A hemodialysis treatment system capable of operating in a priming mode and a treatment mode, the hemodialysis treatment system comprising a blood circuit (101, 620) and a dialysate circuit (102, 625), wherein a patient's blood is circulated in the blood circuit on a first side of a dialyzer membrane and a dialysate is circulated in the dialysate circuit on a second side of the dialyzer membrane, the hemodialysis treatment system comprising: a. a manifold (200, 902) that comprises: i. a plastic substrate comprising a first layer and a second layer; ii. a first flow path of the blood circuit (101, 620) and defined by a first surface of the first layer and a first surface of the second layer; iii. a second flow path of the dialysate circuit (102, 625) and defined by the first surface of the first layer and the first surface of the second layer; and iv. a valve in fluid communication with both the first flow path and the second flow path wherein the valve has first state and a second state and wherein, when in the first state, the first flow path and second flow path are in fluid isolation and when in the second state, the first flow path and second flow path, and the blood and dialysate circuits, are in fluid communication; b. housing defining a cavity capable of receiving the manifold; and c. a valve interface physically attached to the housing, wherein the valve interface is configured to transmit a signal to the valve to cause the valve to switch between the first state and the second state. a. a manifold (200, 902) that comprises: i. a plastic substrate comprising a first layer and a second layer; ii. a first flow path of the blood circuit (101, 620) and defined by a first surface of the first layer and a first surface of the second layer; iii. a second flow path of the dialysate circuit (102, 625) and defined by the first surface of the first layer and the first surface of the second layer; and iv. a valve in fluid communication with both the first flow path and the second flow path wherein the valve has first state and a second state and wherein, when in the first state, the first flow path and second flow path are in fluid isolation and when in the second state, the first flow path and second flow path, and the blood and dialysate circuits, are in fluid communication; i. a plastic substrate comprising a first layer and a second layer; ii. a first flow path of the blood circuit (101, 620) and defined by a first surface of the first layer and a first surface of the second layer; iii. a second flow path of the dialysate circuit (102, 625) and defined by the first surface of the first layer and the first surface of the second layer; and iv. a valve in fluid communication with both the first flow path and the second flow path wherein the valve has first state and a second state and wherein, when in the first state, the first flow path and second flow path are in fluid isolation and when in the second state, the first flow path and second flow path, and the blood and dialysate circuits, are in fluid communication; when in the first state, the first flow path and second flow path are in fluid isolation and when in the second state, the first flow path and second flow path, and the blood and dialysate circuits, are in fluid communication; b. housing defining a cavity capable of receiving the manifold; and c. a valve interface physically attached to the housing, wherein the valve interface is configured to transmit a signal to the valve to cause the valve to switch between the first state and the second state.