title: Treatment of B-cell disorder improves renal outcome of patients with monoclonal gammopathy-associated C3 glomerulopathy.
abstract: The high frequency of monoclonal gammopathy in adult patients with C3 glomerulopathy (C3G) emphasizes the role of monoclonal immunoglobulin (MIg) in the occurrence of renal disease and raises the issue of the therapeutic management. The aim of the study was to evaluate the effect of chemotherapy in a large cohort of patients with MIg-associated C3G. Fifty adult patients with MIg and biopsy-proven C3G were extracted from the French national database of C3G. We retrospectively compared renal outcomes in patients who either received or did not receive chemotherapy targeting the underlying B-cell clone. At diagnosis, renal disease was severe, with nephrotic-range proteinuria in 20/46 (43%) patients and chronic kidney disease stage 3 or above in 42/49 (86%) patients. Monoclonal gammopathy was of IgG type in 47 (94%) patients. Hematological diagnosis was monoclonal gammopathy of renal significance in 30 (60%), multiple myeloma in 17 (34%), and chronic lymphocytic leukemia in 3 (6%) patients. Complement studies showed low C3 level in 22/50 (43%) and elevated soluble C5b-9 level in 27/34 (79%) patients. Twenty-nine patients received chemotherapy (including bortezomib in 22), whereas 8 and 13 patients received various immunosuppressive drugs or symptomatic measures alone, respectively. Patients who achieved hematological response after chemotherapy had higher renal response rates (P= .0001) and median renal survival (hazard ratio, 0.22; 95% confidence interval, 0.05-0.92;P= .009) than those receiving conservative/immunosuppressive therapy. In conclusion, our results suggest that chemotherapy adapted to the B-cell clone may constitute an efficient strategy for C3G in the setting of MIg, as rapid achievement of hematological response appears to result in improved renal survival.
authors.affiliation: Department of Nephrology, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.|INSERM Unité Mixte de Recherche 1138, "Complément et Maladies," Centre de Recherche des Cordeliers, Paris, France.|Université Paris Descartes Sorbonne Paris-Cité, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Chauvet
authors.affiliation: INSERM Unité Mixte de Recherche 1138, "Complément et Maladies," Centre de Recherche des Cordeliers, Paris, France.|Department of Immunology, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Frémeaux-Bacchi
authors.affiliation: INSERM Unité Mixte de Recherche 1138, "Cancer, Immune Control and Escape," Centre de Recherche des Cordeliers, Paris, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Petitprez
authors.affiliation: Department of Nephrology, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Karras
authors.affiliation: Department of Pathology, and.
authors.forename: Laurent
authors.initials: L
authors.lastname: Daniel
authors.affiliation: Department of Nephrology, Centre Hospitalier Universitaire La Conception, Marseille, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Burtey
authors.affiliation: Department of Nephrology, Centre Hospitalier Universitaire d'Amiens, Amiens, France.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Choukroun
authors.affiliation: Department of Nephrology, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
authors.forename: Yahsou
authors.initials: Y
authors.lastname: Delmas
authors.affiliation: Department of Nephrology, and.
authors.forename: Dominique
authors.initials: D
authors.lastname: Guerrot
authors.affiliation: Department of Pathology, Centre Hospitalier Universitaire de Rouen, Rouen, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: François
authors.affiliation: Department of Nephrology Hôpital de Foch, Surennes, France.
authors.forename: Moglie
authors.initials: M
authors.lastname: Le Quintrec
authors.affiliation: Department of Nephrology, Centre Hospitalier Universitaire de Poitiers, Poitiers, France.|Centre National de Référence maladies rares: amylose AL et autres maladies à dépôts d'immunoglobulines monoclonales, Université de Poitiers, Poitiers, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Javaugue
authors.affiliation: Department of Nephrology Centre Hospitalier Universitaire de Toulouse, Toulouse, France.
authors.forename: David
authors.initials: D
authors.lastname: Ribes
authors.affiliation: Department of Nephrology Hôpital de Valenciennes, Valenciennes, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Vrigneaud
authors.affiliation: Department of Immunology and Hematology, Hôpital Saint Louis, AP-HP, Paris, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Arnulf
authors.affiliation: Centre National de Référence maladies rares: amylose AL et autres maladies à dépôts d'immunoglobulines monoclonales, Université de Poitiers, Poitiers, France.|Department of Pathology, Centre Hospitalier Universitaire de Poitiers, Poitiers, France; and.
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Goujon
authors.affiliation: Department of Nephrology, Hôpital Tenon, AP-HP, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Ronco
authors.affiliation: Department of Nephrology, Centre Hospitalier Universitaire de Poitiers, Poitiers, France.|Centre National de Référence maladies rares: amylose AL et autres maladies à dépôts d'immunoglobulines monoclonales, Université de Poitiers, Poitiers, France.
authors.forename: Guy
authors.initials: G
authors.lastname: Touchard
authors.affiliation: Department of Nephrology, Centre Hospitalier Universitaire de Poitiers, Poitiers, France.|Centre National de Référence maladies rares: amylose AL et autres maladies à dépôts d'immunoglobulines monoclonales, Université de Poitiers, Poitiers, France.
authors.forename: Frank
authors.initials: F
authors.lastname: Bridoux
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000473:pathology*; D015331:Cohort Studies; D003176:Complement C3 / Q000032:analysis*; D016208:Databases, Factual; D004358:Drug Therapy / Q000379:methods; D005602:France; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy / Q000209:etiology*; D007678:Kidney Glomerulus / Q000473:pathology; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D010265:Paraproteinemias / Q000150:complications* / Q000188:drug therapy*; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003176:Complement C3