Dense Deposits Research Articles

Segmentation and thickness calculation of glomerular basement membrane using RADS-Net in glomerular microscopic images

Glomerular ultrastructure needs to be observed under transmission electron microscopy during pathological diagnosis of renal biopsies. Evaluating the glomerular basement membranes (GBM) is necessary for the renal pathological diagnosis. There is little work that performs well for full-flow automated analysis of GBM in whole-glomerular electron microscopy images, including GBM segmentation, location, and thickness calculation. To address this problem, we propose a network architecture, RADS-Net, whose segmentation module combines the advantages of ViT and CNN to achieve better performance in GBM and electron dense deposit (EDD) segmentation tasks. It also contains an uncertainty evaluation module and a location module to exclude unsuitable regions for measurement and extract accurate GBM contours. We propose a GBM thickness calculation method based on statistical learning method, skeletonization algorithm, and improved region growth method. Systematic experiments demonstrate that our proposed segmentation network achieves superior accuracy compared to other competing methods. Additionally, the computed GBM thickness, after an automatic screening of suitable fields of view, meets the requirements for pathology evaluation.

Mechanical properties of atherosclerotic plaques, caps and walls of arterial vessels: a mobile test bench experiments

Within the framework of this study, a methodology and a prototype of a test bench for conducting experiments on compression of biological tissue samples have been developed. The test bench for the implementation of the technique consists of high–precision scales (measuring accuracy up to 0.01 g, maximum weight - 5 kg), an electronic caliper (measuring accuracy up to 0.01 mm) with 3D-printer pads that are attached to grips, as well as video cameras. Thanks to such a mobile stand, it was possible to conduct a series of experiments (a total of 99 tests) to determine the Young's modulus of atherosclerotic plaques and areas of vascular walls removed from the body no later than a few hours. This made it possible to collect a database of the mechanical characteristics of the plaques as close as possible to the real properties. In addition, regression dependences were constructed between the Hounsfield numbers corresponding to dense atherosclerotic deposits discernible on a CT scan and the Young modules obtained during experiments. Such dependencies will further allow determining the mechanical properties of plaques in vivo based on computed tomography data. The technique was verified by mechanical experiments on the universal testing machine Instron 3342 and on a mobile test bench on samples of hard (with pronounced calcification) and soft plaques. 7 experiments were conducted for each type of samples. The results differed by no more than 4.3 % for soft plaques and no more than 9.5 % for hard plaques. To test the inter-expert reliability of the methodology, a number of experiments were conducted with the involvement of two independent participants. Each of the three mobile stand operators performed 5 tests on soft rubber samples. The study of inter-expert reliability allowed us to show the independence of the methodology from the skills and qualifications of the operator.

Expert Discussion on Challenges in C3G Diagnosis: A Podcast Article on Best Practices in Kidney Biopsies.

Complement 3 glomerulopathy (C3G) is an ultra-rare, progressive kidney disease resulting from dysregulation of the alternative complement pathway. Clinical presentation of C3G is heterogeneous and definitive diagnosis relies on kidney biopsy and immunofluorescence staining. The term C3G encompasses two subgroups, dense deposit disease and C3 glomerulonephritis, distinguished via electron microscopy. In this podcast article, the authors discuss the challenges associated with C3G diagnosis and the central role of kidney biopsy. Using an illustrative case study, key histological observations are described, and best practices are discussed from the perspectives of a nephrologist and a nephropathologist. Podcast Audio (MP4 141866 KB).

The Association of Class I and II Human Leukocyte Antigen Serotypes With End-Stage Kidney Disease Due to Membranoproliferative Glomerulonephritis and Dense Deposit Disease

Membranoproliferative glomerulonephritis (MPGN), encompassing several distinct diseases, is a rare but significant cause of kidney failure in the United States. The potential etiologies of MPGN are unclear, but prior studies have suggested dysregulation of the alternative complement pathway and, recently, autoimmunity as potential mechanisms driving MPGN pathogenesis. In this study, we examined HLA associations with end-stage kidney disease (ESKD) due to MPGN and dense deposit disease (DDD) in a large racially and ethnically diverse US-based cohort. Case-control study. Using US Renal Data System (USRDS) and United Network for Organ Sharing (UNOS) data, we identified 3,424 patients with kidney failure due to MPGN and 263 due to DDD. We matched patients to kidney donor controls on designated race and ethnicity in a 1:15 ratio. 58 class I and II HLA serotypes. Case-control status. For each disease cohort, univariable and multivariable logistic regression analyses were used to investigate associations between the disease and 58 HLA serotypes. In subgroup analyses, we investigated HLA associations in White and Black patients. We also studied antiglomerular basement membrane (anti-GBM) nephritis as a positive-control outcome. We applied a Bonferroni correction to account for multiple comparisons. Eighteen serotypes were significantly associated with the odds of having MPGN in univariable analyses, with DR17 having the strongest association (odds ratio [OR], 1.55 [95% CI, 1.44-1.68], P=4.33e-28). No significant associations were found between any HLA serotype and DDD. Designated race-specific analyses showed comparable findings. We recapitulated known HLA associations in anti-GBM nephritis. Reliance on HLA serotypes (rather than genotype), lack of biopsy-confirmed diagnoses. HLA-DR17 is associated with ESKD due to MPGN in a racially and ethnically diverse cohort. The strength of association was similar in White and Black patients, suggesting a role in the pathogenesis of MPGN. No HLA associations were observed in patients with DDD. Prior studies have suggested dysregulation of the alternative complement pathway as a potential etiology of membranoproliferative glomerulonephritis (MPGN), but recent evidence from a British White population has implicated an autoimmune mechanism in MPGN pathogenesis. We investigated HLA associations between MPGN and dense deposit disease (DDD) in a large racially and ethnically diverse cohort of patients. We found that HLA-DR17 is associated with end-stage kidney disease (ESKD) due to MPGN in both White and Black patients. By contrast, no significant HLA associations with ESKD due to DDD were identified. These results suggest a role for autoimmunity in some cases of MPGN and highlight differences in the disease etiology of MPGN compared with DDD.

Characterization of Membranous Nephropathy with Microspherular Deposits

Introduction: Membranous nephropathy (MN) is a common cause of adult nephrotic syndrome in the USA. The typical ultrastructural finding is of global uniformly dense subepithelial electron-dense immune complex deposits along glomerular basement membranes. However, early reports described deposits with a unique microspherular substructure. There was variability in what was identified as microspherular, sometimes overlapping with other entities such as podocyte infolding glomerulopathy. Currently, the nature, composition, and clinical significance of these microspherular deposits (MSDs) remain unknown. Method: We report the clinicopathologic features of a series of MN cases with MSD, with detailed ultrastructural characterization as well as PLA2R and THSD7A immunohistochemical and IgG subclass-staining characteristics. The proportion of MSD to overall deposits is segregated into two groups: global MSD with >50% MSD (n = 14) and segmental MSD with <50% (n = 5). Results: The size and appearance of the microspherules were nearly identical in global and segmental MSD groups (mean diameter of 77.9 nm and 77.2 nm, respectively), with subepithelial (n = 19) or intramembranous (n = 12) distributions in all cases. Mesangial MSDs (n = 5) were only found in the global MSD group. The majority of biopsies (86% of global MSD and 100% of segmental MSD) were Ehrenreich-Churg stage 2 or above; early stage 1 was only observed in the global MSD group. All but 3 cases were PLA2R/THSD7A double negative; 1 THSD7A positive in global MSD and 2 PLA2R positive in segmental MSD. IgG1 was the dominant subclass in the global MSD group, and IgG4 was dominant in the segmental MSD group, including the 2 PLA2R-positive cases. Conclusion: The findings suggest that MSDs are more commonly associated with secondary MN. This case series is the largest to date, and the findings may yield etiologic and prognostic information on this rare but unique subset of MN and provide a well-characterized cohort of cases for future studies.

Diagnosis and treatment of glomerular diseases with a membranoproliferative glomerulonephritis (MPGN) pattern of injury

Membranoproliferative glomerulonephritis (MPGN) represents aheterogeneous group of diseases. The common feature of amembranoproliferative lesion pattern in the kidney biopsy can either be idiopathic/primary or-much more frequently-have asecondary cause. The historical classification into MPGN typesI toIII has largely been abandoned and replaced in recent years by apathogenesis-oriented classification. AMPGN with C1q, C3 and/or C4 deposits on light microscopy is referred to as immune complex GN (IC-GN), while aMPGN with dominant C3 deposits is referred to as C3 glomerulopathy (C3G). C3G is further divided into C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). These diagnoses can only be made by akidney biopsy. Possible causes of MPGN are chronic infections (especially hepatitisB andC, bacterial infections, infections with protozoa), autoimmune diseases (especially lupus, rheumatoid arthritis) or malignancies (especially hematological malignancies). Particularly in the case of C3G acomprehensive analysis of the complement system components is strongly recommended. Due to the low incidence and the heterogeneous clinical appearance of MPGN therapeutic decisions must be made individually; an optimal general therapy is unknown, except that supportive treatment as with other glomerular diseases should be optimized. In the case of asecondary MPGN it is generally recommended to treat the potential cause of the MPGN. If significant proteinuria persists and eGFR remains > 30 ml/min/1.73 m2, treatment with systemic steroids and mycophenolate mofetil is recommended. Other treatment options on an individual level after evaluation and discussion of the risk-benefit ratio with the patient are rituximab and eculizumab. Rapidly progressive MPGN should be treated like ANCA-associated vasculitis. The recurrence rates after kidney transplantation are very high and treatment is challenging.

Multimodal Imaging of Coronavirus Disease 2019-Associated Retinal Ischemia in a Patient with Dense Deposit Disease

Multimodal Imaging of Coronavirus Disease 2019-Associated Retinal Ischemia in a Patient with Dense Deposit Disease

Processing map of the in-situ micro-forging (MF) assisted cold spray for additive manufacturing of fully dense metals without MF particle inclusion

The newly developed in-situ micro-forging assisted cold spraying (MFCS) is an economical and convenient way to deposit dense metals with porosity lower than 0.1%. During this process, forging effect induced by impact of large-size hard micro-forging particles to in-situ densification of the deposited materials. Therefore, a fully dense metallic deposit could be produced at moderate gas temperature and pressure without using expensive helium gas. However, it is found that the porosity is highly dependent on the type of depositing materials, shot-penning particle size, and spraying parameters. Shot-peening particle deposition-induced inclusion is frequently observed for soft depositing materials. This makes the application challenging and a universal processing map is in great demand. In this study, pure Al, pure Ti, pure Ni, 2219 Al, 6061 Al, 7055 Al, and TC4 with different hardness values are used as examples to explore a universal spraying processing map for MFCS. The influence of impact velocity and volume fraction of the shot-peening particle, types of the depositing materials, and spraying parameter on densification and shot-peening particle deposition is investigated. Adding 30vol.% of 410 stainless steel MF particles into the depositing powders decreases the porosity of all deposits and particle deposition-induced inclusion is observed in pure Al, all three Al alloys, and pure Ti deposits. The single particle deposition experiment and the numerical simulation reveal that mechanical interlocking is the prime mechanism for MF particle deposition. A critical embedding MF particle size (dcr,e), above which MF particle inclusion can be avoided, is defined. A new concept of MF intensity (IMF) is proposed to comprehensively consider all main factors influencing the densification of the deposit. Finally, optimized processing maps for depositing fully dense metals without MF particle inclusion are established by plotting the critical embedding velocity and IMF against the hardness of the depositing materials.

Can a Single Glomerulus Morphology Implicate Successful Therapy?

Recurrent gross hematuria of glomerular origin is frequently encountered in clinical practice, and in absence of specific serological marker, renal biopsy is mandatory to address the definitive diagnosis, and set out an appropriate therapeutic protocol. Technical deficiencies associated with practice of renal biopsy are frequently encountered, as inadequate number of glomeruli or poor immunofluorescence staining of kidney biopsy specimen; however, these deficiencies can be offset by detailed electron microscopy analysis of a single abnormal glom.We present a single middle-aged Libyan woman, with a rare glomerular disease, related to abnormal activation of alternative complement pathway, where renal biopsy report was initially not adequate and lacking immunohistochemistry workup. However, electron microscopy reports a characteristic abnormal glomerular deposit, coupled with clinical and biochemical data that guided our therapeutic protocol.In a middle-aged female who presented with recurrent gross hematuria and nephrotic range proteinuria, we should suspect a glomerular pathology. Further to immunoglobulin A nephropathy or lupus nephritis, particularly in presence of complement abnormalities and negative serology for glomerulopathy-related autoantibodies, dense deposit disease and C3 glomerulonephritis that are rare complement mediated glomerulopathy should be considered as a seronegative lupus nephritis-equivalent, in terms of their membranoproliferative features on light microscopy, and when setting out appropriate therapeutic protocol. Patient and family counseling for C3 glomerulopathy is essential because this type of glomerulopathy has a recurrence rate after kidney transplant.

#4488 OLD BIOPSY IS ALWAYS GOLD, REVISING MEMBRANOPROLIFERATIVE GN DIAGNOSIS IN A RENAL TRANSPLANT PATIENT

Abstract Background and Aims MPGN resulting from hepatitis C virus (HCV) infection typically shows granular deposition of immunoglobulin M (IgM), C3, and both kappa and lambda light chains. Immunoglobulin G (IgG) may or may not be present, and C1q is typically negative, the same pathology can be found in other viral infections. The recurrence rate post-transplantation is high, with 33% of immune-complex MPGN. Graft loss is even higher 65%, especially among patients with idiopathic MPGN. Treatment of a patient with significant proteinuria can be tricky, as no proven treatment is described yet, but plasmapheresis and induction with cyclophosphamide were described for heavy proteinuria &amp;gt;3.5 g/day. Method 79 year old female patient, known case of live unrelated renal transplantation in December 2013, primary renal disease is unknown. She had a history of equivocal hepatitis C virus antibodies, but Hepatitis C virus RNA was not detected. She is also known to have Type II Diabetes Mellitus and hypertension. The patient had baseline creatinine of 100-120 micromol/L. 24 hr urine protein was 0.8 g/Day but started rising quickly to reach a peak of 9.2 g/g seven months post-transplantation to nephrotic range proteinuria but her serum albumin level was always above 35 g/L. Serum protein electrophoresis showed no M band, a kappa/ Lambda ratio 1.21 within a normal range (0.260-1.65). Anti- nuclear antibody (ANA), P-ANCA, C-ANCA, and Double-stranded DNA all were negative. Complements were within normal range C3 1.39 g/L (0.79 -1.52), C4 0.44 g/L(0.17-0.57)m rheumatoid factor and Anti- citrullinated peptide antibodies were negative. Hepatitis b Virus surface antigen and core antibodies were not reactive, HIV screening was negative. Urine analysis showed RBCs but no RBC casts. Renal biopsy showed mild mesangial expansion and mild l increase in mesangial cells and matrix. Some glomeruli show increased lobulation with increase in mesangial cells and matrix with segmental endocapillary proliferation There is double contour of the glomerular basement membrane with scattered spikes and holes within the basement membrane seen best with silver stain. There is mild increase in the thickness of glomerular basement membrane. There is focal mild lymphocytic infiltration. Tubulitis is not seen in the examined material. One Focal area of mild interstitial fibrosis. Sampled blood vessels are unremarkable. The stain for C4d is negative. Immunofluorescence showed granular capillary wall immunoreactivity to IgM (+2), C4 (+1), C1q (+1), and Lambda light chain (+2). The glomeruli show no immunoreactivity to IgG, IgA, C3, Kappa and fibrin. The glomeruli show (+) staining for albumin. Tubular protein reabsorption droplets showed immunoreactivity for albumin, IgG, IgM, C3, kappa and lambda light chains. Electron microscopy showed many subendothelial, and mesangial electron-dense deposits. The patient was on maintenance immunosuppression medications inform of mycophenolic acid 720 mg, cyclosporine; 250mg BID, and Prednisolone 5 mg daily.Revisiting the new classification of membranoproliferative glomerulonephritis is challenging in this patient, since there is the dominance of IgM deposition by immunofluorescence and C4 but not C3 makes it challenging, the negative monoclonal band in serum electrophoresis and negative autoimmune workup excludes immune complex mediate MPGN, leave idiopathic MPGN a possibility, keeping in mind that hepatitis C virus infection was never confirmed. On the other hand, IF showed IgM with C4 subendothelial and mesangial dense deposits that excludes away the C4 glomerulopathy. Results Whether this is a recurrence of glomerular disease early on post-transplantation or denovo membranoproliferative disease, she responded well to the addition of losartan 100 mg daily, with a reduction of her urinary protein to less than 1 g/g. the patient never received treatment for the hepatitis C virus. Conclusion In our patient, it is difficult to conclude if the cause of MPGN is recurrence or denovo GN, especially with severe proteinuria that responded well to ACEi treatment. The pathological findings can be tricky.

#5478 REAL-WORLD SIGNS AND SYMPTOMS AT DIAGNOSIS IN PATIENTS WITH C3 GLOMERULOPATHY - INTERIM RESULTS FROM A MULTI-COUNTRY STUDY

Abstract Background and Aims C3 glomerulopathy (C3G) is a rare form of glomerulonephritis, with an estimated incidence of 1 – 2 per million per year. C3G is associated with a high risk of disease progression with approximately 50% of patients reaching kidney failure within 10 years of diagnosis. Common signs and symptoms include proteinuria, hematuria, edema and hypertension. The aim of this analysis was to better understand the clinical characteristics of C3G patients from the US, Europe and Asia, at the time of diagnosis. Method An analysis was conducted using interim data from the Adelphi C3G Disease Specific Programme (DSP), a cross-sectional survey of C3G-treating nephrologists in US, EU5 (France, Germany, Italy, Spain, UK), China and Japan (study ongoing since August 2022; interim analysis based on data until November). Nephrologists completed structured forms administered via online links for consecutive patients presenting with C3G. The forms included demographic and clinical information including signs, symptoms, and lab values amongst others. Results In this interim analysis, 88 nephrologists had completed records for 277 patients in this survey, including 95 in US, 120 in EU5, 39 in China and 23 in Japan. Median patient age at diagnosis was 40.9, and 60% were male. 80% had C3 glomerulonephritis (C3GN) and 19% had dense deposit disease (DDD). Median proteinuria at diagnosis was 2.9 g/day, and was ≥1 g/day in 82% of patients. Median eGFR at diagnosis was 50 ml/min/1.73m2 (Table 1). In addition to proteinuria, the main clinical signs and symptoms at diagnosis were hematuria, edema, hypertension and fatigue. Pain, appetite loss and sleep problems were also reported. Physicians described disease severity at diagnosis as moderate in 53% and severe in 31% of patients. Conclusion This study allows evaluation of a rare disease across geographies. C3G patients experience substantial symptomatic and clinical burden at diagnosis. This symptom burden, high proteinuria, and relatively low eGFR is consistent with physician assessment that the disease is moderate or severe by the time of diagnosis. Facilitating early diagnosis of C3G and rapid initiation of treatment could be beneficial for patients in slowing disease progression.

#6598 STUNNING RENAL FUNCTION RECOVERY AFTER TREATMENT WITH DARATUMAMB IN A CASE OF C3 GLOMERULOPATHY WITH MONOCLONAL GAMMOPATHY

Abstract Background and Aims 38 years old man with C3GN linked to Monoclonal Gammopathy recovers from dialysis after treatment with Daratumamb. Case report C3 glomerulonephritis related to monoclonal gammopathy is a challenging entity and the efficacy of treatment with Daratumumab is not clearly defined yet. We would like to describe the case of a stunning renal response to Daratumumab in a young man with MGUS and C3 glomerulonephritis. In July 2021 a 38 years old man presented to our nephrology division with full nephrotic syndrome, creatinine 1.2 mg/dl, low C3 and little IgG lambda spike of 2 g/dL on serum electrophoresis. Kidney biopsy revealed a membranoproliferative GN with bright C3 staining by immunofluorescence, no other positive immune-reactant and no masked deposits on pronase digested tissue. Electron microscopy confirmed the presence of subendothelial electron dense deposits. The diagnosis was consistent with C3 glomerulonephritis. Complement genetic test and C3 nephritic factor were negative. Assuming a form of C3GN associated to monoclonal gammopathy (MGRS), a bone marrow biopsy was performed and revealed a small clonal plasma cells population. In November 2021 he was started on velcade/dexamethasone but unfortunately stopped early due to severe side effects. Subsequently he begun cyclophosphamide and steroids without clinical or serological response. In few months renal function rapidly worsened requiring dialysis since April 2022. A repeat kidney biopsy confirmed C3GN with still moderate activity and low chronicity. In May 2022 he was started on Daratumamab/Lenalidome/Dexamethasone. After eight months of dialysis the diuresis progressively increased and the renal function improved so remarkably that dialysis was discontinued since December 2022. At present the patient renal function is stable with creatinine 3.5 mg/dl, proteinuria 3g/L, and monoclonal component decreased to 1.1 g/L from 3.5 g/L. He continues Daratumumab single agent monthly and we have scheduled a further renal biopsy in the next week. To our knowledge this is the first time a patient recovers from dialysis after treatment with Daratumamb for a C3GN linked to a monoclonal gammopathy. It definitely makes this case unique and inspiring for further studies and considerations regardinf this intriguing field of MGRS.

#6541 GLOMERULONEPHRITIS DIAGNOSIS BY MACHINE LEARNING ON PERIODIC ACID-SCHIFF (PAS) WHOLE SLIDE IMAGES

Abstract Background and Aims Machine learning (ML) holds great promise for improving diagnostics, prognostication and theranostics in nephropathology. So far, applications have not gone much further than segmentation of tissue compartments on whole slide images (WSIs) of paraffin sections. As a proof-of-concept study, we describe the development of a diagnostic classifier for glomerulephritis based on expert-annotated or automatically segmented glomerular transections from periodic-acid Schiff (PAS) paraffin sections only. Method A total of n = 350 biopsies from 5 institutions with 12 classes of glomerulonephritis IgA nephropathy (IgAN), membranous nephropathy (Membranous), anti-glomerular basement membrane antibody GN (ABMGN), infection-associated GN (IAGN), ANCA-associated GN (ANCA-GN), idiopathic membranoproliferative GN (MPGN), SLE GN class IV (SLE-GN-IV), cryglobulinemic GN (CryoGN), C3 GN (C3-GN), dense deposit disease (DDD), fibrillary GN (FibrillaryGN) and proliferative GN with monoclonal immunoglobulin deposits (PGNMID) were included in the study with their respective PAS sections. Glomerular transections were expert-annotated by a nephropathologist and automatically segmented with our own transformer-based segmentation model trained on 100 biopsies with thrombotic microangiopathies and a range of vascular, vasculitic and glomerular diseases closely resembling/mimicking thrombotic microangiopathies. For classification, we divided the cohort into 5 folds for internal cross-validation, performed sample size augmentation with various methods (including shifts in resolution/scale, AutoAugment and others) and trained our proprietary self-attention-based MILx architecture on an EfficientNet backbone with selection of glomerular crop batches by soft Markov chain Monte Carlo sampling in a semi-supervised fashion, with diagnostic class labels for each biopsy. We compared the performance of our proprietary architecture on both expert-annotated and automatically segmented glomerular crops with a recently published benchmark architecture (CLAM) for multiple-instance learning in histopathology. Results Automatic glomerular segmentation performance was excellent with mean AUC and sensitivity (mean average recall) over all classes at 0.904, with near perfect mean average specificity (0.994), as expected best for Membranous, worst for ABMGN. Classification performance of MILx with expert-annotated glomerular crops as inputs had a mean balanced accuracy of 0.84, with AUC metrics in descending order of 0.97 for Membranous, 0.89 for ABMGN, 0.88 for IgAN, 0.86 for Fibrillary, 0.83 for MPGN, 0.80 for ANCA-GN, 0.79 for DDD, 0.78 for PGNMID, 0.75 for IAGN, 0.73 for SLE-GN-IV and CryoGN, 0.67 for C3-GN. Performance with MILx was similar for automatically segmented glomerular crops as input. On this dataset, MILx outperformed CLAM with both entire WSIs as well as expert-annotated glomerular crops as inputs (mean balanced accuracy of 0.72) by a significant margin. Conclusion This proof-of-concept-study indicates that nephropathology-specific architectures like our MILx can be trained for complex tasks on relatively small biopsy cohorts. We should be able to deliver an end-to-end-pipeline for this diagnostic and other tasks based on training sets with case-labels provided by trusted institutions with only minimal expert labeling or annotation required. PAC and HQ contributed equally to this work.

#3618 CLINICAL SIGNIFICANCE OF MILD ABNORMALITIES IN GLOMERULAR FILTRATION BARRIER (GBM) DIAGNOSED BY RENAL BIOPSY

Abstract Background and Aims The well-known GBM abnormalities without immunological reaction are Alport syndrome (ALPORT) and thin basement membrane disease (TMD). Two diseases occasionally share common genetic abnormalities, although, clinical outcomes are worse in ALPORT. Sometimes, there are also mild abnormalities of GBM unable to be classified into ALPROT or TMD without any immunological or hemodynamical abnormalities in the kidney. We compared clinical and pathologic findings among ALPORT, TMD, and GBM abnormalities not classified (GBM NOS) diagnosed by renal biopsy. Method Among 18,134 adult patients who underwent kidney biopsy from 1979 to 2018 in 17 hospitals in Korea (number of IRB: B1707/408-106), we selected patients with ALPORT, TMD, or GBM NOS diagnosed by renal biopsy. GBM NOS was defined as any abnormality of GBM structure of lamellation, thickness, and integrity by electron microscopic examination, which are not able to classify into specific pathologic diagnosis. We excluded ALPORT, TMD, and GBM NOS combined to the other pathologic diagnosis or showing electron dense deposit. We collected clinicopathologic findings at renal biopsy and the last visit to clinics and incidences of mortality and end stage renal disease during follow-up period. Results There were 179 (0.99%) TMDs, 33 (0.18%) ALPORTs, and 8 (0.04%) GBM NOSs among all patients. The clinico-pathologic findings were presented in Table 1. Age and gender proportion at renal biopsy were not different among groups. Patients with ALPORT showed the lowest level of estimated glomerular filtration rate by MDRD equation (eGFR) (p&amp;lt;0.001) and the highest level of urine protein to creatinine ratio (UPCR) (p&amp;lt;0.001). Patients with GBM NOS had similar levels of eGFR and UPCR compared to patients with TMD at renal biopsy. Under microscopic examinations, segmental sclerosis in glomeruli was most prevalent in patients with ALPORT compared to patients with the other disease. Global sclerosis in glomeruli was prevalent in patients with ALPORT and GBM NOS. Other glomerular changes, such as cellular infiltration and matrix change in mesangium, and ischemic glomerular change, were not different among groups. Patients with GBM NOS showed more severe change of interstitial fibrosis and tubular atrophy compared to patients with TMD but similar to patients with ALPORT. Patients with GBM NOS did not show vascular changes. Podocyte foot process effacement was present more frequently in patients with GBM NOS or ALPORT compared to patient with TMD (p&amp;lt;0.001). During 97.9 ± 61.8 months of follow-up period, one (3.0%) patient was dead and 10 (30.3%) patients must have renal replacement therapy (RRT) among patients with ALPORT. The other patients with GBM NOS or TMD had survived and did not need RRT. Conclusion Clinical findings of GBM NOS were similar to TMD, although pathologic changes of glomerular global sclerosis and tubulo-interstitial changes are more severe in GBM NOS compared to TMD. GBM changes in GBM NOS might be related to tubulo-interstitial damages which needs to be defined with more studies.

#5665 C3 GLOMERULOPATHY CURRENT THERAPY AND REAL-WORLD MANAGEMENT - INTERIM RESULTS FROM A MULTI-COUNTRY STUDY

Abstract Background and Aims C3 glomerulopathy (C3G) is a rare form of glomerulonephritis, with an estimated incidence of 1 – 2 per million per year. C3G is associated with a high risk of disease progression with approximately 50% of patients reaching kidney failure within 10 years of diagnosis. No treatments have been proven effective through randomized controlled trials. KDIGO glomerular disease guidelines recommend treating with renin-angiotensin-aldosterone system inhibitors (RAASi) to reduce blood pressure and proteinuria, and, in select patients, utilization of immunosuppressants such as mycophenolate mofetil and corticosteroids. Newer agents, such as eculizumab, are also sometimes used off-label. The aim of this analysis was to better understand the current management of C3G in the US, Europe, and Asia. Method An analysis was conducted using interim data from the Adelphi C3G Disease Specific Programme (DSP), a cross-sectional survey of C3G-treating nephrologists in US, EU5 (France, Germany, Italy, Spain, UK), China and Japan (study ongoing since August 2022; interim analysis based on data until November). Nephrologists completed structured forms administered via online links for consecutive patients presenting with C3G. Forms included information on current and most recent therapy. Results In this interim analysis, 88 nephrologists had completed records for 277 patients, including 95 in US, 120 in EU5, 39 in China and 23 in Japan. Median patient age at time of the survey was 44, and 60% were male. 80% had C3 glomerulonephritis (C3GN) and 19% had dense deposit disease (DDD). At the time of the survey, 82% out of 277 patients were receiving treatment. The majority (69%) of 228 treated patients were receiving RAASi, 27% were receiving mycophenolate mofetil/ mycophenolate sodium, 48% corticosteroids, and biologics were used in almost a third of patients. At the time of the survey, mean proteinuria was 2.1 g/day, with 60% of patients having proteinuria ≥1 g/day (Table 1). Conclusion C3G is a rapidly progressing glomerulonephritis for which there is no approved therapy. Most patients in this real-world study were receiving treatment, with both conventional immunosuppressants and biologics frequently added to RAASi. Despite this, proteinuria remained high, with the majority of patients having proteinuria ≥1 g/day. This highlights the need for novel therapies to actively treat C3G.

Вителлиформная макулярная дистрофия и возрастная макулярная дегенерация: сходство и различия при их выявлении

Background. Adult-onset vitelliform macular dystrophy is one of the pathologies that successfully masks as age-related macular degeneration. Purpose. To assess the incidence of adult-onset vitelliform macular dystrophy and its clinical manifestations. Material and methods. We analyzed frequency cases of adult-onset vitelliform macular dystrophy among 1000 patients aged 40 years and older who applied with various eye complaints. Results. Adult-onset vitelliform macular dystrophy was found in 2 patients – men 43 and 66 years old. In the macular area of both eyes of the 1st patient, rounded yellow lesions in the foveola, local detachment of neuroepithelium, optical dense material deposit on the outer segments of photoreceptors were detected (vitelliruptive stage of adult-onset vitelliform macular dystrophy). On the left eye of the 2nd patient in the foveola, a single rounded yellow focus of 200 µm was determined, optical dense vitelliform material presence between the layers of the pigment epithelium and neuroepithelium without signs of choroidal neovascularization was detected (vitelliform stage of adult-onset vitelliform macular dystrophy). Conclusion. The incidence of adult-onset vitelliform macular dystrophy among patients with various ocular pathologies was 0.2 %. Morphological changes in the macula consist in presence of deposits of vitelliform material, localized between the layers of neuroepithelium and retinal pigment epithelium. Keywords: adult-onset vitelliform macular dystrophy; age-related macular degeneration; optical dense vitelliform material

C3 glomerulopathy

C3 glomerulopathy (C3G) is a rare kidney disease that causes kidney dysfunction as a result of dysregulation of the complement system alternate pathway (AP). C3G encompasses 2 separate disorders, C3 glomerulonephritis and dense deposit disease. The presentation and natural history is variable and kidney biopsy is needed to confirm the diagnosis. The overall prognosis is poor with high recurrence rates after transplant. A better understanding of C3G is needed as is high-quality evidence to guide therapy, which currently includes mycophenolate mofetil and steroids for moderate to severe disease, and terminal complement blockade with anti-C5 therapy in unresponsive cases.

Analysis of the local growth and density evolution of soot deposits generated under hydrocarbon condensation: 3D simulation and detailed experimental validation

The utilization of the Exhaust Gas Recirculation (EGR) system during atypical engine operating conditions in order to meet future type-approval criteria exposes the internal surfaces of the devices to exhaust gas with elevated concentrations of particulate matter and greater amounts of hydrocarbon species, leading to the formation of dense and wet sludge deposits. To broaden the understanding of this phenomenon and contribute to the development of advanced EGR devices, this study presents an extended Computational Fluid Dynamics (CFD) model that, in addition to simulating the growth of fouling deposits caused by the accumulation of soot particles, also takes into account the condensation of hydrocarbons. Two scenarios with varying hydrocarbon concentrations in the exhaust flow are analysed, and the evolution of the deposit's thickness and density is determined. A sequential validation process is carried out by comparing the numerical results to actual deposit profiles at different stages of the fouling process. Additionally, hyperspectral images of the fouling layer have been acquired and analysed to validate the regions where hydrocarbon condensation is predicted to play a crucial role, enabling the verification of the hydrocarbon condensation phenomenon predicted by the numerical model. The results obtained under the studied conditions indicate that, on average, 77.4% of the analysed area exhibits a low level of relative error, demonstrating that the proposed model and the methodology used serve as a valuable tool for examining the propensity for deposit formation in devices subjected to fouling exacerbated by hydrocarbon condensation.

Effect of rare–earth (Ce, La) compounds on the microstructure, mechanical and electrochemical corrosion characteristics of electroplated Ni films

For optimizing the microstructure and performance of Ni–electroplating film, the soluble rare–Earth (RE) compounds CeCl3 or LaCl3 were introduced, which were electrodeposited on Cu substrate by direct current (DC) and pulse current (PC) methods, respectively. The surface characteristics of morphology, composition, and phase of obtained different deposits were investigated, and the relationship between the structure and the performance of internal stress, hardness, and electrochemical responses was discussed. The results show that both RE compounds were conducive to eliminating the surface pits by inhibiting the hydrogen evolution reaction, while did not co–deposit into the Ni film. Moreover, the preferred orientation of Ni (111) crystalline plane was altered into Ni (200) by LaCl3, and its combination with PC–electrodeposition further had a better grain refinement effect than CeCl3. Due to the formation of a relatively dense and fine deposit, the PC–electrodeposited Ni/LaCl3 film exhibited the highest hardness of 320 HV, lowest tensile stress of 55 MPa, and best electrochemical passivation protection, which effectively improved the comprehensive performance of Ni film and demonstrated a good prospect for industrial applications.

Energy-Efficient and Green Extraction of Bismuth Metal in Methanesulfonic Acid-Based Membrane Electrochemical Systems

As the mainstream hydrometallurgical medium of bismuth sulfide concentrate, chloride/hydrochloric acid suffers from high volatility, strong corrosiveness, and inferior deposit quality. In this paper, methanesulfonic acid (MSA) with low volatility and high stability was adopted as the bismuth hydrometallurgical system, and the membrane electrochemical deposition method was proposed to extract bismuth metal from a bismuth-containing solution. The effects of additives, such as calcium lignosulfonate (CL), tetrabutylammonium chloride, β-naphthol, and lugalvan NES, on the morphology of bismuth deposits and electric energy consumption (EEC) were investigated in detail. The addition of CL as an additive could produce dense and flat bismuth deposits while the EEC is reduced simultaneously. Cyclic voltammetry and chronoamperometry analysis reveal the electrochemical behavior of bismuth deposition in the CL-assisted MSA medium, and the nucleation and growth of bismuth grains follow a 3D ″nucleation/growth″ mechanism. Under a cathode current density of 180 A/m2, a flat metallic bismuth deposit (purity > 99.96%) is produced in the presence of 0.5 g/L CL. The cathodic current efficiency (CCE) and EEC of membrane electrodeposition are 98.25% and 705 kWh/t Bi, respectively. Compared with chloride/hydrochloric acid, the bismuth membrane electrodeposition process in the CL-assisted MSA system has the advantages of being energy-saving, green, and safe, and it has a good application prospect in the field of bismuth hydrometallurgy.