Spectrum and Prognosis of Noninfectious Renal Mixed Cryoglobulinemic GN

Mohamad Zaidan (1) , Benjamin Terrier (2, 3) , Agnieszka Pozdzik (4, 5) , Thierry Frouget (6) , Nathalie Rioux-Leclercq (7) , Christian Combe (8, 9, 10) , Sébastien Lepreux (11) , Aurélie Hummel (1) , Laure-Hélène Nöel (12, 13) , Isabelle Marie (14) , Bruno Legallicier , Arnaud François (15) , Antoine Huart (16) , David Launay (17, 18, 19) , Gilles Kaplanski , Franck Bridoux (20) , Philippe Vanhille (21) , Raifah Makdassi , Jean-François Augusto (22) , Philippe Rouvier , Alexandre Karras (23) , Chantal Jouanneau (24) , Marie-Christine Verpont , Patrice Callard (25) , Fabrice Carrat (26, 27) , Olivier Hermine (28, 29, 30) , Jean-Marc Léger (31) , Xavier Mariette (32) , Patricia Senet (33) , David Saadoun (34, 35) , Pierre Ronco (36, 37, 24) , Isabelle Brochériou (24, 25) , Patrice Cacoub (34, 35) , Emmanuelle Plaisier (37, 24)

1 CHU Necker - Enfants Malades [AP-HP]
2 DHU - I2B - Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris]
3 Service de médecine interne et centre de référence des maladies rares [CHU Cochin]
4 Department of Nephrology - Dialysis and Renal Transplantation
5 Laboratory of Experimental Nephrology - Department of Biochimie
6 Service de néphrologie [Rennes]
7 IGDR - Institut de Génétique et Développement de Rennes
8 Service de Néphrologie-transplantation-dialyse [Bordeaux]
9 Centre de compétences des microangiopathies thrombotiques
10 Université Bordeaux Segalen - Bordeaux 2
11 CHU Bordeaux [Bordeaux]
12 UMR_S 845 - Centre de recherche Croissance et signalisation
13 Service d'anatomie pathologique [CHU Necker]
14 Service de Médecine Interne [CHU Rouen]
15 Service d'Anatomie et Cytologie Pathologique [CHU Rouen]
16 Service Médecine interne et immunopathologie clinique [CHU Toulouse]
17 EA 2686 - Laboratoire d'Immunologie
18 Inflammation: mécanismes et régulation et interactions avec la nutrition et les candidoses
19 Service de Médecine Interne et d'Immunologie clinique
20 Service de néphrologie - hémodialyse et transplantation rénale
21 Service de médecine interne et néphrologie
22 UA UFR Médecine - Université d'Angers - Faculté de médecine
23 Service de Néphrologie et Hémodialyse [CHU HEGP]
24 Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation
25 CHU Tenon [AP-HP]
26 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
27 CHU Saint-Antoine [AP-HP]
28 CEREMAST - Centre de référence des mastocytoses
29 Service d'Hématologie Adulte
30 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
31 CIMI - Centre d'Immunologie et de Maladies Infectieuses
32 Régulation de la réponse immune, infection VIH-1 et autoimmunité
33 Service de dermatologie et allergologie [CHU Tenon]
34 I3 - Immunologie - Immunopathologie - Immunothérapie
35 Service d'Immunologie [CHU Pitié-Salpétrière]
36 SU - Sorbonne Université
37 Service de Département de Néphrologie = Service de Néphrologie et Dialyses [CHU Tenon]

Noninfectious mixed cryoglobulinemic GN (MCGN) has been poorly investigated. We analyzed presentation and outcome of 80 patients with biopsy-proven MCGN, which were identified in the retrospective French CryoVas survey. MCGN was related to primary Sjögren's syndrome in 22.5% of patients and to lymphoproliferative disorders in 28.7% of patients, and was defined as essential in 48.8% of patients. At presentation, hematuria, proteinuria ≥1 g/d, hypertension, and renal failure were observed in 97.4%, 84.8%, 85.3%, and 82.3% of cases, respectively. Mean±eGFR was 39.5±20.4 ml/min per 1.73 m2. Membranoproliferative GN was the predominant histologic pattern, observed in 89.6% of cases. Renal interstitium inflammatory infiltrates were observed in 50% of cases. First-line treatment consisted of steroids alone (27.6%) or in association with rituximab (21.1%), alkylating agents (36.8%) or a combination of cyclophosphamide and rituximab (10.5%). After a mean follow-up of 49.9±45.5 months, 42.7% of patients relapsed with a renal flare in 75% of cases. At last follow-up, mean eGFR was 50.2±26.1 ml/min per 1.73 m2 with 9% of patients having reached ESRD; 59% and 50% of patients achieved complete clinical and renal remission, respectively. A rituximab+steroids regimen prevented relapses more effectively than steroids alone or a cyclophosphamide+steroids combination did, but was associated with a higher rate of early death when used as first-line therapy. Severe infections and new-onset B-cell lymphoma occurred in 29.1% and 8.9% of cases, respectively; 24% of patients died. In conclusion, noninfectious MCGN has a poor long-term outcome with severe infections as the main cause of death

Keywords: histopathology; membranoproliferative GN

Domains: Life Sciences [q-bio]

Mohamad Zaidan, Benjamin Terrier, Agnieszka Pozdzik, Thierry Frouget, Nathalie Rioux-Leclercq, et al.. Spectrum and Prognosis of Noninfectious Renal Mixed Cryoglobulinemic GN. Journal of the American Society of Nephrology, 2016, 27 (4), pp.1213--1224. ⟨10.1681/ASN.2015020114⟩. ⟨hal-01308003⟩