The invention provides a hemodialysis system comprising a dialyzer, a blood pump, a blood cassette (150) operatively connected to the dialyzer and the blood pump; a dialysate heater; first and second peristaltic dialysate pump actuators; and a dialysate cassette (10e) separate from the blood cassette (150), the dialysate cassette (10e) including a tubing organizer (168) configured to hold a drain line (24), a to-dialyzer line (152a) and a from-dialyzer line (152b), the dialysate cassette (10e) further including a first pumping tube (148), a second pumping tube (154) and an inline fluid heating pathway (42b), the dialysate cassette (10e) when mounted for operation orienting (i) the first pumping tube (148) for operation with the first peristaltic dialysate pump actuator, (ii) the second pumping tube (154) for operation with the second peristaltic dialysate pump actuator and (iii) the fluid heating pathway (42b) for operation with the dialysate heater.