Monoclonal Gammopathy associates with Kidney Failure in ANCA-Associated Vasculitis

Abstract Background Up to 20% of patients with ANCA-associated vasculitis (AAV) and kidney involvement progress to end-stage kidney disease (ESKD) despite therapy. The role of monoclonal gammopathy (MG) in disease progression in patients with AAV is not well understood. Methods We conducted a retrospective study to identify patients diagnosed with AAV and renal involvement who had undergone monoclonal protein testing between November 1999 and December 2023. A total of 167 patients were included in the renal survival analysis and categorized into monoclonal positive (n=34) and monoclonal negative (n=133) groups. For the mortality analysis, we expanded the cohort to include an additional 26 patients who were dialysis-dependent at baseline and remained on dialysis throughout follow-up, resulting in a total of 193 patients. We performed multivariate Cox analysis to identify predictors of adverse renal events (40% decline in eGFR or ESKD eGFR 15 ml/min/1.73 m², need for dialysis, or transplantation) and mortality. Results Median age of the cohort was 68 58.5-74.5 years, with 50.8% males, 65.8% MPO positive, and 64.6% receiving rituximab as induction therapy. After adjusting for baseline proteinuria, sclerotic Berden class, and induction therapy, MG was associated with adverse renal events (HR 3.29 95% CI 1.12-9.68, p= 0.03). MG at baseline was not associated with mortality (HR: 1.65 0.87–3.12, p= 0.12), however, patients with persistent MG at 6 months had higher mortality compared to those without MG or those whose MG was not sustained (HR: 3.95 95%CI 1.10-14.21, p=0.035). Conclusions Patients with AAV and renal involvement who have MG are at significantly increased risk of adverse renal events even after adjusting for factors such as eGFR and degree of chronicity (known predictors of poor renal outcome). The exact mechanism by which MG portends poor outcomes is poorly understood, and additional research is required.