Kidney Prognosis in ANCA-associated Vasculitis: The ANCLA Risk Score From a Latin American Historical Cohort.

Circulating B Cells, Plasma Cells, and Treg Associate with ANCA Levels in ANCA-associated Vasculitis

Application of the ANCA Renal Risk Score in the United States: A Single-Center Experience

BackgroundThe renal risk score (RRS) is a useful tool to predict end-stage renal disease (ESRD) in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The current study aimed to validate the predictive performance of RRS and to further modify this model in Chinese AAV patients.MethodsTwo hundred and seventy-two patients diagnosed with AAV confirmed by renal biopsies were retrospectively enrolled from a single center. The RRS was calculated based on 3 categorical variables, i.e., the proportion of normal glomeruli, the proportion of interstitial fibrosis and tubular atrophy (IF/TA), and eGFR at biopsy, classifying these patients into low-, medium-, and high-risk groups. In addition, a modified model was developed based on the RRS and was further validated in another independent cohort of 117 AAV patients. The predictive performance of each model was evaluated according to discrimination and calibration.ResultsPatients were classified by the RRS into low- (26.5%), medium- (46.7%), and high-risk (26.8%) groups, with 120-month renal survival rates of 93.3%, 57.2%, and 18.4%, respectively (P < 0.001). The RRS showed good discrimination but less satisfactory calibration. Therefore, a modified model with improved discrimination and calibration was developed in Chinese AAV patients, with eGFR, proportion of normal glomeruli (both as continuous variables), and IF/TA (< 25%, 25–50%, > 50%) included. Internal and external validation of the modified model were performed. Finally, an online risk prediction tool was developed based on the modified model.ConclusionsThe RRS was an independent predictor of ESRD of AAV patients. The modified model could predict the probability of ESRD for AAV patients with improved performance in Chinese AAV patients.

Background and Aims Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disease predominantly characterized by inflammation of small-sized blood vessels along with the presence of circulating ANCA. The kidney is frequently involved and, even though immunosuppressive therapy has dramatically improved the outcome of AAV patients, a significant proportion of patients progress to end-stage kidney disease (ESKD). Therefore, establishing and validating tools to predict renal outcomes in patients with AAV is crucial. Here we analyzed the application of two tools in predicting kidney survival in a Portuguese single-center cohort with AAV. Method We conducted a retrospective cohort study at a tertiary-care hospital in Portugal (Hospital de São João, Porto), from December 2010 to June 2023. Patients with a kidney biopsy-proven AAV were included. Serological ANCA-negative patients and patients with overlap syndromes, such as AAV in combination with anti-glomerular basement membrane disease, were excluded. Based on electronic records, information on demographics and clinical variables were collected. Kidney biopsies were reviewed to calculate: Berden histopathological classification and the Brix Renal Risk Score (RRS). Kidney survival was defined as the time from diagnosis to the need for kidney replacement therapy. A Kaplan-Meier analysis was performed to compare kidney survival based on the mentioned classifications. Results Fifty-one patients were enrolled, 78% (n = 40) of whom were positive for myeloperoxidase (MPO). The majority were men (61%, n = 31) with a mean age of 65 (± 12) years and a mean serum creatinine of 4.59 mg/dL (± 2.74) at diagnosis. During a median follow-up of 39 (IQR, 7-84) months, 20 patients (39%) progressed to end-stage kidney disease (ESKD), 10 patients (20%) died with preserved renal function and 21 patients (41%) did not need hemodialysis. Concerning Berden classification, 13 patients with a crescentic class, 4 patients with a mixed class and 3 patients with a sclerotic class developed ESKD. After 48 months of follow-up, renal survival was 100%, 90%, 61% and 26.7% in the focal, mixed, crescentic and sclerotic class groups, respectively. Berden classification did not correlate with kidney survival (p = 0.211). Concerning RRS, 10 patients in the high-risk group and 5 patients in the medium-risk group developed ESKD. After 48 months of follow-up, renal survival was 100% in the low-risk group, 85.7% in the medium-risk group, and 41.6% in the high-risk group. A correlation was established between kidney survival and RRS score (p = 0.003). Conclusion In our cohort RRS was predictive of ESKD, contrary to Berden histopathological classification. The information derived from these risk models strongly add to standard biochemical and clinical data. Patients with higher risk of ESKD need close follow-up and a tailored treatment plan regarding preparation for renal replacement therapy.

Outcomes in ANCA-Associated Vasculitis in Scotland: Validation of the Renal Risk Score in a Complete National Cohort

Background:Immunoglobin A (IgA) vasculitis (IgAV) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are small vessel vasculitis. IgAV is characterized by IgA1-dominant immune complexes deposition at vessel walls (Type III hypersensitivity...

BackgroundThe 2012 Chapel Hill Consensus Conference (CHCC) definitions and the 2007 European Medicines Agency (EMA) algorithm have been commonly used for the diagnosis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)...

Background: Increasing evidence indicates that clinicopathologic phenotypes and ANCA serotypes may differ ethnically and geographically. This review highlights the progress in the prevalence, pathogenesis, management, and outcomes of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in China. Summary: AAV is not rare in China. Cumulative evidence has demonstrated a significant preponderance of microscopic polyangiitis (MPA) and myeloperoxidase (MPO)-ANCA AAV in China. Even in patients with granulomatosis with polyangiitis (GPA), there is a predominance of MPO-ANCA over proteinase 3 (PR3)-ANCA, presenting a unique subset. The pathogenesis of AAV is multifactorial, with the role of complement activation being highlighted during recent years. Treatment strategies for AAV in China have also been refined recently. A rapid tapering of glucocorticoids to minimize exposure has been recommended by the Chinese guidelines. Along with a better understanding of the disease, B cell-targeted therapy and complement-targeted therapy are developing. A considerable number of patients in China received rituximab treatment and achieved remission. However, infection risk and associated mortality still remain concerns. Therefore, less rituximab exposure should be considered and evaluated in Chinese AAV patients. Prognostic factors have been reviewed. Of note, along with improved outcomes, there is an increase of cardiovascular and malignant-related death, warranting specific care. Recently, a modified renal risk score model has been validated for early risk prediction in Chinese AAV patients. Moreover, emerging biomarkers for AAV, including complement components, have been identified in Chinese patients. Key Messages: There is a preponderance of MPA and MPO-ANCA in China. Treatment strategies for Chinese AAV patients generally align with those in western countries, and to some extent, less aggressive. Prognostic factors and emerging biomarkers for AAV in China have been identified. Further challenges include optimizing interventions, minimizing treatment-related comorbidities, improving disease monitoring, and enhancing life qualities of AAV patients.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by the presence of proteinase‑3 (PR3) or myeloperoxidase (MPO) ANCA. In over 90% of cases, PR3‑ANCA is associated with granulomatosis with polyangiitis (GPA). However, it is also rarely found in microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). On the other hand, MPO‑ANCA being characteristic of MPA (>90% of cases), is also found in about 40% of EGPA and 5% of GPA patients. On the ground of this overlap, clinical importance of ANCA specificity identification has been questioned. In this study, we analyzed the clinical and demographic characteristics of AAV subgroups identified by ANCA serotype. We conducted a multicenter study of AAV patients (417 GPA, 106 MPA, 102 EGPA; diagnosed between 1990 and 2016), included in the POLVAS registry. The data were systematically collected according to a standardized protocol. In the ANCA-positive group (anti‑MPO, anti‑PR3) a male-to-female ratio was 1:1, whereas in the ANCA-negative group it was 1:2, regardless of AAV diagnosis. Anti‑MPO antibodies were present in significantly older patients. Patients with MPO+GPA and MPO+EGPA were older than those with corresponding ANCA‑negative GPA and EGPA as well as PR3+AAV. Moreover, ANCA‑negative AAV was characterized by a low risk of end‑stage kidney disease and death. The presence and specificity of ANCA in AAV patients are related to sex and age, determine their organ involvement and influence mortality as previously shown. Patients with MPO‑ANCA-positive AAV constitute a clinically homogeneous group, whereas PR3‑ANCA-positive patients are much more clinically heterogeneous. ANCA-negative AAV patients are characterized by better prognosis. Thus, ANCA identification is an indispensable element and should not be omitted in establishing AAV diagnosis.

WITHDRAWN

Clinical questionsWhat is the role of plasma exchange and what is the optimal dose of glucocorticoids in the first 6 months of therapy of patients with antineutrophil cytoplasmic antibody (ANCA)-associated...

Introduction We summarize evidence for the role of therapeutic plasma exchange (TPE) in the treatment of anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). TPE rapidly removes ANCA IgG, complement and coagulation factors important in the pathogenesis of AAV. TPE has been used in patients with rapidly deteriorating renal function to achieve early disease control, allowing time for immunosuppressive agents to prevent resynthesis of ANCA. The PEXIVAS trial challenged the utility of TPE in AAV, as it did not show benefit of adjunctive TPE on a combined end point of end stage kidney disease (ESKD) and death. Areas covered We analyze data from PEXIVAS and other trials of TPE in AAV, an up-to-date meta-analysis, and recently published large cohort studies. Expert opinion There remains a role for the use of TPE in AAV in certain groups of patients, in particular those with severe renal involvement (Cr >500 μmol/L or dialysis-dependent). It should be considered in patients with Cr >300 μmol/L and rapidly deteriorating function, or with life-threatening pulmonary hemorrhage. A separate indication is patients double positive for anti-GBM antibodies and ANCA. TPE may have the greatest benefit as part of steroid-sparing immunosuppressive treatment strategies.

This study investigated whether the metabolic syndrome (MetS) severity (MSSS) at diagnosis could predict poor outcomes during follow-up in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients with MetS. The equation for the MSSS at diagnosis used in this study was developed and validated in Korean adults aged 20–59 years. The medical records of 261 patients with AAV were retrospectively reviewed, and finally, 36 AAV patients with MetS aged 20–59 years fulfilling the inclusion criteria were included in this study. All-cause mortality, relapse, end-stage kidney disease (ESKD), cerebrovascular accident, and cardiovascular disease were assessed as the poor outcomes of AAV. Their median age was 51.2 years and 36.1% were male. The MSSS was significantly correlated with age and serum albumin but not AAV-specific indices. Among the five poor outcomes, only ESKD showed a relatively significant area under the curve (area 0.696) in receiver operating characteristic curve analysis. In the multivariable Cox hazards model analysis, both serum creatinine (HR 3.033) and MSSS (HR = 2.221) were significantly associated with ESKD occurrence. When the cut-off of the MSSS for ESKD was set at 1.72, ESKD occurred more frequently in patients with MSSS ≥ 1.72 than in those with MSSS < 1.72 (75.0% versus 14.3%, p = 0.002). Furthermore, patients with MSSS ≥ 1.72 exhibited a significantly lower cumulative ESKD-free survival rate than those with MSSS < 1.72 (p = 0.001). MSSS at the time of AAV diagnosis independently predicted the occurrence of ESKD during follow-up in patients with AAV and MetS.

Objective: To retrospectively review the classification, clinical course, treatment response and investigated prognostic factors. of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods: Patients with positive ANCA that received treatment at the National Taiwan University Hospital (NTUH) between January 1, 2007 and March 31, 2013 were enrolled. The range of involved organs was based on medical records, images and laboratory data. The Birmingham vasculitis activity score (BVAS) was evaluated for each patient. The treatments, clinical outcome and disease recurrences were recorded for statistical analyses. Results: Nineteen myeloperoxidase (MPO)-ANCA-positive patients and seven proteinase 3 (PR3)-ANCApositive patients had newly diagnosed AAV during the study period. Microscopic polyangiitis (MPA) was the most common classification (42% overall). Kidneys and lungs were the most frequently involved organs, with an incidence rate of 73% and 69%, respectively. Moreover, 53% of patients with MPO-AAV had chronic kidney disease before diagnosis. In addition, the all-cause mortality rate in this study was 26% and infection was the most common cause of death. Of the six expired patients, 5 died due to infectious complications. The higher BVAS, Japanese vasculitis activity score (JVAS) for patients with renal vasculitis, or involvement of both lung and kidney, has the higher all-cause mortality. Conclusions: AAV is not common, but does cause considerable morbidity and mortality. MPO-AAV was more common than PR3-AAV in this study, and the majority of the diagnoses were MPA. Both BVAS and JVAS predicted survival outcome. Early diagnosis combined with adequate treatment, and measures to prevent, reduce or monitor infection, may help with overall survival.

AB0500 CLINICAL CHARACTERISTICS AND POTENTIAL BIOMARKERS FOR DISEASE ACTIVITY OF PATIENTS WITH ANCA ASSOCIATED VASCULITIS: A MONOCENTER STUDY IN CHINA