Monoclonal gammopathy in anti-neutrophil cytoplasmic antibodies-associated glomerulonephritis: prevalence, characteristics, and outcomes
Alice Desouche, Anne-Sophie Garnier, Jean-Philippe Coindre, Cécile Vigneau, Philippe Gatault, Vincent Javaugue, Charlotte Boud’hors, Nicolas Henry, Samuel Wacrenier, Assia Djema, Clément Samoreau, Giorgina Barbara Piccoli, Marie-Christine Copin, Emeline Vinatier, Benoit Brilland, Jean-François Augusto, , Céline Beauvillain, Maud Cousin, Anne Croué, Fanny Guibert, Lise-Marie PouteauABSTRACT
Background
Monoclonal gammopathy (MG) is common in older individuals and may influence autoimmune diseases. Its impact in anti-neutrophil cytoplasmic antibodies-associated glomerulonephritis (ANCA-GN) remains poorly evaluated.
Methods
We conducted a multicenter retrospective study including 332 patients with ANCA-GN from seven centers. MG was identified at diagnosis by serum electrophoresis and/or immunofixation. Clinical, laboratory, and histological characteristics were compared according to MG status. Outcomes including end-stage renal disease (ESRD), relapse, major adverse cardiovascular events (MACE), severe infections, cancer, and mortality were analyzed using Kaplan–Meier analysis and factors associated with outcomes were studied using univariable and multivariable Cox regression.
Results
Among 332 patients [median age 65 years (56–75), 59% males], MG was detected in 50 patients (15.1%). MG-positive patients tended to be older, were more frequently males, had more hypertension, and lower serum albumin levels, but similar renal function, Birmingham vasculitis activity score (BVAS), ANCA subtype, and histological findings compared with MG-negative patients. During a median follow-up of 57 months, MG was associated with reduced overall survival [hazard ratios (HR) 2.19, confidence interval (CI) 1.28–3.75, p = 0.004], an increased risk of severe infections (HR 1.76, CI 1.17–2.64, p = 0.007), and an increased risk of cancer (HR 2.07, CI 1.08–3.95, p = 0.028) in univariable analyses. However, after adjustment, MG was no longer an independent predictor of mortality, infection, or cancer, and was not associated with kidney-specific outcomes such as ESRD. No differences were observed for relapse, MACE, or progression to ESRD. Importantly, no patient developed multiple myeloma or related hematological malignancies during follow-up.
Conclusions
MG is frequent in patients with ANCA-GN, mainly reflecting age and comorbidity but does not independently influence renal survival, mortality, or progression to hematological malignancy. MG should be considered a coexisting condition rather than a disease modifier in ANCA-GN, although standardized follow-up remains warranted.