Monoclonal Gammopathy in ANCA-Negative Pauci-immune Crescentic Glomerulonephritis: Is There an Association?

Background: In a small subset of patients with pauci-immune crescentic glomerulonephritis (PICGN), antinuclear cytoplasmic antibodies (ANCA) are not identified, and patients are referred to as having 'ANCA-negative' vasculitis. The cause of the disease in this subset of patients has remained elusive. We explored the role of monoclonal gammopathy (MG) in those with ANCA-negative PICGN.

Methods: We conducted a retrospective study and identified patients with PICGN who had undergone ANCA and monoclonal testing. Those positive for ANCA were excluded.

Results: We identified 14 patients with ANCA-negative vasculitis, of whom 8 (57%) tested positive for MG with a mean age of 60.3 ± 12.2 years, 75% female, and a mean serum creatinine of 4.3 ± 1.92 mg/dL. The most common monoclonal proteins were IgG (n=4, 50%) and Kappa (n=4, 50%). One patient had diagnosis of multiple myeloma. Most common extra-renal manifestations were skin rash (leukocytoclastic vasculitis (LCV)) and neuropathy. Kidney biopsy showed a higher degree of interstitial fibrosis and tubular atrophy compared to those without MG. The median follow-up time was 3.2 years, with 50% mortality in those with MG.

Conclusions: Over 50% of the patients with ANCA-negative PICGN have MG, and patients present with more evidence of fibrosis on kidney biopsy, with higher mortality rate observed in our cohort Monoclonal proteins may trigger development of PICGN their specific role in the pathogenesis of this disease needs further investigation.