Histologic and Clinical Factors Associated with Kidney Outcomes in IgA Vasculitis Nephritis
Authors: Barbour Sean J. , Coppo Rosanna , Er Lee , Pillebout Evangeline , Russo Maria Luisa , Alpers Charles E. , Fogo Agnes B. , Ferrario Franco , Jennette J. Charles , Roberts Ian S.D. , Cook H. Terence , Ding Jie , Su Baige , Zhong Xuhui , Fervenza Fernando C. , Zand Ladan , Peruzzi Licia , Lucchetti Laura , Katafuchi Ritsuko , Shima Yuko , Yoshikawa Norishige , Ichikawa Daisuke , Suzuki Yusuke , Murer Luisa , Wyatt Robert J. , Park Catherine , Nelson Raoul D. , Narus JoAnn H. , Wenderfer Scott , Geetha Duvuru , Daugas Eric , Monteiro Renato C. , Nakatani Shinya , Mastrangelo Antonio , Nuutinen Matti , Koskela Mikael , Weber Lutz T. , Hackl Agnes , Pohl Martin , Pecoraro Carmine , Tsuboi Nobuo , Yokoo Takashi , Takafumi Ito , Fujimoto Shouichi , Conti Giovanni , Santoro Domenico , Materassi Marco , Zhang Hong , Shi Sufang , Liu Zhi-Hong , Tesar Vladimir , Maixnerova Dita , Avila-Casado Carmen , Bajema Ingeborg , Barreca Antonella , Becker Jan U. , Comstock Jessica M. , Cornea Virgilius , Eldin Karen , Hernandez Loren Herrera , Hou Jean , Joh Kensuke , Lin Mercury , Messias Nidia , Muda Andrea Onetti , Pagni Fabio , Diomedi-Camassei Francesca , Tokola Heikki , D'Armiento Maria , Seidl Maximilian , Rosenberg Avi , Sannier Aurélie , Soares Maria Fernanda , Wang Suxia , Zeng Caihong , Haas Mark 
Published: January 2024

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.