BACKGROUND: Nephritis is a common manifestation of IgA vasculitis and is morphologically indistinguishable from IgA nephropathy. While MEST-C scores are predictive of kidney outcomes in IgA nephropathy, their value in IgA vasculitis nephritis has not been investigated in large multiethnic cohorts. METHODS: Biopsies from 262 children and 99 adults with IgA vasculitis nephritis ( N =361) from 23 centers in North America, Europe, and Asia were independently scored by three pathologists. MEST-C scores were assessed for correlation with eGFR/proteinuria at biopsy. Because most patients ( N =309, 86%) received immunosuppression, risk factors for outcomes were evaluated in this group using latent class mixed models to identify classes of eGFR trajectories over a median follow-up of 2.7 years (interquartile range, 1.2-5.1). Clinical and histologic parameters associated with each class were determined using logistic regression. RESULTS: M, E, T, and C scores were correlated with either eGFR or proteinuria at biopsy. Two classes were identified by latent class mixed model, one with initial improvement in eGFR followed by a late decline (class 1, N =91) and another with stable eGFR (class 2, N =218). Class 1 was associated with a higher risk of an established kidney outcome (time to ≥30% decline in eGFR or kidney failure; hazard ratio, 5.84; 95% confidence interval, 2.37 to 14.4). Among MEST-C scores, only E1 was associated with class 1 by multivariable analysis. Other factors associated with class 1 were age 18 years and younger, male sex, lower eGFR at biopsy, and extrarenal noncutaneous disease. Fibrous crescents without active changes were associated with class 2. CONCLUSIONS: Kidney outcome in patients with biopsied IgA vasculitis nephritis treated with immunosuppression was determined by clinical risk factors and endocapillary hypercellularity (E1) and fibrous crescents, which are features that are not part of the International Study of Diseases of Children classification.

Bambino Gesù Children's Hospital IRCCS Rome Italy

BC Renal Vancouver British Columbia Canada

Centre for Research on Inflammation Bichat Hospital Inserm and Université Paris Cité Paris France

Clinical Research Center Takatsuki General Hospital Wakayam Medical University Takatsuki City Japan

Comitato Tecnico Scientifico per la Ricerca e Innovaziione A O Santobono Pausilipon Naples Italy

Department of Cellular Pathology Oxford University Hospitals NHS FT Oxford United Kingdom

Department of Children and Adolescents Oulu University Hospital Oulu Finland

Department of Laboratory Medicine and Pathology Mayo Clinic Rochester Minnesota

Department of Laboratory Medicine and Pathology University of Washington Medical Center Seattle Washington

Department of Medicine and Surgery IRCCS San Gerardo University Milan Bicocca Monza Italy

Department of Medicine Division of Nephrology Johns Hopkins University School of Medicine Baltimore Maryland

Department of Metabolism Endocrinology and Molecular Medicine Osaka Metropolitan University Graduate School of Medicine Osaka Japan

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

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

Department of Nephrology and Hypertension Jikei University School of Medicine Tokyo Japan

Department of Nephrology Juntendo University Faculty of Medicine Tokyo Japan

Department of Pathology and Laboratory Medicine Cedars Sinai Medical Center Los Angeles California

Department of Pathology and Laboratory Medicine University of North Carolina School of Medicine Chapel Hill North Carolina

Department of Pathology and Medical Biology University of Groningen Groningen The Netherlands

Department of Pathology AP HP Hôpital Bichat Université Paris Cité Paris France

Department of Pathology Johns Hopkins University School of Medicine Baltimore Maryland

Department of Pathology Mass General Brigham Salem Hospital Salem Massachusetts

Department of Pathology Microbiology and Immunology Vanderbilt University Medical Center Nashville Tennessee

Department of Pathology The Jikei University School of Medicine Tokyo Japan

Department of Pathology University of Kentucky Medical Center Lexington Kentucky

Department of Pathology University of Toronto Toronto Ontario Canada

Department of Pathology University of Utah Salt Lake City Utah

Department of Pathology Washington University in Saint Louis St Louis Missouri

Department of Pediatric Nephrology and Transplantation New Children's Hospital University of Helsinki and Helsinki University Hospital Helsinki Finland

Department of Pediatrics Peking University 1st Hospital Beijing China

Department of Pediatrics University of Tennessee Health Sciences Center Memphis Tennessee

Department of Pediatrics Wakayama Medical University Wakayama Japan

Division of Dialysis Department of Nephrology University of Miyazaki Hospital Miyazaki Japan

Division of Nephrology and Hypertension Department of Internal Medicine Jikei University School of Medicine Tokyo Japan

Division of Nephrology and Hypertension Department of Internal Medicine St Marianna University School of Medicine Kanagawa Japan

Division of Nephrology and Hypertension Mayo Clinic Rochester Minnesota

Division of Nephrology Bambino Gesù Children's Hospital IRCCS Rome Italy

Division of Nephrology University of British Columbia Vancouver British Columbia Canada

Division of Pediatric Nephrology Department of Pediatrics University of Utah Salt Lake City Utah

Division of Pediatric Nephrology University of British Columbia Vancouver British Columbia Canada

Fondazione Ricerca Molinette Regina Margherita Hospital Turin Italy

Imperial College London London United Kingdom

INSERM U1149 and Université Paris Cité Paris France

Institute of Pathology University Hospital of Cologne Cologne Germany

Kidney Center Department of Internal Medicine Nephrology Teikyo University School of Medicine Teikyo University Chiba Medical Center Chiba Japan

Kidney Division Department of Medicine Peking University 1st Hospital Peking University Institute of Nephrology Beijing China

Kidney Unit National Hospital Organization Fukuokahigashi Medical Center Fukuoka Japan

Laboratory of Electron Microscopy Pathological Center Peking University 1st Hospital Beijing China

Medical Center Department of General Pediatrics Adolescent Medicine and Neonatology Faculty of Medicine University of Freiburg Freiburg Germany

Medical Center University of Freiburg and Faculty of Medicine Institute for Surgical Pathology University of Freiburg Freiburg Germany

National Clinical Research Center of Kidney Diseases Jinling Hospital Nanjing University School of Medicine Nanjing China

Nephrology and Dialysis Unit AOU G Martino University of Messina Messina Italy

Nephrology and Dialysis Unit Meyer Children's Hospital Florence Italy

Nephrology Bichat Hospital AP HP Paris France

Nephrology Unit Saint Louis Hospital Paris France

Pathology Department Bambino Gesù Children's Hospital Rome Italy

Pathology Section Department of Public Health School of Medicine University of Naples Federico 2 Naples Italy

Pathology Unit Città della Salute e della Scienza di Torino University Hospital Turin Italy

Pathology University Oulu and Oulu University Hospital Oulu Finland

PEDEGO Research Unit Research Unit for Pediatrics Dermatology Clinical Genetics Obstetrics and Gynecology Medical Research Center Oulu Oulu Finland

Pediatric Nephrology and Rheumatology Unit AOU Policlinic G Martino University of Messina Messina Italy

Pediatric Nephrology Dialysis and Transplant Unit Department of Women's and Child's Health Azienda Ospedaliera University of Padova Padua Italy

Pediatric Nephrology Dialysis and Transplant Unit Fondazione IRCC Ca' Granda Ospedale Maggiore Policlinico Milan Italy

Pediatric Nephrology Faculty of Medicine and University Hospital Cologne Children's and Adolescents' Hospital University of Cologne Cologne Germany

Pediatric Nephrology Unit Regina Margherita Children's Hospital AOU Città della Salute della Scienza di Torino Turin Italy

Pediatrics Clinical Trials Office University of Utah Salt Lake City Utah

Renal Division Peking University 1st Hospital Beijing China

Texas Children's Hospital Houston Texas

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