Method and apparatus for measuring ultrafiltration rate in renal replacement therapy devices - Patents.com

Abstract

A system for determining an ultrafiltration rate of a renal replacement therapy device is provided. The system includes a controller connected to a first flow sensor that acquires flow data from a blood withdrawal line and a second flow sensor that acquires flow data from a blood inflow line. The controller calibrates (e.g., matches) the first and second flow sensors based on flow values ​​measured during a period in which the renal replacement therapy device is performing ultrafiltration at a known ultrafiltration rate. The controller is further configured to periodically equalize the flow sensors with the ultrafiltration rate set to the known ultrafiltration rate during the treatment period. The controller can use the flow data from the calibrated or equalized first and second flow sensors to measure blood flow to and from the renal replacement therapy device and calculate the ultrafiltration rate of the renal replacement therapy device based thereon. The calibration can be performed before, during, or after blood treatment during the treatment period.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] Not applicable.

[0002] STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT Not applicable.

[0003] Names of parties to the joint research agreement Not applicable.

[0004] Sequence Listing Reference Not applicable.

[0005] Statement of Prior Disclosure by Inventor or Co-Inventors Not applicable. [Technical field]

[0006] The present disclosure relates to an apparatus and method for determining the ultrafiltration rate of a renal replacement therapy device with greater accuracy based on blood flow measured in the drainage line to the renal replacement therapy device and blood flow measured in the inlet line from the renal replacement therapy device. [Background technology]

[0007] There are many different medical procedures that involve the delivery of fluids to, through, or from a patient, or any combination thereof, such as those that involve pumping blood between an extracorporeal system and a patient. For example, hemodialysis, hemofiltration, and hemodiafiltration are all renal replacement therapies that remove waste, toxins, and excess water from the blood by connecting the patient to an extracorporeal system that has a treatment or renal replacement therapy device and pumping blood through the extracorporeal system and the device, which removes waste, toxins, and fluids from the blood and returns the cleaned blood to the patient.

[0008] In dialysis, blood is taken from the body and sent to a dialyzer via an extracorporeal system. The blood enters the dialyzer from the blood inlet port, passes through the hollow fiber membrane, exits the dialyzer from the outlet port, and returns to the patient. At the same time, dialysate is supplied into the housing from the dialysate inlet / outlet ports so that it fills the gaps between the hollow fiber membranes. Material exchange occurs between the blood and the dialysate via the hollow fiber membranes.

[0009] To replace the kidneys in regulating the amount of fluid in the body, dialysis uses a dialyzer to remove fluid and expel excess water from the body. The process of removing fluid involves controlling the flow of dialysate so that the amount of dialysate out is greater than the amount of dialysate in, creating negative pressure within the housing and extracting water from the blood through a semipermeable membrane into the dialysate (i.e., by ultrafiltration).

[0010] The fluid withdrawal performed in the dialyzer is also called ultrafiltration, and is given by the difference between the used dialysate discharged from the dialyzer by pumping and the unused dialysate pumped into the dialyzer by pumping. Since a large amount of dialysate comes into contact with the membrane in the dialyzer during dialysis therapy, ultrafiltration must be controlled accurately. For example, in hemodialysis, about 200 liters of dialysate usually pass through the dialyzer in one treatment. On the other hand, the target amount of ultrafiltrate in one treatment is usually about 2 to 3 liters, and the maximum deviation from this target may need to be controlled to the order of only 0.1 to 0.2 liters. Therefore, in this example, it is considered that ultrafiltration needs to be controlled with a maximum error of about 1:1000 with respect to the total flow rate of the dialysate.

[0011] Currently, to measure ultrafiltration accurately as a standard, expensive equipment must be installed on the hemodialysis machine. For example, in existing systems, two measuring devices are installed before and after the dialysate side of the dialyzer. However, these existing systems are relatively complex and prone to operator error. Summary of the Invention

[0012] The present disclosure addresses a problem currently present in blood flow measurement systems equipped with flow sensors for measuring ultrafiltration, where the error in the measurements obtained from the flow sensors far exceeds the accuracy required for measurements determining fluid removal performed by a renal replacement therapy device.

[0013] For example, current ultrasonic transit time sensor manufacturers' specifications state that the blood flow measurement error "d" in hemodialysis lines is d=±6%. Such errors are caused by multiple factors, including errors in the factory calibration of the equipment, nonlinearity in the flow rate vs. recorded voltage, effects of blood and ambient temperature on the sensor's functionality and electronic performance, differences in the tubing used in the system compared to that used for factory calibration, variations between tubing used in the field, and variations in blood densities such as hematocrit and ion concentrations. These flow measurement errors are manifested as (i) deviations in the slope and (ii) variations in the Y-intercept of the curve (graph) that plots the relationship between the recorded flow rate and the pump set flow rate (actual flow rate) (Figures 3A and 3B).

[0014] In other words, when the error d = ±6%, it means that the error is within ±18 mL / min for an exemplary blood flow of 300 mL / min. A -Q VConsidering that, the error (independent of variables) for a renal replacement therapy device flow rate of 300 mL / min is [(da)2+(dv)2]1 / 2≈±8.5%, i.e., ≈±25 mL / min. Typically, fluid removal from a patient is performed at an ultrafiltration rate (UF) of, for example, 600 mL / h, i.e., on the order of 10 mL / min. With this in mind, if it is desired to measure the UF with an error of within 10% of the flow rate, it is necessary to measure the UF with an error of ±1 mL / min (for UF=10 mL / min). Thus, to achieve an error of ±1 mL / min when the blood flow through the renal replacement therapy device is 300 mL / min, the measurement error must be within ±0.3%. However, the measurement error of the UF rate for currently available flow sensors is about ±25 mL / min, which is about 30 times the error required to ensure the usefulness of the UF rate measurement.

[0015] In general, the methods and apparatus of the present invention involve measuring the blood flow in the inflow and outflow lines of a renal replacement therapy device with a calibrated flow sensor, and estimating fluid removal (ultrafiltration) during a single blood treatment based on the difference between the blood flow entering the renal replacement therapy device (inflow line blood flow) and the blood flow leaving the renal replacement therapy device (outflow line blood flow), the ultrafiltration measurement being performed substantially continuously throughout the treatment.

[0016] The present disclosure contemplates calibrating a first flow sensor measuring blood flow in an inflow line and a second flow sensor measuring blood flow in an outflow line, and using the difference in the measured blood flows to determine ultrafiltration, it being understood that a calibrated flow sensor includes a calibrated first flow sensor, a calibrated second flow sensor, or both a calibrated first flow sensor and a calibrated second flow sensor.

[0017] Generally, the present disclosure contemplates flow sensor calibration, which may be flow sensor adaptation or flow sensor equalization. Flow sensor adaptation involves standardizing both flow sensors to sense different common flow rates through the extracorporeal circuit with the ultrafiltration rate set to a known ultrafiltration rate (e.g., "0"), and to have the same sensor measurements for the same flow. That is, adaptation involves making the measurement signal indications from each flow sensor disposed in the extracorporeal circuit have the same value for the common flow. Then, in a subsequent flow sensor equalization, the flow sensors are equalized to have the same sensor measurements for the common flow by adjusting either the first flow sensor, the second flow sensor, or both flow sensors with the ultrafiltration rate set to a known ultrafiltration rate (e.g., "0"). That is, equalization involves equalizing the signal of one flow sensor with the signal of the other flow sensor. Leveling is contemplated to occur periodically throughout the treatment session.

[0018] The present disclosure provides an apparatus for measuring ultrafiltration, particularly the ultrafiltration rate of a renal replacement therapy device in an extracorporeal circuit. The renal replacement therapy device includes or is operatively coupled to a blood inflow line for delivering blood to the renal replacement therapy device, a pump, a permeable membrane, and a blood outflow line for flowing blood from the renal replacement therapy device, and is configured to provide an ultrafiltration rate of a known ultrafiltration rate (e.g., "0") and a target ultrafiltration rate. The apparatus includes a first flow sensor configured to measure a blood inflow line flow in the blood inflow line, a second flow sensor configured to measure a blood outflow line flow in the blood outflow line, and a controller connected to the first flow sensor and the second flow sensor. The controller is configured to calibrate the first flow sensor and the second flow sensor based on the blood flow through the extracorporeal circuit. It is also contemplated that the controller is further configured to determine an ultrafiltration rate and an ultrafiltration volume of the renal replacement therapy device.

[0019] It is understood that the calibration of the first and second flow sensors may include a step of matching the flow sensors so that they provide equal flow measurements at a given pump flow rate and a known ultrafiltration rate (e.g., "0"), particularly for a single treatment with certain tubing and environmental conditions of the extracorporeal circuit. That is, the calibration may be a match of the flow sensors to accommodate a specific extracorporeal circuit and specific equipment used in a specific treatment, rather than a bench or factory calibration, and the first and second flow sensors are matched to each other based on the blood flow through the extracorporeal circuit. Matching may include adjustment of the flow sensors or adjustment of measurements obtained from the flow sensors, such adjustment being made to account for external factors or to allow comparison with measurement data obtained from other flow sensors in the system. Also, as described below, the matching step may include adjusting the measurements of one or both of the flow sensors, utilizing correction or adjustment factors and look-up tables for the measurements or signals of one or both of the flow sensors, or performing a mechanical adjustment of each of the flow sensors. Thus, after matching, the first and second flow sensors can be said to be calibrated.

[0020] The calibration may also include a step of equalizing the first and second flow sensors, i.e., removing the offset between the signals for a common flow rate when the ultrafiltration rate is a known ultrafiltration rate (or an ultrafiltration rate of "0"). That is, it is understood that the calibration does not require the signals generated by each flow sensor to be equal, but rather requires that the signal from one flow sensor be equal to the signal from the other flow sensor.

[0021] Calibrating a first flow sensor to a second flow sensor means calibrating the flow sensors such that the signals from each flow sensor for a common flow rate when the ultrafiltration rate is a known ultrafiltration rate (or an ultrafiltration rate of "0") are interpreted or processed as indicating the same flow rate. A two-point calibration can be performed by matching the first flow sensor to the second flow sensor for at least two common flow rates with the ultrafiltration rate being a known ultrafiltration rate (or an ultrafiltration rate of "0"). A one-point calibration can be performed by leveling the first and second flow sensors such that they are interpreted or processed as indicating the same flow rate for one common flow rate with the ultrafiltration rate being a known ultrafiltration rate (or an ultrafiltration rate of "0"). That is, the present disclosure contemplates one-point and two-point calibrations for rescaling the output of each flow sensor. Two-point calibration can be used when the sensor output is known to be sufficiently linear over the measurement range, and it has the ability to correct both tilt and offset errors.

[0022] It is understood that a "zero" ultrafiltration rate means that no fluid movement occurs through the permeable membrane in the renal replacement therapy device. A "zero" ultrafiltration rate can be achieved by, but is not limited to, completely reducing the ultrafiltration rate to "zero" by stopping ultrafiltration or bypassing the renal replacement therapy device. It is further contemplated that instead of or in combination with a "zero" ultrafiltration rate, the ultrafiltration rate can be a known ultrafiltration rate in the calibration process of the system. Note that the term "known ultrafiltration rate" is used in the description of this specification, and a "zero" ultrafiltration rate is an example of a known ultrafiltration rate.

[0023] The method and apparatus of the present invention can improve the accuracy of ultrafiltration measurement during a single renal replacement therapy session by: (i) calibrating, e.g., matching, a first flow sensor and a second flow sensor to each other for at least two flow rates or within a range of flow rates during the therapy period before ultrafiltration begins; and (ii) periodically calibrating, e.g., equalizing, the first flow sensor and the second flow sensor to each other with a known ultrafiltration rate during the therapy period to improve the accuracy of ultrafiltration measurement during a single renal replacement therapy session. (iii) averaging the flow measurements of the first and second flow sensors over a sufficient period of time to reduce or substantially eliminate flow measurement errors due to pulsations in the measured flow, (iv) estimating a target ultrafiltration rate based on measurements from the calibrated first and second flow sensors (e.g., the difference between the adjusted flow measurements of the first and second flow sensors), and (v) estimating the amount of fluid removed during the renal replacement therapy session. It is contemplated that the step of calibrating the first and second flow sensors may include a step of adapting the flow sensors, which may allow correction of inaccurate factory sensor calibration.

[0024] The present disclosure provides a method for adapting a first flow sensor and a second flow sensor to account for real-time conditions during a treatment (e.g., tubing material, temperature, etc.), which may occur before, during, or after a blood treatment. The adapting includes (i) registering flow rates measured by the first flow sensor and the second flow sensor for at least two pump flow rates (within a range of flow rates expected during a treatment) with a known ultrafiltration rate (or an ultrafiltration rate of "0"), (ii) determining the slopes of the measured flow rate curves of the first flow sensor and the second flow sensor, (iii) determining a correction factor to match the slope of the first flow sensor with the slope of the second flow sensor, and (iv) applying the correction factor to the flow rates measured by at least one of the first flow sensor and the second flow sensor during the ultrafiltration of the treatment. It will be appreciated that adaptation can be performed before, during, or after the flow sensor measures the flow rate during the treatment period, and then adjustments can be made to the measured value in accordance with the adaptation of the flow sensor.

[0025] The flow sensor can be adapted at any time during the treatment, but it is advantageous to determine the calibration (correction) factor prior to the treatment. If the flow sensor is calibrated during or at the end of the treatment, the ultrafiltration rate or fluid removal is (re)calculated when the sensor calibration is applied.

[0026] The present disclosure also provides a method for removing an offset between the first and second flow sensors during treatment by performing a calibration such as leveling the first and second flow sensors during treatment. The method includes the steps of (i) stopping ultrafiltration (operating with the ultrafiltration rate set to a known ultrafiltration rate (or ultrafiltration rate "0")) for a short period of time (e.g., between 1 second and 360 seconds, between 10 seconds and 90 seconds, or on the order of 30 seconds ± 15 seconds), (ii) determining the offset between the first and second flow sensors by calculating the difference in the measured flow rates between the first and second flow sensors, and (iii) performing a calibration by leveling the subsequent flow measurements of the first and second flow sensors using the determined offset.

[0027] It is recognized that the blood flow signals registered by the first and second flow sensors are highly pulsating and that this pulsatility can cause errors in instantaneous flow measurements (FIGS. 5A-5G). The present method and apparatus provide a method for reducing flow measurement errors due to pulsatile flow signals. The present method also contemplates reducing or eliminating flow measurement errors due to pulsatile flow variations by collecting flow measurements for a period of time sufficient to include at least one full period of the pulsatile flow signal in the average. By measuring the flow rate for a sufficient period of time, errors due to pulsations in the flow can be reduced, and by averaging over a period of time, errors due to pulsatile variations can be reduced. It is further contemplated that the flow rate can be measured at points that are at the same position in one period of the pulsatile waveform.

[0028] In one configuration, the present disclosure provides an apparatus for measuring the ultrafiltration rate of a renal replacement therapy device in an extracorporeal circuit having a pump. The renal replacement therapy device is configured to provide an ultrafiltration rate of a first known ultrafiltration rate, a second known ultrafiltration rate (both of which may be an ultrafiltration rate of "0"), and a target ultrafiltration rate, and includes a blood inflow line for delivering blood to the renal replacement therapy device, a permeable membrane, and a blood outflow line for delivering blood from the renal replacement therapy device. The apparatus includes a first flow sensor configured to measure a flow rate in the blood inflow line, a second flow sensor configured to measure a flow rate in the blood outflow line, and a controller connected to the first flow sensor and the second flow sensor. The control unit includes a step of (i) registering a first flow rate measured by a first flow sensor and a first flow rate measured by a second flow sensor, with the pump flow rate set to a first pump flow rate and the ultrafiltration rate set to a first known ultrafiltration rate; (ii) registering a second flow rate measured by the first flow sensor and a second flow rate measured by the second flow sensor, with the pump flow rate set to a second pump flow rate and the ultrafiltration rate set to a second known ultrafiltration rate; and (iii) registering a second flow rate measured by the first flow sensor and a second flow rate measured by the second flow sensor, with the pump flow rate set to a second pump flow rate and the ultrafiltration rate set to a second known ultrafiltration rate. The system is configured to perform the steps of: (i) calibrating at least one of the first flow sensor and the second flow sensor according to the measured first flow rate, the first flow rate measured by the second flow sensor, the second flow rate measured by the first flow sensor, and the second flow rate measured by the second flow sensor; and (iv) determining the target ultrafiltration rate from a third flow rate measured by the first flow sensor and the third flow rate measured by the second flow sensor when the ultrafiltration rate is the target ultrafiltration rate.

[0029] Also provided is a method for measuring a target ultrafiltration rate of a renal replacement therapy device in an extracorporeal circuit having a pump, the renal replacement therapy device being configured to provide a first known ultrafiltration rate, a second known ultrafiltration rate, and a target ultrafiltration rate, the renal replacement therapy device having a blood inflow line for delivering blood to the renal replacement therapy device, a permeable membrane, and a blood outflow line for delivering blood from the renal replacement therapy device. The method includes the steps of (i) measuring a first flow rate in the blood inlet line with a first flow sensor and (ii) measuring a first flow rate in the blood outlet line with a second flow sensor, with the pump flow rate set to a first pump flow rate and the ultrafiltration rate set to a first known ultrafiltration rate; (i) measuring a second flow rate in the blood inlet line with the first flow sensor and (ii) measuring a second flow rate in the blood outlet line with the second flow sensor, with the pump flow rate set to a second pump flow rate and the ultrafiltration rate set to a second known ultrafiltration rate; and measuring the first flow rate in the blood inlet line measured by the first flow sensor, the first flow rate in the blood outlet line measured by the second flow sensor, and the second flow rate in the blood inlet line measured by the first flow sensor. and a second flow rate in the blood outlet line measured by the flow sensor; (i) measuring a third blood flow rate in the blood inlet line by the calibrated first flow sensor and (ii) measuring a third blood flow rate in the blood outlet line by the calibrated second flow sensor when the ultrafiltration rate is a target ultrafiltration rate and the pump flow rate is a target pump flow rate; and determining the target ultrafiltration rate in response to the third blood flow rate in the blood inlet line measured by the calibrated first flow sensor and the third blood flow rate in the blood outlet line measured by the calibrated second flow sensor, with the ultrafiltration rate set to the target ultrafiltration rate and the pump flow rate set to the target pump flow rate.

[0030] The present disclosure further provides a method for measuring a target ultrafiltration rate of a renal replacement therapy device in an extracorporeal circuit having a pump. The renal replacement therapy device is configured to have an ultrafiltration rate of a first known ultrafiltration rate (e.g., ultrafiltration rate "0"), a second known ultrafiltration rate (e.g., ultrafiltration rate "0"), and a target ultrafiltration rate, and has a blood inflow line for delivering blood to the renal replacement therapy device, a permeable membrane, and a blood outflow line for flowing blood from the renal replacement therapy device. The method includes a step of calibrating a first flow sensor configured to sense a flow rate in a blood inlet line and a second flow sensor configured to sense a flow rate in a blood outlet line, the calibration being performed in response to at least (i) a first flow rate in the extracorporeal circuit measured by the first flow sensor and the first flow rate in the extracorporeal circuit measured by the second flow sensor, with the pump flow rate set to a first pump flow rate and the ultrafiltration rate set to a first known ultrafiltration rate, and (ii) a second flow rate in the extracorporeal circuit measured by the first flow sensor and the second flow rate in the extracorporeal circuit measured by the second flow sensor, with the pump flow rate set to a second pump flow rate and the ultrafiltration rate set to a second known ultrafiltration rate; and a step of determining a target ultrafiltration rate in response to a third flow rate measured by the first flow sensor and a third flow rate measured by the second flow sensor, with the pump flow rate set to a predetermined pump flow rate and the ultrafiltration rate set to a target ultrafiltration rate.

[0031] Hereinafter, the embodiments of the present disclosure will be described, but it is understood that the present disclosure is not limited to the embodiments described in the present description, and various modifications are possible without departing from the basic principles of the present invention. Therefore, the scope of the present disclosure should be limited only by the scope of the attached claims. [Brief description of the drawings]

[0032] [Figure 1] Schematic diagram showing a typical extracorporeal circulation circuit including a renal replacement therapy device [Diagram 2]FIG. 1 is a graph showing the flow profile through the extracorporeal circuit during a treatment period, illustrating calibration, including flow sensor matching and flow sensor equalization. [Figure 3A] A comparative graph illustrating the flow sensor adaptation procedure, showing curves illustrating flow measurement values ​​of a first flow sensor and a second flow sensor (venous sensor) for multiple pump flow settings at an ultrafiltration rate of "0" [Figure 3B] 1 is a comparative graph illustrating a flow sensor calibration procedure, the graph showing a curve illustrating the state where flow data obtained from a second flow sensor (a venous sensor) is calibrated, such as by adjustment based on flow data obtained from a first flow sensor (an arterial sensor); [Figure 4A] A graph showing a flow sensor equalization procedure in which the ultrafiltration UF of a renal replacement therapy device is stopped (UF=0) for each period d, and a first flow sensor (arterial sensor) and a second flow sensor (venous sensor) are mutually calibrated (e.g., adapted, equalized, or adjusted), and the graph shows flow rate measurements before the flow sensors are subjected to periodic equalization or other calibration. [Figure 4B] 1 is a graph showing a flow sensor equalization procedure in which the ultrafiltration UF of a renal replacement therapy device is stopped (UF=0) for each period d, and a first flow sensor (arterial sensor) and a second flow sensor (venous sensor) are mutually calibrated (e.g., adapted, equalized, or adjusted), and the graph shows flow rate measurements after periodic calibration. [Figure 5A] FIG. 5 is one of a series of graphs showing the effect of the length of time (the time shown by the shaded area on the graph) over which the flow rate is measured in order to average the flow rate measurements (from FIG. 5A to FIG. 5G, as the measurement time (the time shown by the shaded area) increases, the number of cycles included in the average increases, and it can be seen from FIG. 5A to FIG. 5G that the length of the period over which the average is taken has the effect of reducing the effect of pulsating components on the measured flow rate). [Figure 5B]FIG. 5 is one of a series of graphs showing the effect of the length of time (the time shown by the shaded area on the graph) over which the flow rate is measured in order to average the flow rate measurements (from FIG. 5A to FIG. 5G, as the measurement time (the time shown by the shaded area) increases, the number of cycles included in the average increases, and it can be seen from FIG. 5A to FIG. 5G that the length of the period over which the average is taken has the effect of reducing the effect of pulsating components on the measured flow rate). [Figure 5C] FIG. 5 is one of a series of graphs showing the effect of the length of time (the time shown by the shaded area on the graph) over which the flow rate is measured in order to average the flow rate measurements (from FIG. 5A to FIG. 5G, as the measurement time (the time shown by the shaded area) increases, the number of cycles included in the average increases, and it can be seen from FIG. 5A to FIG. 5G that the length of the period over which the average is taken has the effect of reducing the effect of pulsating components on the measured flow rate). [Figure 5D] FIG. 5 is one of a series of graphs showing the effect of the length of time (the time shown by the shaded area on the graph) over which the flow rate is measured in order to average the flow rate measurements (from FIG. 5A to FIG. 5G, as the measurement time (the time shown by the shaded area) increases, the number of cycles included in the average increases, and it can be seen from FIG. 5A to FIG. 5G that the length of the period over which the average is taken has the effect of reducing the effect of pulsating components on the measured flow rate). [Figure 5E] FIG. 5 is one of a series of graphs showing the effect of the length of time (the time shown by the shaded area on the graph) over which the flow rate is measured in order to average the flow rate measurements (from FIG. 5A to FIG. 5G, as the measurement time (the time shown by the shaded area) increases, the number of cycles included in the average increases, and it can be seen from FIG. 5A to FIG. 5G that the length of the period over which the average is taken has the effect of reducing the effect of pulsating components on the measured flow rate). [Figure 5F]FIG. 5 is one of a series of graphs showing the effect of the length of time (the time shown by the shaded area on the graph) over which the flow rate is measured in order to average the flow rate measurements (from FIG. 5A to FIG. 5G, as the measurement time (the time shown by the shaded area) increases, the number of cycles included in the average increases, and it can be seen from FIG. 5A to FIG. 5G that the length of the period over which the average is taken has the effect of reducing the effect of pulsating components on the measured flow rate). [Figure 5G] FIG. 5 is one of a series of graphs showing the effect of the length of time (the time shown by the shaded area on the graph) over which the flow rate is measured in order to average the flow rate measurements (from FIG. 5A to FIG. 5G, as the measurement time (the time shown by the shaded area) increases, the number of cycles included in the average increases, and it can be seen from FIG. 5A to FIG. 5G that the length of the period over which the average is taken has the effect of reducing the effect of pulsating components on the measured flow rate). [Figure 6] 1 is an exemplary flow chart illustrating the steps for calibrating a flow sensor by adapting the flow sensor in an extracorporeal circuit. [Figure 7] 1 is an exemplary flow chart illustrating steps for calibrating a flow sensor by equalizing the flow sensor in an extracorporeal circuit. [Figure 8A] 1 is an exemplary flow chart illustrating the steps for calibrating a flow sensor by matching and equalizing the flow sensor in an extracorporeal circuit. [Figure 8B] 1 is an exemplary flow chart illustrating the steps for calibrating a flow sensor by matching and equalizing the flow sensor in an extracorporeal circuit. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0033] The present disclosure generally relates to a renal replacement therapy device 130. In one configuration, the present disclosure relates to an extracorporeal renal replacement therapy device 130 capable of performing ultrafiltration by creating a pressure differential across a semipermeable membrane, thereby producing an ultrafiltration rate.

[0034] Renal replacement therapy has two main goals: first, to remove toxins associated with kidney failure, and second, to remove excess water and salt from the blood. In general, renal replacement therapy utilizes two physiological mechanisms to transfer solutes and fluids, and both methods require blood to be isolated on one side of a semipermeable membrane.

[0035] Such treatments can be performed by pumping dialysate through a treatment device (such as a renal replacement therapy device 130, commonly referred to as a dialyzer), which transfers fluids and substances through a semipermeable membrane. In hemodialysis (HD), mass transfer is primarily by diffusion through a membrane, whereas in hemofiltration (HF), mass transfer is primarily by convection through a semipermeable membrane, and hemodiafiltration (HDF) is a combination of the two methods.

[0036] In diffusive clearance (dialysis), solutes move down a concentration gradient from an area of ​​high concentration to an area of ​​low concentration. Solutes must have the appropriate size and charge to pass through a semipermeable membrane. By passing dialysate across the membrane in the opposite direction to the bloodstream, the solute concentrations in the plasma and dialysate are equilibrated. This process allows solutes to be removed from the water in the plasma or added to the water in the plasma, depending on the relative concentrations between the dialysate and plasma. Water also moves down a gradient (the gradient in this case is the osmolar gradient or osmotic gradient), but this is essentially a "result" of solute movement. Diffusive clearance is more effective at removing small solutes, such as serum ions and urea, than it is at removing relatively large solutes.

[0037] Convective clearance (hemofiltration or ultrafiltration) utilizes pressure gradients rather than concentration gradients. Convective clearance primarily has the effect of moving water, which in turn moves solutes. In convective clearance, the transmembrane pressure difference is increased as needed to "push" water through the membrane according to the pressure gradient. Solutes are "dragged" along with this large flow of plasma water (convective mass transfer) to form the ultrafiltrate. In terms of removing small solutes, convective clearance is almost the same as diffusive clearance, but in terms of removing fluid, convective clearance is much superior. In terms of the clearance rate of small solutes, convective clearance is also comparable to diffusive clearance, but convective clearance has a higher clearance rate of medium molecules (500-5000 Daltons) and is limited by the properties of the membrane. Thus, ultrafiltration involves the generation of a pressure gradient across the permeable membrane of the dialyzer to cause a flow of fluid from the blood to the dialysate.

[0038] In hemodialysis, water and sodium removal is typically achieved by the process of ultrafiltration rather than diffusion. In general, ultrafiltration is achieved by reducing the hydrostatic pressure in the dialysate compartment of the dialyzer, causing water, including permeable substances such as electrolytes, to move from the plasma to the dialysate. For the purposes of this description, the term ultrafiltration is intended to encompass the withdrawal of fluid in the dialyzer, including both ultrafiltration and hemofiltration.

[0039] The present disclosure provides for improved accuracy in measuring fluid withdrawals in a dialyzer by measuring blood flow into the dialyzer and blood flow out of the dialyzer. Specifically, the system allows for calibration (e.g., but not limited to, matching and equalizing) of blood flow measurements from a first flow sensor measuring blood flow into the dialyzer and a second flow sensor measuring blood flow out of the dialyzer, thereby providing a blood side measurement system for identifying and quantifying fluid transfer rates into and out of the blood side of a renal replacement therapy device.

[0040] For purposes of this description, the term "blood" is understood to include processed or unprocessed blood, including synthetic and natural blood, as well as plasma. The term "identify" is also understood to mean to determine or indicate what something is, and to encompass the term "quantify," which means to express or measure a quantity. Ultrafiltration refers to the removal of fluid from blood, which can be measured. Ultrafiltration in this case is defined as the filtration rate (volume per unit time), and thus the volume can be calculated by multiplying the measured ultrafiltration rate by time.

[0041] 1, an extracorporeal circuit 100 is shown connected to a patient's circulatory system via an access device 200. In one configuration, the extracorporeal circuit 100 provides renal replacement therapy and includes a renal replacement therapy device 130 having a permeable membrane 132. Renal replacement therapies include, but are not limited to, hemodialysis, hemofiltration, and hemodiafiltration.

[0042] The access device 200 is fluidly connected to a circulatory system, such as that of a human (or animal). The circulatory system includes blood, a vascular system with a cardiopulmonary system, a systemic system connecting the cardiopulmonary system to the tissues of the body, and the heart. Specifically, the systemic system pumps blood throughout the patient's body via a vascular system (arteries, veins, capillaries). Thus, the access device 200 provides access to the extracorporeal circuit 100 by fluidly connecting to the circulatory system. The term "access device" encompasses any access to a patient's circulatory system, including, but not limited to, catheters, needles, shunts, AV native fistulas, AV-artificial grafts, as well as venous catheters or other vascular implants. The connection of the extracorporeal circuit 100 to the patient via the access device 200 is typically a catheter or cannula or needle, e.g., a dialysis cannula, where fluid communication is established, e.g., by puncturing the access device 200. The access device 200 may thus comprise a patient's blood withdrawal site 110 and a patient's blood inflow site 160. As used herein, the access device 200 encompasses the patient's blood withdrawal site 110 and the patient's blood inflow site 160. The access device 200 thus includes arterial and venous accesses that are separate from one another, as well as arterial and venous accesses that are proximal or adjacent to one another, or that are within a common shunt, line, or graft.

[0043] The extracorporeal circuit 100 extends from a patient's blood withdrawal site 110, through the renal replacement therapy device 130, and back to the patient's blood delivery site 160, and includes a pump 170 configured to pump blood through the extracorporeal circuit 100 from the blood withdrawal site, through the renal replacement therapy device, and to the patient's blood delivery site.

[0044] The renal replacement therapy device 130 includes a blood inlet line 120 that carries blood from the blood withdrawal site 110 to the renal replacement therapy device, a permeable membrane, and a blood outlet line 150 that carries blood from the renal replacement therapy device to a blood inlet site 160 of the patient. The blood outlet line 150 connects the flow of the extracorporeal circuit 100 to the circulatory system, such as through an access device 200. Typically, the blood outlet line 150 includes a return cannula that provides a fluid connection to the access device 200. Although the pump 170 is shown in the figures as being located within the extracorporeal circuit 100, it will be understood that the pump can be built into the renal replacement therapy device 130. Similarly, the blood inlet line 120 and the blood outlet line 150 can be part of the extracorporeal circuit 100 or the renal replacement therapy device 130 without departing from the scope of the present disclosure. As is known in the art, the renal replacement therapy device 130 is configured to provide a known ultrafiltration rate. Such a known ultrafiltration rate may be, for example, a "zero" ultrafiltration rate, at least one target ultrafiltration rate, and in certain configurations, multiple target ultrafiltration rates. A "zero" ultrafiltration rate means that no fluid transfer occurs from the blood side to the dialysate side through the membrane 132. Similarly, the pump 170 is configured to provide multiple flow rates through the extracorporeal circuit 100, and thus the renal replacement therapy device 130.

[0045] The pump 170 may be any of a variety of pump types, including but not limited to a peristaltic pump, roller pump, impeller pump, or centrifugal pump. The pump 170 generates a blood flow rate through the extracorporeal circuit 100. Depending on the particular configuration, the pump 170 may be controlled to provide a predetermined blood flow rate through the extracorporeal circuit 100 by direct control of the pump itself or via the controller 180. The location of the pump 170 may be any of a variety of locations within the extracorporeal circuit 100, including but not limited to the location shown in FIG. 1. In one configuration, the pump 170 is a commercially available pump that may be set or adjusted to provide any of a variety of flow rates. The pump flow rate may be read and may be read by a user, transmitted to and read by the controller 180, or both. In one configuration, the pump 170 may provide multiple flow rates within a predetermined range.

[0046] Depending on the configuration of the extracorporeal circulation circuit 100 and the method of measuring blood parameters, an introduction port as a site for introducing a substance into the extracorporeal circulation circuit 100 may be provided in the blood removal line 120 or may be provided in the blood removal line 120. Although not shown in the drawings, it is contemplated that the extracorporeal circulation circuit 100, specifically the blood delivery line 150, may be provided with an air trap and an air detector between the renal replacement therapy device 130 and the access device 200.

[0047] Since the extracorporeal circulation circuit 100 is configured to perform dialysis, the blood removal line 120 may be called an arterial line, and the blood transfer line 150 may be called a venous line. The "arterial line" or arterial side is the portion of the extracorporeal circulation circuit 100 through which blood passes when it flows from the patient's blood removal site 110 (e.g., the access device 200) to the renal replacement therapy device 130. The "venous line" or venous side is the portion of the extracorporeal circulation circuit 100 through which blood passes when it flows from the renal replacement therapy device 130 to the patient's blood transfer site 160 (e.g., the access device 200). In dialysis terms, blood travels from the patient's blood removal site 110 (in the access device 200) to the arterial line 120 (blood removal line), and returns to the patient's blood transfer site 160 (in the access device 200) through the venous line 150 (blood transfer line).

[0048] In this disclosure, the term "upstream" of a location refers to the direction away from the location against the direction of blood flow, and the term "downstream" of a location refers to the direction away from the location in the direction of blood flow.

[0049] The first flow sensor 126 is configured to measure the flow rate of the blood removal line 120 by acquiring blood flow rate data from the blood removal line, and the second flow sensor 156 is configured to measure the flow rate of the blood transfer line 150 by acquiring blood flow rate data from the blood transfer line. In dialysis terminology, the first flow sensor 126 that acquires flow rate data of the blood removal (arterial) line 120 may be called an arterial flow sensor, and the second flow sensor 156 that acquires flow rate data of the blood transfer (venous) line 150 may be called a venous flow sensor.

[0050] The term "flow sensor" encompasses any sensing device that provides a signal representative of flow data or that provides data upon which flow rate, flow pulsations, fluctuations, frequency changes, or vibrations, or a proxy for flow rate, flow pulsations, fluctuations, frequency changes, or vibrations, can be determined or sensed.

[0051] Normal (forward) blood flow through the extracorporeal circuit 100 includes blood flow removing blood from the access device 200 through the arterial line 120, blood flow sending the removed blood to the extracorporeal circuit (for treatment of the blood in the dialyzer 130), and blood flow introducing the removed (or treated) blood into the access device through the venous line 150. Blood flow from the access device 200 through the extracorporeal circuit 100 and back to the access device can be generated by the pump 170.

[0052] The first flow sensor 126 and the second flow sensor 156 are operatively coupled to the respective lines and configured to obtain flow rate data. The term "flow rate data" refers to any data from which a flow rate can be derived, estimated, or calculated, and any surrogate data from which a flow rate can be derived, estimated, or calculated. It is also contemplated that the flow rate can be an actual, calculated, or predicted blood flow rate, as well as any surrogate value for the actual blood flow rate. Such surrogates include, but are not limited to, flow rate, values ​​proportional to, or related to blood flow or flow rate. Flow rate data encompasses any signal or data related to blood flow, particularly any signal or data related to pulsatile, fluctuating, frequency-dependent, or oscillatory components, characteristics, or fluctuations of blood flow. Flow rate data may be represented by any signal, such as, but not limited to, optical, acoustic, electromagnetic, temperature, or other signals on which frequency analysis can be performed. Thus, flow data includes any signal or data representative of flow rate, or any signal or data on which flow rate, or pulsations, fluctuations, frequency fluctuations, or vibrations in flow rate, or pulsations, fluctuations, frequency fluctuations, or vibrations in flow rate, or any corresponding surrogate data. For example, blood markers, such as particles native to the blood or particles introduced into the blood, can be used as surrogate data. Thus, the term flow rate is intended to encompass any value or measurement that corresponds to, is a surrogate for, or can represent blood flow, particularly blood flow pulsations, fluctuations, frequency fluctuations, vibrations, or characteristics or properties. Thus, the term "flow rate" (or "blood flow rate") encompasses volumetric flow rate, which is a measurement of the volume of liquid passing through a cross-sectional area of ​​a conduit per unit time, and can be expressed in units of volume per unit time, typically milliliters per minute (mL / min) or liters per minute (L / min), or any surrogate thereof.It is understood that blood flow may be measured and calculated by any of a variety of known systems and methods. As used herein, measuring flow includes obtaining flow data or measuring flow data.

[0053] Thus, the first flow sensor 126 and the second flow sensor 156 may include a flow sensor, an ultrasonic sensor, or a dilution sensor for sensing the passage of an indicator through the extracorporeal circuit 100. The first flow sensor 126 and the second flow sensor 156 may be any of a variety of sensors that obtain flow data. In an optional configuration, the first flow sensor 126 and the second flow sensor 156 may measure various blood properties, including but not limited to temperature, Doppler frequency, electrical impedance, optical properties, density, ultrasonic velocity, glucose concentration, oxygen saturation, or other blood substances (any physical, electrical, or chemical property of blood). In one configuration, the first flow sensor 126 is a clamp-on sensor that is provided external to the blood withdrawal line 120, and the second flow sensor 156 is a clamp-on sensor that is provided external to the blood infusion line 150.

[0054] In this manner, the first flow sensor 126 and the second flow sensor 156 measure flow characteristics or parameters to generate flow data from which the flow rate can be determined or, in certain configurations, any pulsations, fluctuations, frequency changes, or oscillatory components in the flow or frequency components of the flow. Alternatively, additional sensors (not shown) can be provided in addition to the first flow sensor 126 and the second flow sensor 156 to measure selected blood characteristics or properties.

[0055] It is also understood that the flow sensors 126, 156 can be located external to the extracorporeal circuit 100. That is, the flow sensors 126, 156 can be located at remote locations and changes in the blood occurring since introduction of the marker, or values ​​related to the introduction of the marker, can be measured in the extracorporeal circuit 100 and communicated or transmitted to the respective sensors by means of diffusion, electromagnetic fields, thermal fields, etc.

[0056] The controller 180 is connected to the flow sensors 126, 156 and may also be connected to the pump 170 and the renal replacement therapy device 130. The term "controller" includes signal processors and computers, including preprogrammed desktop or laptop computers or dedicated processors. Such a controller 180 may be easily programmed to perform the calculations described herein or their derivations to determine flow rates and convert flow data as described herein (e.g., as shown in FIG. 6). The controller 180 may also perform preliminary signal conditioning, such as summing one signal with another signal or summing one signal with a portion of another signal. The controller 180 may be a stand-alone device, such as a personal computer, a dedicated device, or may be integrated into one of the components, such as the pump 170 or the renal replacement therapy device 130. As known in the art, the controller 180 may include or be operably connected to a memory and may include or be operably connected to input / output devices, such as a touch screen, a keypad, a keyboard, etc. In addition, in the figure, the control unit 180 is shown as being connected to the first flow sensor 126, the second flow sensor 156, the pump 170, and the renal replacement therapy device 130, however, it will be understood that the control unit may be connected to any combination of a flow sensor, a flow sensor and a pump, or a flow sensor, a pump, and a renal replacement therapy device.

[0057] The method and apparatus includes: a ) and the blood flow downstream of the renal replacement therapy device 130 (Q v ) and assessing fluid removal (ultrafiltration) during a single blood treatment (HD) based on the difference between blood flow entering and leaving the renal replacement therapy device. The ultrafiltration measurement can be performed substantially continuously during the blood treatment. Specifically, the present disclosure is directed to a problem with existing approaches to addressing errors in clamp-on sensor based blood flow measurement systems that result in errors that far exceed the required accuracy of the measurements to determine fluid removal by the renal replacement therapy device 130.

[0058] Sources of error introduced by clamp-on flow sensors include, but are not limited to, factory calibration, mismatch between the tubing used when the flow sensor was factory calibrated and the tubing used in the field, temperature fluctuations between measurement times, and differences in the characteristics of the arterial and venous flow sensors over the flow range of the renal replacement therapy device 130 (or pump 170, or both) (such differences in characteristics may be greater as the flow rate increases and less as the flow rate decreases, or conversely, may be less as the flow rate increases and greater as the flow rate decreases).

[0059] The system is directed to reducing error in measurements of the flow sensors on the arterial blood line 120 and the venous blood line 150 by calibrating (e.g., matching) the arterial flow sensor 126 and the venous flow sensor 156 from multiple flow rate comparisons in the extracorporeal circuit 100 that may be responsive to real-time existing tubing conditions and existing patient conditions, and by periodically calibrating (e.g., equalizing) the flow sensors throughout the treatment time. Note that calibration of the flow sensors 126, 156 may include matching one of the first flow sensor 126 and the second flow sensor 156 to the other, or matching the first flow sensor 126 and the second flow sensor 156 to a common point. It is also contemplated that calibration may include equalizing the signals from the first flow sensor 126 and the second flow sensor 156 for a common flow with a known ultrafiltration rate, where the signals from at least one of the flow sensors are adjusted (e.g., adjusted to be equal to each other). As shown in Figure 2, calibration may include matching the first flow sensor 126 and the second flow sensor 156 and equalizing the first flow sensor 126 and the second flow sensor 156. As shown in Figures 4A and 4B, the offset between the first flow sensor and the second flow sensor is eliminated by equalization.

[0060] During the treatment period, the patient is fluidly connected to the extracorporeal circuit 100. Prior to the application of blood therapy, such as ultrafiltration, by the renal replacement therapy device 130, blood flow through the extracorporeal circuit 100 is established. Thus, a treatment period includes time during which the patient is operatively connected to the extracorporeal circuit 100 and blood is simply flowing untreated through the extracorporeal circuit, as well as time during which the renal replacement therapy device 130 is performing therapy, such as ultrafiltration, on the blood. A treatment period may last 2, 3, 4, or more hours, with the majority of the time typically spent performing blood therapy. In one configuration, in a first step, the controller 180 or the like modifies blood flow through the renal replacement therapy device (and thus the extracorporeal circuit 100). Typically, this first step is performed during the treatment time, but before the start of the blood treatment process (such as the ultrafiltration process) by the renal replacement therapy device 130, i.e., when blood is being sent through the extracorporeal circuit 100 (including the blood inlet line 120 and the blood outlet line 150) and the ultrafiltration rate is a known ultrafiltration rate (e.g., "0"). In one configuration, the fluctuation or range of blood flow through the extracorporeal circuit 100 (including the renal replacement therapy device 130) falls within the blood flow range expected during treatment (or within a range expanded by a predetermined percentage (%), such as ±5%, ±10%, or ±20%). Then, the flow rates measured by the first flow sensor 126 and the second flow sensor 156 (corresponding generated signals) when the ultrafiltration rate is the known ultrafiltration rate (or "0") are registered (e.g., received) by the controller 180. The registered signal (measured flow rate) obtained from each flow sensor is stored or recorded by the controller 180 and, in one configuration, is further plotted against the pump flow rate to obtain a curve (a curve having a certain slope) for each flow sensor, and the slope of the curve for the arterial flow sensor 126 and the venous flow sensor 156 is calibrated by fitting as shown in Figures 3A and 3B.Alternatively, the extracorporeal circuit 100 and / or the renal replacement therapy device 130 may include a bypass line 140 to keep the blood from contacting the semipermeable membrane so that a known effective ultrafiltration rate (zero ultrafiltration rate) is obtained. In either configuration, the actual flow rate through the first flow sensor in the blood removal line 120 should be the same as the flow rate through the blood delivery line 150 (when the ultrafiltration rate is a known ultrafiltration rate such as zero ultrafiltration rate, bypass ultrafiltration rate, etc., collectively referred to herein as known ultrafiltration rates). Calibrating the first and second flow sensors 126 and 156 (e.g., by fitting, adjusting (using a correction factor), or calibrating by referencing a look-up table) at a common flow rate can account for deviations between the flow sensors, thereby improving the accuracy of the flow measurements in the blood removal (arterial) line 120 and the blood delivery (venous) line 150 during a single treatment with a given ultrafiltration rate. That is, the first flow sensor 126 and the second flow sensor 156 are calibrated so that the flow measurements of the first flow sensor 126 and the second flow sensor 156 are equal for a given common flow rate (usually a flow rate within an expected operating range and with a known ultrafiltration rate). As used herein, calibration can include processing signals received from the flow sensors 126, 156 by the controller 180.

[0061] In the calibration process, flow measurements are taken at at least two different flow rates, allowing the first flow sensor 126 and the second flow sensor 156 to be calibrated, such as matched. It is understood that a number of different flow rates can be provided through the extracorporeal circuit 100, and the corresponding flow measurements of the first flow sensor 126 and the second flow sensor 156 can be used to calibrate the flow sensors relative to each other. Thus, additional flow measurements can be taken at a known ultrafiltration rate (e.g., "0") and used to calibrate the sensors (e.g., add data points to the corresponding curves or add data points to the look-up table). As more data is acquired, the controller 180 can incorporate the additional data using a curve fitting algorithm (e.g., adjustment factors known in the art).

[0062] The step of calibrating the first flow sensor 126 and the second flow sensor 156 may include an adaptation step, which may include, for example, a step of graphing the relationship between the measured flow rate and the actual flow rate of each flow sensor when the flow rate of the extracorporeal circuit 100 is a first flow rate and a second flow rate with the ultrafiltration rate set to a known ultrafiltration rate (for example, "0"). This allows a curve associated with the first flow sensor 126 and a curve associated with the second flow sensor 156 (each curve showing the relationship between the measured flow rate of the corresponding flow sensor and the actual flow rate (or pump flow rate)) to be obtained, and these curves can be matched to each other to measure the flow rate during ultrafiltration. This matching of the curves can be performed, for example, by interpolating based on each curve, or by adjusting or changing the curve of one flow sensor to match the curve of the other flow sensor.

[0063] Alternatively, the calibration step may include adjusting flow data obtained from one of the first flow sensor 126 and the second flow sensor 156 at a given flow rate to correspond, match, or be equal to flow data obtained from the other of the first flow sensor and the second flow sensor.

[0064] Additionally, the step of calibrating may include mechanically adjusting each flow sensor or the signal associated with each flow sensor to result in equal measured flow rates for the first flow sensor 126 and the second flow sensor 156 at a given flow rate. That is, each flow sensor may be mechanically adjusted, calibrated, or tuned to match it to the other flow sensor or to match the actual flow rate at a known ultrafiltration rate (e.g., "0").

[0065] It is further understood that the step of calibrating can be accomplished by applying a look-up table of flow rate data acquired by at least one of the first flow sensor 126 and the second flow sensor 156 for each of a plurality of flow rates when the ultrafiltration rate is a known ultrafiltration rate. The look-up table can be any array that provides an indexing operation, such as index mapping. The look-up table contains an array (matrix) of data that contains items to be searched for. The look-up table can be organized as key-value pairs, where the key refers to the data item to be searched for (retrieved) and the value refers to either the data itself or a pointer to where the data is located.

[0066] In one configuration, the calibration to match the first flow sensor 126 and the second flow sensor 156 is performed prior to ultrafiltration during the treatment time. However, it is understood that the matching step can occur after or during the treatment time. In that case, the flow data acquired from the first flow sensor 126 and the second flow sensor 156 is adjusted according to the flow sensor matching after the data acquisition. However, matching the first flow sensor 126 and the second flow sensor 156 prior to the blood treatment during the treatment time is expected to provide the advantage of reduced data processing and real-time values ​​to guide the treatment.

[0067] In addition to calibrating (e.g., matching) the first and second flow sensors 126 and 156 before starting treatment, the flow sensors can be periodically calibrated (e.g., equalized) to accommodate changes over time that may occur during treatment. The renal replacement therapy device 130 can also be calibrated by periodically setting the ultrafiltration rate to a known ultrafiltration rate (e.g., "0") and then measuring and equalizing the measurements of the first and second flow sensors 126 and 156 for at least one blood flow rate through the extracorporeal circuit 100. This calibration can involve adjusting the measurement of the first flow sensor 126 to that of the second flow sensor 156, adjusting the measurement of the second flow sensor to that of the first flow sensor, or setting both the measurements of the first and second flow sensors to the same other value.

[0068] It is contemplated that during treatment, the first and second flow sensors are calibrated by setting the ultrafiltration rate to a known rate (e.g., "0") at regular intervals and detecting at least one common flow rate by the first and second flow sensors 126, 156 and leveling the flow rates. It is understood that the first and second flow sensors 126, 156 may detect multiple different common flow rates during the time that the ultrafiltration rate is the known ultrafiltration rate. Based on the multiple measurements, the first and second flow sensors 126, 156 are calibrated, such as adapted or leveled. The periodic intervals at which the ultrafiltration rate is set to a known rate (e.g., "0") may be applied by the controller 180 at a predetermined time or at a predetermined threshold or trigger, or may be initiated manually. Thus, at a predetermined period or interval during the treatment time, the ultrafiltration rate can be set to a known flow rate (e.g., "0"), and the flow rate data obtained from the first flow sensor 126 and the second flow sensor 156 is used to determine the offset between the first and second flow sensors as shown in Figures 3A and 3B, and to calibrate both flow sensors by removing and smoothing out this offset.

[0069] A further aspect of the present disclosure relates to the collection of flow data. Specifically, regarding the acquisition of flow data, the flow rates of the blood removal line 120 and the blood feed line 150 are usually pulsating. Therefore, instantaneous indications or data shorter than the total length of one pulse cycle (or several pulse cycles) may be accurate as the flow rate at that moment, but do not provide the required average flow rate. Therefore, in order to deal with the pulsating component in the flow rates of the blood removal line 120 and the blood feed line 150, the flow rate data is collected for a time period sufficient to mitigate the error introduced into the measured flow rate by the pulsating component. In one configuration, it has been found that it is preferable to collect flow rate data over a period of at least two cycles. Alternatively, as shown in Figs. 5A to 5G, the start and end points of the period for taking the average can be selected to be points at the same position on the pulsating waveform, thereby dealing with the pulsating flow.

[0070] By increasing the accuracy of the blood flow measurements (in the inflow line 120 and outflow line 150), the contribution from the renal replacement therapy device 130 can be determined with a corresponding degree of accuracy. v is the flow rate of the blood line 150, and Q a is the flow rate of the blood removal line 120, and Q UF is the ultrafiltration flow rate of the renal replacement therapy device 130, i.e., Q UF If is the ultrafiltration rate, Q a =Q v +Q UF and therefore, Q UF =Q a -Q v Q v and Q a The ultrafiltration rate Q UF The accuracy of the measurement can be known with high reliability.

[0071] Once the ultrafiltration rate is known, the volume of fluid removed can be calculated: [UF volume](mL)=Q UF *T In the formula, Q UF is the ultrafiltration flow rate of the renal replacement therapy device 130, i.e., Q UF is the ultrafiltration rate (unit: mL / min), and T is the period during which ultrafiltration is performed (period during which UF ≠ 0).

[0072] The controller 180 is programmed to calibrate (e.g., match) the first flow sensor 126 and the second flow sensor 156 by any of the mechanisms described herein and any equivalents. The controller 180 further derives an ultrafiltration rate Q from the measured flow rate in the blood removal line 120 obtained from the first flow sensor 126 and the measured flow rate in the blood delivery line 150 obtained from the second flow sensor 156. UFThe fluid removal volume can then be calculated from the calculated ultrafiltration rate as described above. With reference to Figures 8A and 8B, the controller can be configured to perform matching and equalization calibrations on the first flow sensor 126 and the second flow sensor 156 during a given treatment time.

[0073] The control unit 180 can be configured to perform the steps of: setting the ultrafiltration rate to a known ultrafiltration rate by temporarily stopping ultrafiltration while maintaining blood flow through the extracorporeal circulation circuit 100 during the treatment time; registering the flow rates obtained from the first flow sensor 126 and the second flow sensor 156 during the time that the ultrafiltration rate is set to the known ultrafiltration rate; recalibrating the first flow sensor and the second flow sensor according to the registered flow rates obtained from the first flow sensor and the second flow sensor; starting ultrafiltration and registering the flow rates obtained from the recalibrated first flow sensor and the second flow sensor; and determining the ultrafiltration rate based on the flow rates obtained from the recalibrated first flow sensor and the second flow sensor.

[0074] Accordingly, the present disclosure provides a method for measuring ultrafiltration rate and cumulative ultrafiltration by a renal replacement therapy device 130 in an extracorporeal circuit 100 having a pump 170. The renal replacement therapy device is configured to provide an ultrafiltration rate of a first known ultrafiltration rate (e.g., "0"), a second known ultrafiltration rate (e.g., "0"), and a target ultrafiltration rate, and includes a blood inflow line 120 that delivers blood to the renal replacement therapy device, a permeable membrane 132, and a blood outflow line 150 that delivers blood from the renal replacement therapy device. The method includes the steps of: (a) registering a first difference between a first flow rate in the blood inlet line measured by the first flow sensor 126 and a first flow rate in the blood outlet line measured by the second flow sensor 156 when the pump flow rate is a first pump flow rate and the ultrafiltration rate is a first known ultrafiltration rate (e.g., "0"); (b) registering a second difference between a second flow rate in the blood inlet line measured by the first flow sensor and a second flow rate in the blood outlet line measured by the second flow sensor when the pump flow rate is a second pump flow rate and the ultrafiltration rate is a second known ultrafiltration rate (e.g., "0"); (c) calibrating, such as adapting, the first and second flow sensors in response to the first and second differences; and (d) measuring or deriving a target ultrafiltration rate at the target pump flow rate from a third flow measurement obtained from the calibrated first and second flow sensors. As mentioned above, it is contemplated that the step of calibrating may include matching a slope of a curve associated with the first and second measured flow rates of the first flow sensor to a slope of a curve associated with the first and second measured flow rates of the second flow sensor. Further, the first known ultrafiltration rate and the second known ultrafiltration rate may be equal in value, or may be an ultrafiltration rate of "0".

[0075] In a particular application, the present disclosure provides a method for measuring ultrafiltration by a renal replacement therapy device 130. The renal replacement therapy device is configured to provide an ultrafiltration rate in an extracorporeal circuit 100 with a known ultrafiltration rate (e.g., "0") and a target ultrafiltration rate. The extracorporeal circuit 100 includes a blood inflow line 120 that delivers blood to the renal replacement therapy device, a pump 170, a permeable membrane 132, and a blood outflow line 150 that carries blood from the renal replacement therapy device. The method includes (i) calibrating, such as matching, the first flow sensor 126 measuring the blood flow in the inlet line and the second flow sensor 156 measuring the blood flow in the outlet line at a time before ultrafiltration during the treatment time, (ii) recalibrating, such as leveling, the first and second flow sensors with the ultrafiltration rate set to a known ultrafiltration rate (or "0") during the treatment time, and (iii) evaluating a target ultrafiltration rate based on the flow measurements by the recalibrated first and second flow sensors. The present disclosure also provides a step of estimating the amount of fluid removed by ultrafiltration during one treatment as a function of the evaluated target ultrafiltration rate. An additional step to eliminate flow measurement errors caused by pulsatile variations in the measured flow may include averaging the measured flow over a period of multiple pulsations for the first flow sensor 126 and the second flow sensor 156, or taking multiple flow measurements at points that are equal in position to a single pulsation wave. It is also contemplated that the calibration step, such as smoothing, may be performed to adequately account for drift or variations that occur between the flow sensors 126, 156 during a treatment session. It is understood that the calibration step, such as smoothing or smoothing, may be performed periodically throughout a treatment session, and that the step of evaluating the target ultrafiltration rate may then be based on the difference between the calibrated flow measurements from the first flow sensor 126 and the second flow sensor 156.

[0076] The present disclosure also provides yet another method for measuring a target ultrafiltration rate by a renal replacement therapy device 130. The renal replacement therapy device is configured to have an ultrafiltration rate of a known ultrafiltration rate (e.g., "0") and a target ultrafiltration rate, and is operatively connected to a blood inflow line 120 for delivering blood to the renal replacement therapy device, a pump 170, a permeable membrane 132, and a blood outflow line 150 for carrying blood from the renal replacement therapy device. The method includes the steps of (a) calibrating a first flow sensor 126 configured to sense a flow in the blood inflow line and a second flow sensor 156 configured to sense a flow in the blood outflow line, and (b) deriving / calculating a target ultrafiltration rate based on measured flow rates obtained from the calibrated first and second flow sensors. The step of calibrating further includes the steps of: (i) measuring a first flow rate by a first flow sensor and a second flow sensor, respectively, when the pump flow rate is a first pump flow rate and the ultrafiltration rate is a first known ultrafiltration rate, measuring a second flow rate by the first flow sensor and a second flow sensor, respectively, when the pump flow rate is a second pump flow rate and the ultrafiltration rate is a second known ultrafiltration rate, determining the slopes of the curves of the measured first flow rate and the measured second flow rate against a reference flow rate (or pump flow rate) for each of the first flow sensor and the second flow sensor, and performing fitting to make the slopes of both curves the same; (ii) periodically during the treatment period, performing equalization on the first flow sensor and the second flow sensor with the ultrafiltration rate set to a known ultrafiltration rate; (iii) periodically during the treatment period, performing an equalization on the first and second flow sensors by determining an offset between the first and second flow sensors at a pump flow rate of a predetermined pump flow rate and an ultrafiltration rate of a known ultrafiltration rate, and adding or subtracting the offset from subsequent flow measurements of one of the first and second flow sensors; (iv) averaging the flow measurements of the first flow sensor and the second flow sensor over a period of time sufficient to encompass at least one period of pulsation in the flow or a period of time beginning and ending at points in the flow that are equidistant in one period of the pulsation waveform; The method includes at least one of the steps.

[0077] A further method of the present disclosure includes measuring an ultrafiltration rate by a renal replacement therapy device 130 in a system having a pump. The renal replacement therapy device is configured to provide an ultrafiltration rate of a known ultrafiltration rate (e.g., "0") and a target ultrafiltration rate, and has a blood inflow line that delivers blood to the renal replacement therapy device, a permeable membrane, and a blood outflow line that carries blood from the renal replacement therapy device. The method includes the steps of: (a) obtaining (i) a first flow rate measured in the blood inlet line and (ii) a first flow rate measured in the blood outlet line when the pump flow rate is a first pump flow rate and the ultrafiltration rate is a known ultrafiltration rate; (b) obtaining (i) a second flow rate measured in the blood inlet line and (ii) a second flow rate measured in the blood outlet line when the pump flow rate is a second pump flow rate and the ultrafiltration rate is a target ultrafiltration rate; and (c) calculating an ultrafiltration rate in response at least to the first flow rate measured in the blood inlet line, the first flow rate measured in the blood outlet line, the second flow rate measured in the blood inlet line, and the second flow rate measured in the blood outlet line. The method may also include an additional step of performing an initial calibration, such as matching (i) a first flow rate measured in the blood inlet line to a first flow rate measured in the blood outlet line, and (ii) a second flow rate measured in the blood inlet line to a second flow rate measured in the blood outlet line, with the ultrafiltration rate set to a known ultrafiltration rate.

[0078] Also provided is another method of measuring ultrafiltration rate by renal replacement therapy device 130. The renal replacement therapy device is connected to a pump 170. The renal replacement therapy device is configured to provide an ultrafiltration rate of a known ultrafiltration rate (e.g., "0") and a target ultrafiltration rate, and includes a blood inlet line 120 that delivers blood to the renal replacement therapy device, a permeable membrane 132, and a blood outlet line 150 that delivers blood from the renal replacement therapy device. The method includes: (a) equalizing a first flow sensor 126 configured to measure flow in the blood inlet line and a second flow sensor 156 configured to measure flow in the blood outlet line; (b) operating the renal replacement therapy device 130 at a target ultrafiltration rate to obtain a first therapeutic flow measurement from the first flow sensor and a second therapeutic flow measurement from the second flow sensor; and (c) deriving a value for the target ultrafiltration rate based on at least one of the equalized first and second flow sensors and the first and second therapeutic flow measurements.

[0079] The present disclosure also provides an apparatus for measuring the ultrafiltration rate of a renal replacement therapy device 130 in an extracorporeal circuit 100 having a pump 170, depending on the calibration employed. The renal replacement therapy device is configured to provide a first known ultrafiltration rate, a second known ultrafiltration rate, and a target ultrafiltration rate, and includes a blood inflow line 120 for delivering blood to the renal replacement therapy device, a permeable membrane 132, and a blood outflow line 150 for delivering blood from the renal replacement therapy device. The apparatus includes (a) a first flow sensor 126 configured to acquire blood inflow line flow data in the blood inflow line, (b) a second flow sensor 156 configured to acquire blood outflow line flow data in the blood outflow line, and (c) a controller 180 connected to the first flow sensor and the second flow sensor. The control unit 180 is configured to perform the steps of (i) registering a first difference between a first flow rate measured by a first flow sensor and a first flow rate measured by a second flow sensor, with the pump flow rate set to a first pump flow rate and the ultrafiltration rate set to a first known ultrafiltration rate; (ii) registering a second difference between a second flow rate measured by a first flow sensor and a second flow rate measured by a second flow sensor, with the pump flow rate set to a second pump flow rate and the ultrafiltration rate set to a second known ultrafiltration rate; and (iii) determining a target ultrafiltration rate according to the first difference and the second difference. It is contemplated that the second flow rate and the first flow rate can be the same. It is also contemplated that the first known ultrafiltration rate and the second known ultrafiltration rate can be the same value, such as "0".

[0080] Accordingly, the present disclosure provides an apparatus for measuring the ultrafiltration rate of a renal replacement therapy device 130 in an extracorporeal circuit 100 having a pump 170. The renal replacement therapy device is configured to provide a first known ultrafiltration rate, a second known ultrafiltration rate, and a target ultrafiltration rate, and includes a blood inflow line 120 for delivering blood to the renal replacement therapy device, a permeable membrane 132, and a blood outflow (blood outflow) line 150 for delivering blood from the renal replacement therapy device. The apparatus includes a first flow sensor 126 configured to measure the flow rate of the blood inflow line, a second flow sensor 156 configured to measure the flow rate of the blood outflow line, and a controller 180 connected to the first and second flow sensors. The control unit 180 performs the steps of (i) registering a first flow rate measured by a first flow sensor and a first flow rate measured by a second flow sensor, with the pump flow rate set to a first pump flow rate and the ultrafiltration rate set to a first known ultrafiltration rate; (ii) registering a second flow rate measured by the first flow sensor and a second flow rate measured by the second flow sensor, with the pump flow rate set to a second pump flow rate and the ultrafiltration rate set to a second known ultrafiltration rate; and (iii) registering a second flow rate measured by the first flow sensor and a second flow rate measured by the second flow sensor, with the pump flow rate set to a second pump flow rate and the ultrafiltration rate set to a second known ultrafiltration rate. and (iv) calibrating at least one of the first flow sensor and the second flow sensor in response to a first flow rate measured by the first flow sensor, a first flow rate measured by the second flow sensor, a second flow rate measured by the first flow sensor, and a second flow rate measured by the second flow sensor; and (iv) determining the target ultrafiltration rate from a third flow rate measured by the first flow sensor and the third flow rate measured by the second flow sensor when the ultrafiltration rate is the target ultrafiltration rate.

[0081] It is also contemplated that the controller 180 is configured to calibrate the first and second flow sensors using a look-up table. The controller 180 may also be configured to calculate (i) a first curve corresponding to the first and second flow rates measured by the first flow sensor, and (ii) a second curve corresponding to the first and second flow rates measured by the second flow sensor. The controller 180 may be configured to perform a fitting step to match the first and second curves, which may include adjusting one of the first and second curves to the other of the first and second curves, or fitting one of the first and second curves to the other of the first and second curves. The controller 180 may also be further configured to quantify a target ultrafiltration rate. As also discussed above, the extracorporeal circuit 100 may include a bypass line 140 that selectively bypasses the renal replacement therapy device 130. The controller 180 may be configured to register the first flow rate measured by the first flow sensor 126 and the first flow rate measured by the second flow sensor 156 over a sufficient flow measurement data collection period that includes at least one full period of the pulsatile flow signal, with the pump flow rate set to the first pump flow rate and the ultrafiltration rate set to the first known ultrafiltration rate and the second known ultrafiltration rate. It is also understood that the controller 180 may be configured to register the first flow rate measured by the first flow sensor 126 and the first flow rate measured by the second flow sensor 156 at the same point in a period of the pulsatile waveform, with the pump flow rate set to the first pump flow rate and the ultrafiltration rate set to the first known ultrafiltration rate. The control unit 180 can be configured to perform a step of averaging the first flow rate measured by the first flow sensor 126 and the first flow rate measured by the second flow sensor 156 with the pump flow rate set to the first pump flow rate and the ultrafiltration rate set to respective known ultrafiltration rates, and the average can be taken from the registered flows over a sufficient period of time such that the average includes at least one complete period in the pulsating flow signal.The controller 180 may also be configured to employ equal ultrafiltration rates, such as an ultrafiltration rate of "0", as the first known ultrafiltration rate, the second known ultrafiltration rate, or both.

[0082] The present disclosure provides a method for measuring a target ultrafiltration rate by a renal replacement therapy device 130 in an extracorporeal circuit 100 having a pump 170. The renal replacement therapy device is configured to provide a first known ultrafiltration rate, a second known ultrafiltration rate, and a target ultrafiltration rate, and includes a blood inflow line 120 that delivers blood to the renal replacement therapy device, a permeable membrane 132, and a blood outflow line 150 that delivers blood from the renal replacement therapy device. The method includes the steps of (a) measuring a first flow rate in the blood inlet line with a first flow sensor 126 and (ii) measuring a first flow rate in the blood outlet line with a second flow sensor 156, with the pump flow rate set to a first pump flow rate and the ultrafiltration rate set to a first known ultrafiltration rate; (b) measuring a second flow rate in the blood inlet line with the first flow sensor and (ii) measuring a second flow rate in the blood outlet line with the second flow sensor, with the pump flow rate set to a second pump flow rate and the ultrafiltration rate set to a second known ultrafiltration rate; and (c) measuring the first flow rate in the blood inlet line measured by the first flow sensor, the first flow rate in the blood outlet line measured by the second flow sensor, and the first flow rate in the blood outlet line measured by the first flow sensor. The method includes: (a) adapting at least one of the first flow sensor and the second flow sensor in response to the measured second flow rate in the blood inlet line and the second flow rate in the blood outlet line measured by the second flow sensor; (d) (i) measuring a third blood flow rate in the blood inlet line by the adapted first flow sensor and (ii) measuring a third blood flow rate in the blood outlet line by the adapted second flow sensor when the ultrafiltration rate is a target ultrafiltration rate and the pump flow rate is a target pump flow rate; and (e) determining a target ultrafiltration rate in response to the third blood flow rate in the blood inlet line measured by the adapted first flow sensor and the third blood flow rate in the blood outlet line measured by the adapted second flow sensor.After step (e), the method may further include the steps of: (f) setting the ultrafiltration rate to a known ultrafiltration rate and the blood flow rate through the blood inlet line and the blood outlet line to a predetermined blood flow rate; (g) determining an offset between a first measurement of the predetermined blood flow rate in the blood inlet line 120 by the first flow sensor 126 and a second measurement of the predetermined blood flow rate in the blood outlet line 150 by the second flow sensor 156; and (h) adjusting subsequent flow measurements of at least one of the first flow sensor and the second flow sensor by the offset. That is, the method may further include the step of leveling at least one of the first flow sensor and the second flow sensor in response to the flow rates measured by the first flow sensor and the second flow sensor when the ultrafiltration rate is the known ultrafiltration rate and the pump flow rate is a target pump flow rate. It is understood that the target pump flow rate may be one of the first pump flow rate and the second pump flow rate. Furthermore, calibrating the first and second flow sensors includes adjusting at least one of the first and second flow sensors. In the method, adapting the first and second flow sensors can include applying a look-up table. In the method, identifying the target ultrafiltration rate can include quantifying the target ultrafiltration rate. Furthermore, the known ultrafiltration rate can be an ultrafiltration rate of "0", and stopping ultrafiltration of the renal replacement therapy device 130 or bypassing the renal replacement therapy device 130 can set the ultrafiltration rate to the known ultrafiltration rate. In the method, the controller can be configured to reduce or eliminate flow measurement errors due to pulsatile fluctuations by averaging the registered flows over a sufficient period of time such that the average includes at least one full period in the pulsatile flow signal.

[0083] Although the description herein refers to a renal replacement therapy device 130, the present disclosure encompasses any device for performing "blood treatment." "Blood treatment" refers to any blood treatment, including but not limited to dialysis, which includes toxin removal by diffusion and convection therapies, including but not limited to hemofiltration, hemodialysis, hemodiafiltration, or Continuous Renal Replacement Therapy (CRRT). Renal replacement therapy devices include blood treatment devices, such as any device for performing blood treatment. Thus, in one configuration, a blood treatment device, such as a dialyzer, can be configured to controllably transfer solutes and water through a semipermeable membrane that separates the blood flow from the dialysate flow. Such transfer processes can include diffusion (dialysis) and convection (ultrafiltration). Blood treatment devices can also perform any of a number of other blood treatments, such as chemical, electromagnetic, and thermal therapies. This disclosure is described in terms of extracorporeal renal replacement therapy devices, dialysis in renal replacement therapy devices, which is understood to include hemodialysis, hemofiltration, and hemodiafiltration.

[0084] Although the present disclosure has been described in detail above, particularly with reference to one embodiment, it will be understood that variations and modifications can be made without departing from the spirit and scope of the present disclosure. Therefore, the embodiments disclosed herein are illustrative in all respects and are not intended to be limiting. The scope of the present invention is defined by the appended claims, and it is intended to embrace all modifications that do not depart from the meaning and scope of equivalents. [Explanation of symbols]

[0085] 100 Extracorporeal circulation circuit 110 Patient's blood drainage site 120 Blood inflow line, blood outflow line, arterial line 126 First flow sensor, arterial flow sensor 130 Renal replacement therapy devices, dialysis machines 132 Permeable membrane 140 Bypass Line 150 Blood outflow lines, blood inflow lines, venous lines 156 Second flow sensor, venous flow sensor 160 Patient blood supply site 170 Pump 180 Control Unit 200 Access Devices

Claims

1. An apparatus for measuring the ultrafiltration rate of a renal replacement therapy device in an extracorporeal circulation circuit having a pump, comprising: the renal replacement therapy device is configured to provide an ultrafiltration rate of a first known ultrafiltration rate, a second known ultrafiltration rate, and a target ultrafiltration rate, and includes a blood inflow line for delivering blood to the renal replacement therapy device, a permeable membrane, and a blood outflow line for delivering blood from the renal replacement therapy device; The apparatus comprises: (a) a first flow sensor configured to measure a flow rate in the blood inlet line; (b) a second flow sensor configured to measure a flow rate in the blood outflow line; and (c) a controller connected to the first flow sensor and the second flow sensor; The control unit: (i) registering a first flow rate measured by the first flow sensor and a first flow rate measured by the second flow sensor with a pump flow rate set to a first pump flow rate and an ultrafiltration rate set to the first known ultrafiltration rate; (ii) registering a second flow rate measured by the first flow sensor and a second flow rate measured by the second flow sensor with a pump flow rate set to a second pump flow rate and an ultrafiltration rate set to the second known ultrafiltration rate; (iii) calibrating at least one of the first flow sensor and the second flow sensor according to the first flow rate measured by the first flow sensor, the first flow rate measured by the second flow sensor, the second flow rate measured by the first flow sensor, and the second flow rate measured by the second flow sensor; (iv) determining the target ultrafiltration rate from a third flow rate measured by the first flow sensor and a third flow rate measured by the second flow sensor when the ultrafiltration rate is the target ultrafiltration rate; An apparatus configured to:

2. The control unit: a step of periodically registering a fourth flow rate measured by the first flow sensor and a fourth flow rate measured by the second flow sensor, with the ultrafiltration rate being a predetermined known ultrafiltration rate; determining a future measurement of the target ultrafiltration rate in response at least in part to the fourth flow rate measured by the first flow sensor and the fourth flow rate measured by the second flow sensor; The apparatus of claim 1 , further configured to:

3. The control unit: registering the fourth flow rate measured by the first flow sensor and the fourth flow rate measured by the second flow sensor over a data collection period sufficient for the measured flows to include at least one full period of the pulsatile flow signal for each measured flow. The apparatus of claim 2 , further configured to:

4. The control unit: registering the first flow rate measured by the first flow sensor and the first flow rate measured by the second flow sensor over a sufficient flow measurement data collection period to include at least one complete period of the pulsatile flow signal. The apparatus of claim 1 , further configured to:

5. The device of claim 1 , wherein the control unit is configured to employ an ultrafiltration rate of "0" for each known ultrafiltration rate.

6. The control unit: averaging the first flow rate measured by the first flow sensor and the first flow rate measured by the second flow sensor with the pump flow rate set to a first pump flow rate and the ultrafiltration rate set to a known ultrafiltration rate. [0023] 20. The method according to claim 1, further comprising:

2. The apparatus of claim 1, wherein the average is taken of the registered flow over a sufficient period such that at least one complete period in the pulsatile flow signal is included in the average.

7. An apparatus for measuring the ultrafiltration rate of a renal replacement therapy device in an extracorporeal circulation circuit having a pump, comprising: The renal replacement therapy device is configured to provide an ultrafiltration rate having a known ultrafiltration rate and a target ultrafiltration rate, and includes a blood inlet line for delivering blood to the renal replacement therapy device, a permeable membrane, and a blood outlet line for delivering blood from the renal replacement therapy device; The apparatus comprises: (a) a first flow sensor configured to measure a flow rate in the blood inlet line; (b) a second flow sensor configured to measure a flow rate in the blood outflow line; and (c) a controller connected to the first flow sensor, the second flow sensor, and the renal replacement therapy device; The control unit: (i) temporarily setting the ultrafiltration rate to a known ultrafiltration rate during the treatment period; (ii) determining an offset between the first flow sensor and the second flow sensor; (iii) adjusting a subsequent flow measurement of at least one of the first flow sensor and the second flow sensor by the offset; An apparatus configured to:

8. The apparatus of claim 7 , wherein the control unit is configured to periodically provide an ultrafiltration rate of “0” as the known ultrafiltration rate.

9. The apparatus of claim 7, wherein the step of temporarily setting the ultrafiltration rate to the known ultrafiltration rate occurs for a period between 1 second and 360 seconds.

10. The control unit: (i) registering a first flow rate measured by the first flow sensor and a first flow rate measured by the second flow sensor with a pump flow rate set to a first pump flow rate and an ultrafiltration rate set to a first known ultrafiltration rate; (ii) registering a second flow rate measured by the first flow sensor and a second flow rate measured by the second flow sensor with a pump flow rate set to a second pump flow rate and an ultrafiltration rate set to a second known ultrafiltration rate; (iii) calibrating at least one of the first flow sensor and the second flow sensor according to the first flow rate measured by the first flow sensor, the first flow rate measured by the second flow sensor, the second flow rate measured by the first flow sensor, and the second flow rate measured by the second flow sensor; (iv) determining the target ultrafiltration rate from a third flow rate measured by the first flow sensor and a third flow rate measured by the second flow sensor when the ultrafiltration rate is the target ultrafiltration rate; The apparatus of claim 7 , configured to:

11. The control unit: averaging the first flow rate measured by the first flow sensor and the first flow rate measured by the second flow sensor with the pump flow rate set to a first pump flow rate and the ultrafiltration rate set to a known ultrafiltration rate. [0023] 20. The method according to claim 1, further comprising:

8. The apparatus of claim 7, wherein the average is taken of the registered flows over a sufficient period such that the average includes at least one complete period in the pulsatile flow signal.

12. 1. A method for measuring a target ultrafiltration rate of a renal replacement therapy device in an extracorporeal circulation circuit having a pump, comprising: the renal replacement therapy device is configured to provide an ultrafiltration rate at a first known ultrafiltration rate, a second known ultrafiltration rate, and the target ultrafiltration rate, and includes a blood inlet line for delivering blood to the renal replacement therapy device, a permeable membrane, and a blood outlet line for delivering blood from the renal replacement therapy device; The method further comprising: (a) calibrating a first flow sensor configured to sense a flow rate in the blood inlet line and a second flow sensor configured to sense a flow rate in the blood outlet line, the calibration being performed in response to at least: (i) a first flow rate in the extracorporeal circuit measured by the first flow sensor and a first flow rate in the extracorporeal circuit measured by the second flow sensor, with a pump flow rate set to a first pump flow rate and an ultrafiltration rate set to the first known ultrafiltration rate; and (ii) a second flow rate in the extracorporeal circuit measured by the first flow sensor and a second flow rate in the extracorporeal circuit measured by the second flow sensor, with a pump flow rate set to a second pump flow rate and an ultrafiltration rate set to the second known ultrafiltration rate; (b) determining the target ultrafiltration rate in response to a third flow rate measured by the calibrated first flow sensor and a third flow rate measured by the second flow sensor, with a pump flow rate set to a predetermined pump flow rate and an ultrafiltration rate set to the target ultrafiltration rate; A method comprising:

13. (i) periodically during a treatment period, setting an ultrafiltration rate to a second known ultrafiltration rate and a predetermined flow rate through the blood inlet line and the blood outlet line; (ii) determining an offset between the flow rate measured by the first flow sensor and the flow rate measured by the second flow sensor when the ultrafiltration rate is the known ultrafiltration rate and the flow rate is the predetermined flow rate; and The method of claim 12 further comprising:

14. 14. The method of claim 13, wherein the step of setting the ultrafiltration rate to the second known ultrafiltration rate lasts for between 1 second and 360 seconds.

15. 13. The method of claim 12, wherein the first flow rate of the extracorporeal circuit measured by the first flow sensor and the second flow rate of the extracorporeal circuit measured by the second flow sensor, with a pump flow rate set to a first pump flow rate and an ultrafiltration rate set to the first known ultrafiltration rate, comprise an average of a first measurement of the predetermined blood flow rate in the blood outflow line by the first flow sensor and a second measurement of the predetermined blood flow rate in the blood outflow line by the first flow sensor, the average being taken from registered flows over a sufficient period of time such that at least one entire period in the pulsatile flow signal is included in the average.

16. The method of claim 12, wherein the known ultrafiltration rate is an ultrafiltration rate of "0".

17. 1. A method of operating a renal replacement therapy device in an extracorporeal circuit having a pump, comprising: The renal replacement therapy device is configured to provide an ultrafiltration rate having a known ultrafiltration rate and a target ultrafiltration rate, and includes a blood inlet line for delivering blood to the renal replacement therapy device, a permeable membrane, and a blood outlet line for delivering blood from the renal replacement therapy device; The method further comprising: (a) setting an ultrafiltration rate to the known ultrafiltration rate and setting a blood flow rate through the blood inflow line and the blood outflow line to a predetermined blood flow rate; (b) determining an offset between a first measurement of the predetermined blood flow rate in the blood inlet line by a first flow sensor and a second measurement of the predetermined blood flow rate in the blood outlet line by a second flow sensor; (c) adjusting a subsequent flow measurement of at least one of the first flow sensor and the second flow sensor by the offset; A method comprising:

18. (a) adapting a first flow sensor configured to sense a flow rate in the blood inlet line and a second flow sensor configured to sense a flow rate in the blood outlet line, the adaptation being dependent at least on (i) a first flow rate in the extracorporeal circuit measured by the first flow sensor and a first flow rate in the extracorporeal circuit measured by the second flow sensor, with a pump flow rate set to a first pump flow rate and an ultrafiltration rate set to a first known ultrafiltration rate, and (ii) a second flow rate in the extracorporeal circuit measured by the first flow sensor and a second flow rate in the extracorporeal circuit measured by the second flow sensor, with a pump flow rate set to a second pump flow rate and an ultrafiltration rate set to a second known ultrafiltration rate.

20. The method of claim 17, further comprising:

19. taking an average of the first measurement of the predetermined blood flow rate in the blood inlet line by the first flow sensor and the second measurement of the predetermined blood flow rate in the blood outlet line by the second flow sensor. Further comprising:

20. The method of claim 17, wherein the average is taken of registered flow over a sufficient period such that at least one full period in the pulsatile flow signal is included in the average.

20. 18. The method of claim 17, wherein the known ultrafiltration rate is an ultrafiltration rate of "0".

21. 18. The method of claim 17, wherein the step of setting the ultrafiltration rate to the known ultrafiltration rate lasts for between 1 second and 360 seconds.

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