BACKGROUND AND OBJECTIVES: The histopathologic classification for ANCA-associated GN distinguishes four classes on the basis of patterns of injury. In the original validation study, these classes were ordered by severity of kidney function loss as follows: focal, crescentic, mixed, and sclerotic. Subsequent validation studies disagreed on outcomes in the crescentic and mixed classes. This study, driven by the original investigators, provides several analyses in order to determine the current position of the histopathologic classification of ANCA-associated GN. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A validation study was performed with newly collected data from 145 patients from ten centers worldwide, including an analysis of interobserver agreement on the histopathologic evaluation of the kidney biopsies. This study also included a meta-analysis on previous validation studies and a validation of the recently proposed ANCA kidney risk score. RESULTS: The validation study showed that kidney failure at 10-year follow-up was significantly different between the histopathologic classes (P<0.001). Kidney failure at 10-year follow-up was 14% in the crescentic class versus 20% in the mixed class (P=0.98). In the meta-analysis, no significant difference in kidney failure was also observed when crescentic class was compared with mixed class (relative risk, 1.15; 95% confidence interval, 0.94 to 1.41). When we applied the ANCA kidney risk score to our cohort, kidney survival at 3 years was 100%, 96%, and 77% in the low-, medium-, and high-risk groups, respectively (P<0.001). These survival percentages are higher compared with the percentages in the original study. CONCLUSIONS: The crescentic and mixed classes seem to have a similar prognosis, also after adjusting for differences in patient populations, treatment, and interobserver agreement. However, at this stage, we are not inclined to merge the crescentic and mixed classes because the reported confidence intervals do not exclude important differences in prognosis and because an important histopathologic distinction would be lost.

Clinical Institute of Pathology Medical University of Vienna Vienna Austria

Department of Clinical Epidemiology Leiden University Medical Center Leiden The Netherlands

Department of Internal Medicine 4 Medical University Innsbruck Innsbruck Austria

Department of Internal Medicine National Referral Center for Rare Autoimmune and Systemic Diseases Hôpital Cochin Assistance Publique Hôpitaux de Paris Paris France

Department of Internal Medicine St Antoniusziekenhuis Nieuwegein The Netherlands

Department of Medical Statistics and Bioinformatics Leiden University Medical Center Leiden The Netherlands

Department of Nephrology 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Department of Nephrology Japan Community Healthcare Organization Sendai Hospital Sendai Japan

Department of Nephrology Leiden University Medical Center Leiden The Netherlands

Department of Nephrology Meander Medical Center Amersfoort The Netherlands

Department of Nephrology Rigshospitalet University of Copenhagen Copenhagen Denmark

Department of Nephrology Teine Keijinkai Hospital Sapporo Japan

Department of Pathology Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Pathology Leiden University Medical Center Leiden The Netherlands

Department of Pathology Necker Hospital René Descartes University Paris France

Department of Pathology The Jikei University School of Medicine Tokyo Japan

Department of Pathology Weill Cornell Medical College New York New York

Department of Rheumatology Leiden University Medical Center Leiden The Netherlands

Hokkaido Renal Pathology Center Sapporo Japan

Nephropathology Center San Gerardo Hospital Monza Italy

Pathology Laboratory Pathan Rotterdam The Netherlands

Clin J Am Soc Nephrol. 2020 Aug 7;15(8):1078-1080. doi: 10.2215/CJN.09600620. PubMed

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