Outcome of Renal Transplantation in Patients With Both ANCA and Anti-GBM Antibodies (2012)

Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) and anti–glomerular basement membrane (anti-GBM) antibody disease, common causes of end-stage renal disease (ESRD) are both characterized by the presence of circulating autoantibodies. A subset of patients have serologic evidence of both antibodies, also called “double-positive” disease. Patients with double-positive disease present often with multisystem disease like in AAV but have a much worse renal prognosis than AAV (1). The outcome of renal transplantation in these double-positive patients is not known. We report for the first time the results of renal transplantation in six patients with double-positive disease. We reviewed records of all patients followed in the Vasculitis and Transplant Clinics at the Johns Hopkins Hospital, Baltimore, MD, between 1999 and 2011. Patients with a diagnosis of double-positive disease as a cause of ESRD were selected, and the following data were extracted: demographics, ANCA and anti-GBM serologies, pretransplantation immunosuppressive regimen, time on dialysis, type of transplant, posttransplantation immunosuppressive regimen, episodes of vasculitis relapse defined clinically by Birmingham vasculitis assessment/Wegener granulomatosis score of more than 1 or by tissue biopsy, episodes of rejection, and serum creatinine level at 12 months, 24 months, and at last follow-up after transplantation. We summarize descriptive data as median and range. The study protocol was approved by the institutional review board. A total of 10 patients were identified to have double-positive disease as a cause of ESRD. Six of these patients received a renal transplant between 1999 and 2011. Detailed follow-up data is available for these six patients, representing 406 patient-months of observation. The median follow-up was 66.5 months. This patient cohort included four women and two men. There were 4 whites, 1 Native American, and 1 Asian of Middle Eastern decent. All patients received dialysis before transplantation, with a median duration on dialysis of 24 months. The median age at transplant was 63 years, with 50% patients receiving live-donor renal transplantation. At the time of initial diagnosis, five of the six patients were c-ANCA/PR3 positive, one patient was p-ANCA/MPO positive, and all were anti-GBM positive. At the time of transplant, all patients were anti-GBM antibody negative; one patient was ANCA positive and remaining were ANCA negative. Four of the six patients received antibody induction therapy with antithymocyte globulin. None of the patients experienced delayed graft function. All patients were maintained on maintenance immunosuppression with mycophenolate mofetil, prednisone, and tacrolimus. There were no episodes of allograft rejection. There were no episodes of vasculitis relapse after transplantation clinically. Four of the six patients were tested routinely for ANCA and anti-GBM antibody after transplantation. The anti-GBM antibody remained negative in all four patients at 1 year after transplantation. One patient who was ANCA positive at the time of transplant remained ANCA positive after transplantation and the remaining three were ANCA negative after transplantation. One patient developed BK viremia, and there was one patient with BK viruria after transplantation. The median serum creatinine level was 1.0 mg/dL at 12 months, 0.9 mg/dL at 24 months, and 1.05 mg/dL at last follow-up. Table 1 summarizes posttransplantation outcomes for all patients.TABLE 1: Posttransplantation outcomesThe prevalence of double-positive disease is 5% to 15% in patients with AAV (1–4) and 20% to 40% in patients with anti-GBM disease (2, 5). The relationship between the ANCA and anti-GBM antibody in these patients is not known, but at least in some patients, ANCA has been shown to precede development of anti-GBM antibody (6). Clinically, some of these patients have multisystem presentation similar to vasculitis. The renal prognosis of these patients is poor. Our report shows favorable prognosis of our six patients that have undergone renal transplantation. The two major types of AAV, granulomatosis with polyangiitis and microscopic polyangiitis are the commonest cause of rapidly progressive renal failure. Renal transplantation for ESRD caused by AAV is safe with very low vasculitis relapse rates after transplantation with the currently used modern immunosuppressive agents (7). Anti-GBM antibody disease may progress to ESRD, requiring transplantation. Recurrent anti-GBM antibody disease in the renal allograft is rare and is believed to be because of delay in transplantation until the disease has been quiescent and the antibody has been undetectable for 12 months (8–10). Our six patients with double-positive disease showed immediate graft function after transplantation. All were treated with mycophenolate mofetil, prednisone, and tacrolimus with four of six receiving antibody induction therapy. There were no episodes of allograft rejection and no episodes of vasculitis relapse. Two patients developed BK virus replication, one in urine and one in plasma. There was no graft loss at a median follow-up of 66.5 months. We conclude that renal transplantation is a safe and effective for patients with double-positive disease. The modern immunosuppressive drugs are effective in preventing vasculitis relapses. Gaurav Raman 1 Amar Srivastava2 Duvuru Geetha1 1 Division of Nephrology Department of Medicine Johns Hopkins University Baltimore, MD 2 Johns Hopkins University School of Medicine Baltimore, MD