Monoclonal gammopathy in ANCA-associated glomerulonephritis: prevalence, characteristics and outcomes.

BACKGROUND: Monoclonal gammopathy (MG) is common in older individuals and may influence autoimmune diseases. Its impact in ANCA-associated glomerulonephritis (ANCA-GN) remains poorly evaluated. METHODS: We conducted a multicenter retrospective study including 332 patients with ANCA-GN from 7 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 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, 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 (HR 2.19, 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, cardiovascular events (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.