Search Results (19)

Background/Objectives: Nontuberculous mycobacterial pulmonary disease (NTM-PD) has been associated with myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)-positive ANCA-associated vasculitis (AAV). However, clinical factors associated with MPO-ANCA positivity in patients with NTM-PD remain unclear. This study determined the frequency of MPO-ANCA positivity among tested patients with NTM-PD and explored the clinical factors associated with MPO-ANCA positivity. Methods: This study retrospectively analyzed patients aged ≥15 years old with NTM-PD who were treated at Tokyo Shinagawa Hospital and underwent MPO-ANCA testing between April 2020 and March 2024. Clinical data, including nontuberculous mycobacterial species, serum Mycobacterium avium complex (MAC) antibody titers, radiographic findings, and nodule, infiltration/consolidation, cavity, and ectasis scores, were collected from their electronic medical records. Patients were classified into MPO-ANCA-positive and negative groups, and clinical factors were compared. Results: Among 109 patients with NTM-PD, 49 underwent testing for MPO-ANCA and proteinase 3 (PR3)-ANCA. MPO-ANCA was positive in five patients (10.2%), whereas PR3-ANCA was positive in one (2.0%). Among the five MPO-ANCA-positive patients, three had MAC antibody titers above the upper limit of measurement (>10 U/mL), and one developed AAV with biopsy-proven pauci-immune crescentic glomerulonephritis and mononeuritis multiplex. The MAC antibody titer was significantly higher in the MPO-ANCA-positive group than in the MPO-ANCA-negative group [10.0 (3.89–10.0) vs. 1.92 (0.19–6.19) U/mL, p = 0.038]. Conclusions: MPO-ANCA positivity was observed in a subset of tested patients with NTM-PD and was associated with higher MAC antibody titers. These findings suggest that chronic MAC-related antigen exposure or local pulmonary disease activity in NTM-PD may be associated with MPO-ANCA positivity. Full article

Background: Rapidly progressive glomerulonephritis (RPGN) is a severe nephrological emergency, frequently secondary to anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. In older adults, the coexistence of comorbidities and monoclonal gammopathy of undetermined significance (MGUS) makes it difficult to distinguish between ANCA vasculitis and monoclonal gammopathy of renal significance (MGRS), which differ in prognosis and treatment. The coexistence of PR3-ANCA-associated vasculitis and MGUS is uncommon and sparsely documented. Case Presentation: A 72-year-old woman with hypertension and type 2 diabetes presented with acute deterioration and rapidly progressive renal failure, requiring hemodialysis. She had subnephrotic proteinuria, hematuria, and an active urinary sediment. The autoimmune workup showed ANCA negativity using immunofluorescence, but PR3-ANCA positivity using ELISA. Hematologic characterization documented an IgG kappa monoclonal spike; no bone lesions, amyloidosis, or criteria for multiple myeloma were found; and the patient was classified as MGUS. Renal biopsy revealed necrotizing extracapillary pauci-immune glomerulonephritis with cellular and fibrocellular crescents and no monoclonal deposits, consistent with PR3-ANCA vasculitis. Induction therapy with methylprednisolone pulses and oral prednisone was initiated; cyclophosphamide was not administered because of catheter-associated Staphylococcus aureus bacteremia and upper gastrointestinal bleeding complicated by disseminated intravascular coagulation. The patient died on day 25 due to infectious and hemorrhagic complications. Conclusions: This case provides additional documentation of an uncommon overlap between PR3-ANCA-associated vasculitis and MGUS in a Latin American patient and highlights the role of renal biopsy in distinguishing MGRS from pauci-immune vasculitis in the presence of paraproteinemia. It also underscores the need to tailor immunosuppression in frail older adults, balancing disease control against the risk of severe infection. Full article

Background and Clinical Significance: Granulomatosis with polyangiitis (GPA) is an ANCA-associated vasculitis that often affects the respiratory tract and kidneys, while ocular involvement is less common and may delay diagnosis. Bilateral dacryoadenitis as an initial manifestation is particularly uncommon and can obscure early recognition. Case Presentation: A 24-year-old woman presented with recurrent epistaxis, headaches, and progressive bilateral eyelid swelling. MRI showed enlarged lacrimal glands consistent with granulomatous dacryoadenitis. Over the following weeks, she developed systemic symptoms and rapidly progressive renal impairment. Serology revealed positive c-ANCA and anti-PR3 antibodies, and HRCT demonstrated pulmonary nodules and ground-glass opacities. Renal biopsy confirmed necrotizing pauci-immune crescentic glomerulonephritis. Despite treatment with glucocorticoids, cyclophosphamide, and rituximab, renal recovery was incomplete, necessitating hemodialysis. Conclusions: This case illustrates bilateral dacryoadenitis as an early sign of GPA and emphasizes the need for prompt ANCA testing and renal evaluation. Early recognition is crucial to prevent irreversible kidney damage. Full article

Background: Rituximab is a monoclonal antibody targeting CD20, commonly used to treat autoimmune diseases such as granulomatosis with polyangiitis (GPA) and rheumatoid arthritis. While generally well-tolerated, serious adverse events, including infusion reactions and infections, are well-documented. Case Summary: We report a rare case of rituximab-induced ST-elevation myocardial infarction (STEMI) in a 26-year-old woman with no cardiovascular risk factors. She developed crushing chest pain after her first 1 g rituximab infusion, with recurrent symptoms upon re-exposure. Cardiac catheterization revealed a left circumflex artery occlusion. Additional workup showed c-ANCA positivity, cryoglobulinemia, pauci-immune glomerulonephritis, and findings consistent with GPA. Rituximab was discontinued, and she was transitioned to steroids, cyclophosphamide, and leuprolide, with no further cardiac events. Discussion: This is the first reported case in a young, previously healthy woman. Clinicians should consider rituximab-associated myocardial injury, especially in autoimmune or hypercoagulable states. Take-Home Message: Remain vigilant for cardiac events during rituximab infusions in patients with inflammatory diseases. Full article

Background: The COVID-19 (coronavirus disease 2019) pandemic has presented a serious challenge to nephrologists, since it can lead to severe kidney injury in the form of acute tubular necrosis, with many patients requiring renal replacement therapy. This is predominantly seen in people who develop severe respiratory manifestations like ARDS (acute respiratory distress syndrome) from the viral infection, a cytokine storm or septic shock with unstable hemodynamics. It also presents with various glomerular injuries, mainly collapsing glomerulopathy in high-risk APOL1 (Apolipoprotein L1) genotype patients, thrombotic microangiopathy-related renal failure due to hyper coagulopathy and occasionally pauci-immune glomerulonephritis due to immune dysregulation. All the glomerular disorders that are caused by COVID-19 infection have been described under the designation COVAN (COVID-19-associated nephropathy). Proteinuria is a predominant presentation in glomerular disorders. Gross hematuria and AKI without any respiratory symptoms from COVID-19 infection have not been described so far in the literature. We are presenting one such rare case here. Methods: We have encountered a rare case of gross hematuria and severe acute renal failure. His serological work up was negative for all autoimmune etiologies that can cause Glomerulonephritis. He was found to have infection-related crescentic glomerulonephritis due to active COVID-19 infections discovered via kidney biopsy. He tested positive for SARS-CoV-2 but didn’t have any clinical respiratory symptoms. He has responded well to treatment with a steroid taper and antiviral medication (Remdesivir). This is a very rare renal manifestation of COVID-19 infection. Results: COVID-19 infection can result in crescentic glomerulonephritis. This can be diagnosed by kidney biopsy which shows extensive c3 deposits, tubuloreticular inclusion bodies along with crescentic lesions. This responds to treatment with steroids and Antiviral agents. Conclusions: Crescentic Glomerulonephritis should be considered as a possible etiology for severe acute kidney injury with hematuria in patients with active covid-19 infection without any respiratory symptoms. Kidney biopsy helps in diagnosing it and responds to treatment with steroids and antivirals. Full article

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (ANCA-vasculitis) is an autoimmune disease characterized by inflammation and necrosis of small or medium vessels. In the past, the role of the complement in the pathogenesis of ANCA-vasculitis has been underestimated, due to the paucity of the complement at sites of injured glomeruli. Following evidence from animal models of the major role of the complement in pathogenesis of ANCA-vasculitis, the complement has again attracted interest. Immunohistology analysis of pauci-immune glomerulonephritis—ANCA glomerulonephritis (ANCA-GN)—reveals the presence of complement products and membrane attack complex, suggesting their involvement in the disease process. Researchers emphasize the complement classical or lectin pathway as a contributor to the development of ANCA-vasculitis. The era of targeted therapies to suspend the complement activation as a therapy for ANCA-vasculitis has arrived, and thus, the comprehension of its role is very important. This review summarizes recent insights on the important role of complement activation in the development of ANCA-vasculitis as well as the emerging therapeutic possibilities that target complement components for the treatment of this condition. Full article

Background: Since the introduction of the SLICC criteria in 2012, biopsy-proven lupus nephritis (LN) has been the only independent diagnostic criterion for systemic lupus erythematosus (SLE). This was reaffirmed by the EULAR/ACR in 2019, emphasizing the importance of renal biopsy in LN. However, the current classification lacks specific histopathological criteria for defining LN. This study describes the histological findings of patients with LN, compares them with those of other glomerular diseases, and evaluates their diagnostic accuracy in a large Latin American population. Methods: This retrospective cohort included 731 kidney biopsies from two distinct academic centers. The patients were divided into two groups as follows: a LN group and a control group comprising patients with membranous nephropathy, IgA nephropathy, membranoproliferative glomerulonephritis, pauci-immune glomerulonephritis, and proliferative glomerulonephritis. Sensitivity and specificity analyses were conducted for various histopathological features. Results: We identified the following five features strongly correlated with LN: mesangial proliferation, subendothelial deposits, C1q staining ≥1+, dominant IgG, and ≥4 positive immunofluorescence elements. Combined, these features yielded an area under the ROC curve of 0.94 (95% CI: 0.91–0.95). These results were validated in a diverse population. In membranous nephropathy, histological features such as mesangial deposits, C1q positivity, and ≥4 positive immunofluorescence elements effectively distinguished class V LN from non-lupus membranous nephropathy, with an area under the ROC curve of 0.85 (95% CI: 0.76–0.93). Conclusions: The combination of mesangial proliferation, subendothelial deposits, C1q staining ≥1+, dominant IgG, and ≥4 positive immunofluorescence elements offer good accuracy for diagnosing renal involvement in SLE in a large Latin American population. In the absence of pathognomonic features, combined criteria are valuable diagnostic tools, particularly when other SLE criteria are lacking. Full article

The monocyte–macrophage lineage of inflammatory cells is characterized by significant morphologic and functional plasticity. Macrophages have broad M1 and M2 phenotype subgroups with distinctive functions and dual reno-toxic and reno-protective effects. Macrophages are a major contributor to injury in immune-complex-mediated, as well as pauci-immune, glomerulonephritis. Macrophages are also implicated in tubulointerstitial and vascular disease, though there have not been many human studies. Patrolling monocytes in the intravascular compartment have been reported in auto-immune injury in the renal parenchyma, manifesting as acute kidney injury. Insights into the pathogenetic roles of macrophages in renal disease suggest potentially novel therapeutic and prognostic biomarkers and targeted therapy. This review provides a concise overview of the macrophage-induced pathogenetic mechanism as a background for the latest findings about macrophages’ roles in different renal compartments and common renal diseases. Full article

Vaccines against SARS-CoV-2 (COVID-19) proved beneficial for COVID-19 disease attenuation and preventing virus spreading. Cumulative reports of the rarity of antineutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitis (AAV) raise concerns about its relationship with COVID-19 vaccination. Several case reports described ANCA-associated pauci-immune glomerulonephritis (ANCA-GN) following COVID-19 vaccination with some uniqueness. We systematically reviewed COVID-19 vaccine-induced ANCA-GN from PubMed, SCOPUS, and Cochrane library databases until 1 January 2023 according to PRISMA guidelines and presented our three cases. Twenty-six cases from 25 articles, including our 3 cases, were analyzed. Most cases were diagnosed following the second dose of the COVID-19 vaccine (59%) with a median (IQR) interval onset of 14 (16) days. The highest prevalence was related to the mRNA-type vaccine. Anti-myeloperoxidase (MPO) ANCA was far more common than the other ANCAs, with various positive autoantibodies. Fourteen cases (out of 29 cases, 48%) had extra-kidney AAV manifestation. Although severe kidney injury was observed in 10/29 (34%), remission was achieved in 89% (25/28) with no death. The mechanisms of the vaccine-inducing ANCA-GN were postulated here. Since ANCA-GN after the COVID-19 vaccine was rare, the benefit of the COVID-19 vaccine could outweigh the risk of ANCA-GN side effects in the pandemic era. Full article

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a potentially life-threatening systemic small-vessel vasculitis that is characterized by pauci-immune glomerulonephritis in case of kidney involvement, representing a major denominator of AAV mortality. Innate immunity with complement system activation is increasingly recognized in the pathogenesis of AAV and as an attractive therapeutic target. Although C-reactive protein (CRP) was thought to be a passive, nonspecific marker of inflammation, recent studies indicate that CRP plays a key role in the innate immune system by recognizing pathogens and altered self-determinants. Elevated baseline CRP at disease onset of AAV has already been described as a determinant of poor long-term outcomes. However, its clinical implications at disease onset of AAV, with respect to vasculitis manifestations and complement system activation that might also affect long-term outcomes, remain elusive. CRP levels were retrospectively analyzed in 53 kidney-biopsy-confirmed cases of ANCA-associated renal vasculitis; a total of 138 disease controls were also evaluated. Univariate and multivariate regression analysis was performed on clinicopathological parameters associated with CRP levels in ANCA-associated renal vasculitis. Results: Compared to disease controls, CRP elevation was common in ANCA-associated renal vasculitis and associated with de novo disease (p = 0.0169), critical illness (p = 0.0346), and severe deterioration of kidney function (p = 0.0167), independent of extrarenal disease manifestations. As confirmed by multiple regression analysis, CRP levels were correlated with active lesions predominated by interstitial arteritis in renal vasculitis, specifically with MPO-ANCA seropositivity (p = 0.0017). Based on analysis of systemic complement system activation and intrarenal complement deposits, CRP elevation was correlated specifically with complement C4 deposits in interstitial arteries in the subgroup with myeloperoxidase (MPO)-ANCA seropositivity (p = 0.039). Finally, this association was independent of systemic complement system activation, as reflected by the consumption of respective complement components. Here, we expand our current understanding of CRP in ANCA-associated renal vasculitis not only as an inflammatory marker, but potentially also as being involved in the pathogenesis of kidney injury by interaction with the complement system. Full article

Stimulation of the antitumor activity of the immune system using immune checkpoint inhibitors (ICIs) has proven efficacy in the treatment of multiple types of cancer, inducing the speedily expanding approval of therapeutic indications for ICIs. The literature regarding the immune-related toxicities and nephrotoxicity of ICIs is limited. Herein, we present a patient with lung cancer treated with atezolizumab, an IgG1 monoclonal antibody aimed at the programmed death ligand 1 (PD-L1), who presented with vasculitic skin rash and rapidly deteriorating renal function, new onset of significant glomerular hematuria and proteinuria. The renal biopsy revealed acute necrotizing pauci-immune vasculitis, with fibrinoid necrosis. The patient received a course of high-dose glucocorticoids with recovery of renal function and skin lesions. Further immunosuppressive therapy was withheld, due to active malignancy in the lung, while oncology consultation recommended the continuation of treatment with atezolizumab, as the patient had shown substantial response. Full article

Early diagnosis and initiation of appropriate immunosuppressive treatment remain the cornerstone of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis at the cost of significant toxicity. In this report, we present a case of a 69-year-old female who presented with advanced renal insufficiency and evidence of pulmonary hemorrhage and was MPO–ANCA-positive with a clinical phenotype of granulomatosis with polyangiitis. Organ involvement included rapidly progressive glomerulonephritis (GN), along with extrarenal manifestations (skin, upper and lower respiratory system involvement, and onset of saddle-nose deformity). Kidney biopsy established the diagnosis of pauci-immune crescentic, sclerotic GN. She received therapy with glucocorticoids and cyclophosphamide, mainly due to life-threatening extra-renal manifestations, such as pulmonary hemorrhage. She avoided vasculitis-related death but she developed severe therapy-related toxicity, resulting in the discontinuation of immunosuppressive therapy. Continuous re-evaluation of patients with ANCA-associated vasculitis in terms of response to immunosuppressive therapy and treatment-related toxicity is crucial for their management. Full article

Due to complex comorbidity, high infectious complication rates, an elevated risk of relapsing for primary renal disease, as well as inferior recipient and allograft survivals, individuals with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAVs) are often considered as poor transplant candidates. Although several aspects of recurrent and de novo AAVs remain unclear, recent evidence suggests that kidney transplantation (KT) represents the best option, which is also the case for this particular subgroup of patients. Special counselling and individualized approaches are strongly recommended at the time of enlistment and during the entire post-transplant follow-up. Current strategies include avoiding transplantation within one year of complete clinical remission and thoroughly assessing the recipient for early signs of renal or systemic vasculitis. The main clinical manifestations of allograft AAV are impaired kidney function, proteinuria, and hematuria with ANCA positivity in most cases. Mixed results have been obtained using high-dose steroids, mycophenolate mofetil, or cyclophosphamide. The aim of the present review was to summarize the available literature on AAVs in KT, particularly focusing on de novo pauci-immune glomerulonephritis. Full article

Rapidly progressive glomerulonephritis (RPGN) is a syndrome which presents rapid loss of renal function. Vasculitis represents one of the major causes, often related to anti-neutrophil cytoplasmic antibodies (ANCA). Herein, we report a case of methimazole-induced ANCA-associated vasculitis. A 35-year-old woman complained of weight loss and fatigue for 2 weeks and attended the emergency room with alveolar hemorrhage. She had been diagnosed with Graves’ disease and had been taking methimazole in the past 6 months. Her physical examination showed pulmonary wheezing, hypertension and signs of respiratory failure. Laboratory tests revealed urea 72 mg/dL, creatinine 2.65 mg/dL (eGFR CKD-EPI: 20 mL/min/1.73 m²), urine analysis with >100 red blood cells per high-power field, 24 h-proteinuria: 1.3 g, hemoglobin 6.6 g/dL, white-cell count 7700/mm³, platelets 238,000/mm³, complement within the normal range, negative viral serological tests and ANCA positive 1:80 myeloperoxidase pattern. Chest tomography showed bilateral and diffuse ground-glass opacities, and bronchial washing confirming alveolar hemorrhage. A renal biopsy using light microscopy identified 27 glomeruli (11 with cellular crescentic lesions), focal disruption in glomerular basement membrane and fibrinoid necrosis areas, tubulitis and mild interstitial fibrosis. Immunofluorescence microscopy showed IgG +2/+3, C3 +3/+3 and Fibrinogen +3/+3 in fibrinoid necrosis sites. She was subsequently diagnosed with crescentic pauci-immune glomerulonephritis, mixed class, in the setting of a methimazole-induced ANCA vasculitis. The patient was treated with methimazole withdrawal and immunosuppressed with steroids and cyclophosphamide. Four years after the initial diagnosis, she is currently being treated with azathioprine, and her exams show creatinine 1.30 mg/dL (eGFR CKD-EPI: 52 mL/min/1.73 m²) and negative p-ANCA. Full article

ANCA-associated vasculitis (AAV) poses a significant risk of kidney failure; kidney biopsy remains a key prognostic tool. The histopathologic classification of AAV glomerulonephritis (GN) developed by Berden et al. showed correlation between GN classes and kidney outcomes; ANCA Renal Risk Score (ARRS) included tubular atrophy and interstitial fibrosis (TA/IF) as an additional parameter for risk assessment. We aimed to evaluate kidney survival across AAV GN classes and ARRS groups. A single-center retrospective study included 85 adult patients with biopsy-proven AAV kidney disease followed in the period of 2000–2020. Primary outcome was kidney survival at the end of 18 (5; 66) months follow-up, and kidney death was considered as stage 5 CKD. We found significant differences in kidney survival for sclerotic, mixed, crescentic and focal AAV GN classes: 19%, 76.2%, 91.7% and 100%, respectively (p = 0.009). Kidney survival was 0%, 75.6% and 100% for the high-, medium- and low-risk ARRS groups, respectively (p < 0.001); TA/IF analysis showed kidney survival at 49.6% vs. 87.7% for widespread and mild TA/IF, respectively (p = 0.003). Kidney survival was significantly lower in anti-MPO-ANCA versus anti-PR3-ANCA carriers (50.3% and 78.1%, respectively, p = 0.045). We conclude that unfavorable AAV kidney outcomes are associated with sclerotic GN class by Berden’s classification, ARRS high risk group, and anti-MPO-ANCA subtype. Full article