Apixaban in patients on haemodialysis: a single-dose pharmacokinetics study.

BACKGROUND: Apixaban, a direct oral anticoagulant inhibiting factor Xa, has been proven to reduce the risk of atrial fibrillation-related stroke and thromboembolism in patients with mild to moderate renal insufficiency. Patients on renal replacement therapy, however, were excluded from randomized controlled trials. Therefore, uncertainty remains concerning benefits, dosing and timing of intake in haemodialysis population. METHODS: We conducted a Phase II pharmacokinetics study in which 24 patients on maintenance haemodialysis were given a single dose (2.5 mg or 5 mg) of apixaban, either 30 min before or immediately after dialysis on the mid-week dialysis day. RESULTS: Apixaban 5 mg resulted in higher area under the curve (AUC0-48) in comparison with 2.5 mg, although significance could only be reached for dosing pre-dialysis (2.5 mg versus 5 mg, P = 0.008). In line, peak concentrations (Cmax) after dosing pre-dialysis were significantly higher in the 5 mg than in the 2.5 mg groups (P = 0.02). In addition, dialysis resulted in significant reduction of drug exposure. AUC0-48 pre-dialysis were on average 48% (2.5 mg) and 26% (5 mg) lower than the AUC0-48 post-dialysis, in line with Cmax. As a result, a dose of 2.5 mg post-dialysis and a dose of 5 mg pre-dialysis resulted in similar AUC0-48. In contrast, significant differences were found between the 5 mg group post-dialysis and the 2.5 mg group pre-dialysis (P = 0.02). CONCLUSIONS: Our data suggest that exposure to apixaban in patients on maintenance haemodialysis is dependent not only on drug dose but also on timing of intake relative to the haemodialysis procedure.

Multiple myeloma and kidney transplantation: the beginning of a new era.

The introduction of several novel therapeutic agents has improved the outcome in multiple myeloma (MM) patients including those with chronic kidney disease, and it is predicted that MM will become a curable disease in a substantial subset of MM patients. While in the past-because of inferior posttransplant outcomes-renal transplantation was not offered to MM patients, recent data suggest that renal transplantation is a viable treatment option in patients treated with modern anti-myeloma induction therapy followed by autologous stem cell transplantation achieving durable complete responses. The article of Shah, Ibrahim, Delaney et al. [Risk of relapse of multiple myeloma following kidney transplantation: a case series report. Clin Kidney J 2018 (in this issue)] in the current issue of Clinical Kidney Journal adds to this evidence and highlights the limitations and outstanding questions concerning renal transplantation in MM patients.