Histopathologic and Clinical Predictors of Kidney Outcomes in ANCA-Associated Vasculitis

Ford, Sharon L.; Polkinghorne, Kevan R.; Longano, Anthony; Dowling, John P.; Dayan, Sukhpal; Kerr, Peter G.; Holdsworth, Stephen R.; Kitching, A. Richard; Summers, Shaun A.

doi:10.1053/j.ajkd.2013.08.025

Cited by 80 publications

(59 citation statements)

References 24 publications

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“…The most frequent renal histological class in our analysis was sclerotic, opposite to other single-center studies and multicentric clinical trials that have validated the histological classification, where sclerotic class was absent or very infrequent [7,22,24,25]. A study that analyzed the histopathological classification in 156 Australian patients reported 20 cases (17%) with sclerotic class, and concluded that the sclerotic patterns are the lesions more reliably identified by pathologists [26]. A possible explanation for the predominance of sclerotic class in our population is a delay in diagnosis or referral to specialized medical centers due to socioeconomic reasons.…”

Section: Discussioncontrasting

confidence: 94%

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis in Mexican Population: Clinical Phenotype, Autoantibody Profile and Renal Characteristics

Hinojosa‐Azaola¹,

Núñez‐Álvarez²,

Uriarte-Hernández³

et al. 2016

J Vasc

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Objective: To describe the clinical, serological characteristics, and renal histology in Mexican patients with antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). Methods:Forty patients with diagnosis of AAV and renal biopsy, followed at a tertiary care center in Mexico City from 2002-2012 were retrospectively studied. Demographics, comorbidities, clinical, laboratory variables, disease activity, mortality, renal variables and histological classes were analyzed. Additionally, 50 patients with AAV, and a control group (other systemic vasculitis, systemic lupus erythematosus, infections, healthy subjects) were studied transversally to assess the prevalence of specific antibodies (ANCA, MPO, PR3, cathepsin G, lysozyme, lactoferrin, BPI and elastase), and their association with clinical manifestations.Results: Granulomatosis with polyangiitis (GPA) was the predominant phenotype, and median age at diagnosis was 53 years. High disease activity (BVAS/GPA=24), general symptoms (98%), renal (80%), pulmonary (63%), and ear, nose and throat (ENT) (58%) involvement were frequent at diagnosis. Renal damage was present at diagnosis (serum creatinine 3.9 mg/dl, estimated glomerular filtration rate 16 ml/min, 24 hr proteinuria 2.5 g, 15% on dialysis). The most prevalent renal histological class was sclerotic (58%), followed by mixed (32%), focal (8%), and crescentic (2%). No significant differences were found between histological classes in comorbidities, clinical, renal and laboratory variables, or survival. The main ANCA immunofluorescence pattern was C-ANCA (68%), followed by X-ANCA (22%), and P-ANCA (18%). PR3-ANCA (high sensitive) was the most frequent antibody, positive in 86%, while positivity for MPO-ANCA was observed in 18%. ANCA positivity was more frequent in patients with AAV than the control group (p<0.001). Antibodies directed to minor targets were infrequent in patients with AAV (2%). No significant correlations were identified between autoantibodies and clinical manifestations. Conclusion:GPA phenotype, C-ANCA and PR3-ANCA positivity, high disease activity, chronic renal damage, general symptoms, ENT and lung involvement at diagnosis distinguish our population with AAV.

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Section: Discussioncontrasting

confidence: 94%

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis in Mexican Population: Clinical Phenotype, Autoantibody Profile and Renal Characteristics

Hinojosa‐Azaola¹,

Núñez‐Álvarez²,

Uriarte-Hernández³

et al. 2016

J Vasc

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“…Patients with sclerotic class GN have adverse prognosis with persistently elevated risk of ESRD or death in multiple cohorts [13,14,25]. The 1-and 5-year renal survival in validation studies have ranged from 29 to 52% and 29 to 75% [19,23,26].…”

Section: Discussionmentioning

confidence: 99%

Predictors of Renal Outcomes in Sclerotic Class Anti-Neutrophil Cytoplasmic Antibody Glomerulonephritis

et al. 2018

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Background: The prognostic value of the anti-neutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis (GN) classification has been demonstrated in several cohorts with sclerotic class having the worst renal outcome. Relevant published data on factors predicting outcomes in sclerotic ANCA GN is limited. Methods: Sclerotic ANCA GN patients were recruited from 5 centers worldwide for this retrospective cohort study. We describe the clinical characteristics of this cohort and evaluate predictors of 1-year glomerular filtration rate (GFR) and end-stage renal disease (ESRD). Kidney function at 12 months as measured by Modification of Diet in Renal Disease estimated GFR (eGFR) was modeled by simple and multiple linear regression analyses. We used Cox proportional hazards regression modeling to evaluate ESRD-free survival. Results: Of the 50 patients, 92% were Caucasian and 60% male with a mean age of 61 years. While 72% had renal limited disease, 82% were MPO ANCA positive. Kidney biopsies contained a median of 20 (interquartile range [IQR] 15–34) glomeruli with 96% showing moderate to severe interstitial fibrosis. Overall, 96% of patients received immunosuppressive drug therapy and 16% received plasmapheresis. Treatment response was achieved in all but 1 patient. The median (IQR) eGFR at entry was 14.5 (9–19) mL/min/1.73 m². Over a median (IQR) follow-up of 33.5 (17–82) months, 26 patients reached ESRD. Ten patients died with 6 of the deaths occurring within the first year of diagnosis. The hazard of progression to ESRD was significantly higher in those with lower GFR at study entry (p = 0.003) and with higher degree of tubular atrophy (p = 0.043). Conclusions: Renal recovery is rare among sclerotic ANCA GN patients requiring dialysis at entry and 12% of patients died in the first year. Entry GFR and tubular atrophy were significant predictors of GFR at 12 months and renal survival in patients with sclerotic class ANCA GN.

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“…Tubulointerstitial disease was graded by the extent of interstitial fibrosis and atrophy as Grade 1 (mild) or Grade 2 (severe). 43 Renal function was assessed by eGFR (ml/min per 1.73 m 2 ) assessed at the time of renal biopsy. Nine patients with thin basement membrane disease or adult minimal change GN were used as 'normal' controls.…”

Section: Discussionmentioning

confidence: 99%

Mast Cell Stabilization Ameliorates Autoimmune Anti-Myeloperoxidase Glomerulonephritis

Gan

O’Sullivan

Ooi

et al. 2015

JASN

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Observations in experimental murine myeloperoxidase (MPO)-ANCA-associated vasculitis (AAV) show mast cells degranulate, thus enhancing injury as well as producing immunomodulatory IL-10. Here we report that, compared with biopsy specimens from control patients, renal biopsy specimens from 44 patients with acute AAV had more mast cells in the interstitium, which correlated with the severity of tubulointerstitial injury. Furthermore, most of the mast cells were degranulated and spindle-shaped in patients with acute AAV, indicating an activated phenotype. We hypothesized that the mast cell stabilizer disodium cromoglycate would attenuate mast cell degranulation without affecting IL-10 production. We induced anti-MPO GN by immunizing mice with MPO and a low dose of anti-glomerular basement membrane antibody. When administered before or after induction of MPO autoimmunity in these mice, disodium cromoglycate attenuated mast cell degranulation, development of autoimmunity, and development of GN, without diminishing IL-10 production. In contrast, administration of disodium cromoglycate to mast cell-deficient mice had no effect on the development of MPO autoimmunity or GN. MPO-specific CD4 + effector T cell proliferation was enhanced by co-culture with mast cells, but in the presence of disodium cromoglycate, proliferation was inhibited and IL-10 production was enhanced. These results indicate that disodium cromoglycate blocks injurious mast cell degranulation specifically without affecting the immunomodulatory role of these cells. Thus as a therapeutic, disodium cromoglycate may substantially enhance the regulatory role of mast cells in MPO-AAV. 27: 132127: -133327: , 201627: . doi: 10.1681 Mast cells (MCs) are best characterized in pathology by their effector roles in IgE-dependent degranulation and by their release of pro-inflammatory mediators in allergy and anaphylaxis. 1 However, it is now recognized that MCs also play important roles in host defense and also in non-allergic inflammatory diseases, particularly those initiated by autoimmunity. The functional diversity of MC phenotypes allows for their participation in the generation of adaptive immune responses, playing either injurious or modulatory roles in many chronic human diseases and animal models of these diseases. 2 A functional role for MCs in a particular human disease can be suspected by confirming MC presence in diseased target organs and demonstrating a correlation between MC activation status and disease outcome. This potential cause and effect association can be strengthened by studies in relevant murine models of the particular diseases comparing disease patterns and outcomes between MC-deficient (Kit Wsh/Wsh ) mice and Kit Wsh/Wsh mice reconstituted with MCs. [2][3][4][5] The mechanistic basis of J Am Soc Nephrol

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Histopathologic and Clinical Predictors of Kidney Outcomes in ANCA-Associated Vasculitis

Cited by 80 publications

References 24 publications

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis in Mexican Population: Clinical Phenotype, Autoantibody Profile and Renal Characteristics

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis in Mexican Population: Clinical Phenotype, Autoantibody Profile and Renal Characteristics

Predictors of Renal Outcomes in Sclerotic Class Anti-Neutrophil Cytoplasmic Antibody Glomerulonephritis

Mast Cell Stabilization Ameliorates Autoimmune Anti-Myeloperoxidase Glomerulonephritis

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