Pauci-immune necrotizing glomerulonephritis in a 24-year-old female with negative ANCA antibodies: A rare case report.

Key Clinical Message: Pauci-immune necrotizing glomerulonephritis (PING) is a small vessel renal vasculitis usually associated with the presence of antineutrophil cytoplasmic antibodies (ANCA) against myeloperoxidase or proteinase. A small proportion of PING patients do not have ANCA antibodies. Abstract: A condition known as Pauci-immune necrotizing glomerulonephritis, or PING for short, is a type of kidney inflammation that affects small blood vessels. This condition is typically linked with the existence of certain antibodies, specifically antineutrophil cytoplasmic antibodies or ANCA, which target myeloperoxidase or proteinase. However, it's worth noting that a minor percentage of individuals diagnosed with PING do not possess these ANCA antibodies. A 24-year-old woman with no previous medical history arrived at the ER due to various symptoms including joint pain, fever, difficulty swallowing, and shortness of breath. Despite multiple symptoms suggesting systemic lupus erythematosus (SLE), this diagnosis was ruled out based on the EULAR/ACR 2019 classification criteria and laboratory tests. Other potential diagnoses such as rheumatoid arthritis (RA) and eosinophilic garnulomatosis with polyaniitis (EGPA) were also excluded based on respective criteria. The patient was treated with a 3-day course of methylprednisolone, followed by prednisolone, which improved her creatinine levels. Subsequent tests for P-ANCA and C-ANCA were negative. A kidney biopsy confirmed necrotizing glomerulonephritis, consistent with pauci-immune vasculitis. A bronchoscopy revealed bleeding and hemorrhage in her lungs, but bacterial culture analysis was negative. The patient was given piperacillin, tazobactam, and vancomycin for septic coverage, as well as intravenous immunoglobulin (IVIg), which led to symptom improvement.

Clinicopathological characteristics and renal outcomes of adult patients with pauci-immune necrotizing glomerulonephritis according to ANCA status.

BACKGROUND: Pauci-immune necrotizing glomerulonephritis (PING) is commonly associated with the presence of antineutrophilic cytoplasmic antibodies (ANCAs) but a significant number of patients do not have these antibodies. The significance of ANCA-negativity in the context of Berden's classification of PING is not known. METHODS: A retrospective analysis was conducted on all patients with histopathological diagnosis of idiopathic PING irrespective of ANCA status diagnosed between January 1998 to December 2018 and followed up at renal clinic for > 12 months. All biopsies were reclassified by Berden's classification. Clinicopathological characteristics and renal outcomes of ANCA-positive and ANCA-negative patients were compared. RESULTS: Out of 134 patients, 66 (49.5%) were ANCA-negative. The mean age was 34.76 ± 13.3 years. Compared with the ANCA-positive patients, ANCA-negative patients had significantly greater prevalence of nephrotic-range proteinuria (74.23% Vs 57.9%, P = 0.036) with less extra-renal manifestations (P < 0.05)). On histology, focal and crescentic classes dominated with less number of globally sclerosed glomeruli (2.7% Vs 5.07%, P = 0.02) and more mesangial proliferation (22.7% Vs 4.41%, P = 0.002) in the ANCA-negative group, whereas sclerotic was predominant in the ANCA-positive group (P = 0.05). More patients achieved complete and partial recovery in ANCA-negative patients (42.4% Vs 20.5%, P < 0.05) with better renal survival (27.27% Vs 16.17%, log-rank test: P = 0.03) and less patient mortality (13.63% vs 30.8%, log-rank test: P = 0.04) at 2 years. CONCLUSION: Our study confirms high prevalence of ANCA negativity among our cohort and this group presents with isolated renal involvement with better renal and patient survival. The ANCA-positive group showed significantly more patients in the sclerotic class, lower 2-year renal survival, and higher 2-year mortality as compared to the ANCA-negative group. However, the complete and partial responses to treatment were significantly better in the ANCA-negative group. Key Points • This study shows a high prevalence of ANCA negativity in cases of PING in Pakistani population, as almost half of patients in this study did not have these antibodies. • This negativity is more prevalent in the Asian populations but its significance in the context of Berden's classification of PING is unknown. • ANCA-negative group exhibited less severe phenotype and better outcomes compared with ANCA-positive group.

Antineutrophil Cytoplasmic Autoantibody-negative Pauci-immune Necrotizing Glomerulonephritis with Plasma Cell-rich Tubulointerstitial Nephritis Complicated with Pleuritis and Digital Ischemia.

Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) predominantly affects small vessels. Almost all AAV patients are positive for myeloperoxidase- or proteinase 3-ANCA, and ANCA plays a crucial role in the pathogenesis of AAV. We herein report an ANCA-negative AAV patient with pauci-immune necrotizing glomerulonephritis and plasma cell-rich tubulointerstitial nephritis who was complicated with pleuritis and digital ischemia. ANCA-negative AAV is a rare clinical entity that is difficult to diagnose, and pleuritis and digital ischemia are rare manifestations of AAV. An early diagnosis and appropriate treatment are important, as any delay in the diagnosis may worsen the prognosis.

The Diagnostic Conundrum of Glomerular Crescents With IgA Deposits.

Introduction: Glomerulonephritis (GN) with crescents and IgA deposits in kidney biopsy poses a frequent diagnostic and therapeutic dilemma because of multiple possibilities. Methods: Native kidney biopsies showing glomerular IgA deposition and crescents (excluding lupus nephritis) were identified from our biopsy archives between 2010 and 2021. Detailed clinicopathologic features were assessed. One-year clinical follow-up on a subset of cases was obtained. Results: A total of 285 cases were identified, and these clustered into IgA nephropathy (IgAN, n = 108), Staphylococcus or other infection-associated GN/infection-related GN (SAGN/IRGN, n = 43), and antineutrophil cytoplasmic antibody-associated GN (ANCA-GN, n = 26) based on a constellation of clinicopathologic features, but 101 cases (group X) could not be definitively differentiated. The reasons have been elucidated, most important being atypical combination of clinicopathologic features and lack of definitive evidence of active infection. Follow-up (on 72/101 cases) revealed that clinicians' working diagnosis was IgAN in 43%, SAGN/IRGN in 22%, ANCA-GN in 28%, and others in 7% of the cases, but treatment approach varied from supportive or antibiotics to immunosuppression in each subgroup. Comparing these cases as "received immunosuppression" versus "non-immunosuppression," only 2 features differed, namely C3-dominant staining, and possibility of recent infection (both higher in the no-immunosuppression group) (P < 0.05). Renal loss was higher in the non-immunosuppression subgroup, but not statistically significant (P = 0.11). Conclusion: Diagnostic overlap may remain unresolved in a substantial number of kidney biopsies with glomerular crescents and IgA deposits. A case-by-case approach, appropriate antibiotics if infection is ongoing, and consideration for cautious immunosuppressive treatment for progressive renal dysfunction may be needed for best chance of renal recovery.

Enfermedad por citomegalovirus en los pacientes inmunodeprimidos por glomerulonefritis necrosante pauciinmune / Cytomegalovirus disease in immunosuppressed patients with necrotizing pauci-immune glomerulonephritis

Introducción: La afectación renal por glomerulonefritis necrosante pauciinmune (GNPI) asociada a vasculitis de pequeño vaso requiere tratamiento inmunodepresor, cuyos efectos secundarios incluyen un mayor riesgo de procesos infecciosos, como la enfermedad por citomegalovirus (CMV), aunque no hay recomendaciones sobre su manejo en las guías de práctica clínica (GPC).ObjetivoEstudiar la incidencia de enfermedad por CMV y sus determinantes.Pacientes y métodosPacientes con diagnóstico histológico de GNPI en los últimos 10 años, determinando la carga viral de CMV y analizando los determinantes de su concurrencia.ResultadosSe realizaron 44 biopsias durante el periodo de estudio. Del total, 11 pacientes (25%) desarrollaron enfermedad por CMV; todos habían recibido tratamiento inmunodepresor. Cuatro (30,8%) fallecieron durante el ingreso. Los factores determinantes de la enfermedad fueron la edad (por cada 10 años OR: 3,0, IC 95%: 1,0 a 8,9, p = 0,012) y la albúmina (por cada g/L OR: 0,8, IC 95%: 0,6 a 1,0, p = 0,012).ConclusionesLa incidencia de enfermedad por CMV en pacientes inmunodeprimidos por GNPI es alta, con alta mortalidad. Sería necesario incluir estrategias en las GPC para prevenir su desarrollo. (AU)

Introduction: Renal involvement due to necrotizing pauci-immune glomerulonephritis (PIGN) associated with small vessel vasculitis requires the use of immunosuppressive. Associated side effects include an increased risk of infectious processes, such as cytomegalovirus (CMV) disease; therefore, there are no recommendations on its management in the various clinical practice guidelines (CPG).ObjectiveTo study the incidence of CMV disease and its determinants.Patients and methodsPatients with histological diagnosis of necrotizing pauci-immune glomerulonephritis in the last 10 years, who were determined the viral load of CMV, analyzing the determinants of its occurrence.ResultsForty-four biopsies were performed during the study period. Eleven patients (25%) developed CMV disease; all had received immunosuppressive treatment. Four (30.8%) died during admission. The determinants of CMV disease were age (for every 10 years OR: 3.0, 95% CI: 1.0-8.9, p = 0.012), and plasma albumin (for each g/L OR: 0.8, 95% CI: 0.6-1.0, p = 0.012).ConclusionsThe incidence of CMV disease in immunocompromised patients due to PIGN is high, with high mortality. It would be necessary to include strategies in the CPGs to prevent it. (AU)

Bartonella henselae Infective Endocarditis: A Rare Cause of Pauci-Immune Necrotizing Glomerulonephritis-A Case Report.

Rationale: Bartonella sp. are the most common causes of culture-negative infective endocarditis (IE) cases in the United States. Although, infection-related glomerulonephritis can frequently mimic primary vasculitis due to pauci-immune pattern, majority of previously reported cases of Bartonella henselae-associated glomerulonephritis have immune-complex deposits on immunofluorescence. We present a rare case of B henselae IE-related pauci-immune necrotizing glomerulonephritis. Timely recognition of this atypical presentation led to appropriately directed medical therapy. Presenting concerns of the patient: A 33-year-old Caucasian male with a history of human immunodeficiency virus (HIV) on highly active antiretroviral therapy (HAART), alcohol abuse, previous subarachnoid hemorrhage (SAH), and recent wisdom tooth extraction (on amoxicillin) was transferred from an outside hospital for further evaluation of severe headache. He was diagnosed with an SAH and right anterior cerebral artery mycotic aneurysm. The serum creatinine at the outside hospital was 292 umol/L (3.3 mg/dL) with a previously normal baseline around 2 years ago. The serum creatinine at our institution was 256 umol/L (3.0 mg/dL). The urinalysis demonstrated +100 protein, +3 blood and 29 red blood cells/high power field. The urine protein creatinine ratio (UPC) was 1.7 g/g. Serologic evaluation was positive for a low C4 10.2 mg/dL, elevated rheumatoid factor 40 IU/mL and an elevated proteinase 3 (PR-3) antineutrophilic cytoplasmic antibodies (ANCA Ab) 4.0 U/mL. A transesophageal echocardiogram (TEE) showed echo densities on both mitral and aortic valve. Blood cultures were negative. Further serologic evaluation was positive for B henselae IgG titer of 1:2560 (normal <1:320) with a negative IgM titer. Diagnoses: A percutaneous kidney biopsy revealed pauci-immune necrotizing glomerulonephritis, with 14/16 glomeruli globally sclerotic, and 2 glomeruli with active segmental necrotizing lesions. There was no evidence of immune-complex deposition on immunofluorescence or electron microscopy. Clinical findings were consistent with B henselae IE associated mycotic aneurysm and necrotizing glomerulonephritis. Intervention: Empiric treatment for an active glomerulonephritis with immunosuppressive agents was deferred on admission, given concern for an underlying infectious process and mycotic aneurysms in an HIV-positive patient. He received antibiotic treatment with doxycycline and ceftriaxone with gentamicin for synergy. Despite this, the mitral and aortic valve regurgitation worsened, and he developed congestive heart failure requiring aortic valve replacement and mitral valve repair. The explanted aortic valve was positive for B henselae by polymerase chain reaction (PCR) confirming the diagnosis of B henselae IE. Outcomes: Immunosuppression was deferred due to timely identification of an atypical presentation of B henselae-associated ANCA antibodies-positive, pauci-immune necrotizing glomerulonephritis. A course of antibiotic treatment resulted in improved renal functions along with undetectable B henselae and PR3 Ab titers. The serum creatinine decreased to 176 umol/L (2 mg/dL) and remained stable 12 months after discharge. Teaching points: B henselae IE should be suspected in patients with pauci-immune necrotizing glomerulonephritis and culture-negative IE. This is imperative for optimal decision making in the management of such patients. Having high clinical suspicion can avoid unnecessary and potentially deleterious use of immunosuppressive agents.

Justification: La bactérie Bartonella sp est la cause la plus fréquente des cas d'endocardite infectieuse (EI) à culture négative aux États-Unis. Bien qu'il arrive souvent que les glomérulonéphrites, en raison de leur schéma auto-immun, puissent ressembler à des vascularites primaires, la majorité des cas précédemment signalés de glomérulonéphrites associées à B. henselae présentent des dépôts de complexes immuns sur immunofluorescence. Nous présentons un cas rare d'endocardite infectieuse à B. henselae associée à une glomérulonéphrite pauci-immune nécrosante. La reconnaissance rapide de cette présentation atypique a conduit à un traitement médical bien dirigé. Présentation du cas: Un homme caucasien de 33 ans atteints du virus de l'immunodéficience humaine (VIH) sous traitement antirétroviral hautement actif (HAART) qui avait été transféré d'un autre hôpital pour une évaluation plus approfondie de céphalées intenses. Le patient avait des antécédents d'abus d'alcool, d'une hémorragie sous-arachnoïdienne (HSA) antérieure et d'une récente extraction de dents de sagesse (prise d'amoxicilline). Le patient a reçu un diagnostic d'HSA et d'anévrisme mycotique de l'artère cérébrale antérieure droite. Le taux de créatinine sérique mesuré à l'hôpital externe était de 292 umol/L (3,3 mg/dL); le patient présentait une valeur normale environ 2 ans auparavant. Le taux de créatinine sérique mesuré dans notre établissement était de 256 umol/L (3,0 mg/dL). L'analyze d'urine a révélé un décompte supérieur à 100 pour les protéines et de + 3 pour le sang avec 29 globules rouges/champ à puissance élevée. Le rapport protéine/créatinine urinaire (UPC) était de 1,7 g/g. L'évaluation sérologique était positive pour un faible taux de C4 (10,2 mg/dL), un taux élevé de facteur rhumatoïde (40 UI/mL) et un taux élevé (4,0 U/mL) d'anticorps anti-cytoplasme des neutrophiles (ANCA) anti-protéinase 3 (PR-3). Une échocardiographie transœsophagienne (ÉTO) a montré des végétations sur les valves mitrale et aortique. Les hémocultures étaient négatives. Une évaluation sérologique plus poussée s'est avérée positive pour le titer d'IgG de B. henselae, avec un rapport de 1:2560 (normale = inférieur à 1:320), et négative pour le titer d'IgM. Diagnostics: Une biopsie rénale percutanée a révélé une glomérulonéphrite pauci-immune nécrosante avec un taux de 14/16 glomérules sclérotiques et 2 glomérules présentant des lésions segmentaires nécrosantes actives. Aucune preuve de dépôt de complexe immun n'a été observée par immunofluorescence ou par microscopie électronique. Les résultats cliniques correspondaient à une endocardite infectieuse à B. henselae associée à l'anévrisme mycotique et à la glomérulonéphrite nécrosante. Intervention: Le traitement empirique d'une glomérulonéphrite active avec des agents immunosuppresseurs a été reporté lors de l'admission, en raison de la crainte d'un processus infectieux sous-jacent et d'anévrismes mycotiques chez un patient séropositif. Le patient a reçu un traitement antibiotique de doxycycline et de ceftriaxone avec gentamicine pour la synergie. Malgré cette intervention, la régurgitation des valves mitrale et aortique s'est aggravée et le patient a développé une insuffisance cardiaque congestive qui a nécessité le remplacement de la valve aortique et la réparation de la valve mitrale. Une analyze par PCR (réaction en chaîne de la polymérase) sur la valve aortique explantée s'est avérée positive pour B. henselae, ce qui a confirmé le diagnostic d'endocardite infectieuse à B. henselae. Résultats: Le traitement immunosuppresseur a été reporté en raison de l'identification opportune d'une présentation atypique de glomérulonéphrite pauci-immune nécrosante positive pour les anticorps anti-cytoplasme des neutrophiles (ANCA) associés à B. henselae. Un traitement antibiotique a permis d'améliorer la fonction rénale et a ramené les titres de B. henselae et d'Ac PR3 à des niveaux indétectables. Le taux de créatinine sérique est passé à 176 umol/L (2 mg/dL) et est demeuré stable 12 mois après le congé du patient. Enseignements tirés: L'endocardite infectieuse associée à B. henselae doit être suspectée chez les patients atteints d'une glomérulonéphrite pauci-immune nécrosante et d'une endocardite infectieuse à culture négative. Ceci est impératif afin d'assurer une prise de décision optimale pour la prise en charge de ces patients. Dans ce cas particulier, une suspicion clinique importante peut prévenir l'utilization inutile et potentiellement délétère d'agents immunosuppresseurs.

[Cytomegalovirus disease in immunosuppressed patients with necrotizing pauci-immune glomerulonephritis]. / Enfermedad por citomegalovirus en los pacientes inmunodeprimidos por glomerulonefritis necrosante pauciinmune.

INTRODUCTION: Renal involvement due to necrotizing pauci-immune glomerulonephritis (PIGN) associated with small vessel vasculitis requires the use of immunosuppressive. Associated side effects include an increased risk of infectious processes, such as cytomegalovirus (CMV) disease; therefore, there are no recommendations on its management in the various clinical practice guidelines (CPG). OBJECTIVE: To study the incidence of CMV disease and its determinants. PATIENTS AND METHODS: Patients with histological diagnosis of necrotizing pauci-immune glomerulonephritis in the last 10 years, who were determined the viral load of CMV, analyzing the determinants of its occurrence. RESULTS: Forty-four biopsies were performed during the study period. Eleven patients (25%) developed CMV disease; all had received immunosuppressive treatment. Four (30.8%) died during admission. The determinants of CMV disease were age (for every 10 years OR: 3.0, 95% CI: 1.0-8.9, p = 0.012), and plasma albumin (for each g/L OR: 0.8, 95% CI: 0.6-1.0, p = 0.012). CONCLUSIONS: The incidence of CMV disease in immunocompromised patients due to PIGN is high, with high mortality. It would be necessary to include strategies in the CPGs to prevent it.

Sarcoidosis-associated renal AA amyloidosis and crescentic necrotizing glomerulonephritis.

Sarcoidosis has a rare and independent association with renal AA amyloidosis and crescentic necrotizing glomerulonephritis. However, coexisting entities in sarcoidosis have not been previously described. Herein, we report a 66-year-old Caucasian woman who presented with generalized fatigue, weight loss, and acute kidney injury in the setting of likely sarcoidosis. Renal biopsy revealed AA amyloid fibrils with fibrocellular crescents. The patient's clinical symptoms and laboratory results improved with high-dose glucocorticoids and azathioprine.

MPO-ANCA-associated vasculitis after the Pfizer/BioNTech SARS-CoV-2 vaccination.

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has demonstrated high efficacy at preventing coronavirus disease 2019 (COVID-19) and a favorable safety profile, however it has also been reported that COVID-19 vaccines may put increase of immune-mediated disease. We herein report a case of MPO-anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis following the mRNA vaccine BNT162b2 (Pfizer/BioNTech) for COVID-19. Although the causal relationship between vaccine and ANCA-associated vasculitis is uncertain, environmental and genetic factors may have set the stage for the development of vasculitis, and the vaccine may have triggered a domino effect.

ANCA-Negative Pauci-immune Necrotizing Glomerulonephritis: A Case Series and a New Clinical Classification.

RATIONALE & OBJECTIVE: Pauci-immune necrotizing glomerulonephritis (PING) is usually associated with the presence of antineutrophil cytoplasmic antibodies (ANCA). However, a minority (2%-3%) of patients with PING do not have detectable ANCA. We assessed the clinical spectrum and outcome of patients with ANCA-negative PING. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 74 patients with ANCA-negative PING diagnosed in 19 French nephrology centers between August 2006 and December 2018 were included in the series. Patients' medical files were reviewed, and kidney biopsies were centrally reexamined by pathologists who were masked to the diagnosis. FINDINGS: Median age at diagnosis was 69 (IQR, 61-76) years. The clinical and pathological features were remarkable for a high frequency of extrarenal manifestations (54%), nephrotic syndrome (32%), and endocapillary hypercellularity (31%). Three main subtypes of ANCA-negative PING were observed: infection-associated (n=9[12%]), malignancy-associated (n=6[8%]), and primary (n=57[77%]). For patients with primary PING, induction treatment included mainly corticosteroids (n=56[98%]), cyclophosphamide (n=37[65%]), and rituximab (n=5[9%]). Maintenance treatment consisted mainly of corticosteroids (n=42[74%]), azathioprine (n=18[32%]), and mycophenolate mofetil (n=11[19%]). After a median follow-up period of 28 months, 28 (38%) patients had died and 20 (27%) developed kidney failure (estimated glomerular filtration rate<15mL/min/1.73m2). Eleven (21%) patients (9 with primary and 2 with malignancy-associated PING) relapsed. LIMITATIONS: Retrospective study and limited number of patients; electron microscopy was not performed to confirm the absence of glomerular immune deposits. CONCLUSIONS: Within the spectrum of ANCA-negative PING, infection and malignancy-associated forms represent a distinct clinical subset. This new clinical classification may inform the management of ANCA-negative PING, which remains a severe form of vasculitis with high morbidity and mortality rates despite immunosuppressive treatments.

Vasculitis and Kidney Disease.

Pediatric vasculitis is a complex group of disorders that commonly presents with multisystem involvement. Renal vasculitis can be isolated to the kidneys or can occur as part of a broader multiorgan vasculitis. Depending on severity, renal vasculitis may present as acute glomerulonephritis (AGN) often associated with hypertension and sometimes with a rapidly deteriorating clinical course. Prompt diagnosis and initiation of therapy are key to preserving kidney function and preventing long-term morbidity and mortality. This review focuses on the clinical presentation, diagnosis, and treatment objectives for common forms of renal vasculitis seen in pediatric patients.

Anti-myeloperoxidase and proteinase 3 antibodies for nephritis flare prediction in anti-neutrophil cytoplasmic antibody-associated vasculitis.

BACKGROUND: The value of myeloperoxidase (MPO) and proteinase 3 (PR3) antibody titres in the assessment of renal disease activity and flare prediction in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is not well known. METHODS: We performed a retrospective study including 113 AVV patients with renal biopsy-proven pauci-immune necrotizing glomerulonephritis from seven Spanish hospitals. The main inclusion criteria were assessment of MPO antibodies using multiplex flow immunoassay and PR3 antibody measurements using immunoassay chemiluminescence with an identical range of values for all participating centres. RESULTS: Serum MPO antibodies 3 ± 1.2 months before relapse were higher in patients who relapsed [19.2 ± 12.2 versus 3.2 ± 5.1 antibody index (AI); P < 0.001]. The discrimination value of MPO antibodies 3 months before renal relapse had an area under the receiver operating characteristics curve (AUC) of 0.82 [95% confidence interval (CI) 0.73-0.92; P < 0.001]. ΔMPO antibodies (change in antibodies titration 6 months before relapse) were higher in patients who relapsed (8.3 ± 12 versus 0.9 ± 3.1 AI; P = 0.001). The discrimination value of ΔMPO had an AUC of 0.76 (95% CI 0.63-0.88; P < 0.001). The positive predictive value of renal relapse in PR3 patients is 100% and the negative predictive value of renal relapse in patients with PR3-positive titres is 57.1%. Serum PR3 antibodies were higher in patients who relapsed 2.8 ± 1.4 months before relapse (58.6 ± 24.6 versus 2.0 ± 0.6 AI; P < 0.001). CONCLUSIONS: MPO level monitoring using multiplex flow immunoassay and PR3 measurements using immunoassay chemiluminescence are useful and sensitive tools for the prediction of renal relapse in the follow-up of AAV patients with renal disease and relevant surrogate markers of renal disease activity.

ANCA-Associated Vasculitis Following Pfizer-BioNTech COVID-19 Vaccine.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread around the world. As of the end of June 2021, there were approximately 181 million confirmed cases and more than 3.9 million deaths across the globe. The colossal impact of coronavirus disease 2019 (COVID-19) is driving the biggest vaccination campaign in human history. All 3 vaccines authorized for emergency use by the US Food and Drug Administration (Pfizer-BioNTech, Moderna, and Janssen/Johnson & Johnson) have been thoroughly studied and found to be safe and effective in preventing severe COVID-19 cases. While short-term side effects of COVID-19 vaccine resemble those of other vaccines, long-term side effects remain unknown. Rare side effects continue to surface as millions of people receive COVID-19 vaccines around the world, as compared with the thousands enrolled in the clinical trials. We report a case of new-onset renal-limited ANCA-associated vasculitis (AAV) in a 78-year-old woman with previously normal kidney function after receiving the Pfizer-BioNTech COVID-19 vaccine. The patient developed acute kidney injury with proteinuria and microscopic hematuria with many dysmorphic red blood cells in the urine. Anti-myeloperoxidase antibody titer was elevated. Kidney biopsy showed pauci-immune crescentic necrotizing glomerulonephritis. Kidney function improved after treatment with steroids and rituximab. Our patient had normal routine laboratory testing before the vaccination. Although this case cannot demonstrate a causal relationship between COVID-19 vaccination and AAV, ongoing surveillance for similar complications would be prudent as worldwide vaccination efforts continue.

Acute necrotizing glomerulonephritis associated with COVID-19 infection: report of two pediatric cases.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is thought to cause kidney injury via a variety of mechanisms. The most common reported kidney injury following COVID-19 infection is acute tubular injury (ATI); however, the procoagulant state induced by the virus may also damage the kidneys. CASE-DIAGNOSIS/TREATMENT: Herein, we report two cases of acute necrotizing glomerulonephritis (GN) with fibrinoid necrosis in the context of COVID-19 infection. The one with more chronic features in the kidney biopsy progressed to permanent kidney failure but the second one had an excellent response to glucocorticoid pulse therapy with subsequent normal kidney function at 2-month follow-up. CONCLUSIONS: Both reported cases had an acute presentation of kidney injury with positive nasopharyngeal PCR test for COVID-19. Based on the data review by the researchers, this is the first report of acute necrotizing GN associated with COVID-19 infection.

Systemic complement activation in anti-neutrophil cytoplasmic antibody-associated vasculitis and necrotizing glomerulonephritis.

AIM: Due to the accumulating evidence of complement activation in anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV), we decided to investigate the possibility of systemic complement activation in patients with Necrotizing Glomerulonephritis secondary to AAV. METHODS: Clinical, laboratory and histological findings, and serum levels of complement components, C3a, C5a and Bb fragment of Factor B and C4d, were estimated in patients with AAV and glomerulonephritis, at time of diagnosis, before any treatment had been applied. All patients were treated with the same immunosuppressive protocol and followed up for total 24 months. Twenty age and sex matched healthy individuals served as controls. RESULTS: Serum levels of all complement components were significantly increased in patients, compared to controls; C5a: 19.9(0.02-48) vs 9.06(2.1-16.3)pg/mL, P = .002, Bb: 7.3(0.02-31.4) vs 0.2(0.02-1.6)pg/mL, P < .0001, C3a: 4.7(0.4-7.2) vs 2.4(1.09-5)pg/mL, P = .05 and C4d: 11.6(0.07-70) vs 0.7(0.07-8.2)pg/mL, P = .001, respectively. There was strong correlation between serum Bb levels and eGFR and FFS2009 score at time of diagnosis (r = -.41, P = .002 and r = .41, P = .003 respectively). Also, serum Bb levels were increased in patients with severe interstitial infiltration (P = .04) and focal necrosis (P = .01) on renal biopsy. Serum Bb levels could also predict renal function outcome during the acute phase of disease, but not at the end of follow up. CONCLUSION: We provided strong evidence of systemic activation of complement alternative pathway in the development and progression of AAV and glomerulonephritis. Serum Bb seem to play a critical role in the induction, also predicting disease activity and outcome, yet activation of classical pathway cannot be excluded.

Microscopic polyangiitis necrotizing glomerulonephritis associated with pregnancy: case with a 20-year clinical course and review of the literature.

A 29-year-old woman with past medical history of hypertension was referred to our hospital for the evaluation of kidney dysfunction (serum creatinine 1.0 mg/dL), proteinuria (0.54 g/gCre), and microscopic hematuria. Renal biopsy before the first pregnancy was supportive for benign nephrosclerosis with no evidence of vasculitis. After her second pregnancy and delivery when she was 32 years old, she developed proteinuria of 3.2 g/gCre, hematuria, and elevated serum creatinine level of 2.6 mg/dL. Second renal biopsy revealed necrotizing glomerulonephritis and her serum MPO-ANCA was positive, leading to the diagnosis of MPA/renal-limited vasculitis (RLV). Interestingly, frozen preserved serum from 4 years earlier also tested positive for MPO-ANCA. Despite intensive treatment, hemodialysis was required 10 years later due to progressive deterioration of renal function. At that time, she developed pericarditis, bloody cardiac tamponade, and pulmonary alveolar hemorrhage, resulting in a diagnosis of systemic vasculitis MPA. She received living donor kidney transplantation at the age of 44 years, after which serum creatinine has been stable around 1.1 mg/dL without proteinuria or hematuria and MPO-ANCA has remained negative. The association of vasculitis with pregnancy and delivery is not well documented, especially in patients with MPA. Here, we report this MPO-ANCA positive woman developing MPA necrotizing glomerulonephritis after her second pregnancy and a 20-year clinical course.

Rapidly progressive glomerulonephritis associated to afebrile endocarditis and anti-proteinasa 3 anca / Glomerulonefritis rápidamente progresiva asociada a endocarditis afebril y anca anti-proteinasa 3

Absctrat Endocarditis associated with antiPR3 ANCA and acute kidney injure generates a challenge in its diagnosis and treatment. In order to make a review about that combination, we presented a patient with necrotizing glomerulonephritis produced by a Enterococcus faecalis's subacute endocarditis and antiPR3 ANCA positive. Differential diagnosis is made between an acute kidney failure produced by ANCA's vasculitis vs necrotizing glomerulonephritis by endocarditis. Frequently it is necessary to make a biopsy to get a diagnosis. Negative immunofluorescence will guide to vasculitis associated ANCA, while positive immune complexes will guide to poststreptococcal glomerulonephritis. Other challenge that generates the association of acute kidney disease, endocarditis and antiPR3 ANCA is the treatment. ANCA positive can prompt to start immunosuppressant treatments. However, in the context of endocarditis, it could be inadvisable and even dangerous to use it. For this reason, it is controversial the use of immunosuppressant in combination with antibiotics in the acute process, in contrast with the use of only antibiotics. In the current paper we collect the 19 reports in the literature about endocarditis associated with antiPR3 ANCA, the treatment and the renal evolution of each patient. We concluded, generally, a better improvement of kidney function in patients treated with only antibiotics than those patients treated with the combination of antibiotics and corticoids. However, there are so few reports that we can't consider significant the different between both treatment groups.

Resumen La endocarditis asociada a ANCA anti-PR3 e insuficiencia renal plantea un dilema tanto en su diagnóstico como tratamiento. Para abordar una revisión de dicho tema, se presenta el caso de un paciente con glomerulonefritis rápidamente progresiva secundaria a endocarditis subaguda por Enterococcus faecalis y positividad para ANCA anti-PR3. El diagnóstico diferencial principal se establecería entre una afectación renal de una vasculitis asociada a ANCA no diagnosticada previamente vs una glomerulonefritis postinfecciosa secundaria a la endocarditis. En muchos casos es necesario disponer de una biopsia renal que esclarezca el diagnóstico, ya que una inmunofluorescencia negativa orientará hacia una vasculitis, mientras que una positividad para inmunocomplejos iría a favor de una glomerulonefritis postestreptocócica. El tratamiento a seguir es otro reto que se plantea en la coexistencia de insuficiencia renal aguda, endocarditis y ANCA anti-PR3 positivo. La positividad de ANCAs induce a valorar iniciar tratamiento con inmunosupresores, no obstante, en el lecho de una endocarditis puede resultar desaconsejado e incluso poner en riesgo la vida del paciente someterlo a un estado de inmunosupresión. Es, por tanto, controvertido el uso de inmunosupresión en combinación con antibioterapia en el proceso agudo en contraposición al uso de antibioterapia exclusivamente. En el actual artículo se recogen los 19 casos publicados en la literatura de endocarditis asociados a ANCA anti-PR3, así como el tratamiento que se realizó en cada uno de los casos y la evolución en la función renal de cada paciente, concluyendo, en general, una mejor recuperación de la función renal en los pacientes tratados con antibioterapia en exclusiva que en aquellos tratados con la combinación antibiótico-corticoides. Sin embargo, dado el pequeño tamaño muestral, no se puede considerar significativa la diferencia entre ambos tratamientos.

MPO-ANCA-associated necrotizing glomerulonephritis in rheumatoid arthritis; a case report and review of literature.

BACKGROUND: Renal involvement in rheumatoid arthritis (RA) is common and has a negative impact on patient survival. Only few cases have been reported of necrotizing glomerulonephritis (GN) associated with myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) in patients with RA. CASE PRESENTATION: We report a patient with RA who developed a necrotizing GN associated with ANCA-MPO, treated with rituximab (RTX). A 55-year-old man with a 27-year history of RA under secukinumab was referred to our nephrology clinic with worsening renal function associated with microhematuria and proteinuria. Our laboratory evaluation showed hypocomplementemia and positive titers for MPO-ANCA (615 U/mL). A renal biopsy demonstrated pauci-immune necrotizing GN. The patient was treated with 3 consecutive pulses of methylprednisolone followed by oral prednisolone (1 mg/Kg) and rituximab (1000 mg, repeated 14 days later). After a 10-month follow-up, the arthritis remains well-controlled, renal function stabilized, proteinuria improved and MPO-ANCA titer normalized (6.3 U/mL). CONCLUSIONS: Necrotizing GN is a rare but a serious condition and an early diagnosis is essential to treatment. This is the first case of necrotizing GN (without extra-renal manifestations of vasculitis) in a patient with active RA, successfully treated with RTX.

Th1, Th2 and Treg/T17 cytokines in two types of proliferative glomerulonephritis.

IgA nephropathy (IgAN) and focal segmental necrotizing glomerulonephritis (FSNGN) are characterized by proliferation of native glomerular cells and infiltration by inflammatory cells. Several cytokines act as mediators of kidney damage in both diseases. The aim of the present study was to investigate the role of Th1, Th2 and Treg/T17 cytokines in these types of proliferative glomerulonephritis. Simultaneous measurement of Th1 interleukin (IL-2, IL-12, tumor necrosis factor-alpha [TNF-α], interferon-gamma [INF-γ]), Th2 (IL-4, IL-5, IL-6, IL-10, IL-13), Treg/T17 transforming growth factor-beta 1 (TGF-ß1, granulocyte-macrophage colony-stimulating factor [GM-CSF], IL-17) cytokines and C-C chemokines Monocyte chemoattractant protein-1 (MCP-1, macrophage inflammatory protein-1 [MIP-1] ß) was performed in first-morning urine samples, at the day of renal biopsy, using a multiplex cytokine assay. Cytokine concentrations were correlated with histological findings and renal function outcome. Urinary excretion of Th1, Th2 and Treg/Th17 cytokines were significantly higher in FSNGN compared to IgAN patients. In IgAN patients (n = 50, M/F: 36/14, M age: 40.7 [17-67] years), Th1, Th2 and T17 cytokines correlated significantly with the presence of endocapillary proliferation, while in FSNGN patients (n = 40, M/F: 24/16, M age: 56.5 [25-80] years), MCP-1 and TGF-ß1 had a positive correlation with severe extracapillary proliferation (P = 0.001 and P = 0.002, respectively). Urinary IL-17 was the only independent parameter associated with endocapillary proliferation in IgAN and with MCP-1 urinary excretion in FSNGN. Response to treatment was mainly predicted by IL-6 in IgAN, and by Th2 (IL-4, IL-6), Treg (GM-CSF) cytokines and MIP-1 ß in FSNGN. Th1, Th2 and T17 cytokines were directly implicated in renal pathology in IgAN and possibly through MCP-1 production in FSNGN. IL-17 and IL-6 seem to have a central role in inflammation and progression of kidney injury.