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

• Published in: American journal of kidney diseases Vol. 63; no. 2; pp. 227 - 235
• Main Authors: Ford, Sharon L., MBBS, Polkinghorne, Kevan R., PhD, MBChB, Longano, Anthony, MBBS, Dowling, John, MBBS, Dayan, Sukhpal, MBBS, Kerr, Peter G., PhD, MBBS, Holdsworth, Stephen R., PhD, MBBS, MD, Kitching, A. Richard, PhD, MBChB, Summers, Shaun A., PhD, MRCP, FRACP, MBBCh
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-02-2014; Elsevier
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - diagnosis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - pathology; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - therapy; Antineutrophil cytoplasmic antibody–associated vasculitis; Biological and medical sciences; Child; classification; clinical outcomes; Cohort Studies; Disease Progression; end-stage kidney disease; Female; Follow-Up Studies; Glomerulonephritis; Humans; interstitial injury; Kidney - metabolism; Kidney - pathology; kidney biopsy; Male; Medical sciences; Middle Aged; mortality; Nephrology; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Predictive Value of Tests; Retrospective Studies; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; sclerotic glomerular injury; Treatment Outcome; Young Adult; Antineutrophil cytoplasmic antibody–associated vasculitis; interstitial injury; clinical outcomes; kidney biopsy; end-stage kidney disease; sclerotic glomerular injury; mortality; glomerulonephritis; classification; Glomerulonephritis; Nephrology; Prognosis; Antineutrophil cytoplasmic antibody; Injury; Cardiovascular disease; Epidemiology; Kidney; Urology; Vascular disease; Histopathology; Vasculitis; Classification; Interstitial; Kidney disease; Urinary system disease; Mortality; Terminal stage; Anatomic pathology; Urinary system; Biopsy; Lesion; Predictive factor; Antineutrophil cytoplasmic antibody―associated vasculitis
• ISSN: 0272-6386; 1523-6838
• DOI: 10.1053/j.ajkd.2013.08.025

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.