Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy.

BACKGROUND: B-cell anomalies play a role in the pathogenesis of membranous nephropathy. B-cell depletion with rituximab may therefore be noninferior to treatment with cyclosporine for inducing and maintaining a complete or partial remission of proteinuria in patients with this condition. METHODS: We randomly assigned patients who had membranous nephropathy, proteinuria of at least 5 g per 24 hours, and a quantified creatinine clearance of at least 40 ml per minute per 1.73 m2 of body-surface area and had been receiving angiotensin-system blockade for at least 3 months to receive intravenous rituximab (two infusions, 1000 mg each, administered 14 days apart; repeated at 6 months in case of partial response) or oral cyclosporine (starting at a dose of 3.5 mg per kilogram of body weight per day for 12 months). Patients were followed for 24 months. The primary outcome was a composite of complete or partial remission of proteinuria at 24 months. Laboratory variables and safety were also assessed. RESULTS: A total of 130 patients underwent randomization. At 12 months, 39 of 65 patients (60%) in the rituximab group and 34 of 65 (52%) in the cyclosporine group had a complete or partial remission (risk difference, 8 percentage points; 95% confidence interval [CI], -9 to 25; P = 0.004 for noninferiority). At 24 months, 39 patients (60%) in the rituximab group and 13 (20%) in the cyclosporine group had a complete or partial remission (risk difference, 40 percentage points; 95% CI, 25 to 55; P<0.001 for both noninferiority and superiority). Among patients in remission who tested positive for anti-phospholipase A2 receptor (PLA2R) antibodies, the decline in autoantibodies to anti-PLA2R was faster and of greater magnitude and duration in the rituximab group than in the cyclosporine group. Serious adverse events occurred in 11 patients (17%) in the rituximab group and in 20 (31%) in the cyclosporine group (P = 0.06). CONCLUSIONS: Rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria at 12 months and was superior in maintaining proteinuria remission up to 24 months. (Funded by Genentech and the Fulk Family Foundation; MENTOR ClinicalTrials.gov number, NCT01180036.).

Endoscopic repair of an injured internal carotid artery utilizing femoral endovascular closure devices.

OBJECTIVES/HYPOTHESIS: Injury to the internal carotid artery is a feared complication of endoscopic endonasal surgery of the skull base. Such an event, although rare, is associated with high morbidity and mortality. Even if bleeding is controlled, permanent neurological defects frequently persist. Many techniques have been developed to manage internal carotid artery rupture with varying degrees of success. The purpose of this study was to explore endoscopic management of arterial damage with endovascular closure devices used for a femoral arteriotomy. The ability to remotely suture a damaged artery permits the possible adaptation of this technology in managing endoscopic arterial complications. STUDY DESIGN: Technical note. METHODS: After the creation of an endoscopic endonasal corridor in a cadaveric specimen, an arteriotomy was created at the cavernous portion of the internal carotid artery. The Angio-Seal, StarClose, and MynxGrip vascular closure devices were utilized under endoscopic guidance to repair the arteriotomy. Angiography was then done on a cadaver sutured with the StarClose. RESULTS: Both the Angio-Seal and StarClose were deployed quickly and appeared to provide sufficient closure of the arteriotomy. The Angio-Seal required the use of a guidewire and was longer to deploy when compared with the StarClose. The StarClose deployment was quick and facile. The MynxGrip also deployed without difficulty. CONCLUSIONS: The Angio-Seal and StarClose systems were both successfully deployed utilizing an endoscopic endonasal approach. The MynxGrip was the easiest to deploy and has the greatest potential to be of benefit in this application. Further studies with hemodynamic models are required to properly assess the appropriateness in this setting. LEVEL OF EVIDENCE: NA.