and immunotactoid (microtubular) GN (IT/MTGN)-on the basis of ultrastructural organization, is debated. METHODS: Twenty-three patients with organized glomerular Ig deposits were classified into two groups based on the fibrillar or microtubular ultrastructural appearance of the deposits. Kidney biopsy samples were studied by immunofluorescence microscopy, using anti-light chain conjugates (all cases) and anti-IgG subclass conjugates (13 patients). In each group, we studied clinicopathological features, associated monoclonal gammapathy (detected by immunoelectrophoresis and/or immunoblot) or B-cell lymphoproliferative disease, effects of chemotherapy and long-term renal outcome. RESULTS: In 14 IT/MTGN and 9 FGN patients, clinical symptoms [hypertension, nephrotic syndrome (NS) and hematuria] and the mean diameters of the substructures were similar. In 13 IT/MTGN patients, glomerular (IgG1, 2 or 3) deposits were monotypic (kappa, 7 cases; lambda, 6 cases). Glomerular deposits were associated with a monoclonal Ig of the same isotype in eight patients, detected in the serum (5 cases), and/or in the cytoplasm of lymphocytes (4 cases), and with lymphoproliferative disease in seven patients. The ultrastructural features of monoclonal Ig inclusions in lymphocytes were similar to those of glomerular microtubular deposits. In contrast, none of the FGN patients presented lymphoplasmocytic proliferation or paraproteinemia. Glomerular Ig deposits were polyclonal in eight cases and contained IgG4 in all three cases studied. Although patient and renal survival did not differ significantly between the two groups, chemotherapy led to remission of NS in ten IT/MTGN patients, with parallel improvement in hematological parameters. CONCLUSIONS: The identification of ultrastructural patterns in these nephropathies is important. GN with organized microtubular monoclonal deposits (GOMMID) probably accounts for a large proportion of immunotactoid (microtubular) GN cases.     

Membranous glomerulopathy with Bowman's capsular and tubular basement membrane deposits

Bowman's capsular and tubular basement membrane (TBM) deposits are an extremely unusual finding in non-lupus membranous glomerulopathy (MGN). We report three atypical cases of MGN with abundant Bowman's capsular and TBM deposits. In two cases, MGN was idiopathic; in the third case, MGN occurred in the renal allograft in the setting of HCV seropositivity. In addition to the usual glomerular capillary wall deposits, immunofluorescence and electron microscopy revealed extensive immune deposits within Bowman's capsule and TBMs, predominantly at the base of parietal and tubular epithelial cells. These cases suggest a potential pathomechanism of autoantibody to secreted epithelial antigens shared by visceral, parietal, and tubular epithelial cells. In all three cases, indirect immunofluorescence was unable to detect autoantibody to normal renal epithelial or matrix constituents. Furthermore, ELISA was unable to demonstrate circulating antibody to major extracellular matrix components. The implications of these findings for the pathogenesis of MGN are explored.     

Ⅲ型胶原肾小球病一例

Ⅲ型胶原肾小球病又名胶原纤维性肾小球病（collagenofibrotie glomerulopatby），是1979年由日本学者首次报道的一种新肾小球疾病，其病理特点为肾小球内有显著的Ⅲ型胶原沉积。临床首发症状主要为肾病综合征（NS）或大量蛋白尿，呈缓慢进展，最终发展为肾功能衰竭。近年来本病在世界各地均有陆续报道。为提高对Ⅲ型胶原肾小球病的认识，现报告1例。     

纤维样肾小球病二例

例1女性,54岁,因双眼睑水肿2年,乏力25 d于2003年6月16日入我院.入本院前曾在外院,诊断为慢性肾炎,经治疗无好转.体检除双下肢水肿外,余无异常.     

Glomerulopathy associated with glomerular microtubular deposits: a report of a case]

A male aged 58 was admitted to our hospital because of proteinuria, hematuria and bilateral pretibial edema. Laboratory tests showed normocytic, normochromic anemia and moderately impaired renal function. Antinuclear antibodies were negative. Neither M-protein nor Bence-Jones protein were detected. Light microscopic study on the biopsied renal specimen indicated a moderate mesangial proliferation accompanying with the deposition of PAS-positive and Congo red-negative materials in the subendothelial area. C3 accumulated segmentally along the capillary walls, which was clarified by immunofluorescence microscopy. Staining for IgG, IgA, IgM and light chains were negative. Electron microscopy demonstrated the deposition of microtubules in the mesangial, subepithelial and subendothelial areas. The diameter of these microtubules ranged from 40 to 80 nm. Such type of the microtubules have been reported to exist in the glomeruli in the patients with systemic diseases such as amyloidosis, systemic lupus erythematosus, cryoglobulinemia and light chain disease. In our patient, however, any clinical or serological findings suggestive of these systemic diseases were not obtained. On the other hand previous report pointed out that microtubules deposited in the glomeruli in the patients with immunotactoid glomerulopathy or other glomerulopathies. Our patient had the clinical features consistent with these glomerulopathies. However, no depositions of immunoglobulins were observed. This case is an atypical glomerulopathy accompanying with the glomerular microtubular deposits.     

Fibrillary-immunotactoid glomerulopathy with renal deposits of IgAlambda: a rare cause of glomerulonephritis

We describe a 24-year-old patient who presented with a nephrotic syndrome. His renal biopsy revealed a diffuse mesangioproliferative glomerulonephritis with eosinophilic deposits. Electron microscopy showed organized, Congo-red negative deposits, forming microtubules of about 20 nm width in the capillary walls and in the mesangium, establishing a diagnosis of fibrillary-immunotactoid glomerulopathy. Fibrillary-immunotactoid glomerulopathy is a rare cause of glomerulonephritis, characterized by Congo-red-negative glomerular deposits of fibrils, sometimes organized in microtubules, predominantly containing IgG and C3. Patients clinically present with the nephrotic syndrome, hematuria and hypertension. The pathogenesis of this glomerulopathy has not been elucidated yet. In our patient, the renal deposits contained IgAlambda. This peculiar feature is suggestive of an underlying paraproteinemia. However, in the serum no paraproteins or cryoglobulins were found, and also microscopical examination and immunophenotyping of the bone marrow did not point to the presence of a monoclonal plasma cell dyscrasia. Our patient was not treated with immunosuppressive drugs and he is currently progressing to end-stage renal disease.     

Ultrastructural study on membranoproliferative glomerulonephritis with special reference to subepithelial deposits

The distribution of electron dense deposits in the glomerulus was scrutinized by electron microscopy in 34 cases of membranoproliferative glomerulonephritis (MPGN). Seven cases underwent serial biopsies. Results are summarized as follows. (1) Mesangial deposits (MD) and subendothelial deposits (SEND) were demonstrated in nearly all biopsy specimens. Intramembranous deposits (IMD) and subepithelial deposits (SEPD), which had hitherto been considered uncommon in MPGN, were also seen in over three- fourths of the specimens. (2) According to these findings, Burkholder's Type III MPGN, characterized by the frequent presence of SEPD, seems not to be essential in the classification of MPGN. In contrast, Strife's type III MPGN, defined by the disruption of the glomerular basement membrane (GBM), appears to be appropriate for the classification, because the cases diagnosed as Strife's type III showed quite peculiar histology among the MPGN. (3) In most cases having undergone serial biopsies, cellular proliferation in the glomeruli was more improved at the second biopsy than at the first, which probably resulted from intensive medications such as the combined therapy of corticosteroids, immunosuppressants, and anticoagulants. On electron microscopy, however, electron dense deposits were not decreased, and SEPD was rather increased. Furthermore, the GBM was more thickened and showed more irregular structure in the second biopsy. (4) Humps were observed in 14 out of 41 biopsy specimens of MPGN. They were seen not only in the acute but also in the chronic stage of the disease, especially in the cases with persistent hypocomplementemia. These results suggest that the subepithelial deposits are more common in MPGN than considered previously, and are more closely related to the morphological changes and the progression of MPGN. In particular, humps should be a marker indicating the activity of the disease associated with hypocomplementemia, whether it is acute or chronic.     

Genetical, histological, and clinical characteristics of IgA-negative mesangioproliferative glomerulopathy

Background  

Mesangioproliferative glomerulopathy (MesPGN) is a well-defined pathohistological entity. However, the clinical characteristics and prognosis have not been fully established in patients without immunoglobulin (Ig)A (N-IgAN) in contrast to patients with IgA nephropathy (IgAN).     

Clinical features and long-term renal outcomes of Japanese patients with obesity-related glomerulopathy

Background

Studies have suggested that obesity-related glomerulopathy (ORG) is one of the important disease entities leading to end-stage renal disease. However, information is limited regarding the clinical features and renal outcomes of Japanese ORG patients.

Methods

Among the patients whose renal biopsy was performed at our institute during the past 10 years, we identified 28 ORG patients. Among them, the renal prognosis of the 20 patients with more than 2 years of follow-up was further analyzed. The clinical features at biopsy and the renal outcomes were compared with those of other ORG cohorts.

Results

The average values at diagnosis were a body mass index of 32.0 kg/m², eGFR of 65 ml/min/1.73 m², and urinary protein excretion of 1.7 g/day. These features were less serious than those of the US cohort or the Spanish cohort and were compatible with those of the Chinese cohort. At the last observation, seven patients (35 %) showed a 50 % increase in their serum creatinine, and two patients (10 %) had a 100 % increase in serum creatinine and/or end-stage renal disease (end point). A multivariate analysis identified the time-averaged proteinuria during follow-up as an independent factor that was associated with the slope of renal function. The annual rate of patients reaching the end point in the US cohort, the Spanish cohort and the current cohort were 6.7, 6.9 and 1.6 % per year, respectively.

Conclusion

The long-term outcomes of Japanese ORG patients include progression to renal failure, emphasizing the importance of an accurate early diagnosis of this entity.     

Lobular membranoproliferative glomerulonephritis with organized microtubular monoclonal immunoglobulin deposits associated with B cell small lymphocytic lymphoma.

Sir, Fibrillary glomerulonephritis (FGN) and immunotactoid glomerulopathy(ITG) are well known glomerular diseases with Congo-red-negativedeposits [1–4]. While FGN is characterized by randomlyarranged microfibrils around 20 nm in diameter with no underlyingsystemic disorder, ITG is defined by orderly arranged microtubulardeposits, usually >30 nm in diameter with a hollow core;patients with ITG tend to have underlying lymphoproliferativediseases.     

Clinicopathological and genetic characteristics in Chinese patients with lipoprotein glomerulopathy

OBJECTIVE: In this study, we report on 16 Chinese patients with biopsy-proven lipoprotein glomerulopathy (LPG) investigated for clinical manifestations, pathological characteristics and apolipoprotein E (apoE) genetic analysis. METHODS: A retrospective analysis of the clinical and pathological features was made in 16 patients with LPG. Plasma concentrations and genetic analysis of apoE were completed. Glomerular depositions of apoA, apoB and apoE were detected using monoclonal antibodies on cryostatic sections in all patients. RESULTS: All 16 patients presented with edema; 14 presented with nephrotic syndrome. Anemia, microhematuria, hypertension and abnormal levels of serum creatinine were detected in 12 patients (75%), 11 patients (69%), 8 patients (50%) and 6 patients (37.5%), respectively. All the patients showed hypertriglyceridemia, while only 7 showed slight hypercholesterolemia. The characteristic features of hyperlipidemia in these patients were approximately in accord with those of type IV hyperlipoproteinemia. Concentrations of apoB correlated with urine protein, triglycerides and cholesterol (r=0.558, p=0.038; r=0.6, p=0.023; r=0.65, p=0.012; respectively). No correlation was found between serum level of apoE and clinicopathological features in patients with LPG. The genotype of apoE-epsilon3/epsilon4 is the predominant one in Chinese patients with LPG. No mutated forms of apoE were found, compared with previous reports. CONCLUSION: Unique clinicopathological and genetic features were found in this group of Chinese patients with LPG compared with the general population, including lower serum levels of apoE and cholesterol, as well as anemia and microhematuria. Multiple factors other than apoE were involved in the pathogenesis of LPG.