A microfluidic device comprising: a first layer defining an infusate channel, the infusate channel having a first pressure profile with a first slope along a length of the infusate channel; a second layer defining a blood channel in fluidic communication with the infusate channel, the blood channel having a second pressure profile with a second slope along a length of the blood channel; a filtrate layer defining a filtrate channel in fluidic communication with the blood channel, the filtrate channel having a third pressure profile with a third slope along a length of the filtrate channel; a first interchannel flow barrier separating the infusate channel and the blood channel, wherein the first interchannel flow barrier includes a plurality of openings defined through the first interchannel flow barrier, allowing passage of fluid from the infusate channel into the blood channel; a second interchannel flow barrier separating the filtrate channel and the blood channel; a first controllable flow control device configured to actively control the third slope of the third pressure profile along the length of the filtrate channel relative to the second slope of the second pressure profile along the length of the blood channel; a second controllable flow control device configured to actively control the first slope of the first pressure profile along the length of the infusate channel relative to the second slope of the second pressure profile along the length of the blood channel; an outflow pump configured to draw filtrate out of the filtrate channel; an influx pump configured to introduce fresh infusate into the infusate channel; and a control system configured to control the outflow pump, the influx pump and to modify a state of the first controllable flow control device and the second controllable flow control device such that the first slope of the first pressure profile along the length of the infusate channel corresponds to the third slope of the third pressure profile along the length of the filtrate channel. a first layer defining an infusate channel, the infusate channel having a first pressure profile with a first slope along a length of the infusate channel; a second layer defining a blood channel in fluidic communication with the infusate channel, the blood channel having a second pressure profile with a second slope along a length of the blood channel; a filtrate layer defining a filtrate channel in fluidic communication with the blood channel, the filtrate channel having a third pressure profile with a third slope along a length of the filtrate channel; a first interchannel flow barrier separating the infusate channel and the blood channel, wherein the first interchannel flow barrier includes a plurality of openings defined through the first interchannel flow barrier, allowing passage of fluid from the infusate channel into the blood channel; a second interchannel flow barrier separating the filtrate channel and the blood channel; a first controllable flow control device configured to actively control the third slope of the third pressure profile along the length of the filtrate channel relative to the second slope of the second pressure profile along the length of the blood channel; a second controllable flow control device configured to actively control the first slope of the first pressure profile along the length of the infusate channel relative to the second slope of the second pressure profile along the length of the blood channel; an outflow pump configured to draw filtrate out of the filtrate channel; an influx pump configured to introduce fresh infusate into the infusate channel; and a control system configured to control the outflow pump, the influx pump and to modify a state of the first controllable flow control device and the second controllable flow control device such that the first slope of the first pressure profile along the length of the infusate channel corresponds to the third slope of the third pressure profile along the length of the filtrate channel.