Charles Ronsin1, Marie Georges2, Agnès Chapelet-Debout3, Jean-François Augusto4, Vincent Audard5, Ludivine Lebourg6, Sebastien Rubin7, Thomas Quemeneur8, Pierre Bataille9, Alexandre Karras10, Eric Daugas11, Dimitri Titeca-Beauport12, Jean-Jacques Boffa13, Cécile Vigneau14, Jean-Michel Halimi15, Corinne Isnard-Bagnis16, Sandrine Durault17, Eric Renaudineau18, Frank Bridoux19, Angelo Testa20, Moglie Le Quintrec21, Karine Renaudin22, Fadi Fakhouri23. 1. Department of Nephrology and Immunology, Center Hospitalier Universitaire de Nantes, Nantes, France. 2. Department of Pathology, Center Hospitalier Universitaire de Nantes, Nantes, France. 3. Department of Nephrology and Immunology, Center Hospitalier Universitaire de Nantes, Nantes, France; Centre de Recherche en Transplantation et en Immunologie, UMR 1064, INSERM, Université de Nantes, France. 4. Department of Nephology, CHU Angers, Angers, France. 5. Department of Nephrology and Renal Transplantation, Assistance Publique des Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, INSERM U955, Université Paris Est Créteil, Paris, France. 6. Department of Nephrology, CHU Rouen, Rouen, France. 7. Department of Nephrology, CHU Bordeaux, Bordeaux, France. 8. Department of Nephrology and Internal Medicine, Centre Hospitalier de Valenciennes, Valenciennes, France. 9. Department of Nephrology, Centre Hospitalier de Boulogne-sur-Mer, Boulogne sur Mer, France. 10. Department of Nephrology, Hôpital Européen Georges-Pompidou, Université Paris Descartes, Paris, France. 11. Department of Nephrology, CHU Bichat, Paris, France. 12. Department of Nephrology, CHU Amiens, Amiens, France. 13. Department of Nephrology, Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Paris, France. 14. Department of Nephrology, CHU Rennes, Rennes, France. 15. Department of Nephrology, CHU Tours, Tours, France. 16. Department of Nephrology, Groupe Hospitalier Universitaire Pitié-Salpêtrière, Paris, France. 17. Department of Nephrology, Centre Hospitalier de Saint Nazaire, Saint Nazaire, France. 18. Department of Nephrology, Centre Hospitalier de Saint Malo, Saint Malo, France. 19. Department of Nephrology, CHU Poitiers, Poitiers, France. 20. Centre ECHO, Site Confluent-Rezé, Nantes, France. 21. Department of Nephrology, CHU Montpellier, Montpellier, France. 22. Department of Pathology, Center Hospitalier Universitaire de Nantes, Nantes, France; Centre de Recherche en Transplantation et en Immunologie, UMR 1064, INSERM, Université de Nantes, France. Electronic address: karine.renaudin@chu-nantes.fr. 23. Department of Nephrology and Immunology, Center Hospitalier Universitaire de Nantes, Nantes, France; Centre de Recherche en Transplantation et en Immunologie, UMR 1064, INSERM, Université de Nantes, France. Electronic address: fadi.fakhouri@unil.ch.
Abstract
RATIONALE & OBJECTIVE: Pauci-immune necrotizing glomerulonephritis (PING) is usually associated with the presence of antineutrophil cytoplasmic antibodies (ANCA). However, a minority (2%-3%) of patients with PING do not have detectable ANCA. We assessed the clinical spectrum and outcome of patients with ANCA-negative PING. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 74 patients with ANCA-negative PING diagnosed in 19 French nephrology centers between August 2006 and December 2018 were included in the series. Patients' medical files were reviewed, and kidney biopsies were centrally reexamined by pathologists who were masked to the diagnosis. FINDINGS: Median age at diagnosis was 69 (IQR, 61-76) years. The clinical and pathological features were remarkable for a high frequency of extrarenal manifestations (54%), nephrotic syndrome (32%), and endocapillary hypercellularity (31%). Three main subtypes of ANCA-negative PING were observed: infection-associated (n=9[12%]), malignancy-associated (n=6[8%]), and primary (n=57[77%]). For patients with primary PING, induction treatment included mainly corticosteroids (n=56[98%]), cyclophosphamide (n=37[65%]), and rituximab (n=5[9%]). Maintenance treatment consisted mainly of corticosteroids (n=42[74%]), azathioprine (n=18[32%]), and mycophenolate mofetil (n=11[19%]). After a median follow-up period of 28 months, 28 (38%) patients had died and 20 (27%) developed kidney failure (estimated glomerular filtration rate<15mL/min/1.73m2). Eleven (21%) patients (9 with primary and 2 with malignancy-associated PING) relapsed. LIMITATIONS: Retrospective study and limited number of patients; electron microscopy was not performed to confirm the absence of glomerular immune deposits. CONCLUSIONS: Within the spectrum of ANCA-negative PING, infection and malignancy-associated forms represent a distinct clinical subset. This new clinical classification may inform the management of ANCA-negative PING, which remains a severe form of vasculitis with high morbidity and mortality rates despite immunosuppressive treatments.
RATIONALE & OBJECTIVE: Pauci-immune necrotizing glomerulonephritis (PING) is usually associated with the presence of antineutrophil cytoplasmic antibodies (ANCA). However, a minority (2%-3%) of patients with PING do not have detectable ANCA. We assessed the clinical spectrum and outcome of patients with ANCA-negative PING. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 74 patients with ANCA-negative PING diagnosed in 19 French nephrology centers between August 2006 and December 2018 were included in the series. Patients' medical files were reviewed, and kidney biopsies were centrally reexamined by pathologists who were masked to the diagnosis. FINDINGS: Median age at diagnosis was 69 (IQR, 61-76) years. The clinical and pathological features were remarkable for a high frequency of extrarenal manifestations (54%), nephrotic syndrome (32%), and endocapillary hypercellularity (31%). Three main subtypes of ANCA-negative PING were observed: infection-associated (n=9[12%]), malignancy-associated (n=6[8%]), and primary (n=57[77%]). For patients with primary PING, induction treatment included mainly corticosteroids (n=56[98%]), cyclophosphamide (n=37[65%]), and rituximab (n=5[9%]). Maintenance treatment consisted mainly of corticosteroids (n=42[74%]), azathioprine (n=18[32%]), and mycophenolate mofetil (n=11[19%]). After a median follow-up period of 28 months, 28 (38%) patients had died and 20 (27%) developed kidney failure (estimated glomerular filtration rate<15mL/min/1.73m2). Eleven (21%) patients (9 with primary and 2 with malignancy-associated PING) relapsed. LIMITATIONS: Retrospective study and limited number of patients; electron microscopy was not performed to confirm the absence of glomerular immune deposits. CONCLUSIONS: Within the spectrum of ANCA-negative PING, infection and malignancy-associated forms represent a distinct clinical subset. This new clinical classification may inform the management of ANCA-negative PING, which remains a severe form of vasculitis with high morbidity and mortality rates despite immunosuppressive treatments.