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

doi:10.1053/j.ajkd.2013.08.025

American Journal of Kidney Diseases

Volume 63, Issue 2, February 2014, Pages 227-235

https://doi.org/10.1053/j.ajkd.2013.08.025 Get rights and content

Background

A predictive histologic classification recently was proposed to determine the prognostic value of kidney biopsy in patients with antineutrophil cytoplasmic antibody–associated renal vasculitis (AAV).

Study Design

A dual-purpose retrospective observational cohort study to assess the reproducibility of the new classification and clinical variables that predict outcomes.

Setting & Participants

169 consecutive patients with AAV were identified; 145 were included in the reproducibility study, and 120, in the outcomes study.

Predictor

Kidney biopsy specimens were classified according to the predominant glomerular lesion: focal, mixed, crescentic, and sclerotic. An assessment of tubular atrophy also was performed.

Outcomes

The primary outcome was time to end-stage kidney disease or all-cause mortality, modeled using Cox regression analysis.

Measurements

Estimated glomerular filtration rate, requirement for renal replacement therapy.

Results

For the reproducibility study, the overall inter-rater reliability of the classification demonstrated variability among 3 histopathologists (intraclass correlation coefficient, 0.48; 95% CI, 0.38-0.57; κ statistic = 0.46). Although agreement was high in the sclerotic group (κ = 0.70), it was less consistent in other groups (κ = 0.51, κ = 0.47, and κ = 0.23 for crescentic, focal, and mixed, respectively). For the clinical outcomes study, patients with sclerotic patterns of glomerular injury displayed the worst outcomes. Patients with focal (HR, 0.26; 95% CI, 0.12-0.58; P = 0.001), crescentic (HR, 0.33; 95% CI, 0.16-0.69; P = 0.003), and mixed (HR, 0.39; 95% CI, 0.18-0.81; P = 0.01) patterns of injury had lower risk of the primary outcome. Tubular atrophy correlated with outcome, and advanced injury was associated with worse outcomes (HR, 5.9; 95% CI, 2.25-15.47; P < 0.001). Level of kidney function at presentation strongly predicted outcome (HR per 10-mL/min/1.73 m² increase in estimated glomerular filtration rate, 0.63; 95% CI, 0.46-0.81; P < 0.001).

Limitations

Data availability, given the retrospective nature of the study.

Conclusions

Reproducibility of the classification was seen only in patients with sclerotic patterns of glomerular injury. Sclerotic pattern of glomerular injury, advanced chronic interstitial injury, and decreased kidney function all predicted poor outcomes.

Section snippets

Setting and Participants

This single-center, retrospective, observational cohort study included all consecutive patients with AAV with renal involvement who underwent kidney biopsy at Monash Medical Center, Clayton, Victoria, Australia, between July 1, 1993, and October 31, 2011.

Patients were eligible for inclusion if they: (1) demonstrated positive ANCA serologic test results, (2) fulfilled the Chapel Hill Consensus Conference criteria for AAV, and (3) underwent kidney biopsy showing histology consistent with AAV at

Cohort Description

We identified 169 consecutive patients with positive ANCA serologic test results who underwent kidney biopsy within the study period (Fig 1). Of those, 13 were excluded from further analysis (4 had an additional histologic diagnosis and 9 had missing kidney biopsy specimens), leaving 156 patients for analysis. For the reproducibility study, 11 were further excluded because they were not scored by all 3 pathologists (scored by 2 pathologists due to logistic constraints). For the clinical

Discussion

The diagnostic value of the kidney biopsy in AAV is well established, although its usefulness in predicting renal survival or overall mortality is less clear, with conflicting results described. The AGN classification proposes a system based on glomerular injury to predict kidney disease outcomes, which could be extended to guide treatment algorithms. Using a large cohort of patients with AAV, we assessed the reproducibility of the AGN classification and successfully demonstrated that long-term

Acknowledgements

Support: This work was funded by the National Health and Medical Research Council in Australia (Dr Summers, grant 1024289; Dr Holdsworth, grant 1046585) and Monash Health (Dr Ford, Emerging Researcher Fellowship).

Financial Disclosure: The authors declare that they have no other relevant financial interests.

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Cited by (84)

Development of a Kidney Prognostic Score in a Japanese Cohort of Patients With Antineutrophil Cytoplasmic Autoantibody Vasculitis
2024, Kidney International Reports
Glomerulonephritis is frequent in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and crucial to disease outcomes. We conducted a detailed assessment of renal pathology in Japanese patients with AAV, and developed a new score that would predict renal outcome.
Two hundred twenty-one patients who were diagnosed with AAV and underwent a kidney biopsy were enrolled. Data on glomerular, tubular, interstitial, and vascular lesions from kidney biopsies were analyzed; the 3 established classification and prognostic scoring systems (Berden Classification, Mayo Clinic/RPS Chronicity Score [MCCS], and ANCA Renal Risk Score [ARRS]) were validated. Further, we developed a new prognostic score by including variables relevant for Japanese patients with ANCA-glomerulonephritis.
Median follow-up was 60 months (interquartile range: 6–60). End-stage kidney disease (ESKD) risk prediction by the MCCS and the ARRS was confirmed. Moreover, our analysis identified 4 items with significant ESKD risk prediction capacity, namely percentage of cellular, fibrocellular, and fibrous crescents; and sclerotic glomeruli. Based on our findings, we created a score evaluating the percentage of these lesions to total glomeruli, the Percentage of ANCA Crescentic Score (PACS). The area under the receiver operating characteristic (ROC) curve evaluating PACS was 0.783. The PACS had a comparable performance as the ARRS in predicting ESKD. The optimal PACS cut-off for ESKD risk over 60 months was 43%. In addition, the percentage of cellular crescents and presence of interstitial inflammation were independent predictors of kidney function recovery.
We developed a new score predicting renal prognosis using histopathological data of Japanese patients with ANCA-glomerulonephritis. Studies are needed to validate our results in international cohorts.
Outcomes in ANCA-Associated Vasculitis in Scotland: Validation of the Renal Risk Score in a Complete National Cohort
2023, Kidney International Reports
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) causes autoimmune-mediated inflammation of small blood vessels in multiple organs, including the kidneys. The ability to accurately predict kidney outcomes would enable a more personalized therapeutic approach.
We used our national renal biopsy registry to validate the ability of ANCA Renal Risk Score (ARRS) to predict end-stage kidney disease (ESKD) for individual patients. This score uses histopathological and biochemical data to stratify patients as high, medium, or low risk for developing ESKD.
A total of 288 patients were eligible for inclusion in the study (low risk n = 144, medium risk n = 122, high risk n = 12). Using adjusted Cox proportional hazard models with the low-risk group as reference, we show that outcome differs between the categories: high-risk hazard ratio (HR) 16.69 (2.91–95.81, P = 0.002); medium risk HR 4.14 (1.07–16.01, P = 0.039). Incremental multivariable-adjusted Cox proportional hazards models demonstrated that adding ARRS to a model adjusted for multiple clinical parameters enhanced predictive discrimination (basic model C-statistic 0.864 [95% CI 0.813–0.914], basic model plus ARRS C-statistic 0.877 [95% CI 0.823–0.931]; P <0.01).
The ARRS better discriminates risk of ESKD in AAV and offers clinicians more prognostic information than the use of standard biochemical and clinical measures alone. This is the first time the ARRS has been validated in a national cohort. The proportion of patients with high-risk scores is lower in our cohort compared to others and should be noted as a limitation of this study.
Histopathological prognostic factors in ANCA-associated glomerulonephritis.
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Citation Excerpt :
A recent study by our group confirmed the prognostic value of RRS and interestingly found that the performance in predicting ESKD was similar including or not IF/TA [81]. The IF/TA threshold is likewise not fully afreed: 25% was chosen for the RRS, while some authors proposed 20% and 50% [38], 30% [28], 30% and 60% [22]. All these thresholds were able to discriminate for renal survival.
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are a group of multisystemic autoimmune diseases characterized by necrotizing inflammation of small vessels. Kidney involvement is frequent in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), and accounts for a significant proportion of the morbidity and mortality related to these diseases.
Despite improvement in therapeutic management of ANCA-glomerulonephritis (ANCA-GN), end-stage kidney disease (ESKD) still occurs in up to 30% of affected patients within 5 years following diagnosis. Thus, identifying patients for whom aggressive immunosuppressive therapy will be more beneficial than deleterious is of great importance. Several clinical, biological and histological factors have been proposed as predictors of ESKD. The kidney biopsy is essential not only for the diagnosis, but also for evaluating renal prognosis.
In this review, we discuss the prognostic value of renal lesions at the diagnosis of ANCA-GN by analyzing each compartment of the nephron. We also review existing ESKD risk classification in ANCA-GN and finally propose an example of a standardized pathology report that could be used in routine practice.
Validation of a Histologic Scoring Index for C3 Glomerulopathy
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A previous study that evaluated associations of kidney biopsy findings with disease progression in patients with C3 glomerulopathy (C3G) proposed a prognostic histologic index (C3G-HI) that has not yet been validated. Our objective was to validate the performance of the C3G-HI in a new patient population.
Multicenter, retrospective cohort study.
111 patients fulfilling diagnostic criteria of C3G between January 1995 and December 2019, from 33 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases (GLOSEN).
Demographic, clinical parameters, C3G-HI total activity score, and the C3G-HI total chronicity score.
Time to kidney failure.
Intraclass correlation coefficients and κ statistic were used to summarize inter-rater reproducibility for assessment of histopathology in kidney biopsies. The nonlinear relationships of risk of kidney failure with the total activity score and total chronicity score were modeled using Cox proportional hazards analysis that incorporated cubic splines.
The study group included 93 patients with C3 glomerulonephritis and 18 with dense-deposit disease. Participants had an overall mean age of 35 ± 22 (SD) years. Forty-eight patients (43%) developed kidney failure after a mean follow-up of 65 ± 27 months. The overall inter-rater reproducibility was very good for the total activity score (intraclass correlation coefficient [ICC] = 0.63) and excellent for total chronicity score (ICC = 0.89). Baseline estimated glomerular filtration rate (eGFR), 24-hour proteinuria, and treatment with immunosuppression were the main determinants of kidney failure in a model with only clinical variables. Only tubular atrophy and interstitial fibrosis were identified as predictors in a model with histological variables. When the total activity score and total chronicity score were added to the model, only the latter was identified as an independent predictor of kidney failure.
Only a subset of the kidney biopsies was centrally reviewed. Residual confounding.
We validated the performance of C3G-HI as a predictor of kidney failure in patients with C3G. The total chronicity score was the principal histologic correlate of kidney failure.
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2021, Vascular Disease in Women: An Overview of the Literature and Treatment Recommendations
This chapter reviews the evolving pathologies and diagnostic paradigm related to vasculitis in large, medium, and small vessels of the body. We examine the role of autoimmunity and the disproportionate impact of many of these diseases on female patients. Underlying pathology and evidence for etiology, when known, are presented. Preferred evaluatory and diagnostic techniques are discussed to provide the framework for appropriate clinical assessment as well as currently available treatment modalities and ongoing investigation of future therapies.
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This chapter provides practical up-to-date information on common and uncommon neoplastic and non-neoplastic lesions of the ureter, urinary bladder and kidney, including glomerular, vascular and tubulointerstitial diseases. For each entity, pertinent details on clinical features, gross findings, histopathology, and diagnostic techniques are offered with particular emphasis on differential diagnosis.

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^†: Dr Summers died subsequent to the acceptance of this article.

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Original InvestigationPathogenesis and Treatment of Kidney DiseaseHistopathologic and Clinical Predictors of Kidney Outcomes in ANCA-Associated Vasculitis

Background

Study Design

Setting & Participants

Predictor

Outcomes

Measurements

Results

Limitations

Conclusions

Section snippets

Setting and Participants

Cohort Description

Discussion

Acknowledgements

Am J Kidney Dis

Am J Kidney Dis

Am Heart J

Kidney Int

Long-term patient survival in ANCA-associated vasculitis

Ann Rheum Dis

Histopathologic classification of ANCA-associated glomerulonephritis

J Am Soc Nephrol

A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies

N Engl J Med

Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis

J Am Soc Nephrol

Nomenclature of systemic vasculitides. Proposal of an international consensus conference

Arthritis Rheum

European therapeutic trials in ANCA-associated systemic vasculitis: disease scoring, consensus regimens and proposed clinical trials. European Community Study Group on Clinical Trials in Systemic Vasculitis ECSYSVASTRIAL

Clin Exp Immunol

The CARI guidelines. Induction and maintenance therapy in ANCA-associated systemic vasculitis

Nephrology (Carlton)

The role of flow cytometric ANCA detection in screening for acute pauci-immune crescentic glomerulonephritis

Nephrol Dial Transplant

Original Investigation
Pathogenesis and Treatment of Kidney Disease
Histopathologic and Clinical Predictors of Kidney Outcomes in ANCA-Associated Vasculitis