Development of a Kidney Prognostic Score in a Japanese Cohort of Patients With Antineutrophil Cytoplasmic Autoantibody Vasculitis

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: ANCA-associated vasculitis; crescent; glomerulonephritis; outcome measure; renal pathology.

Graphical abstract

Figure 1

Kaplan-Meier curves show renal survival according to previously reported histopathologic classifications in 221 Japanese renal biopsy patients with AAV. (a) Kaplan-Meier curves show renal survival according to Berden classification. (b) Kaplan-Meier curves show renal survival according to the Mayo Clinic chronicity score. (c) Kaplan-Meier curves show renal survival according to ANCA renal risk score. Renal survival is defined as end-stage kidney disease (ESKD) and/or eGFR<15 ml/min per 1.73 m². Renal survival rates were calculated using the Kaplan-Meier method, and the rates between groups were compared by the log-rank test. P values < 0.05 were considered statistically significant. AAV, ANCA-associated vasculitis; ANCA, antineutrophil cytoplasmic antibody

Figure 2

Receiver operator characteristic curves for the PACS and ESKD risk over 60 months in 221 Japanese renal biopsy patients with AAV. The percentage of ANCA crescentic score (PACS) is the sum of the percentages of cellular crescents, fibrocellular crescents, fibrous crescents, and sclerotic glomeruli to total glomeruli. AAV, ANCA-associated vasculitis; ANCA, antineutrophil cytoplasmic antibody; ESKD, end-stage kidney disease; PACS, percentage of ANCA crescentic score.

Figure 3

Comparison of ROC curves of ESKD risk over 60 months between PACS and percentage of normal glomeruli in 221 Japanese renal biopsy patients with AAV. The area under the ROC curve was 0.783% (CI: 0.715–0.852) for PACS and 0.735% (CI: 0.662–0.808) for the percentage of normal glomeruli. There was no significant difference between PACS and the percentage of normal glomeruli (P = 0.09). The percentage of ANCA crescentic score (PACS) is the sum of the percentages of cellular crescents, fibrocellular crescents, fibrous crescents, and sclerotic glomeruli to total glomeruli. AAV, ANCA-associated vasculitis; ANCA, antineutrophil cytoplasmic antibody; CI, confidence interval; ESKD, end-stage kidney disease; PACS, percentage of ANCA crescentic score; ROC, receiver operator characteristic curves.

Figure 4

Comparison of ROC curves of ESKD risk over 60 months between PACS and previously reported outcomes in 221 Japanese renal biopsy patients with AAV. (a) Comparison of ROC curves of ESKD risk over 60 months for PACS between PACS and ARRS. (b) Comparison of ROC curves of ESKD risk over 60 months for PACS between PACS and MCCS. (c) Comparison of ROC curves of ESKD risk over 60 months for PACS between ARRS and MCCS. AUC was the best for ARRS 0.827 (95% CI: 0.765–0.889), second for PACS 0.783% (CI: 0.715–0.852), and worst for MCCS 0.694 (95% CI: 0.619–0.768). There was no significant difference between PACS and ARRS (P = 0.126) (Figure 4a). There were significant differences between PACS and MCCS (P = 0.013) (Figure 4b), ARRS and MCCS (P = 0.018) (Figure 4c). The percentage of ANCA crescentic score (PACS) is the sum of the percentages of cellular crescents, fibrocellular crescents, fibrous crescents, and sclerotic glomeruli to total glomeruli. AAV, ANCA-associated vasculitis; ANCA, antineutrophil cytoplasmic antibody; ARRS, ANCA renal risk score; AUC, area under the ROC curve; CI, confidence interval; ESKD, end-stage kidney disease; MCCA, Mayo Clinic/RPS chronicity score; PACS, percentage of ANCA crescentic score; ROC, receiver operator characteristic curves.