A hemodialysis system includes (i) blood tubing; (ii) a peristaltic blood pump contacting the blood tubing to pump blood through the blood tubing; (iii) a dialyzer in fluid communication with the blood tubing; (iv) first and second peristaltic dialysate pumps; (v) a dialysate heater; (vi) a plurality of pinch valves; and (vii) a cassette including a rigid structure, a heating portion, first and second dialysate pumping tubes, and a plurality of incoming tubes, the rigid structure when the cassette is mounted for operation orienting (a) the heating portion adjacent to the dialysate heater so that dialysate can be heated by the dialysate heater, (b) the first and second dialysate pumping tubes adjacent to the first and second peristaltic dialysate pumps, and (c) the plurality of incoming tubes adjacent to the plurality of pinch valves to enable the tubes to be individually closed by the pinch valves.