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Immunotactoid glomerulopathy (ITG), a condition characterised by highly organised microtubules on electron microscopy, and cryoglobulin glomerulopathy (CG) are rare forms of kidney injury that may be encountered in patients with cryoglobulinaemia. It has been proposed these two entities are part of the same disease process following observed clinical and histological similarities. [ABSTRACT FROM AUTHOR]

Background: Fibrillary (FGN) and immunotactoid (IT) glomerulonephritis are uncommon. Aims: To evaluate the prevalence, clinicopathological correlations and outcomes of FGN and IT in our regional centre in Australia. Methods: We interrogated a renal biopsy database for cases of FGN and IT from 2000 to 2020. Data included demographics, serum creatinine, haematuria status, proteinuria, comorbidities and histopathological findings. Results: We had 14 cases of FGN and t of IT. The mean presenting age was 59.8 years, and 42.9% were males. No patients with FGN had dysproteinaemia, whereas both patients with IT had chronic lymphocytic leukaemia. At presentation, 75% of patients with FGN and both patients with IT had haematuria; all had proteinuria. Mean albumin‐creatinine ratio at presentation was 254 mg/mmol for FGN and 604 mg/mmol for IT. Mean presenting serum creatinine was 149 μmol/L for FGN and 95 μmol/L for IT. Four patients with FGN (28.6%) received immunomodulatory therapy. The prognosis of FGN was poor, with six patients (46.2%) reaching end‐stage kidney disease after a median of 42 months (range 1–96 months). All patients presenting with proteinuria <30 mg/mmol entered complete remission; patients with higher‐grade proteinuria exhibited progressive chronic kidney disease. Patients with IT had complete remission with treatment of underlying haematological disease. Conclusion: FGN is rare, with poor response to immunomodulatory therapy. It carries poor renal prognosis. Less proteinuria at diagnosis may predict a more benign disease course. IT is associated with haematological malignancy and carries better prognosis and response to treatment. [ABSTRACT FROM AUTHOR]

Introduction: The pathologic approach to glomerulonephritis (GN) with fibrillar IgG deposits and light chain restriction remains a diagnostic challenge. Method: All GN with fibrillar deposits of IgG and apparent light chain restriction on standard immunofluorescence on frozen tissue (IF-F) accessioned at the Columbia Renal Pathology Laboratory from 2012 to 2019 were identified. Additional studies including staining for Congo red, DNAJB9, IgG subtypes, and immunofluorescence on pronase-digested paraffin sections (IF-P) were performed. Result: Based on the results, biopsy samples were reclassified as polytypic DNAJB9-positive fibrillary glomerulonephritis (pFGN, n = 14), monotypic DNAJB9-positive FGN (mFGN, n = 7), GN with polytypic DNAJB9-negative fibrillar IgG deposits (n = 2), and GN with monotypic DNAJB9-negative fibrillar IgG deposits (n = 6). Among DNAJB9-positive FGN samples, IgG subtype staining was able to exclude monotypic deposits by demonstrating reactivity for ≥2 IgG subtypes (usually IgG1 and IgG4) in 67% (14 of 21), including 9 that would have been misclassified as monotypic by IF-F and IF-P alone. Monotypic DNAJB9-positive fibrillary glomerulonephritis (FGN) was not associated with monoclonal gammopathy in 5 of 6 patients. GN with monotypic DNAJB9-negative fibrillar IgG deposits exhibited focal parallel fibril alignment and frequent association with chronic lymphocytic leukemia, but lacked the diagnostic microtubules of immunotactoid GN. Conclusion: A systematic diagnostic approach with ancillary techniques is essential for proper classification and assignment of monoclonal gammopathy of renal significance status in cases of GN with fibrillary IgG deposits and light chain restriction by IF-F.

Introduction: The term monoclonal gammopathy of renal significance (MGRS) has been described to include patients with renal manifestations associated with circulating monoclonal proteins with or without a clonal lymphoproliferation (B-cell or plasma cell) and not meeting diagnostic criteria for an overt hematological malignancy. A host of MGRS-associated lesions have been described that involve various renal compartments. Our study describes the histomorphological spectrum of MGRS cases at our center in the last 5 years and description as per the classification system of the International Kidney and Monoclonal Gammopathy Research Group (IKMG). Material and Methods: Retrospective analysis was carried out of all the renal biopsies with characteristic monoclonal immunoglobulin lesions for histopathological diagnosis between years 2015 and 2020 and reviewed by two independent pathologists. Results: Most patients in the study belonged to the fifth decade, with a median age of 50 years (mean 50.14 ± 10.43) range (24–68 years) with a male preponderance. Most patients presented with proteinuria as the sole manifestation (66.6%). Many of the patients (48%) had an M spike by serum protein electrophoresis or urinary protein electrophoresis with an abnormal serum free light chain assay (60.8%). AL amyloidosis was the most common diagnosis observed on histopathological evaluation (68.7%), followed by light chain deposition disease (10.4%). Conclusion: MGRS lesions are infrequently encountered in the practice of nephropathology and pose a diagnostic challenge due to the limitation of a congruent clinical or hematological picture. A thorough histological examination with immunofluorescence and electron microscopy often precipitates in the right diagnosis and prompts timely management.

Monoclonal Gammopathy of Renal Significance (MGRS) is a group of heterogeneous disorders characterized by renal dysfunction secondary to the production of a monoclonal immunoglobulin by a nonmalignant B cell or plasma cell clone. We report the clinical and histological outcomes of two patients with biopsy-proven MGRS: one patient showed membranoproliferative glomerulonephritis with monoclonal k-light chain and C3 deposits, the second patient showed immunotactoid glomerulopathy. Both patients were treated with a 9-month chemotherapy protocol including bortezomib, cyclophosphamide, and dexamethasone. Renal biospy was repeated after 1 year. The estimated glomerular filtration rate (eGFR) increased from 22.5 (baseline) to 40 ml/min per 1.73 m2 after 12 months, then to 51.5 ml/min per 1.73 m2 after 24 months; proteinuria decreased from 4.85 (baseline) to 0.17 g/day after 12 months, then to 0.14 g/day after 24 months. Repeat renal biopsies showed a dramatic improvement of the glomerular proliferative lesions and near complete disappearance of the immune deposits. A bortezomib-based treatment proved very effective and was well-tolerated in the two patients presenting with clinically and histologically aggressive MGRS.

Renal diseases involving glomerular deposits of fibrillary material are an important diagnostic challenge for an ultrastructural pathologist. Several renal diseases are characterised by the presence of fibrillary material in the glomeruli. Two disorders of this type, termed ‘fibrillary glomerulonephritis’ (characterised by fibrils measuring approximately 20 nm in diameter) and ‘immunotactoid glomerulonephritis’ (characterised by larger, microtubular deposits), have been described. The possible relatedness of these two disorders and their potential association with other systemic illnesses are the subjects of current debate. Other multisystemic diseases, including amyloidosis and various forms of cryoglobulinaemia, can also present with fibrillary or microtubular deposits in the kidney. The distinction between fibrillary glomerulonephritis, immunotactoid glomerulonephritis, and other processes that have similar ultrastructural features are discussed in this review. Recently, both in fibrillary glomerulonephritis and in immunotactoid glomerulonephritis, the presence of a DnaJ homolog subfamily member 9 has been detected. This antigen is not present in amyloidosis and could be involved in the pathogenesis of these diseases. This review will discuss the role and the relevance of this antigen.

Recently, the term monoclonal gammopathy of renal significance (MGRS) was used to describe monoclonal gammopathies capable of causing kidney damage resulting in chronic kidney impairement and end-stage renal disease. By definition, patients with MGRS have small plasma-cell or B-cell clones that do not meet the criteria for multiple myeloma or lymphoma, and are frequently mistaken as monoclonal gammopathies of undetermined significance (MGUS). As treatment is not recommended for MGUS, appropriate therapy is commonly withheld. Therefore, a high index of clinical suspicion for MGRS and a multidisciplinary approach are essential to avoid delayed diagnosis and the development of MGRS-related end-stage renal disease. [ABSTRACT FROM AUTHOR]

[english] Purpose: To present a case with posterior segment findings in a patient with cloudy corneas secondary to immunotactoid glomerulonephritis (ITG).Methods: A 57-year-old female was known to have bilateral cloudy corneas diagnosed 12 years ago secondary to immunotactoid glomerulonephritis. Clinically, fundus examination was difficult to visualise due to the density of her corneal opacities. Results: B-scan ultrasound revealed significant retino-choroidal & non-inflammatory scleral thickening. The macula also showed signs of thickening in both eyes. Optical coherence tomography (OCT) showed thinning of the inner retinal layers and significant choroidal folds in both eyes. Electrodiagnostic tests (EDT) concluded loss of retinal ganglion cells with preservation of retinal function in both eyes.Conclusion: This case widens the spectrum of findings seen in patients diagnosed with Immunotactoid Glomerulonephritis and alerts us to undertake detailed posterior segment examination where possible. Ocular coherence tomography (OCT) and B-scan ultrasonography are important adjuvants to help assess the posterior segment in patients with corneal opacities secondary to ITG.

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Renal disease is a common complication of human immunodeficiency virus (HIV) infection in adults. In children, however, HIV pathology of the gastrointestinal and respiratory tracts predominates, whereas renal disease is often an incidental finding. In this report, we describe a child with stage III HIV infection associated with immunotactoid glomerulonephritis (IT). The patient was referred for investigation of idiopathic nephrotic syndrome. Electron microscopy of his renal biopsy specimen revealed numerous electron-dense microtubular deposits, arranged in parallel fashion, consistent with a diagnosis of IT. He received highly active antiretroviral therapy (HAART) as well as corticosteroids and is currently in remission. To our knowledge, this is the first report of IT in a child. [ABSTRACT FROM AUTHOR]

Fibrillary and immunotactoid glomerulonephritis: Distinct entities with different clinical and pathologic features. Background. Controversy surrounds the relatedness of fibrillary glomerulonephritis (FGN) and immunotactoid glomerulonephritis (IT). Methods. To better define their clinicopathologic features and outcome, we report the largest single center series of 67 cases biopsied from 1980 to 2001, including 61 FGN and 6 IT. FGN was defined by glomerular immune deposition of Congo red–negative randomly oriented fibrils of < 30 nm (mean, 20.1 ± 0.4 nm). IT was defined by glomerular deposition of hollow, stacked microtubules of ≥ 30 nm (mean, 38.2 ± 5.7 nm). Results. FGN comprised 0.6% of total native kidney biopsies and IT was tenfold more rare (0.06%). Deposits in FGN were immunoglobulin G (IgG) dominant and polyclonal in 96%. IgG subtype analysis in 19 FGN cases showed monotypic deposits in four (two IgG1 and two IgG4) and oligotypic deposits in 15 (all combined IgG1 and IgG4). In IT, deposits were IgG dominant in 83% and monoclonal in 67% (three IgG1κ and one IgG1λ). FGN patients were a mean age of 57 years, 92% were Caucasian, and 39% were male. At biopsy, FGN patients had the following clinical characteristics (mean, range): creatinine 3.1 mg/dL (0.5 to 14), proteinuria 6.5 g/day (0.8 to 25), 60% microhematuria, and 59% hypertension. Histologic patterns of FGN were diverse, including diffuse proliferative glomerulonephritis (DPGN) (nine cases), membranoproliferative glomerulonephritis (MPGN) (27 cases), mesangial proliferative/sclerosing (MES) (13), membranous glomerulonephritis (MGN) (four), and diffuse sclerosing (DS) (eight). The more proliferative (MPGN and DPGN) and sclerosing (DS) forms presented with a higher creatinine and greater proteinuria compared to MES and MGN. Median time to end-stage renal disease (ESRD) was 24.4 months for FGN and mean time to ESRD varied by histologic subtype: DS 7 months, DPGN 20 months,... [ABSTRACT FROM AUTHOR]