A dialysis system includes a dialysis machine having a pump actuator, a valve actuator and a sorbent device, and a disposable cassette including (i) a housing having a dialyzer inlet port, a dialyzer outlet port, a pump portion configured to operate with the pump actuator, a valve portion configured to operate with the valve actuator, a venous port, and an arterial port, (ii) at least one dialyzer in fluid communication with the housing, the at least one dialyzer including a dialysate inlet, and a dialysate outlet; (iii) an arterial line for connecting to a patient, the arterial line connected to and extending externally from the arterial port of the housing; (iv) a venous line for connecting to a patient, the venous line connected to and extending externally from the venous port of the housing; and (v) first and second dialysate fluid connections in fluid communication with the sorbent device.