Patients double-seropositive for ANCA and anti-GBM antibodies have varied renal survival, frequency of relapse, and outcomes compared to single-seropositive patients

Abstract

Co-presentation with both ANCA and anti-GBM antibodies is thought to be relatively rare. Current studies of such 'double-positive' cases report small numbers and variable outcomes. To study this further we retrospectively analyzed clinical features and long-term outcomes of a large cohort of 568 contemporary patients with ANCA-associated vasculitis, 41 patients with anti-GBM disease, and 37 double-positive patients with ANCA and anti-GBM disease from four European centers. Double-positive patients shared characteristics of ANCA-associated vasculitis (AAV), such as older age distribution and longer symptom duration before diagnosis, and features of anti-GBM disease, such as severe renal disease and high frequency of lung hemorrhage at presentation. Despite having more evidence of chronic injury on renal biopsy compared to patients with anti-GBM disease, double-positive patients had a greater tendency to recover from being dialysis-dependent after treatment and had intermediate long-term renal survival compared to the single-positive patients. However, overall patient survival was similar in all three groups. Predictors of poor patient survival included advanced age, severe renal failure, and lung hemorrhage at presentation. No single-positive anti-GBM patients experienced disease relapse, whereas approximately half of surviving patients with AAV and double-positive patients had recurrent disease during a median follow-up of 4.8 years. Thus, double-positive patients have a truly hybrid disease phenotype, requiring aggressive early treatment for anti-GBM disease, and careful long-term follow-up and consideration for maintenance immunosuppression for AAV. Since double-positivity appears common, further work is required to define the underlying mechanisms of this association and define optimum treatment strategies.

Keywords: Goodpasture syndrome; anti-GBM disease; anti–neutrophil cytoplasm antibody; glomerulonephritis; vasculitis.

Figure 1

Age distribution of patients with anti–glomerular basement membrane (GBM) disease, anti-neutrophil cytoplasm antibody–associated vasculitis (AAV), and double positive disease at presentation.

Figure 2

Transition to and from dialysis dependence in the first 3 months (mo) following treatment, in double-positive and single-positive anti–glomerular basement membrane disease cases. Censored for death in the first 3 months.

Figure 3

Unadjusted Kaplan–Meier survival functions describing long-term patient, renal, and relapse-free survival rates of the study cohort during 10 years’ follow-up. (a) Overall patient survival. (b) End-stage renal disease-free survival. (c) Relapse-free survival (censored for death). AAV, anti-neutrophil cytoplasm antibody–associated vasculitis; DP, double positive; ESRD, end-stage renal disease; GBM, glomerular basement membrane.

Figure 4

Cox proportional hazards regression curves describing long-term risk of (a) death, (b) end-stage renal disease (ESRD), and (c) death or ESRD. Measures being controlled for include diagnosis, age, requirement for renal replacement therapy at presentation, and presence of lung hemorrhage at presentation. AAV, anti-neutrophil cytoplasm antibody–associated vasculitis; DP, double positive; GBM, anti-glomerular basement membrane disease.