Nocturnal home hemodialysis (NHD) is associated with an increase in hemoglobin level. We hypothesized that NHD enhances the removal of toxins of hematopoietic progenitor cells (HPCs), thereby improving HPC growth and function. Among 16 patients with ESRD, 2 mo of NHD nearly doubled Kt/V per session and significantly lowered both parathyroid hormone levels and serum phosphate concentration. In addition, treatment with NHD improved hemoglobin levels from 113 +/- 3 to 125 +/- 4 g/L (P = 0.03) without altering erythropoietin requirements or iron status. To assess whether NHD may enhance removal of HPC toxins, we collected paired plasma samples from the same patient during treatment with conventional HD and NHD. In vitro, growth of erythroid (BFU-E) and granulocytic (CFU-GM) colonies was superior when cultured with NHD plasma compared with conventional HD plasma. Differential gene expression profiles obtained from peripheral blood and HPC colonies revealed similar upregulation of genes responsible for HPC mobilization and growth and production of red blood cells. In conclusion, the enhanced clearance by NHD is associated with an improvement in HPC growth and a coordinated increase in expression of genes relevant to production of red blood cells.