Pauci-immune Crescentic Glomerulonephritis Research Articles

A case of ANCA-negative pauci-immune crescentic glomerulonephritis with lung adenocarcinoma with mediastinal involvement successfully treated by corticosteroid and radiation therapy.

Pauci-immune crescentic glomerulonephritis (PICGN) is one of the pathologies causing rapidly progressive glomerulonephritis, often associated with anti-neutrophil cytoplasmic antibody (ANCA); however, in 10-30% of cases, ANCAs are negative. While a relatively large number of cases of ANCA-positive PICGN complicated with malignancy have been previously reported, the number of cases of ANCA-negative PICGN with malignancy is limited. The prognosis for such cases was poor, and many patients died within a relatively short period. Here, we report the case of ANCA-negative PICGN complicated with malignancy successfully treated by corticosteroid and radiation therapy. A 63-year-old Japanese man was admitted to our hospital due to spiking fevers in the previous 3months. Based on the findings of imaging and pathological tests, he was diagnosed with locally advanced lung adenocarcinoma with mediastinal involvement. After admission, his renal function rapidly deteriorated, and urinalysis showed heavy proteinuria. In serological tests, serology for autoantibodies, including ANCAs, was negative. The kidney biopsy revealed PICGN with prominent endocapillary proliferation. We administered corticosteroid therapy for glomerulonephritis and subsequent radiation therapy for lung carcinoma, both of which were effective. He has been alive without progression of malignancy or kidney disease for 5 years after discharge. In patients with malignancy presenting with acute deterioration of kidney function, although infrequent, one of the conceivable pathological conditions to consider is ANCA-negative PICGN associated with malignancy. In such cases, even with negative antibodies such as ANCA, pathological examination is warranted, and a combination of anti-tumor therapy and immunosuppressive therapy is expected to be effective.

Kidney Failure in Pauci-immune Crescentic Glomerulonephritis: Rationale for Immunosuppression to Improve Kidney Outcome.

Pauci-immune crescentic glomerulonephritis is the hallmark finding in ANCA-associated vasculitis (AAV) when the kidneys are affected. The rationale for immunosuppression in AAV is based on the underlying autoimmune nature of the disease. Overall remission rates, kidney outcomes, and the burden of disease have greatly improved since the discovery of various immunosuppressive therapies, but relapses remain common, and a significant proportion of patients continue to progress to end-stage kidney disease. Here, we review the role of immunosuppressive therapies for the treatment of pauci-immune crescentic glomerulonephritis. Besides the recognized role of B and T cells in the pathogenies of AAV, the focus on the contribution of inflammatory cytokines, neutrophil extracellular traps (NETs), and the complement system allowed the discovery of new therapies. Specifically, the C5a receptor blocker (avacopan) has been approved as a glucocorticoid-sparing agent. Additionally, based on observational data, more clinicians are now using combination therapies during the induction phase. There is also an evolving understanding of the role of plasma exchange in removing ANCA antibodies. Furthermore, the recent development of risk score systems provides physicians with valuable prognostic information that can influence decisions on immunosuppression, although future validation from larger cohorts is needed. The over-activation of various immune pathways plays a significant role in the pathogenesis of pauci-immune crescentic glomerulonephritis in AAV. Immunosuppression is, therefore, an important strategy to halt disease progression and improve overall outcomes. Relapse prevention while minimizing adverse events of immunosuppression is a major long-term goal in AAV management.

Clinical Presentation and Treatment Outcomes of Renal Medullary Angiitis in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Single-Center Case Series.

Antineutrophil cytoplasmic antibody-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. In this single-center cohort, renal pathology samples classified as AAV with renal involvement underwent secondary review to determine if they met histopathologic criteria for RMA. Demographic, clinical, and laboratory data were obtained via electronic medical record review. Descriptive statistical analysis was performed on key variables. Of the 136 kidney biopsy samples classified as AAV 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 extrarenal manifestations of disease. Initial median (IQR) estimated glomerular filtration rate and proteinuria on presentation were 16 (10-19) mL/min/1.73 m2 and 1,100 (687-2,437) mg, respectively. The primary histologic features were high degrees of interstitial inflammation comprised 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, 1 patient reached ESKD and 1 patient died. In 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 multisystem 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.

Crescentic Glomerulonephritis in Human Immunodeficiency Virus Infection

The spectrum of kidney disease among human immunodeficiency virus (HIV) infected patients is extensive. We describe a young male who was recently detected with HIV infection and antineutrophil cytoplasmic antibody (ANCA) negative pauci-immune crescentic glomerulonephritis. The patient had no extrarenal vasculitis involvement. Patient was successfully managed with highly active antiretroviral therapy (HAART) and oral steroids. In our case report, we have also reviewed the literature of crescentic glomerulonnephritis in HIV infection.

#1782 Clinicopathological study of renal limited pauci-immune vasculitis and its short-term outcome: a single centre observational study

Abstract Background and Aims Pauci immune crescentic glomerulonephritis, is a leading cause of RPGN. The majority of patients with PICGN have glomerular diseases as a part of a systemic small vessel vasculitis, a minority may present as renal-limited vasculitis. In north-east India, there are still no major studies in this group of patients. Therefore, our study involving north-east Indian population constitutes an effort to prospectively study the clinico-pathological feature of patients with PICGN and assess the short-term outcome. Method This single-centre, prospective, observational, study was conducted over 12 months at the Department of Nephrology, Gauhati Medical College. All renal biopsy-proven patients with pauci-immune renal vasculitis were included, excluding those with secondary vasculitis. Baseline characteristics and laboratory data were recorded, and disease activity was assessed using the Birmingham Vasculitis Activity Score. The ANCA tests were performed using a standardised essay for both indirect immunofluorescence assay and antigen-specific ELISA. The renal biopsy specimen obtained was evaluated by light microscopy and direct immunofluorescence. The sample size was calculated based on the prevalence of pauci-immune glomerulonephritis, and data were analysed using SPSS. Results The study involved 24 patients, predominantly females (70.83%), aged 14-65 years, presenting predominantly with pedal oedema and oliguria. Laboratory findings showed varying levels of haemoglobin, total count, platelet count, creatinine, and 24-hour urine protein. 50% of the patients were (MPO) positive, 33.3% were (PR3) positive while 16% were ANCA negative. Renal biopsy analysis showed a majority with mixed class according to the Berden classification. Treatment involved induction with Methylprednisolone and Cyclophosphamide, with dialysis administered to 58.3% of patients. At six months, 36.3% had a stable GFR, and 50% were on maintenance hemodialysis. Factors predicting renal loss included oliguria, dialysis at presentation, and fibrous/fibrocellular crescents. The best predictor of renal outcome was serum creatinine at presentation. Conclusion Pauci-immune CrGN is a severe disease affecting a wide age range. Early diagnosis and treatment initiation are crucial for better outcomes, including lower ESRD risk and relapse rates. Prognostic factors include baseline serum creatinine levels and fibrous crescents. Optimising treatment regimens may improves outcomes.

Myeloperoxidase-Associated Membranous Nephropathy in Antineutrophil Cytoplasmic Antibody-Associated Glomerulonephritis

IntroductionAnti-neutrophil cytoplasmic antibody (ANCA)–associated glomerulonephritis (GN) is characterized by pauci-immune crescentic GN. Although myeloperoxidase ANCA-associated GN (MPO-ANCA GN) with membranous nephropathy (MN), where bright granular capillary myeloperoxidase (MPO) and immunoglobulin G (IgG) staining along the glomerular basement membrane (GBM) is present, has been reported; however, its clinicopathological features remain unclear. MethodsWe investigated 7 MPO-ANCA GN with MN and 11 control cases (6 MPO-ANCA GN and 5 primary MN cases). Proteomics of laser microdissected glomeruli followed by immunohistochemical analysis was performed to identify causal antigens in MPO-ANCA GN with MN. We described the clinicopathological features of MPO-associated MN compared with those of MPO-ANCA GN and primary MN. ResultsWe detected proteomic MPO and granular capillary MPO deposits in all MPO-ANCA GN with MN cases. Confocal microscopy revealed MPO and IgG co-localization along the GBM. MPO-associated MN clinicopathological features include greater proteinuria, a higher fibrous crescent rate, and a lower MPO-ANCA titer than MPO-ANCA GN. The estimated glomerular filtration rate and urinary protein excretion were lower in MPO-associated MN than in primary MN. ConclusionMPO-associated MN, a unique type of secondary MN where MPO serves as the causal antigen, is a subset of MPO-ANCA GN with MN. Prolonged periods of MPO-ANCA GN and a low MPO-ANCA titer might be related to MPO-associated MN development.

Glomerulonephritis following COVID-19 infection or vaccination: a multicenter study in South Korea.

Despite the widespread impact of the severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019, COVID-19) and vaccination in South Korea, our understanding of kidney diseases following these events remains limited. We aimed to address this gap by investigating the characteristics of glomerular diseases following the COVID-19 infection and vaccination in South Korea. Data from multiple centers were used to identify de novo glomerulonephritis (GN) cases with suspected onset following COVID-19 infection or vaccination. Retrospective surveys were used to determine the COVID-19-related histories of patients who were initially not implicated. Bayesian structural time series and autoregressive integrated moving average models were used to determine causality. Glomerular diseases occurred shortly after the infection or vaccination. The most prevalent postinfection GN was podocytopathy (42.9%), comprising primary focal segmental glomerulosclerosis and minimal change disease, whereas postvaccination GN mainly included immunoglobulin A nephropathy (IgAN; 57.9%) and Henoch-Schönlein purpura nephritis (HSP; 15.8%). No patient progressed to end-stage kidney disease. Among the patients who were initially not implicated, nine patients with IgAN/HSP were recently vaccinated against COVID-19. The proportion of glomerular diseases changed during the pandemic in South Korea, with an increase in acute interstitial nephritis and a decrease in pauci-immune crescentic GN. This study showed the characteristics of GNs following COVID-19 infection or vaccination in South Korea. Understanding these associations is crucial for developing effective patient management and vaccination strategies. Further investigation is required to fully comprehend COVID-19's impact on GN.

Assessment of some cytokines levels in a pauci-immune crescentic glomerulonephritis patients

Background: Glomerulonephritis is the common cause of end-stage of renal failure. Rapidly progressive glomerulonephritis (RPGN) is characterized by glomerular injuries and formation of crescents. Moreover, anti-neutrophil cytoplasmic antibodies (ANCA), and pro-inflammatory cytokines play a damaging role in a crescent glomerulonephritis. Objectives: The main goal of the current study was aimed to determine the ANCA autoantibodies, and the serum levels of pro-inflammatory cytokines (IL-6, IL-17, IL-18, INF-γ), as well as the relationship between these cytokines and ANCA test in a pauci-immune crescentic glomerulonephritis patients. Methodology: The study was carried out in AL-Yarmouk teaching hospital and AL-Sader teaching hospital during the period from April 2022 to April 2023. This study was involved 90 patients with a crescentic glomerulonephritis disease, the diagnosis was made by the consultant medical staff. In addition to a 60 samples of healthy individuals as control group was involved to comparison the results. ANCA test was made by Indirect immunofluorescence method for the detection of ANCA autoantibodies in serum, in addition to measure the serum level of cytokines including IL6, IL-17, IL-18, and IFN-γ by using Enzyme Linked Immune Sorbent Assay methods. Results: This study has shown that the majority of patients were male (66.7%). Moreover, the most effected age groups within the age ≥ 61 years in percentage (65.5%) followed by the age group 51-60 years old (28.8%). There were 59 (65.5%) positive cases for ANCA from total patients and all of these cases were MPO-ANCA. The total RPGN patients were showed a highly significant increased mean serum levels of IL-18, IL-17, IL-6, and INF-γ as compared to healthy controls, as well as, the same cytokines were showed significant increased levels in myeloperoxidase (MPO)-ANCA positive serum in crescent glomerulonephritis patients as compared to ANCA –negative serum of patients. These results indicate a functional role of IL-6, IL-17, IL-18, and INF-γ in ANCA-mediated neutrophil activation by the interdependence of IL-6, IL-17, IL-18, and INF-γ priming for ANCA responses. Conclusion: It can be drawn from the present study that, the pro-inflammatory cytokines play an integral role in determining the course of disease and it can be used as major drug targets for therapy, as well as these cytokines have the ability to priming neutrophils thus contribute in the progression of a pauci-immune crescentic glomerulonephritis disease.

Renal involvement in eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a necrotizing vasculitis, which typically affects small-to medium-sized blood vessels. It is characterized by the presence of tissue infiltrates rich in eosinophils, along with the formation of granulomatous lesions. About 40% of cases have positive anti-neutrophil cytoplasm antibodies (ANCA), with predominant perinuclear staining, and anti-myeloperoxidase (anti-MPO) specificity in about 65% of cases. Typical manifestations of EGPA include the late onset of asthma, nasal and sinus-related symptoms, peripheral neuropathy, and significant eosinophilia observed in the peripheral blood. In contrast to granulomatosis with polyangiitis and microscopic polyangiitis, renal involvement in EGPA is less frequent (about 25%) and poorly studied. Necrotizing pauci-immune crescentic glomerulonephritis is the most common renal presentation in patients with ANCA-positive EGPA. Although rarely, other forms of renal involvement may also be observed, such as eosinophilic interstitial nephritis, mesangial glomerulonephritis, membranous nephropathy, or focal sclerosis. A standardized treatment for EGPA with renal involvement has not been defined, however the survival and the renal outcomes are usually better than in the other ANCA-associated vasculitides. Nonetheless, kidney disease is an adverse prognostic factor for EGPA patients. Larger studies are required to better describe the renal involvement, in particular for patterns different from crescentic glomerulonephritis, and to favor the development of a consensual therapeutic approach. In this article, in addition to personal data, we will review recent findings on patient clinical phenotypes based on ANCA, genetics and the impact of biological drugs on disease management.

Comparison of Clinico-pathologic features and outcomes of ANCA negative and ANCA positive pauci immune crescentic glomerulonephritis: A single centre study.

Pauci-immune crescentic glomerulonephritis (PICN) is an important cause of rapidly progressive renal failure. 10-40% of PICN cases have ANCA (antineutrophil cytoplasmic antibody) negative serology. The present study compared clinico-pathologic features, Brix's renal risk score, Berden's histopathological classes and differences in outcome between ANCAnegative vs ANCA positive PICN patients. Sixty-one patients of biopsy-proven PICN were studied. Biochemical findings and ANCA serology were recorded. Renal biopsy slides were reviewed along with direct immunofluorescence. Clinical and histological features were compared between ANCA negative and positive PICN using the Man Whitney U test and Chi-square test. Patients were compared for distribution in Berden's histological classes and Brix's renal risk categories. Patient and renal survival were compared using Kaplan-Meier survival analysis. ANCA negative PICN patients were younger (44.9 ± 16.5 years vs 53.6 ± 15.1 years, P = 0.049). Nasal (0 vs 18%, P = 0.035) and pulmonary involvement (9% vs 38%, P = 0.014) were lower in ANCA negative group. Both ANCA groups had similar renal biochemical profiles, percentage normal glomeruli, 16.3 ± 18.2 vs 21.7 ± 20.4 and percentage glomeruli with crescents, 64.5 ± 28.1 vs 64.3 ± 27.1. Twenty-seven per cent of ANCA negative cases fell in the sclerotic class in Berden's classification vs just 2.5% in ANCA positive group (p = 0.037) without significant difference in Brix's renal risk categories (p = 0.329). Thirteen per cent of ANCA negative patients achieved complete remission on treatment compared to 33% in ANCA positive patients. Patient survival and overall probability of progressing to ESRD were similar in the two groups. ANCA negative PICN cases present at younger ages. Nasal and pulmonary involvement is uncommon in these patients. Patient survival and progression to ESRD are similar in both ANCA groups.

#6930 TOO ELDERLY FOR A KIDNEY BIOPSY?

Abstract Background and Aims As we age, we lose kidney function and accumulate risk factors and comorbidities that predispose to kidney damage. However, kidney disease can develop at any time. Life expectancy continues to improve worldwide. For that reason, more elderly patients are undergoing diagnostic kidney biopsies (KB). There is a general reluctance in performing KB in those patients. It is important to know if a diagnosis KB in elderly patients can have a positive therapeutic impact. Method In this retrospective cohort study, we analyzed the medical charts of all patients aged ≥ 80years who underwent a native kidney biopsy (KB) between January and December 2021, in a central hospital in Portugal. Results Between January and December 2021, 59 patients underwent a native KB, 6 of them over 80 years of age (10% of all patients). Between those elderly patients, the median age was 82 years. The indications for KB were chronic kidney disease with a nephrotic range proteinuria in 3 patients, nephrotic syndrome, acute glomerulonephritis and acute kidney injury in 1 patient each. Median serum creatinine was 2.27 mg/dL (minimum 0.8 and maximum 5.4 mg/dL) and median protein-to-creatinine ratio was 5.7g/g (minimum 3.3 and maximum 13g/g). The pathological diagnoses found were focal and segmental glomerulosclerosis (FSGS) (n=2), pauci-immune crescentic glomerulonephritis (n=1), membranous nephropathy in a patient with a follicular lymphoma (n=1), acute interstitial nephritis (AIN) (n=1), and diabetic glomerulosclerosis in a patient with a monoclonal gammopathy of undetermined significance (n=1). 3 patients have received a kidney-specific treatment – the patient with AIN started corticosteroids, one patient with FSGS was submitted to corticosteroids plus tacrolimus, and the patient with pauci-imune crescentic glomerulonephritis to corticosteroids plus rituximab. The patient with membranous nephropathy and follicular lymphoma received a specific chemotherapy regimen according with lymphoproliferative disease. An improvement in kidney function occurred only in one patient and the other three developed adverse effects (particularly corticosteroids induced diabetes and infections). One year later, one of patients who received treatment was dead, another one was on hemodialysis, and the other two patients had a glomerular filtration rate lower than 15mL/min/1.73 m2. Conclusion Elderly patients have a higher risk of adverse effects from the kidney-specific treatment. It is important to assess the therapeutic risk/benefit when considering performing a renal biopsy in these patients.

#4710 CYCLOPHOSPHAMIDE INDUCTION TREATMENT IN ANCA-ASSOCIATED VASCULITIS WITH RENAL AND PULMONARY INVOLVEMENT: OUTCOMES AND SIDE EFFECTS

Abstract Background and Aims ANCA associated vasculitis are necrotaizing vasculitis of small and medium vassels - which cause organ damage. They are relatively rare diseases with an estimated prevalence of 200–400 cases per million people [1]. Pauci-immune necrotizing and crescentic glomerulonephritis (GN) is a frequent component of ANCA-associated vasculitis that can cause rapidly progressive Acute Kidney Injury (AKI). Less frequently, it can cause low progressive Chronic Kidney Disease (CKD) [2]. Combination therapy of steroids and cyclophosphamide has improved 5-years survival up to 70-90% but it can cause serious side effects including infectious episodes [3], bone marrow suppression and myelodysplasia. We present a case highlighting treatment modalities and our decision making. Method Our retrospective study analyzes the case of a 63-year-old male presenting with progressive dyspnea and hemoptysis. A chest CT suggested diffuse alveolar hemorrhage. The blood tests showed onset of AKI with 7.68 mg/dl serum creatinine (normal values 0.72-1.25), mild proteinuria and hematuria. A kidney and pulmonary vasculitis was suspected and the c-ANCA serum value was elevated at >500 IU/ml. Three cycles of Plasma Exchange (PEX) were performed and methylprednisolone was given (500 mg for 3 days, 1 g on the 4th day) followed by cyclophosphamide boluses of 1 g/week for 4 weeks. Broad-spectrum antibiotics and antifungal therapy was administered to prevent secondary infections. Due to the further worsening of the renal function, three hemodialysis treatments and a cascade filtration were performed continuing with cyclophoshamide 1 g/day orally and methylprednisolone 60 mg/day. Cyclophosphamide therapy was discontinued due to thrombocytopenia and progressive leukopenia. Filgastrim 30MU/0.5 ml was administered for five days until the resolution of the pancytopenia when cyclophosphamide 50 mg 2cp+1cp was resumed. Results A one-month follow-up CT showed reduction in hemorrhagic opacities and the c-ANCA level was significantly reduced. Steroid dosing was progressively reduced and the patient was discharged with methylprednisolone 16mg 2cp+1/2cp tapering over 6 months and cyclophosphamide 50 mg 2cp+1cp. Serum creatinine levels improved from 2.64 mg% at discharge to 1.6 mg% at follow up. Conclusion When treating c-ANCA vasculitis with corticosteroids and cyclophosphamide, routine evaluation of complete blood count parameters is necessary to prevent bone marrow toxicity. We continued methylprednisolone and cyclophosphamide for six months, obtaining a total clinical remission despite side effects induced by the state of immunosuppression (oral cavity mycosis, bone marrow toxicity and CMV reactivation).

AB1651 DIFFUSE ALVEOLAR HEMORRHAGE IN RHEUMATOLOGY: CLINICAL PRESENTATION, ETIOLOGY, TREATMENT AND OUTCOME

BackgroundDiffuse alveolar hemorrhage (DAH) is characterized by rapid onset of pulmonary infiltrates and hypoxemia. It is a potentially life threatening complication associated with systemic autoimmune conditions.ObjectivesTo describe the presentation, clinical features, etiology, treatment and outcome of DAH in rheumatological conditions.MethodsThis a retrospective, multicentre study involveing 3 rheumatology centers, wherein data about DAH cases seen over the past 5 years was collected.ResultsThere were 19 patients (Female = 15). The mean age was 38 years (18 - 67). DAH was the presenting feature in 15 patients (78%). The mean duration of symptoms was 20 days (1 - 60). The symptoms of DAH were: dyspnea 16 (84%), cough 15 (78%), hemoptysis 13 (68%). Other features of DAH like hypoxemia (18 patients), fall in hemoglobin (19 patients) were common. Fever was observed in 9 (47%). Nephritis was noted in 14 (73%). Renal biopsy was done in 6 (Lupus nephritis class 3 & 5 = 1; lupus nephritis class 4 = 1; Pauci immune crescentic glomerulonephritis = 3;Anti GBM associated crescentic glomerulonephritis =1). The most common feature on chest radiograph was diffuse opacities (Image 1). The etiology of DAH was as follows (Table 1) - granulomatosis with polyangiitis (GPA = 8); Systemic lupus erythematosus (SLE =7); anti GBM disease (2); Microscopic polyangiitis (MPA=1) and undifferentiated vasculitis [1]. The treatment of DAH included - Intravenous methylprednisolone (IV MP)=18; Intravenous immunoglobulin (IVIG) = 2; Extracorporeal membrane oxygenation (ECMO) = 1; Therapeutic plasma exchange = 3; Intravenous cyclophosphamide = 11; Rituximab (RTX) = 4; Mycophenolate mofetil (MMF) = 1. Most of the patients were managed in the intensive care unit (ICU) (13/ 19) and needed ventilatory support (11/ 19). Most patients required more than 10 days of hospitalization (12/ 19 = 63%). There were a total of 5 deaths (GPA =2; SLE =2; anti-GBM disease =1).ConclusionDAH was the presenting feature in most of the cases. GPA and SLE were the common causes. Dyspnea, cough and Hemoptysis were the common DAH symptoms. Fever and nephritis were the common Non - DAH clinical feature. Most of the patients were treated with IV MP and required ICU care; Approximately half of the patients required ventilatory support. DAH is a potentially life threatening condition with an overall mortality rate of approximately 25%.Early recognition and appropriate treatment is needed for better outcome.Reference[1]Park, M. S. (2013). Diffuse alveolar hemorrhage.Tuberculosis and Respiratory Diseases,74(4), 151–162.https://doi.org/10.4046/trd.2013.74.4.151Table 1.DAH - Causes, clinical features, treatment and outcomeDiagnosisDAH featuresNon DAH featuresTreatmentOutcomeGPA (N=8)(M/ F= 4/4)DAH as presenting feature = 6Cough - 5Dyspnea - 6Hemoptysis - 3Nephritis - 5Fever - 4LRT - 3Skin rash - 2ENT - 1Oral ulcers - 1Scleritis – 1IV MP - 8TPE - 3IV CYC - 6RTX - 2ICU - 5Ventilatory support - 4Discharge within days - 2Discharge after 10 days - 5Death - 2SLE (N=7)(F = 6)DAH as presenting feature = 3Cough - 6Dyspnea - 6Hemoptysis - 6Nephritis - 6ITP - 5Fever - 5Alopecia - 2Oral ulcers - 2AIHA - 2CNS - 1Serositis – 1IV MP - 6IVIG - 2IV CYC - 2RTX - 2ICU - 5Ventilatory support - 4Discharge within days - 1Discharge after 10 days - 4Death - 2Anti-GBM disease (N = 2; All female)DAH at presentation = 2Cough - 2Dyspnea - 2Hemoptysis - 2Nephritis - 2Arthritis – 1IV MP - 2TPE -IVIG -IV CYC - 1RTX -ECMO - 1ICU - 2Ventilatory support - 2Discharge after 10 days - 1Death - 1MPA (N=1)(Female)DAH at presentation = YCough - YDyspnea - YHemoptysis - YNephritis – 1IVMP - YIV CYC - YICU - NVentilatory support- NDischarge after 10 days - 1Undifferentiated vasculitis (N = 1)(Female)DAH at presentation = YCough - YDyspnea - YHemoptysis - YSkin rashIVMP - YIV CYC - YTPE - YICU - YVentilatory support - YOngoing treatment> 10 days of hospitalizationLRT - lower respiratory tract; ENT - Ear, nose, throat; AIHA - Autoimmune hemolytic anemia; ITP - Idiopathic thrombocytopenic purpura; CNS - Central nervous system; M - Male; F - Female: Y = Yes;N = No.Image 1: Chest X rayAcknowledgements:NIL.Disclosure of InterestsNone Declared.

An unusual form of kidney injury without glomerulonephritis in microscopic polyangiitis: a case report

BackgroundMicroscopic polyangiitis (MPA), a kind of antineutrophil cytoplasmic autoantibody associated vasculitis (AAV), predominantly affects small-sized vessels. MPA is a significant cause of the pulmonary-renal syndrome. Pauci-immune necrotizing and crescentic glomerulonephritis is the typical renal histological feature of AAV. Tubulointerstitial lesions may occur and mostly form with inflammatory cell infiltration in the interstitium. However, a few cases reported only tubulointerstitial involvement without glomerular lesions in patients with MPA.Case presentationWe present an MPA case, a 70-year-old male patient diagnosed with acute kidney injury accompanying the dialysis requirement. Only acute tubulointerstitial nephritis was revealed in kidney biopsy without evidence of glomerular injury. Also, interstitial pulmonary fibrosis was determined on computerized tomography, and myeloperoxidase antineutrophil cytoplasmic autoantibody was positive. Consequently, we have considered the main diagnosis as MPA. We did not prefer a standard tubulointerstitial nephritis treatment regimen due to the presence of life-threatening systemic vasculitis. Treatment was established like crescentic glomerulonephritis. Induction therapy consisted of pulse steroid, cyclophosphamide, and plasmapheresis. Unfortunately, severe SARS-CoV-2 infection caused death during induction therapy in this case.ConclusionsThe lack of glomerular injury and solely interstitial inflammation is atypical regarding AAV involvement in the kidney. This diversity might be initially considered as only a simple histological elaboration. However, it is a significant entity for guiding the treatment of AAV.

ANCA-negative pauci-immune crescentic glomerulonephritis associated with Fabry disease: lesson for the clinical nephrologist.

ANCA-negative pauci-immune crescentic glomerulonephritis associated with Fabry disease: lesson for the clinical nephrologist.

Divergent manifestations and outcomes of diffuse crescentic immunoglobulin A nephropathy and pauci-immune crescentic glomerulonephritis on long-term.

Diffuse crescentic IgAN (CIgAN) is an uncommon phenotype of IgAN, which presents as rapidly progressive renal failure, similar to patients with pauci-immune crescentic glomerulonephritis(PCGN). There are limited data on outcomes comparisons between the two. In this single-center, retrospective cohort study, we compared the clinical features, pathological presentation, and renal outcomes of 52 patients with CIgAN and 42 patients with renal-limited PCGN from January 2007 to December 2019. The CIgAN patients were younger (30.5 ± 13.8years) than PCGN patients (46.1 ± 11.8years) (P = 0.001). The CIgAN patients had a higher prevalence of hypertension (86.5% Vs. 41.3%, P = 0.001); and degree of proteinuria (4.2 ± 2.7g/24h Vs. 2.3 ± 1.16g/24h; P = 0.001) than PCGN patients. The chronicity in terms of global glomerulosclerosis, interstitial fibrosis, and tubular atrophy was higher in the CIgAN group than in the PCGN group. The remission rate with immunosuppression was significantly higher in the PCGN group than in the CIgAN group (P = 0.016). The end-stage renal disease (ESRD) or death within 1year of diagnosis was significantly more in the CIgAN group (62.3% Vs. 39.1%) than PCGNgroup. For patients who were dialysis-dependent at presentation, the primary outcome of ESRD or death within one year was seen in 90.9% of patients of CIgAN and 44.1% in the PCGN group (P = 0.001). The long-term death non-censored renal survival is poor in the CIgAN group than in PCGN patients. However, patient survival is poor in PCGN patients. CIgAN is a different form of RPGN compared to PCGN and carries a poor prognosis despite similar immunosuppressive therapy in the long term.

A case of Alport syndrome with pregnancy-related atypical hemolytic uremic syndrome and crescentic glomerulonephritis

Kidney function may be impaired during pregnancy due to various reasons, and the physiological changes of pregnancy may unmask or worsen pre-existing kidney disease. Herein, we report a pregnant patient presenting with nephrotic-range proteinuria. She later developed acute kidney injury and pre-eclampsia. However, hemolytic anemia and thrombocytopenia persisted after delivery, and she was diagnosed with atypical hemolytic uremic syndrome (aHUS). Although hematological abnormalities resolved with eculizumab treatment, her renal functions did not improve. Kidney biopsy showed crescentic glomerulonephritis without thrombotic microangiopathy features. Concurrently, she was evaluated for hearing impairment, and a diagnosis of Alport syndrome was confirmed with genetic testing. Kidney function may worsen in patients with Alport syndrome during pregnancy. However, crescentic glomerulonephritis (GN) is a rare finding in Alport disease. Pauci-immune crescentic GN has been shown to be related to dysregulated activation of the alternative complement pathway, which is also the underlying pathophysiological mechanism in aHUS.

PS-R06-4: POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME TRIGGERED BY FLUID RETENTION AND HYPERTENSION AFTER STEROID INITIATION IN PATIENTS WITH ANCA-ASSOCIATED VASCULITIS

Objectives: Central nervous system (CNS) involvement in antineutrophil cytoplasmic antibody (ANCA) -associated vasculitis is common, with hypertrophic pachymeninges, cerebrovascular events, hypophysitis, or posterior reversible encephalopathy syndrome (PRES) being the most common CNS presentations. Design and Methods: Case report. Results: A 73-year-old Japanese woman presented with a fever and cough. The patient had no relevant medical history. Her c-reactive protein (CRP) level increased to 22.38 mg/dl, and meropenem was initiated; however, her fever and CRP levels did not improve. Furthermore, creatinine level increased from 0.83 to 3.44 mg/dl during hospitalization. She was transferred to our hospital for evaluation of renal function deterioration. Her consciousness level was alert, and her blood pressure was 140/80 mm Hg. A renal biopsy was performed, and histological examination of the kidneys revealed diffuse pauci-immune necrotizing and crescentic glomerulonephritis. Myeloperoxidase (MPO) -ANCA was 2.9 IU/mL and proteinase 3 (PR3) -ANCA was negative. On the basis of these findings, the patient was diagnosed with ANCA-associated vasculitis. On the fourth hospital day, she was treated with 500 mg intravenous methylprednisolone, once daily, for 3 days, followed by oral prednisolone (40 mg; 0.8 mg/kg). Although her fever and CRP levels improved after the initiation of immunosuppressive therapy, she required renal replacement therapy on the eighth hospital day. Rituximab (500 mg) was administered on the ninth hospital day. Her blood pressure subsequently increased, with the systolic blood pressure being 190 mmHg, and consciousness suddenly deteriorated on the 11th hospital day. Head fluid-attenuated inversion-recovery (FLAIR) MRI showed multiple lesions with high signal intensity, and she was diagnosed with PRES. After intravenous administration of nicardipine and fluid removal by hemodialysis, her blood pressure decreased and her consciousness dramatically improved. Conclusion: In addition to the vascular endothelial damage associated with vasculitis itself, steroid therapy, renal failure, elevated blood pressure, and administration of rituximab are related to an increased susceptibility of PRES. In particular, steroid administration increases blood pressure due to fluid retention and can be a risk factor for the development of PRES, suggesting the need for adequate fluid management during steroid administration.

Leukocyturia and hematuria enable non-invasive differentiation of Bowman’s capsule rupture severity in PR3-ANCA glomerulonephritis

BackgroundRenal involvement is a common and severe complication of anti-neutrophil cytoplasmic antibody-(ANCA)-associated vasculitis potentially resulting in pauci-immune necrotizing and crescentic ANCA glomerulonephritis (GN) with rapid deterioration of kidney function, progression to end stage kidney disease or, if left untreated, lethal exitus. Analysis of the urinary sediment routinely supports clinical management of ANCA GN, but histopathological implications of aberrancies in the urinary sediment mostly remain elusive. Therefore, we aimed to systematically assess the correlation of aberrancies in the urinary sediment and clinico-pathologic findings.MethodsA total of 42 kidney biopsies with ANCA GN were retrospectively analyzed in a single-center observational study. Laboratory and histopathological parameters were systematically analyzed and correlated with findings of the urinary sediment.ResultsIn the overall ANCA GN cohort, leukocyturia and hematuria were associated among each other, and with markers for non-selective glomerular damage, respectively. Non-invasive measurement of leukocyturia indicated focal (but not extensive) Bowman’s capsule rupture (BCR) specifically in proteinase-3 (PR3)-ANCA GN, whereas hematuria correlated with extensive (but not focal) BCR. Concerning intrarenal immune cell infiltration, leukocyturia was associated with tubulointerstitial plasma cell infiltration in PR3-ANCA GN. Finally, none of these associations were detectable in myeloperoxidase-ANCA GN, implying different modes of kidney damage.ConclusionWe herein expand our current knowledge by providing evidence that leukocyturia and hematuria enable non-invasive differentiation of BCR severity specifically in PR3-ANCA GN.Graphical abstract

A RARE CASE OF ANTINEUTROPHIL CYTOPLASMIC ANTIBODY (ANCA)-NEGATIVE PAUCI- IMMUNE FOCAL NECROTIZING AND CRESCENTIC GLOMERULONEPHRITIS PRESENTING WITH DIFFUSE ALVEOLAR HEMORRHAGE

A RARE CASE OF ANTINEUTROPHIL CYTOPLASMIC ANTIBODY (ANCA)-NEGATIVE PAUCI- IMMUNE FOCAL NECROTIZING AND CRESCENTIC GLOMERULONEPHRITIS PRESENTING WITH DIFFUSE ALVEOLAR HEMORRHAGE