The Prevalence of Mesangial Electron-Dense Deposits in PLA2R-Positive Membranous Nephropathy

<b><i>Introduction:</i></b> Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults and can be primary or secondary. The antigenic target of antibodies in 70% of primary cases is phospholipase A2 receptor (PLA2R). The presence or absence of mesangial electron-dense deposits has been used to distinguish between primary and secondary MN. Mesangial deposits suggest MN due to lupus, infection, or other causes, though they are reported to occur in approximately 10% of primary MN. Staining for PLA2R is now frequently used for confirming a diagnosis of primary MN. If mesangial deposits predict a secondary cause, they should be more frequent in PLA2R-negative biopsies. <b><i>Methods:</i></b> A review of institutional kidney biopsies between March 2017 and June 2020 identified all cases of MN. Cases with a diagnosis of lupus or near “full-house” staining by immunofluorescence microscopy (IF) were excluded. Light microscopy, IF, and electron microscopy (EM) were performed. PLA2R staining was performed by IF. EM for all cases was reviewed and electron-dense deposit location, distribution, and size were determined. <b><i>Results:</i></b> Ninety-three cases of MN were identified, of which 86 had both PLA2R staining and EM performed. Of these, 51 cases (59%) were positive for PLA2R and 35 (41%) were negative. Mesangial electron-dense deposits were present in 22 (25.6%) of the 86 cases, including 27.5% (14/51) of PLA2R-positive cases and 22.8% (8/35) of PLA2R-negative cases. No difference was seen in size or distribution of deposits, or other features considered suggestive of secondary MN. <b><i>Conclusion:</i></b> PLA2R-negative cases were not more likely to have mesangial deposits than PLA2R-positive cases. Mesangial deposits should not be used as an indicator of secondary MN.

Clinical and morphological presentation of C3 glomerulopathy: a single-center study of 60 cases

INTRODUCTION. СЗ-glomerulopathy (СЗ-GP) is a spectrum of diseases caused by dysregulation of the alternative complement pathway. The present study was carried out taking into account the limited number of foreign and the absence of original studies in the Russian population.THE AIM. Analysis of clinical and morphological manifestations of СЗ-GP at the time of primary diagnosis.PATIENTS AND METHODS. Retrospective analysis of the etiology, clinical data and morphology of СЗ-GP identified in the period 2006-2021.RESULTS. The study included 60 cases. The average age of patients is 4З±17 years. Nephrotic syndrome was detected in 47 % of patients; in 58 % of cases the estimated glomerular filtration rate was <60 ml/ min/иЗ m2. The dominant morphological pattern was membranoproliferative glomerulonephritis (75% cases). In 2 cases, СЗ-GP debuted with clinical and morphological manifestations of the disease of minimal changes, in which the identification of characteristic electron-dense deposits became obvious when performing a second biopsy. 4 cases had at the onset classical signs of complement-mediated thrombotic microangiopathy (atypical hemolytic uremic syndrome) in combination with C3-GP or its subsequent development.Ultrastructural examination was performed in 40 cases. 8 patients (20%) were diagnosed dense deposit disease, 32 patients - C3-glomerulonephritis. Primary C3-GP was detected in 87 % of patients, secondary - in 13 % (monoclonal gammopathies - 10 %, autoimmune diseases - 3 %).Increased level of antibodies to factor H was detected in 2 of 12 patients who underwent this study. Nucleotide variants of unknown clinical significance in complement genes were detected in 2 out of 6 patients during molecular genetic testing.CONCLUSION. C3-GP is a severe variant of glomerular damage with a heterogeneous etiological structure, which requires the use of ultrastructural and molecular diagnostics, as well as clinical analysis and identification of pathogenetic mechanisms to determine approaches to therapy.

The Life Cycle and Ultrastructure of the Host Response of the Smut Pathogen, Anthracocystis destruens, on Broomcorn Millet

Broomcorn millet smut caused by the fungus Anthracocystis destruens is one of the most destructive diseases in broomcorn millet production. The life cycle of A. destruens and host defense responses against A. destruens remain elusive. Here we investigated the disease symptom development and the parasitic process of A. destruens as well as the ultrastructure of the host-pathogen interface. The results showed that there are four typical symptoms of broomcorn millet smut, which are blackfly, cluster leaves, hedgehog head and incomplete fruiting. A. destruens colonizes all tissues of broomcorn millet but only produces teliospores in the inflorescence. After infection, A. destruens proliferates in the host likely in a systemic manner. Ultrastructural study of the infected inflorescence showed that the pathogen grows intercellularly and intracellular within the host. The host active defense response against pathogen invasion, includes host secrets callose analogs and highly electron-dense deposits to prevent pathogen infection.

Immunotactoid Glomerulopathy with Nontuberculous Mycobacterial Infection: A Novel Association

A 70-year-old woman underwent a renal biopsy due to nephrotic syndrome. She had suffered from nontuberculous mycobacterial infection (NTM) for 14 years. The patient was diagnosed as having membranoproliferative glomerulonephritis (MPGN) type 3 and immunoglobulin (Ig)-associated MPGN based upon LM/erythromycin and IF findings, respectively. In high-magnification imaging, electron-dense deposits showed immunotactoid glomerulopathy (ITG). There was no evidence of hematological cancer, and the patient improved after receiving treatments for NTM. To the best of our knowledge, this patient is the first to show an association between ITG and NTM. Although ITG is generally considered as related to lymphoproliferative disease, it is suggested that ITG is driven by bacterial infection and is a potential outcome of Ig-associated MPGN.

Novel Powder Modification Method for the Cold Spray of Hard Steels

A novel powder modification method based on the simultaneous softening and agglomeration of steel powders via heat treatment in a rotary tube furnace has been investigated as a means to improve the cold sprayability of H13 tool steel powder. By adjusting starting powder size and shape as well as heat treatment conditions (maximum temperature, cooling rate, and atmosphere), cold spray of H13 powder went from virtually no deposition to the production of thick dense deposits with a deposition efficiency of 70%. Powder agglomeration, surface state, microstructure evolution, and softening are identified as key factors determining powder deposition efficiency and resulting deposit microstructure.

Infection-Related Glomerulonephritis

<b><i>Background:</i></b> There has been a long, storied relationship between various bacterial infections and glomerular injury, which is now encompassed under the term of infection-related glomerulonephritis (GN). The clinical and pathologic manifestations vary depending on the duration, magnitude, and underlying pathogen associated with the inciting infectious process. A brief and acute episode may lead to a self-limiting glomerular manifestation while a chronic or repetitive infection can result in persistent and irreversible injury. In this review, we will discuss the clinical and pathologic findings associated with the infection-related glomerulonephritides. <b><i>Summary:</i></b> An acute exudative GN with an influx of neutrophils is the most characteristic morphologic alteration associated with infection-related glomerular injury. The immunofluorescence staining pattern often reveals prominent complement component C3 deposition in both capillary walls and mesangial regions with or without accompanying immunoglobulin. Large subepithelial electron-dense deposits known as “humps” are the hallmark ultrastructural finding; however, these features can also be present in C3 glomerulopathies, which are often triggered by infections and may have similar underlying abnormalities in alternative pathway complement activation. In addition, other glomerular injuries can simultaneously be present along with infection-related GN, such as diabetic nephropathy, lupus nephritis, or immunoglobulin A nephropathy, constituting a true diagnostic challenge for the pathologist. <b><i>Key Messages:</i></b> Bacterial infection-related GN represents a spectrum of glomerular injury with variable clinical and pathologic presentations. The pathologic findings can show overlap with other glomerular diseases, and different forms of infection-related GN vary in terms of prognosis and treatment approach.

Light chain deposition disease involving kidney and liver in a patient with IgD myeloma

Background IgD multiple myeloma (MM) is a rare subtype of MM and light chain deposition disease (LCDD) outside the kidney is also a rare and has scarcely been reported. We report herein the details of the first reported case of LCDD involving the kidney and liver co-occurring with IgD myeloma. Case presentation A 66-year-old female with IgD MM presented with rapidly progressive acute renal failure, ascites and pleural effusion. Immunofluorescent study of revealed the characteristic linear deposition of Igκ light chain along the glomerular and tubular basement membrane in kidney. Electron microscopy showed the powdery electron-dense deposits along the tubular and glomerular basement membrane consistent with the diagnosis of LCDD. Laser microdissection followed by mass spectrometry identified only Igκ light chain with more than 95% probability confirm the diagnosis of κ-LCDD but not heavy/light chain deposition disease. Liver biopsy with immunofluorescence study revealed the linear deposition of Igκ chain along the perisinusoidal space indicating the hepatic involvement of κ-LCDD. The patient was successfully treated with combination therapy with bortezomib, cyclophosphamide, dexamethasone, and daratumumab. Conclusions This report emphasizes that prompt biopsy of affected organs and initiation of clone directed therapy led to the correct diagnosis and favorable outcome in patient with LCDD who has extrarenal involvement.

Characteristics of patients with coexisting DNAJB9-associated fibrillary glomerulonephritis and IgA nephropathy

Background Coexistence of fibrillary glomerulonephritis (FGN) and immunoglobulin A (IgA) nephropathy (IgAN) in the same kidney biopsy (FGN–IgAN) is rare, and the clinicopathologic characteristics and outcome of this dual glomerulopathy are unknown. Methods In this study, 20 patients with FGN–IgAN were studied and their characteristics were compared with 40 FGN and 40 IgAN control patients. Results Concurrent IgAN was present in 1.8% of 847 consecutive FGN cases and was the second most common concurrent glomerulopathy after diabetic nephropathy. FGN–IgAN patients were overwhelmingly White (94%) and contrary to FGN patients were predominantly (60%) males. Compared with IgAN patients, FGN–IgAN patients were older, had higher proteinuria, a higher incidence of renal insufficiency, and a lower incidence of microhematuria and gross hematuria at diagnosis. Six (30%) patients had malignancy, autoimmune disease or hepatitis C infection, but none had a secondary cause of IgAN or clinical features of Henoch–Schonlein purpura. Histologically, all cases exhibited smudgy glomerular staining for immunoglobulin G and DnaJ homolog subfamily B member 9 (DNAJB9) with corresponding fibrillary deposits and granular mesangial staining for IgA with corresponding mesangial granular electron-dense deposits. On follow-up (median 27 months), 10 of 18 (56%) FGN–IgAN patients progressed to end-stage kidney disease (ESKD), including 5 who subsequently died. Serum creatinine at diagnosis was a poor predictor of renal survival. The proportion of patients reaching ESKD or died was higher in FGN–IgAN than in IgAN. The median Kaplan–Meier ESKD-free survival time was 44 months for FGN–IgAN, which was shorter than IgAN (unable to compute, P = 0.013) and FGN (107 months, P = 0.048). Conclusions FGN–IgAN is very rare, with clinical presentation and demographics closer to FGN than IgAN. Prognosis is guarded with a median renal survival of 3.6 years. The diagnosis of this dual glomerulopathy requires careful evaluation of immunofluorescence findings, and electron microscopy or DNAJB9 immunohistochemistry.