A hemodialysis system (180) comprising a dialyzer (20, 30); a blood circuit including a blood pump in fluid communication with the dialyzer (20, 30); a dialysate circuit including a dialysate circulation pump in fluid communication with the dialyzer, at least a portion of the dialysate circuit incorporated into a disposable dialysate cassette (100c), the dialysate circuit including a regeneration loop (220) comprising a sorbent cartridge (222) for cleaning used dialysate flowing from the dialyzer (20, 30); and a reservoir (14, 16, 18, 188, 612) holding an initial supply of dialysate, wherein the initial supply of dialysate is mixed from water and concentrate in the reservoir (14, 16, 18, 188, 612).