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Treatment of B-cell disorder improves renal outcome of patients with monoclonal gammopathy-associated C3 glomerulopathy

Sophie Chauvet, Véronique Frémeaux-Bacchi, Florent Petitprez, Alexandre Karras, Laurent Daniel, Stéphane Burtey, Gabriel Choukroun, Yahsou Delmas, Dominique Guerrot, Arnaud François, Moglie Le Quintrec, Vincent Javaugue, David Ribes, Laurence Vrigneaud, Bertrand Arnulf, Jean Michel Goujon, Pierre Ronco, Guy Touchard and Frank Bridoux

Key points

  • Monoclonal gammopathy is associated with C3 glomerulopathy

  • Specific treatment of the underlying B-cell clone improves renal survival

Abstract

The high frequency of monoclonal gammopathy in adult patients with C3 glomerulopathy (C3G) emphasizes the role of the 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 received or not 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%). Monoclonal gammopathy was of IgG type in 47 (94%) patients. Hematological diagnosis was MGRS 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 received various immunosuppressive drugs or symptomatic measures alone, respectively. Patients who achieved haematological response after chemotherapy had higher renal response rates (P=0.0001) and median renal survival (HR 0.22; 95% CI 0.05 to 0,92; p=0.009) 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, since rapid achievement of haematological response appears to result in improved renal survival.

  • Submitted August 31, 2016.
  • Accepted December 30, 2016.