Marta Calatroni1, Filippo Consonni2, Marco Allinovi3, Alessandra Bettiol4, Natasha Jawa5, Susanna Fiasella6, Dritan Curi6, Sarah Abu Rumeileh2, Leonardo Tomei2, Laura Fortunato6, Elena Gelain6, Davide Gianfreda7, Elena Oliva8, Guido Jeannin9, Chiara Salviani9, Giacomo Emmi4, Monica Bodria10, Renato A Sinico10, Gabriella Moroni11, Giuseppe A Ramirez12, Enrica Bozzolo12, Enrico Tombetti12, Sara Monti13, Claudia Bracaglia14, Giulia Marucci14, Serena Pastore15, Pasquale Esposito16, Maria G Catanoso17, Barbara Crapella18, Giovanni Montini18, Rosa Roperto19, Marco Materassi19, Giovanni M Rossi20, Salvatore Badalamenti1, Rae S M Yeung21, Paola Romagnani6,20, Gian M Ghiggeri10, Damien Noone5,22, Augusto Vaglio23,24. 1. Nephrology Unit, Humanitas Clinical and Research Center, Rozzano, Italy. 2. Department of Health Sciences, University of Florence, Florence, Italy. 3. Nephrology Unit, Careggi Hospital, Florence, Italy. 4. Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy. 5. Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada. 6. Nephrology and Dialysis Unit, Meyer Children's Hospital, Florence, Italy. 7. Nephrology Unit, Fondazione Panico Hospital, Tricase, Italy. 8. Nephrology Unit, Riuniti Hospital Marche, Ancona, Italy. 9. Nephrology Unit, Spedali Civili Hospital, Brescia, Italy. 10. Laboratory of Molecular Nephrology and Division of Nephrology and Transplantation, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Giannina Gaslini Institute, Genoa, Italy. 11. Nephrology Unit, University of Milano-Bicocca, Monza, Italy. 12. Nephrology Unit, IRCCS Ca 'Granda Foundation Maggiore Policlinico Hospital, Milan, Italy. 13. Unit of Immunology, Allergy, Rheumatology and Rare Disease, San Raffaele Hospital, Milan, Italy. 14. Department of Rheumatology, IRCCS Policlinico S. Matteo Foundation, University of Pavia, Pavia, Italy. 15. Division of Rheumatology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy. 16. Institute for Maternal and Child Health, IRCCS Burlo Garofolo Hospital, Trieste, Italy. 17. Unit of Nephrology, Dialysis and Transplantation, Department of Internal Medicine, University of Genoa and Ospedale Policlinico San Martino-IRCCS, Genoa, Italy. 18. Rheumatology Unit, IRCCS Reggio Emilia Hospital, Reggio Emilia, Italy. 19. Pediatric Nephrology, Dialysis and Transplant Unit, IRCCS Ca 'Granda Foundation Maggiore Policlinico Hospital, Milan, Italy. 20. Department of Biomedical, Experimental and Clinical Sciences "Mario Serio," University of Florence, Florence, Italy. 21. Nephrology Unit, Parma University Hospital, Parma, Italy. 22. Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada. 23. Nephrology and Dialysis Unit, Meyer Children's Hospital, Florence, Italy augusto.vaglio@unifi.it. 24. Pediatric Translational Research Chair, University of Toronto, Toronto, Ontario, Canada.
Abstract
BACKGROUND AND OBJECTIVES: ANCA-associated vasculitis is extremely rare in children. We report the clinicopathologic features, long-term outcomes, and prognostic factors of a large pediatric cohort of patients with ANCA-associated kidney vasculitis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective study included 85 consecutive patients with kidney biopsy specimen-proven ANCA-associated vasculitis from tertiary referral centers in Italy and Canada. Kidney biopsy specimens were categorized as focal, crescentic, sclerotic, or mixed, according to the Berden classification. The prognostic significance of baseline clinical, laboratory, and histologic findings was analyzed with respect to kidney failure or CKD stage 3-5/kidney failure. RESULTS: A total of 53 patients had microscopic polyangiitis (62%), and 32 had granulomatosis with polyangiitis (38%). Rapidly progressive GN was the most frequent presentation (39%); a third of the patients also had nephrotic-range proteinuria. Kidney biopsy specimens were classified as focal in 21% of the patients, crescentic in 51%, sclerotic in 15%, and mixed in 13%. Remission-induction therapies included cyclophosphamide in 78% of patients. A total of 25 patients (29%) reached kidney failure. The median (interquartile range) time to kidney failure or last follow-up was 35 (6-89) months in the whole cohort, and 73 (24-109) months among the patients who did not reach this outcome. Patients whose biopsy specimens showed sclerotic histology had significantly shorter kidney survival (hazard ratio, 11.80; 95% confidence interval, 2.49 to 55.99) and survival free of CKD stage 3-5 (hazard ratio, 8.88; 95% confidence interval, 2.43 to 32.48), as compared with those with focal/mixed histology. Baseline eGFR, low serum albumin, hypertension, central nervous system complications, and sclerotic histology, which reflected severe kidney involvement, were associated with both kidney failure and CKD stage 3-5/kidney failure at unadjusted analysis; no independent prognostic factors emerged at multivariable analysis. CONCLUSIONS: Children with ANCA-associated kidney vasculitis often have aggressive presentation; a third of such children progress to kidney failure and this usually occurs early during follow-up. A severe clinical presentation is associated with the development of CKD or kidney failure.
BACKGROUND AND OBJECTIVES: ANCA-associated vasculitis is extremely rare in children. We report the clinicopathologic features, long-term outcomes, and prognostic factors of a large pediatric cohort of patients with ANCA-associated kidney vasculitis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective study included 85 consecutive patients with kidney biopsy specimen-proven ANCA-associated vasculitis from tertiary referral centers in Italy and Canada. Kidney biopsy specimens were categorized as focal, crescentic, sclerotic, or mixed, according to the Berden classification. The prognostic significance of baseline clinical, laboratory, and histologic findings was analyzed with respect to kidney failure or CKD stage 3-5/kidney failure. RESULTS: A total of 53 patients had microscopic polyangiitis (62%), and 32 had granulomatosis with polyangiitis (38%). Rapidly progressive GN was the most frequent presentation (39%); a third of the patients also had nephrotic-range proteinuria. Kidney biopsy specimens were classified as focal in 21% of the patients, crescentic in 51%, sclerotic in 15%, and mixed in 13%. Remission-induction therapies included cyclophosphamide in 78% of patients. A total of 25 patients (29%) reached kidney failure. The median (interquartile range) time to kidney failure or last follow-up was 35 (6-89) months in the whole cohort, and 73 (24-109) months among the patients who did not reach this outcome. Patients whose biopsy specimens showed sclerotic histology had significantly shorter kidney survival (hazard ratio, 11.80; 95% confidence interval, 2.49 to 55.99) and survival free of CKD stage 3-5 (hazard ratio, 8.88; 95% confidence interval, 2.43 to 32.48), as compared with those with focal/mixed histology. Baseline eGFR, low serum albumin, hypertension, central nervous system complications, and sclerotic histology, which reflected severe kidney involvement, were associated with both kidney failure and CKD stage 3-5/kidney failure at unadjusted analysis; no independent prognostic factors emerged at multivariable analysis. CONCLUSIONS: Children with ANCA-associated kidney vasculitis often have aggressive presentation; a third of such children progress to kidney failure and this usually occurs early during follow-up. A severe clinical presentation is associated with the development of CKD or kidney failure.