Atypical ANCA-Associated Vasculitis Relapse in ESKD

Introduction: Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV) are a group of autoimmune diseases affecting small-sized arteries. Despite treatment, many patients have progressive kidney disease. In patients with renal-limited AAV, relapse is rare once dialysis is started. We present a patient with a granulomatous with polyangiitis (GPA) flare four years after diagnosis and one year after starting peritoneal dialysis (PD). Case Description: A 73 year old male originally presented to the hospital with fatigue, elevated creatinine (3.0 mg/dl), microscopic hematuria (26-40 RBC) and non-nephrotic range proteinuria (800 mg/g). Work-up and kidney biopsy at that time were consistent with AAV. His induction treatment included intravenous (IV) cyclophosphamide for 6 months; and he continued prednisone as maintenance therapy, as he could not tolerate azathioprine. He continued to have mild hematuria and proteinuria, and progressed from chronic kidney disease stage 4 to ESRD three years later. He was started on PD; prednisone was stopped at that time. One year later, he presented with new onset hemoptysis for one week. Serology workup revealed elevated cytoplasmic-ANCA (1:4096), proteinase-3 antibody (4.5 units). Pulmonary hemorrhage was suggested on imaging and confirmed with bronchoscopy--all consistent with active AAV, despite no previous pulmonary involvement. Discussion: Relapse is recurrence of signs or symptoms of active vasculitis in any organ system after remission is achieved, not due to another cause. Residual proteinuria can reflect active vasculitis or previous, scarred areas in the glomeruli. Risks of continued immunosuppression may outweigh benefits on kidney function. In this case, the patient had only a partial response to his initial treatment, as signified by persistent hematuria, proteinuria, and progression of kidney disease over the next few years. With new symptoms of systemic vasculitis a year later, could he have benefited from continued immunosuppression? However, relapse of renal-limited AAV is rare after progression to ESRD. Uremic toxins are thought to cause a quiescene of the immune system. This “functional” immunosuppression reduces risk of autoimmune disease relapse as compared to those with normal renal function. This case illustrates the need to consider AAV relapse in ESRD patients with recurrent or new systemic symptoms.