Objective.To determine the incidence of arterial thrombotic events (ATE) and venous thromboembolism (VTE) in antineutrophil cytoplasmic antibody–associated vasculitis (AAV).Methods.This is a retrospective cohort study presenting the incidence of ATE (coronary events or ischemic stroke) and VTE [pulmonary embolism (PE) or deep venous thrombosis (DVT)] in patients diagnosed with AAV between 2005 and 2014.Results.There were 204 patients with AAV who were identified. Median followup for surviving patients was 5.8 (range 1–10) years, accounting for 1088 person-years (PY). The incidence of ATE was 2.67/100 PY (1.56 for coronary events and 1.10 for ischemic stroke) and for VTE was 1.47/100 PY (0.83 for DVT only and 0.64 for PE with/without DVT). On multivariate analysis, prior ischemic heart disease (IHD) and advancing age were the only independent predictors of ATE. Among patients without prior IHD or stroke, the incidence of ATE remained elevated at 2.32/100 PY (1.26 for coronary events and 1.06 for ischemic stroke). ATE, but not VTE, was an independent predictor of all-cause mortality. Event rates for both ATE and VTE were highest in the first year after diagnosis of AAV but remained above the population incidence during the 10-year followup period. In comparison to reported rates for the UK population, the event rates in our AAV patients were 15-times higher for coronary events, 11-times higher for incident stroke, and 20-times higher for VTE.Conclusion.Patients with AAV have a high incidence of arterial and venous thrombosis, particularly in the first year after diagnosis.

We thank Dr. Rothschild for his interest 1 in our article 2 on the incidence of arterial and venous thrombosis in antineutrophil cytoplasmic antibodyassociated vasculitis (AAV). He raises the interesting issue of susceptibility to both arterial and venous thrombotic events, which is also characteristic of antiphospholipid syndrome. The question arises as to the possible role of antiphospholipid antibodies (aPL) in the thrombotic events seen in AAV. We also thought that this possibility should be examined, but unfortunately our data on aPL are limited, because we studied a retrospective cohort in which these tests were not routinely performed. In fact, we tested for anticardiolipin IgG and IgM in only 49 of the 210 patients in the study. We found positive results in 3 patients, none of whom were in the group with thrombosis 2. In the patients who had a thrombosis, we found negative results in 4 out of the 24 who had an arterial thrombosis, and 5 out of 14 who had a venous thrombosis. These findings were not reported in the original paper because of the low proportion of patients tested and because they were tested only at baseline. It is possible that some patients may have developed aPL during the course of their disease, which could have gone undetected. Even in the absence of aPL, the high incidence of arterial and venous thrombosis in patients with AAV should encourage us to consider the relative benefits and risks of antiplatelet agents or anticoagulants, as discussed by Rothschild 1 .

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ABSTRACT:Positive B cell crossmatch accompanied by high levels of pre-transplant human leukocyte antigen donor-specific antibodies are associated with adverse graft outcomes in kidney transplant recipients. Targeting plasma cells, the main antibody producing cells, with the proteasome inhibitor bortezomib may be a promising desensitization strategy. We report using a combination of bortezomib and plasmapheresis to desensitize a highly sensitized kidney transplant recipient for an ABO-incompatible living donor kidney transplant. The flow cytometric B cell crossmatch was positive on presentation. After treatment, the anti-A titres fell from 1:64 to 1:4, and a negative B flow cytometric crossmatch was achieved prior to transplantation. The combined approach of bortezomib to abrogate antibody production at the plasma cell level, followed by plasmapheresis and low-dose intravenous immunoglobulin to remove in-circulation alloantibodies, has proven to be effective in our case. Bortezomib may play a role in highly sensitized renal transplants.Kidney transplantation is the optimal mode of renal replacement therapy, offering better quality of life and survival advantage compared with chronic dialysis.1,2 There is an increasing disparity between the growing demand for kidney allografts worldwide and available donors. ABO incompatibility and HLA sensitization are the two main barriers to achieving successful transplantation, especially among the highly sensitized population, particularly patients seeking a repeat kidney transplant. 3,4 Various integrated approaches to desensitization are currently available, such as plasmapheresis (PP), intravenous immunoglobulin (IVIg; low and high dose) with or without rituximab, and immunoadsorption (IA)-based regimens [5][6][7] . The optimal desensitization protocol remains unproven, and new agents continue to be explored. The proteasome inhibitor bortezomib presents as one such promising therapy. CASE REPORTA 36 year-old man from regional New South Wales with end-stage kidney disease secondary to reflux nephropathy received a first HLA-identical kidney transplant from his brother in 2007. Despite optimal compliance, suitable matching and good early function, he developed antibodymediated rejection at 1 year post-transplant and subsequent graft failure necessitating return to peritoneal dialysis in 2011. Six months later, he was transitioned to haemodialysis and graft nephrectomy performed.Following this, the prospect of an ABO-incompatible transplant from his wife (A1 to O blood group) was explored. Repeated flow B cytometric crossmatches were found to be positive without the presence of auto-antibodies or HLA donor-specific antibodies. The search for antibodies to non-HLA polymorphic antigens was initiated, and antiangiotensin ii type-1 receptor (AT1R) antibodies and antiendothelin receptor-A antibodies were found at a titre of 23.4 U/mL (<10.0 U/mL) and 30.3 U/mL (<10.0 U/mL), respectively. Desensitization protocol and immunosuppressionThe initial desensitization protocol consisted o...