Effect of hemodialysis and hemofiltration on plasma C.E.R.A. concentrations

C.E.R.A., a continuous erythropoietin receptor activator, is a long-acting erythropoiesis-stimulating agent approved for the treatment of anemia in patients with chronic kidney disease. Although the large molecular weight and the carbohydrate chain make it unlikely that C.E.R.A. could be removed during hemodialysis or hemofiltration, no such data have been published. In vitro studies were performed to assess the removal of C.E.R.A. during hemodialysis and hemofiltration, using both low-flux and high-flux membranes and parameters very similar to those used in clinical practice. Clinical pharmacokinetic studies of plasma C.E.R.A. concentrations in patients undergoing hemodialysis were also performed following subcutaneous injection of C.E.R.A. In the in vitro studies, plasma C.E.R.A. concentrations were not significantly different from baseline values in the primed blood reservoir over a 4-hour period during hemodialysis (P = 0.12). C.E.R.A. concentrations in the plasma obtained from the venous end of the hemofilter increased proportionally with the plasma total protein concentrations, reflecting the consequence of hemoconcentration and suggesting that C.E.R.A and plasma total proteins were retained by hemofiltration membranes to a similar degree. These in vitro studies showed that C.E.R.A. was not removed by simulated hemodialysis or hemofiltration either via transmembrane transport or adsorption to the membrane. The results were corroborated by the clinical pharmacokinetic data, which showed no detectable changes in plasma C.E.R.A. concentrations during hemodialysis using either low-flux or high-flux dialyzers. These results suggest that C.E.R.A. can be administered to patients at any time during hemodialysis or hemofiltration without appreciable loss in the extracorporeal circuit.