Glomerular diseases最新文献

{"title":"Role of Epigenetic Changes in the Pathophysiology of Diabetic Kidney Disease.","authors":"Marita Liebisch, Gunter Wolf","doi":"10.1159/000541923","DOIUrl":"10.1159/000541923","url":null,"abstract":"<p><strong>Background: </strong>Diabetic kidney disease (DKD) is a global health issue. Epigenetic changes play an important role in the pathogenesis of this disease.</p><p><strong>Summary: </strong>DKD is currently the leading cause of kidney failure worldwide. Although much is known about the pathophysiology of DKD, the research field of epigenetics is relatively new. Several recent studies have demonstrated that diabetes-induced dysregulation of epigenetic mechanisms alters the expression of pathological genes in kidney cells. If these changes persist for a long time, the so-called \"metabolic memory\" could be established. In this review, we highlight diabetes-induced epigenetic modifications associated with DKD. While there is a substantial amount of literature on epigenetic changes, only a few studies describe the underlying molecular mechanisms. Detailed analyses have shown that epigenetic changes play an important role in known pathological features of DKD, such as podocyte injury, fibrosis, accumulation of extracellular matrix, or oxidative injury, all of which contribute to the pathophysiology of disease. The transforming growth factor-β plays a key role as it is involved in all-mentioned epigenetic types of regulation.</p><p><strong>Key messages: </strong>Epigenetic is crucial for the development and progression of DKD, but the detailed molecular mechanisms have to be further analyzed more in detail.</p>","PeriodicalId":73177,"journal":{"name":"Glomerular diseases","volume":"4 1","pages":"211-226"},"PeriodicalIF":0.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11623970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunofluorescence Use and Techniques in Glomerular Diseases: A Review.","authors":"Nidia Messias","doi":"10.1159/000542497","DOIUrl":"10.1159/000542497","url":null,"abstract":"<p><strong>Background: </strong>Immunofluorescence (IF) studies play an essential role in the evaluation of medical renal biopsies. Particularly, in the study of renal glomerular diseases, where it provides fundamental data for the diagnosis, classification, and etiology of the glomerular pathologies. Diverse techniques may be used to optimize the utilization of IF studies, from variations on the test methodologies to expertise on the interpretation of the results and knowledge of potential pitfalls.</p><p><strong>Summary: </strong>This manuscript presents a brief review on the history of IF and its utilization in kidney pathology, followed by a description of the IF methods, including the use of IF on paraffin-embedded tissue (paraffin IF), and other novel techniques. Guidelines on how to best report IF findings are reviewed, along with a description of antibodies commonly used in glomerular diseases, highlighting their distribution within the normal kidney and potential pitfalls in interpretation. Finally, the use and interpretation of IF are discussed in more detail in individual entities on a range of glomerular diseases.</p><p><strong>Key messages: </strong>IF is crucial for interpretation of renal biopsies and diagnosis of glomerular diseases. Knowledge of IF techniques, alternative procedures, its use and proper interpretation is essential for optimal utilization of IF in renal pathology, and this review proposes to serve as a simplified and practical guide on this topic.</p>","PeriodicalId":73177,"journal":{"name":"Glomerular diseases","volume":"4 1","pages":"227-240"},"PeriodicalIF":0.0,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11644094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"C3 Glomerulopathy: A Current Perspective in an Evolving Landscape.","authors":"Eric Keoni Magliulo, Prasanth Ravipati","doi":"10.1159/000542354","DOIUrl":"https://doi.org/10.1159/000542354","url":null,"abstract":"<p><strong>Background: </strong>Complement 3 (C3) glomerulopathy (C3G) is a heterogenous disease characterized by dysregulation of the complement alternative pathway. Within 10 years of a diagnosis, roughly 50% of patients with C3G will progress to end-stage kidney disease. Historically, treatment options have been limited to nonspecific immune suppression with suboptimal response rates to recommended therapies. Advances in immunology and the emergence of novel complement-targeted therapies have shifted the focus toward identifying the distinct underlying etiologies of C3G.</p><p><strong>Summary: </strong>In this review, we provide a description of the current landscape and challenges faced in the classification, evaluation, and treatment of patients with C3G.</p><p><strong>Key message: </strong>C3G can be broadly separated into four distinct groups: (1) genetic mutations/variants, (2) autoimmune/acquired autoantibodies, (3) monoclonal immunoglobulin-associated C3G, and (4) C3G without an identified cause. Therapy directed toward the underlying pathogenetic cause of C3G may improve outcomes in a disease in which current treatment options are largely ineffective.</p>","PeriodicalId":73177,"journal":{"name":"Glomerular diseases","volume":"4 1","pages":"200-210"},"PeriodicalIF":0.0,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11606624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ANCA-Negative Pauci-Immune Glomerulonephritis: A Review.","authors":"Cristián Juanet, Isabel Hassi, Abbal Koirala","doi":"10.1159/000541792","DOIUrl":"10.1159/000541792","url":null,"abstract":"<p><strong>Background: </strong>Pauci-immune glomerulonephritis (PIGN) is typically secondary to antineutrophil cytoplasmic antibodies (ANCA) small-vessel vasculitis. However, some cases lack detectable circulating ANCA and are called ANCA-negative PIGN (seronegative PIGN). The reported incidence of this varies greatly. Its relationship to ANCA-associated vasculitis (AAV) is unclear.</p><p><strong>Summary: </strong>This review explores the pathophysiology of seronegative PIGN and summarizes findings from 12 studies focusing on this disease. The role of neutrophils appears to be central, with activation through cellular and humoral mechanisms. Most studies have noted less extrarenal involvement and more chronic changes in the kidney biopsy in seronegative PIGN compared to ANCA-positive cases. Studies have mostly reported using corticosteroids with cyclophosphamide for induction therapy and azathioprine for maintenance. The renal survival was noted to be lower compared to ANCA-positive PIGN.</p><p><strong>Key messages: </strong>Whether ANCA-negative PIGN represents a distinct disease or is part of the AAV spectrum remains unclear. Prospective large-scale studies are needed to understand this disease for optimal diagnosis and management.</p>","PeriodicalId":73177,"journal":{"name":"Glomerular diseases","volume":"4 1","pages":"189-199"},"PeriodicalIF":0.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kidney-Limited Microangiopathy Associated with Methionine Synthase (Cobalamin G) Deficiency in a Pediatric Patient: Case Report and Review of the Literature.","authors":"Jonathan E Zuckerman, Rachana Srivastava","doi":"10.1159/000540382","DOIUrl":"https://doi.org/10.1159/000540382","url":null,"abstract":"<p><p>Thrombotic microangiopathy (TMA) is a recognized sequela of inborn errors of metabolism impacting vitamin B12 (cobalamin) synthesis. Methylmalonic aciduria and homocystinuria, cobalamin deficiency type C is a well-known etiology for TMA. TMA has only rarely previously been reported in methionine synthase (cobalamin G) deficiency. Furthermore, results of only 7 kidney biopsies have previously been reported in this clinical setting. Here, we report a case of kidney- and glomerular-limited chronic active microangiopathy demonstrated on kidney biopsy in a patient with biochemically confirmed cobalamin G deficiency. A literature review of all prior reported cases is also presented and demonstrates hypertension, proteinuria, and hematuria to be common presenting symptoms. Age on onset ranged from 7 months to 14 years. Kidney-limited phenotype was less common and occurred only in older children. Acute kidney injury was more common in younger patients. Therapy with hydroxocobalamin and angiotensin-converting enzyme inhibitors resulted in variable clinical responses.</p>","PeriodicalId":73177,"journal":{"name":"Glomerular diseases","volume":"4 1","pages":"183-188"},"PeriodicalIF":0.0,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11521432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Overlap of Anticoagulant-Related and IgA Nephropathy: A Case Report.","authors":"Mercedes Galloway, John J Sim, Andrew Slater, Christopher Bray, Daniel Bishev, Patrick Walker","doi":"10.1159/000541116","DOIUrl":"https://doi.org/10.1159/000541116","url":null,"abstract":"<p><strong>Introduction: </strong>Anticoagulant-related nephropathy (ARN) is an increasingly recognized cause of acute kidney injury (AKI), initially associated with warfarin use. Supratherapeutic warfarin levels were implicated in kidney toxicity. With the widespread adoption of direct oral anticoagulants (DOACs), it becomes imperative to understand their potential risk for ARN and its clinical presentation.</p><p><strong>Case presentation: </strong>We report a case of a 64-year-old male prescribed DOAC for paroxysmal atrial fibrillation management, presenting with heart failure and worsening AKI. Hematuria and mild proteinuria were also observed. Despite management attempts, AKI persisted, prompting a kidney biopsy. Histopathological examination revealed acute tubular injury with numerous intratubular red blood cell casts consistent with ARN. Additionally, findings indicative of IgA nephropathy (IgAN), including mesangial hypercellularity and IgA dominant deposition, were noted.</p><p><strong>Conclusion: </strong>This case underscores the emerging risk of ARN associated with DOACs and emphasizes the potential exacerbation of ARN in the presence of underlying glomerular diseases such as IgAN. Clinicians should maintain a high index of suspicion for ARN in patients on anticoagulation therapy, particularly DOACs, who present with AKI and urinary abnormalities, as early recognition and intervention are crucial in preventing further renal damage.</p>","PeriodicalId":73177,"journal":{"name":"Glomerular diseases","volume":"4 1","pages":"167-171"},"PeriodicalIF":0.0,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11521512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preparation and Rationale for a Patient-Centered Clinical Outcome Assessment Set of Fluid Overload for Drug Development in Nephrotic Syndrome.","authors":"Eloise Salmon, Noelle E Carlozzi, Jin-Shei Lai, Catherine Spino, Yujie Wang, Emily Capellari, Rebecca Scherr, Kayla Sifre, Shawn Sullivan, Courtney Hurt, Tina Creguer, Kelly Helm, Richard A Lafayette, Patrick H Nachman, David T Selewski, John Devin Peipert","doi":"10.1159/000539921","DOIUrl":"https://doi.org/10.1159/000539921","url":null,"abstract":"<p><strong>Introduction: </strong>Fluid overload is a source of substantial morbidity for adults and children with nephrotic syndrome (NS). Preparation and Rationale for a Fluid Overload in Nephrotic Syndrome Clinical Outcomes Assessment Set for Drug Development (Prepare-NS, 5UG3FD007308) was funded by the US Food and Drug Administration to develop a core set of patient-reported and observer-reported (for young children) outcome measures of fluid overload for use in pharmaceutical trials across the lifespan.</p><p><strong>Methods: </strong>The Prepare-NS study team developed the proposed context of use with input from stakeholders. We conducted a scoping review to assess the available literature on relevant patient- and observer-reported measures and performed secondary analyses of existing qualitative and quantitative data.</p><p><strong>Results: </strong>The outcome set will aim to serve individuals 2 years of age and older with primary NS conditions (specifically focal segmental glomerulosclerosis, minimal change disease, IgM nephropathy, membranous nephropathy, and childhood-onset NS not biopsied). The existing literature describing patient-reported outcomes in NS largely relies on nonspecific measures of health-related quality of life; fluid overload has been associated with lower scores on these measures.</p><p><strong>Conclusion: </strong>To address the gap in measure availability and fluid overload content, the Prepare-NS team has launched a set of qualitative studies for concept elicitation from the population of interest to inform development of new measures. The resulting measures subsequently will undergo psychometric evaluation and validation in a survey study.</p>","PeriodicalId":73177,"journal":{"name":"Glomerular diseases","volume":"4 1","pages":"172-182"},"PeriodicalIF":0.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11521406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Membranoproliferative Glomerulonephritis over 20 Years at a Tertiary Referral Center in the UK.","authors":"Hannah O'Keeffe, Joshua Storrar, Chethana Ramakrishna, Sara Metaoy, Constantina Chrysochou, Rajkumar Chinnadurai, Philip A Kalra, Smeeta Sinha","doi":"10.1159/000540672","DOIUrl":"https://doi.org/10.1159/000540672","url":null,"abstract":"<p><strong>Introduction: </strong>Membranoproliferative glomerulonephritis (MPGN) is a pattern of injury seen on kidney biopsy, with various underlying etiologies. The component types, including complement-mediated MPGN, are relatively rare. This study presents longitudinal real-world data over 20 years in a tertiary renal center in the UK.</p><p><strong>Methods: </strong>All patients with an MPGN pattern on kidney biopsy between 2000 and 2020 were identified. After applying exclusion criteria, 38 patients remained. Data including patient demographics, details of the renal histology from the kidney biopsy, baseline laboratory results, treatments received, and clinical outcomes including renal replacement therapy and death were collected from the organization's electronic patient record.</p><p><strong>Results: </strong>Twenty-eight of the cohort had immune complex-mediated MPGN, and 10 had complement-mediated MPGN (8 with C3 glomerulonephritis and 2 with dense deposit disease). Median follow-up was 72 months. Median age was 61 years. Overall, 60.5% were female, and 92.1% white. At presentation, median eGFR was 31.5 mL/min/1.73 m² and uPCR 394 mg/mmol. Here, 78.9% received renin-angiotensin-aldosterone system inhibitors and 71.1% received any immunosuppression. In total, 47.4% progressed to ESKD and 50% died during follow-up.</p><p><strong>Conclusions: </strong>The study found an older patient population than typically reported. Poor outcomes were observed in the overall cohort with progression to ESKD and mortality both at almost 50%. This may be influenced by the older patient population. Individualized management of patients with an MPGN biopsy finding is paramount, with comprehensive evaluation for triggers and complement abnormalities. Going forward, registry enrolment and collaborative studies may enhance knowledge and outcomes.</p>","PeriodicalId":73177,"journal":{"name":"Glomerular diseases","volume":"4 1","pages":"159-166"},"PeriodicalIF":0.0,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11521467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pneumocystis jiroveci Pneumonia Prophylaxis in patients with ANCA Vasculitis on Rituximab maintenance therapy","authors":"Faten Aqeel, Michael Joseph Cammarata, Dustin Le, D. Geetha","doi":"10.1159/000539993","DOIUrl":"https://doi.org/10.1159/000539993","url":null,"abstract":"Introduction: Although an increased risk of Pneumocystis jirovecii pneumonia (PJP) has been reported in adults receiving rituximab for induction therapy, current evidence is lacking on the utility of PJP prophylaxis in ANCA-associated vasculitis (AAV) patients on maintenance rituximab therapy. The purpose of this study was to compare the incidence of PJP pneumonia and the outcomes of AAV patients with and without PJP prophylaxis. \u0000\u0000Methods: We performed an observational, single-center, retrospective study examining patients with AAV in clinical remission and on rituximab maintenance therapy. We divided the patients into two groups: those with and without PJP prophylaxis. We explored factors associated with PJP prophylaxis use. We additionally looked at several outcomes, including PJP infections, infections requiring hospitalizations, end-stage kidney disease (ESKD), and death. Data were analyzed using T test, Fisher exact test, univariate, and multivariate logistic regression as appropriate.\u0000\u0000Results: A total of 129 patients with mean (SD) follow-up time of 7.2 (5.4) years were included: 44% received PJP prophylaxis and 56% of patients did not. There were no PJP infections in the entire cohort. Lung involvement was associated with increased odds of prescribing PJP prophylaxis (OR 4.09 (95% CI 1.8-9.82)). PJP prophylaxis did not decrease infection rates requiring hospitalizations, ESKD, or death. Glucocorticoid use, however, was associated with increased rates of infections requiring hospitalizations (OR 5.54 (95% CI 2.01-15.4)) and death (OR 4.67 (95% CI 1.36-15.71)) even after adjustment for age, gender, and use of PJP prophylaxis.\u0000\u0000Conclusion: Regardless of the use of PJP prophylaxis during the maintenance phase of AAV management, PJP pneumonia was not observed. AAV patients with lung involvement were more likely to be on PJP prophylaxis.","PeriodicalId":73177,"journal":{"name":"Glomerular diseases","volume":"117 18","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141801929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical presentation and treatment outcomes of Renal Medullary Angiitis in ANCA associated vasculitis: A single-center case series.s","authors":"Grant Kirby, Antonio Salas, Abdulrahman K. Alabdulsalam, Alana Dasgupta, D. Geetha","doi":"10.1159/000539553","DOIUrl":"https://doi.org/10.1159/000539553","url":null,"abstract":"Introduction:\u0000Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) with renal involvement primarily affects the renal cortex and presents with key histopathologic findings of a pauci-immune necrotizing and crescentic glomerulonephritis. Infrequently reported and poorly characterized is renal medullary angiitis (RMA), a pathologic variant of AAV primarily involving the renal medulla. This study seeks to describe the presentation and treatment outcomes of RMA.\u0000Methods: \u0000In this single center cohort, renal pathology samples classified as AAV with renal involvement underwent secondary review to determine if they met histopathologic criteria for renal medullary angiitis (RMA). Demographic, clinical, and laboratory data were obtained via electronic medical record review. Descriptive statistical analysis was performed on key variables. \u0000Results:\u0000Of the 136 kidney biopsy samples classified as ANCA associated vasculitis with renal involvement, histopathologic features of RMA were present in 13 cases. The mean (SD) age at the time of RMA diagnosis was 65 (19) years and 54% were female. Most cases presented with extra-renal manifestations of disease. Initial median (IQR)eGFR and proteinuria on presentation was 16 (10-19) mL/min/1.73m2 and 1100 (687-2437)mg respectively. The primary histologic features were high degrees of interstitial inflammation comprised of leukocytes, neutrophils, plasma cells, and eosinophils along with either interstitial hemorrhage or necrosis. All patients were treated with glucocorticoids in combination with either cyclophosphamide, rituximab or mycophenolate. All patients achieved disease remission. During a median (IQR) follow up of 42 (14-68) months, one patient reached ESKD and one patient died. \u0000Conclusions:\u0000In this single center case series, we identified the presence of RMA in 9.5% of AAV samples that underwent secondary review. RMA presented with severe impairment in renal function and multi-system disease. Standard of care immunosuppression for AAV was effective for remission induction in RMA. It remains unclear whether standard prognostication tools are useful in this population. \u0000","PeriodicalId":73177,"journal":{"name":"Glomerular diseases","volume":" 1172","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141823143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}