An apparatus (100, 200, 300, 500) for controlling flow in a fluid circuit (121, 221, 321, 505), comprising: a treatment machine (114, 512, 550) with flow regulators (16, 104, 110, 115, 116, 128, 130, 142, 144, 145, 153, 154, 161, 170, 186, 302, 304, 306, 502, 504, 514, 540, 541, 542, 554, 556, 558, 562, 563, 571, 572, 578, 581, 583,) and sensors (14, 18, 102, 106, 108, 118, 119, 112, 166, 168, 171, 180, 182, 301, 312, 516, 549, 555, 552, 557, 559, 560, 564, 565, 566, 567, 568, 569, 570, 575, 576, 577, 579, 580), the flow regulators including pumping actuators (104, 110, 116, 128, 142, 144, 153, 154, 502, 504, 514, 540, 541, 542, 563); the treatment machine having a controller (140, 195, 240, 340) connected to control the flow regulators and receive signals from the sensors to implement a therapeutic treatment by regulating a flow of blood and treatment fluid when a predefined fluid circuit (121, 221, 321, 505) is connected in operative engagement with said flow regulators and sensors; where the predefined fluid circuit has a plurality of fluid lines (125, 127, 137, 138, 139, 143, 147, 149, 316, 318, 320, 536, 537, 585, 586, 591, 593, 594, 595) including first and second fluid lines (125, 127, 137, 139) and other (138, 143, 147, 149, 316, 318, 320, 536, 537, 585, 586, 591, 593, 594, 595) fluid lines all interconnected by the fluid circuit, each of the fluid lines being used to transport a fluid during a treatment mode in order to implement said therapeutic treatment; the flow regulators being controlled by said controller, during a synchronization mode thereof, to selectively block flow in first ones (137, 139, 125, 127) of said fluid lines while selectively pumping fluid serially through second ones (125, 127, 137, 139) of said fluid lines such that first and second pumping actuators (104, 110, 128, 153, 154, 563, 573, 574) pump fluid in a fixed volume channel that interconnects the second ones of said fluid lines, the fixed volume channel being sealed in part by said first ones of said fluid lines; the controller, during said synchronization mode, regulating relative speeds of the first and second pumping actuators responsively to at least one of the sensors to estimate commanded rates of said first and second pumping actuators corresponding to equal flows throughout said fixed volume channel and deriving one or more control parameters permitting said controller to implement a predefined ratio of flow rates by said first and second pumping actuators during a treatment mode of said controller; the flow regulators being controlled by said controller to, during the treatment mode, regulate a net flow through said second ones of said fluid lines by commanding the relative rates of the first pump actuator responsively to said one or more control parameters. a treatment machine (114, 512, 550) with flow regulators (16, 104, 110, 115, 116, 128, 130, 142, 144, 145, 153, 154, 161, 170, 186, 302, 304, 306, 502, 504, 514, 540, 541, 542, 554, 556, 558, 562, 563, 571, 572, 578, 581, 583,) and sensors (14, 18, 102, 106, 108, 118, 119, 112, 166, 168, 171, 180, 182, 301, 312, 516, 549, 555, 552, 557, 559, 560, 564, 565, 566, 567, 568, 569, 570, 575, 576, 577, 579, 580), the flow regulators including pumping actuators (104, 110, 116, 128, 142, 144, 153, 154, 502, 504, 514, 540, 541, 542, 563); the treatment machine having a controller (140, 195, 240, 340) connected to control the flow regulators and receive signals from the sensors to implement a therapeutic treatment by regulating a flow of blood and treatment fluid when a predefined fluid circuit (121, 221, 321, 505) is connected in operative engagement with said flow regulators and sensors; where the predefined fluid circuit has a plurality of fluid lines (125, 127, 137, 138, 139, 143, 147, 149, 316, 318, 320, 536, 537, 585, 586, 591, 593, 594, 595) including first and second fluid lines (125, 127, 137, 139) and other (138, 143, 147, 149, 316, 318, 320, 536, 537, 585, 586, 591, 593, 594, 595) fluid lines all interconnected by the fluid circuit, each of the fluid lines being used to transport a fluid during a treatment mode in order to implement said therapeutic treatment; the flow regulators being controlled by said controller, during a synchronization mode thereof, to selectively block flow in first ones (137, 139, 125, 127) of said fluid lines while selectively pumping fluid serially through second ones (125, 127, 137, 139) of said fluid lines such that first and second pumping actuators (104, 110, 128, 153, 154, 563, 573, 574) pump fluid in a fixed volume channel that interconnects the second ones of said fluid lines, the fixed volume channel being sealed in part by said first ones of said fluid lines; the controller, during said synchronization mode, regulating relative speeds of the first and second pumping actuators responsively to at least one of the sensors to estimate commanded rates of said first and second pumping actuators corresponding to equal flows throughout said fixed volume channel and deriving one or more control parameters permitting said controller to implement a predefined ratio of flow rates by said first and second pumping actuators during a treatment mode of said controller; the flow regulators being controlled by said controller to, during the treatment mode, regulate a net flow through said second ones of said fluid lines by commanding the relative rates of the first pump actuator responsively to said one or more control parameters.