A manifold comprising: a manifold body comprising a first transom comprising a first edge, and second and third edges (430, 432) substantially parallel to the first edge, a trunk substantially perpendicular to and adjacent the first transom, a second transom comprising a fourth edge, and fifth and sixth edges (436, 438) substantially parallel to the first, second, and third edges (428, 430, 432), the second transom being substantially perpendicular to and adjacent the trunk and substantially parallel to the first transom, a first external port and a second external port located on the fourth edge, a first intra-manifold port located on the second edge, a second intra-manifold port located on the second edge, a third intra-manifold port located on the fifth edge, and a fourth intra-manifold port located on the fifth edge; a first conduit in the second transom and in fluid communication with the second external port and the third intra-manifold port; a second conduit (490, 496) in the manifold body and in fluid communication with both the second intra-manifold port and the first external port; a first pump tube connected to and in fluid communication with the first and third intra-manifold ports; and a second pump tube connected to and in fluid communication with the second and fourth intra-manifold ports (442, 450); characterized in that the manifold further comprises: a first external tube connected to and in fluid communication with the first external port and comprising an external main segment, a first external branch segment, and a second external branch segment; and an external blood tube in fluid communication with and extending from the second external port, wherein the external main segment is connected to the first external port, the first external branch segment is connected to the external main segment and is configured to be connected to a dialyzer, the second external branch segment is connected to the external main segment and is in fluid communication with the external blood tube upstream of the first pump tube, and the entire manifold comprises disposable components. a manifold body comprising a first transom comprising a first edge, and second and third edges (430, 432) substantially parallel to the first edge, a trunk substantially perpendicular to and adjacent the first transom, a second transom comprising a fourth edge, and fifth and sixth edges (436, 438) substantially parallel to the first, second, and third edges (428, 430, 432), the second transom being substantially perpendicular to and adjacent the trunk and substantially parallel to the first transom, a first external port and a second external port located on the fourth edge, a first intra-manifold port located on the second edge, a second intra-manifold port located on the second edge, a third intra-manifold port located on the fifth edge, and a fourth intra-manifold port located on the fifth edge; a first transom comprising a first edge, and second and third edges (430, 432) substantially parallel to the first edge, a trunk substantially perpendicular to and adjacent the first transom, a second transom comprising a fourth edge, and fifth and sixth edges (436, 438) substantially parallel to the first, second, and third edges (428, 430, 432), the second transom being substantially perpendicular to and adjacent the trunk and substantially parallel to the first transom, a first external port and a second external port located on the fourth edge, a first intra-manifold port located on the second edge, a second intra-manifold port located on the second edge, a third intra-manifold port located on the fifth edge, and a fourth intra-manifold port located on the fifth edge; a first conduit in the second transom and in fluid communication with the second external port and the third intra-manifold port; a second conduit (490, 496) in the manifold body and in fluid communication with both the second intra-manifold port and the first external port; a first pump tube connected to and in fluid communication with the first and third intra-manifold ports; and a second pump tube connected to and in fluid communication with the second and fourth intra-manifold ports (442, 450); characterized in that the manifold further comprises: a first external tube connected to and in fluid communication with the first external port and comprising an external main segment, a first external branch segment, and a second external branch segment; and an external blood tube in fluid communication with and extending from the second external port, a first external tube connected to and in fluid communication with the first external port and comprising an external main segment, a first external branch segment, and a second external branch segment; and an external blood tube in fluid communication with and extending from the second external port, wherein the external main segment is connected to the first external port, the first external branch segment is connected to the external main segment and is configured to be connected to a dialyzer, the second external branch segment is connected to the external main segment and is in fluid communication with the external blood tube upstream of the first pump tube, and the entire manifold comprises disposable components.