JP5641459B1 - A device that determines the initial dissolved mass in the body fluid of a patient from dialysis drainage - Google Patents

Abstract

An apparatus capable of non-invasively determining the clearance of a cell membrane and the concentration of intracellular urea is provided. An apparatus for determining an initial dissolved mass Mpre in a body fluid of a patient from dialysis drainage, and measuring a time variation characteristic of a solute concentration CD (t) in the dialysis drainage to determine a cell membrane clearance K1. Means for determining, means for determining the initial solute concentration C1 (0) in the intracellular fluid from the clearance K1 of the cell membrane, and means for determining the initial solute mass Mpre from the initial solute concentration C1 (0) in the intracellular fluid. This is a device characterized by that. [Selection] Figure 1

Description

  The present invention relates to an apparatus for determining an initial dissolved mass in a patient's body fluid from dialysis drainage.

  In the artificial dialysis medical treatment, a tubular hollow fiber assembly called a dialyzer made of a semipermeable membrane having an inner diameter of about 100 μm is used. Solutes such as urea present in the blood are removed from the body by permeating into the dialysate side while passing through the dialyzer. Conventionally, the amount of urea in blood has been analyzed by collecting blood, and has been evaluated as a value of blood urea nitrogen (hereinafter sometimes abbreviated as “BUN”).

  As a method for measuring the urea concentration in a sample solution containing urea, a colorimetric method that measures the urea concentration by using a reagent that develops color by reacting with urea and comparing it with the standard color of the reagent, specific to urea An enzyme thermistor method that measures urea concentration by immobilizing urease, which is a working enzyme, around glass beads and measuring the heat of reaction accompanying the hydrolysis reaction of urea, an oxidizing agent that reacts with urea to produce chemiluminescence, for example A chemiluminescence method for measuring urea concentration based on the intensity of chemiluminescence (hereinafter sometimes abbreviated as “CL”) using hypohalite is known.

In artificial dialysis medical treatment, the urea removal rate is an important factor affecting a patient's prognosis, and is one of the most important factors for determining dialysis conditions such as dialysis time. Conventionally, the blood urea concentration C _pre at the start of dialysis treatment and the blood urinary concentration C _post at the end of dialysis treatment are measured about twice a month by blood test, and the following formula (a) or the following formula (b ), An index representing the urea removal efficiency such as Kt / V and URR was calculated.

However, as an index for evaluating the efficiency of dialysis treatment, an index SRI (the following formula (c)) indicating how much urea amount (urea mass) has been removed from the body of a patient is in principle the most accurate. However, there has been no means for noninvasively measuring the amount of urea in the patient's body at the start of dialysis treatment and at the end of dialysis treatment.

Therefore, assuming that the body fluid amount V is constant and the urea concentration (C _pre , C _post ) in the body is uniform, M _pre = C _pre × V and M _post = C _post × V are _expressed in equation (c). The urea removal rate URR was determined based on the formula (b) obtained by substitution. However, it was pointed out that the obtained URR is inaccurate because the urea concentration in the body is not uniform in reality. Similarly, Kt / V is an index of dialysis efficiency that is derived on the assumption that the body fluid volume V is constant, the urea concentration in the body (C _pre , C _post ) is uniform, and the clearance K is constant. Was inaccurate. Furthermore, it takes about 90 minutes to obtain C _pre and C _post values by blood test, and the cost of blood test is expensive, so it is difficult to obtain blood test results every time before dialysis treatment. there were. There is also a problem that dialysis conditions according to the symptoms of the patient immediately before dialysis treatment cannot be set accurately.

In Patent Document 1, by moving a piston in a cylinder, one of a sample solution containing urea or a reactant solution containing hypohalite ions is sucked into the cylinder, and then the other solution is sucked. Indirectly by measuring the chemiluminescence produced by uniformly mixing the sample solution containing urea and the reactant solution containing hypohalite ions by generating turbulent flow in the cylinder by the jet of the solution of urine degree concentration measuring device to quantify the urea concentration C _D of dialysis effluent containing urea are described. By integrating the product of the flow rate Q _D and C _D of the dialysis effluent until completion of the dialysis time from start of dialysis time period, the mass of urea removed from the body of the (M _{pre -M post)} can be obtained accurately. However, since the urea amount M _pre in the patient's body immediately before dialysis treatment could not be measured accurately, it was difficult to calculate an accurate urea removal rate.

Patent Document 2 discloses a hemodialysis system having means for continuously measuring a substance concentration in dialysis drainage and calculating the total amount of substance exchanged between blood and dialysate by a dialyzer during dialysis treatment. Is described. According to this method, since the total amount of exchange material is calculated, it is said that it is possible to evaluate dialysis conditions each time dialysis treatment is performed. However, since the solute removal index (SRI), which is an index of dialysis efficiency, is a value (M / M _pre × 100) obtained by dividing the total amount M of the removed solute by the initial solute mass M _pre (M / M _pre × 100). When M _pre is unknown or not constant, there is a problem that appropriate dialysis conditions cannot be set.

WO2009 / 035008A1 JP 2009-273749 A

  The present invention has been made to solve the above-described problems, and an object of the present invention is to provide an apparatus capable of non-invasively determining cell membrane clearance and intracellular urea concentration. Also, by incorporating it into an artificial dialysis machine, it is possible to improve the patient's QOL by controlling the optimal dialysis time, blood flow rate, and dialysate flow rate, and to provide a device that can automate dialysis treatment. It is the purpose.

The above-mentioned problem is a device for determining the initial dissolved mass M _pre in the patient's body fluid from the dialysis drainage, and by measuring the time-varying characteristics of the solute concentration C _D (t) in the dialysis drainage, the cell membrane clearance is measured. Means for determining K ₁ , means for determining intracellular fluid initial solute concentration C ₁ (0) from clearance K _{1 of the} cell membrane, and intracellular fluid initial solute concentration C ₁ (0) , extracellular fluid initial solute And means for determining the initial dissolved mass M _{pre according} to the following formula (5) using the concentration C ₂ (0), the volume V ₁ of the intracellular fluid, and the volume V _{2 of the} extracellular fluid: Solved by providing.
[In formula (5), C ₁ (0) is the intracellular fluid initial solute concentration, C ₂ (0) is the extracellular fluid initial solute concentration, V ₁ is the volume of the intracellular fluid, and V ₂ Is the volume of extracellular fluid. ]

In this case, further, comprising means for determining a solute removal amount ΔM from the dialysate effluent flow rate Q _D and solute concentration C _{D (t),} and means for determining a solute removal index (SRI) from the following equation (1) A device is preferred.

At this time, the means for determining the solute removal amount ΔM uses the solute concentration C _D (t) continuously measured or the solute concentration C _Di measured n times every Δt _i time, using the following formula (2) or (3 ) Is preferably a means for determining the solute removal amount ΔM.

At this time, it is preferable to determine the intracellular fluid initial solute concentration C ₁ (0) by the simultaneous ordinary differential equation of the following formula (4).
[In formula (4), C ₁ is the intracellular fluid solute concentration at time t, C ₂ is the extracellular fluid solute concentration at time t, V ₁ is the volume of the intracellular fluid, and V ₂ is the cell The volume of the external liquid, K ₁ is the clearance of the cell membrane, and K ₂ is the clearance of the dialyzer. ]

  At this time, it is preferable to determine the urea removal rate from the dialysis effluent, and an artificial dialysis apparatus including the above apparatus is a preferable embodiment of the present invention.

  With the apparatus of the present invention, cell membrane clearance and intracellular urea concentration can be determined non-invasively. Thereby, an accurate urea removal rate can be calculated. In addition, an artificial dialysis apparatus incorporating such an apparatus can improve the patient's QOL by controlling the optimal dialysis time, blood flow rate, and dialysate flow rate, and can automate the dialysis treatment.

In Example 1, a graph obtained by plotting the concentration of urea in the blood C _{B (t)} and urea concentration in the dialysis effluent C _{D (t)} to the semi-log plot as a function of the dialysis time t. In the case of calculating the clearance K ₁ of the cell membrane as a parameter, a graph showing the urea concentration C ₂ of the resulting extracellular fluid by simulation. In the case of calculating intracellular fluid initial solute concentration C ₁ of the ₍₀₎ as the parameter, is a graph showing the urea concentration C ₂ of the resulting extracellular fluid by simulation. In Example 1, a graph of the comparison between the values and the simulation curves plotted on semi-log plot urea concentration in blood C _{B (t)} and the urea concentration C _D in the dialysis effluent _(t) as a function of the dialysis time t It is. In Example 2, it is the graph obtained by plotting each density | concentration of urea, (beta) 2-MG, and albumin in a dialysis waste_water | drain as a function of the dialysis time t on a semi-logarithmic graph.

The apparatus of the present invention is an apparatus for determining an initial dissolved mass M _pre in a body fluid of a patient from dialysis drainage, and by measuring a time-varying characteristic of a solute concentration C _D (t) in the dialysis drainage, a cell membrane Means for determining the clearance K ₁ of the cell, means for determining the initial solute concentration C ₁ (0) in the intracellular fluid from the clearance K _{1 of the} cell membrane, and the initial solute mass from the initial solute concentration C ₁ (0) in the intracellular fluid And means for determining M _pre . With such a configuration, the clearance K _{1 of the} cell membrane and the initial solute concentration C ₁ (0) in the intracellular fluid can be determined non-invasively, whereby the initial dissolved mass M _pre in the body fluid of the patient can be determined. Can be determined. The solute that can be determined is not particularly limited, but is preferably a solute having a molecular weight of 50,000 or less. Among these, urea, β2-MG, and albumin can be suitably determined, urea and β2-MG can be more preferably determined, and urea can be particularly preferably determined.

In the present invention, the cell membrane clearance K ₁ is determined by measuring the time-varying characteristics of the solute concentration C _D (t) in the dialysis drainage. Preferably, the cell membrane clearance K ₁ is determined by measuring a time-varying characteristic using a value obtained by plotting a solute concentration C _D (t) in the dialysis drainage as a function of the dialysis time t on a semi-logarithmic graph. Can do. More preferably, the value of the slope (late phase) of the linear region obtained from the plot of the actually measured solute concentration logC _D (t) in the dialysis drainage and the solute concentration logC _D (t) in the dialysis drainage as the value of the slope of the linear region (late) in the numerical calculation curve of pair t is almost coincident, the clearance K ₁ of the cell membrane is determined.

The means for actually measuring the solute concentration C _D (t) in the dialysis effluent is not particularly limited, and can be measured by an enzyme-UV method, a chemiluminescence method, a colorimetric method or the like. In particular, when measuring the urea concentration C _D (t) in the dialysis effluent, an enzyme-UV method such as urease / indophenol method, a urea concentration measuring device described in the examples of WO2009 / 035008A1 (hereinafter referred to as “urea”). A chemiluminescence method using a urea sensor may be used more preferably from the viewpoint of real-time measurement.

The method for obtaining the logC _D (t) vs. t numerical calculation curve is not particularly limited, but the body fluid is composed of intracellular fluid (ICF) and extracellular fluid (ECF), and the concentrations of ICF and ECF are different from each other. It is preferable to use a simultaneous ordinary differential equation of the following formula (4) based on the defined 2-pool model. The following equation (4) is a binary simultaneous ordinary differential equation, but may be a ternary system or a quaternary system.
[In formula (4), C ₁ is the intracellular fluid solute concentration at time t, C ₂ is the extracellular fluid solute concentration at time t, V ₁ is the volume of the intracellular fluid, and V ₂ is the cell The volume of the external liquid, K ₁ is the clearance of the cell membrane, and K ₂ is the clearance of the dialyzer. ]

In the above formula (4), the case where the solute is urea will be described below as an example. The volume _{V 1} of the intracellular fluid, the volume _{V 2} of the extracellular fluid, the entire fluid 27.1L volume of intracellular fluid: extracellular fluid volume = 7: When as an example the case of 3, _{V 1} is 27 1 × 7/10 = 18.97 L, and V ₂ can be determined by calculation as 27.1 × 3/10 = 8.13 L. Moreover, it can measure using the commercially available body component analyzer by the impedance method (InBody S10 by Biospace) etc.

The method for determining the initial value C ₂ (0) of the urinary concentration of the extracellular fluid is not particularly limited, but is preferably determined using the following formula (4 ′).

In the above formula (4 '), the initial value C _{2 (0)} of the urine of the concentration of the extracellular fluid is to equal to the initial value C _{B (0)} of the urea concentration in the blood, the flow rate Q _D of the dialysis _effluent, measured It can be determined using the value of the urea concentration C _D (0) of the dialysis drainage obtained in this way and the value of the clearance K ₂ of the dialyzer.

Here, in the case of calculating the clearance K ₁ of the cell membrane as a parameter, a graph showing the urea concentration C ₂ in the extracellular liquid obtained by simultaneous ordinary differential equations of the formula (4) in FIG. 2, the intracellular fluid When the initial solute concentration C ₁ (0) is calculated as a parameter, a graph showing the urea concentration C ₂ in the extracellular fluid obtained by the simultaneous ordinary differential equation of Equation (4) is shown in FIG. As shown in FIG. 2 and FIG. 3, the logC ₂ (t) vs. t curve is generally composed of two straight lines, and the slopes of the two straight lines differ from each other at the time point t _c that is the bending point. . As shown in FIG. 2, the clearance K ₁ of the cell membrane is changed, it is changing the slope of the straight line after the time t _c. On the other hand, as shown in FIG. 3, when the intracellular solution solute concentration C ₁ changes, the slope of the straight line after time t _c does not change, and only the value of t _c , that is, the position of the bending point, changes. . This process can be automatically performed by a computer.

The clearance K _{1 of the} cell membrane can be suitably determined using the values of V ₁ , V ₂ , C _2, and K ₂ determined as described above and the simultaneous ordinary differential equation of Expression (4). Specifically, the value of the slope (late stage) of the linear region obtained from the plot of the actually measured solute concentration logC _D (t) in the dialysis drainage and the solute concentration logC _D (t) in the dialysis drainage as the value of the slope of the linear region (late) in the numerical calculation curve of pair t is good agreement, it is possible to suitably determine the clearance K ₁ of the cell membrane. At this time, an arbitrary value can be provisionally used as the value of the initial solute concentration C ₁ (0) of the intracellular fluid.

In the present invention, the intracellular fluid initial solute concentration C ₁ (0) is determined from the clearance K _{1 of the} cell membrane. Hereinafter, the case where the solute is urea will be described as an example. The method for determining the initial urea concentration C ₁ (0) of the intracellular fluid from the cell membrane clearance K ₁ is not particularly limited, but the value of the cell membrane clearance K _{1 and} the values of V ₁ , V ₂ , C _2, and using the value of K _2, a method for determining by using a simultaneous ordinary differential equations of the formula (4) is preferably employed. Specifically, the log C ₂ (t) vs. t curve obtained from the numerical calculation of the simultaneous ordinary differential equation of the formula (4) and the smoothing curve of the measured plot of log C ₂ (t) are compared, and the log C ₂ The initial value C ₁ (0) of the urea concentration of the intracellular fluid can be suitably determined so that the dialysis time tc until (t) shifts from a curve to a straight line matches the numerical calculation result and the actual measurement result.

Next, in the present invention, the initial solute mass M _pre is determined from the intracellular fluid initial solute concentration C ₁ (0). Hereinafter, the case where the solute is urea will be described as an example. The method for determining the initial dissolved mass M _pre from the initial urea concentration C ₁ (0) of the intracellular fluid is not particularly limited, but is preferably determined by the following equation (5).

As described above, the apparatus of the present invention has a means for determining the cell membrane clearance K ₁ by measuring the time-varying characteristics of the solute concentration C _D (t) in the dialysis effluent, and the cell membrane clearance K _1. From the intracellular fluid initial solute concentration C ₁ (0), and means for determining the initial solute mass M _pre from the intracellular fluid initial solute concentration C ₁ (0). Apparatus of the invention further comprises means for determining a solute removal amount ΔM from the dialysate effluent flow rate Q _D and solute concentration C _{D (t),} means for determining a solute removal index (SRI) from the following equation (1) It is preferable to provide.

The method for determining the solute removal amount ΔM from the dialysis drainage flow rate Q _D and the solute concentration C _D (t) is not particularly limited, but it was measured n times for every continuously measured solute concentration C _D (t) or Δt _i time. A method of determining the solute removal amount ΔM by the following formula (2) or (3) using the solute concentration C _Di is preferably employed. When Δt _i is relatively short, a method of determining the solute removal amount ΔM by the following formula (3) is preferable. On the other hand, when Δt _i is relatively long, a method of determining the solute removal amount ΔM by the following formula (2) with respect to the smoothing curve is preferable.

In the present invention, the solute removal index (SRI) is preferably determined by the above equation (1) using the value of the initial solute mass M _{pre and} the value of the solute removal amount ΔM obtained as described above. it can. As is clear from the comparison in Examples described later, the urea removal rate (URR) obtained by the conventionally known formula (b) was 76.5 (%), whereas Example 1 Then, the solute removal index (SRI) corresponding to the urea removal rate (URR) was 83.5 (%). That is, it can be understood that the apparatus of the present invention can calculate an accurate urea removal rate in principle, and conventional URR does not agree with this.

The apparatus of the present invention can non-invasively determine cell membrane clearance K ₁ and intracellular fluid initial solute concentration C ₁ (0), thereby determining the initial dissolved mass M _pre in the patient's body fluid. Can do. Then, the case where the solute is urea will be described as an example. The urea concentration in the dialysis drainage is measured by a urea sensor, and the clearance K ₁ of the cell membrane is obtained by using the simultaneous ordinary differential equation of the above formula (4) or the like. And the value of the initial urea concentration C ₁ (0) of the intracellular fluid can be suitably obtained. An accurate urea removal rate can be calculated from the value thus obtained. The present inventors infer about this as follows. That is, at the initial stage of dialysis, the difference in concentration between the extracellular fluid solute concentration C ₂ and the dialysate (urea concentration: 0 mg / dL), rather than the concentration difference between the intracellular fluid solute concentration C ₁ and the extracellular fluid solute concentration C _2. is large, urea is mainly removed from the extracellular fluid volume V ₂ of the extracellular fluid. Therefore, extracellular fluid solute concentration C ₂ decreases rapidly with time. When the extracellular fluid solute concentration C ₂ decreases with time, the difference in concentration between the intracellular fluid solute concentration C ₁ and the extracellular fluid solute concentration C ₂ increases. As a result, two-stage diffusion of urea diffusion from the intracellular fluid to the extracellular fluid and urea diffusion from the extracellular fluid to the dialysate occurs, and a straight line having a certain slope is obtained. The slope of this straight line depends on the cell membrane clearance K ₁ and the dialyzer clearance K _2, and therefore changes depending on the cell membrane clearance K ₁ when the dialyzer clearance K ₂ is a constant. In addition, since the concentration difference between the intracellular fluid solute concentration C ₁ and the extracellular fluid solute concentration C ₂ depends on the intracellular fluid initial solute concentration C ₁ (0), the time t _{c at the} bending point is determined by the intracellular fluid solute concentration C _1. It will depend on the concentration C _1.

From the numerical calculation result obtained from the simultaneous ordinary differential equation of equation (4) and the measured value of urea concentration, cell membrane clearance K ₁ , intracellular fluid initial solute concentration C ₁ (0), initial solute mass M _pre and solute Another method for determining the removal index (SRI) is a method for determining in real time. Hereinafter, the case where the solute is urea will be described as an example. When the urea concentration C _D (t) of the dialysis drainage is measured in real time at regular time intervals using a urea sensor, the urea concentration C _B (t) in the blood, that is, C ₂ (t) is calculated according to the equation (4 ′). Can be determined in real time. After three or more C ₂ (t) measurements are obtained, an approximate curve that substantially matches these log C ₂ (t) vs. t plots can be calculated in real time. In other words, the curve coincides with a straight line at the later stage of dialysis. Therefore, after three or more measured values are obtained after reaching the straight line area, it can be determined from the numerical calculation results that these plots match the straight line, so the boundary between the initial curved area and the subsequent straight line area. The dialysis time t _c until reaching the value can be calculated, and the slope S of the straight line in the straight line region can be calculated. On the other hand, the log C ₂ (t) vs. t curve reaches the linear region in the latter stage of dialysis from the numerical calculation by the simultaneous ordinary differential equation of Equation (4). The slope S of the straight line region is a specific value regardless of the value of C ₁ (0) when V ₁ , V ₂ , K ₂ , and C ₂ (0) are known. Therefore, it is possible to select K ₁ in which the value of the slope S obtained from the measurement by the values and urea sensor slope S coincide. When the value of K ₁ is determined in this way, the relationship between the value of C ₁ (0) and t _c can be obtained from the numerical calculation result obtained from the simultaneous ordinary differential equation of equation (4). Since the value of t _c can be calculated from the measured value of the urea sensor, the value of t ₁ is compared with the value of t _c obtained by numerical calculation, and the value of C ₁ (0) that matches both is selected. Thus, the value of C ₁ (0) can be determined. That is, after measurement of three or more points after the value of C _D (t) by the urea sensor reaches the linear region, the value of the initial dissolved mass M _pre is already determined from the equation (5). Therefore, thereafter, the solute removal index (SRI) can be determined in real time from the equation (1) using the urea removal amount ΔM calculated in real time by the equation (2) or (3). Dialysis can be automatically terminated when a solute removal index (SRI) value appropriate for the patient is reached.

The apparatus of the present invention can non-invasively determine the cell membrane clearance K ₁ and the intracellular fluid initial solute concentration C ₁ (0), thereby determining the initial dissolved mass M _pre in the body fluid of the patient. Can do. Preferably, it is a device for determining the urea removal rate from the dialysis drainage, and an artificial dialysis device equipped with the device of the present invention is a preferred embodiment. By using the apparatus of the present invention, it is possible to control the rate of solute transfer from the inside of the cell to the outside of the cell. If the solute rapidly moves from the inside of the cell to the outside of the cell, the patient may be in a poor physical condition, and it is very useful to be able to control the solute moving speed from the inside of the cell to the outside of the cell. Since the apparatus of the present invention can control the optimal dialysis time, blood flow rate, and dialysate flow rate, the patient's QOL can be improved and the dialysis treatment can be automated.

  Hereinafter, the present invention will be described more specifically with reference to examples.

Example 1
(1) Determination of cell membrane clearance K ₁ The patient's blood during dialysis treatment is sampled 3 times every 2 minutes from the start of dialysis treatment, and then the blood of the same patient when dialysis treatment passes 80 minutes and 240 minutes. Each was sampled once. At the same time, dialysis drainage during the dialysis treatment of the patient was sampled multiple times every 2 minutes and then multiple times every 30 minutes. The enzyme -UV method (urease-indophenol method) were measured urea concentration in blood _C B (t) and the urea concentration _C D in the dialysis effluent (t). At the same time, the urea concentration C _D (t) in the dialysis effluent is set to 2 using the urea concentration measuring device described in the example of WO2009 / 035008A1 (hereinafter sometimes abbreviated as “urea sensor”). Measured every minute. The results obtained by plotting the urea concentration C _B (t) and the urea concentration C _D (t) on a semi-logarithmic graph as a function of the dialysis time t are shown in FIG. As can be seen from FIG. 1, the value of the urea concentration in the dialysis drainage measured by the enzyme-UV method and the value of the urea concentration in the dialysis drainage measured by the urea sensor are almost the same. Are both represented by C _D (t).

The cell membrane clearance K ₁ was determined by measuring the time-varying characteristics of the urea concentration C _D (t) in the dialysis drainage. That is, the dialysis drainage obtained by simulation using the value obtained by plotting the urea concentration C _D (t) in the dialysis drainage as a function of the dialysis time t on a semilogarithmic graph and the simultaneous ordinary differential equation of the following formula (4) It was determined clearance K ₁ of the cell membrane by comparing the slope of the urine of the concentration C ₂ of the liquid.

When the total liquid is 27.1 L, the volume of the intracellular liquid: the volume of the extracellular liquid = 7: 3, V ₁ is 27.1 × 7/10 = 18.97 L, and V ₂ is 27.1 × 3 / 10 = 8.13L. Here, the volume of the intracellular fluid and the volume of the extracellular fluid can be measured using a commercially available body component analyzer (InBody S10 manufactured by Biospace) or the like based on the impedance method. Assuming that the initial value C ₂ (0) of the urinary concentration of the extracellular fluid is equal to the initial value C _B (0) of the blood urea concentration, the measured value of the urea concentration C _D (0) of the dialysis drainage by the urea sensor C _B (0) = (500/230) × 24.9 = 54.1 mg / dL can be calculated from 24.9 mg / dL using the following formula (4 ′). This value almost coincides with the measured value of urea concentration of 56.6 mg / dL by enzyme-UV method of blood at the start of dialysis treatment.

Here, the flow rate _{Q D} of the dialysis effluent is 500 mL / min, clearance _{K 2} of the dialyzer used is 230 mL / min. The initial value C ₁ (0) of the urea concentration in the intracellular fluid was provisionally 60 mg / dL. Using these values and the simultaneous ordinary differential equation of the above equation (4), the slope of the late linear region in the numerical calculation curve of the urinary concentration logC ₂ vs. t in the dialysis drainage was actually measured. as the value of the slope of the late linear region derived from a plot of urea concentrations log C D in the dialysis effluent _(t) is generally coincident to determine the clearance K ₁ of the cell membrane. Clearance _{K 1} of the thus cell membranes was determined was 250 mL / min.

(2) Determination of urea concentration C _{1 in} intracellular fluid Next, using the determined value of cell membrane clearance K _{1 and} the values of V ₁ , V ₂ , C ₂ and K ₂ , the above formula (4 by comparing the smoothing curves of measured plot of simultaneous ordinary differential logC obtained from the numerical calculation of equation ₂ (t) versus t curve and logC ₂ (t)) of, in a straight line from logC ₂ (t) curve The initial value C ₁ (0) of the urea concentration of the intracellular fluid was determined so that the dialysis time tc until the transfer matched between the numerical calculation result and the actual measurement result. The initial value C ₁ (0) of the urea concentration of the intracellular fluid determined in this manner was 85 mg / dL.

(3) Determination of initial dissolved mass M _{pre Using} the determined values of the urea concentration C ₁ of the intracellular fluid and the values of V ₁ , V ₂ and C ₂ , the initial dissolved mass M _pre is expressed by the following formula (5 ).

The initial urea concentration C ₁ (0) in the intracellular fluid is 85 mg / dL, the initial urea concentration C ₂ (0) in the extracellular fluid is 58 mg / dL, V ₁ is 18.97 L, and V ₂ is 8.13 L. The initial dissolved mass M _pre was determined to be 0.85 [g / L] × 18.97 [L] +0.58 [g / L] × 8.13 [L] = 20.84 [g].

(4) to determine the decision dialysis effluent flow rate _{Q D} and solute concentration _C D (t) from the solute removal amount ΔM of solute removal amount ΔM by the following equation (2).

Dialysis effluent flow _{Q D} was 500 mL / min. From the smoothing curve C _D (t) in the graph of FIG. 4, the solute removal amount ΔM could be determined as 17.4 g from the above equation (2).

(5) Determination of solute removal index (SRI) Next, the solute removal index (SRI) was determined by the following equation (1).

  The solute removal index (SRI) could be determined as (17.4 / 20.84) × 100 = 83.5 (%).

Comparative Example 1
The urea removal rate (URR) was calculated by the following formula (b) which has been conventionally known.

As shown in FIG. 4, the initial urea concentration C _{pre in} blood is 58 mg / dL, and the final urea concentration C _post after dialysis treatment is 13.6 mg / dL. From these values, the URR (%) was [(58-13.6) / 58] × 100 = 76.5 (%).

  Thus, in Comparative Example 1, the urea removal rate (URR) was 76.5 (%), whereas in Example 1, the solute removal index (SRI) corresponding to the urea removal rate (URR) was It was 83.5 (%). That is, an accurate urea removal rate can be calculated by the apparatus of the present invention, and the conventional URR deviates from this value.

Example 2
In Example 1, for another patient, the dialysis drainage is sampled every 2 minutes until 10 minutes have passed since the start of dialysis treatment, and every 10 minutes until 30 minutes thereafter, and then 240 minutes have passed. The concentration of urea (molecular weight: 60), β2-MG (molecular weight: about 12,000) and albumin (molecular weight: about 66,000) were respectively set in the same manner as in Example 1 except that the dialysis drainage was sampled every 30 minutes until It was measured. FIG. 5 shows the results obtained by plotting the respective concentrations of urea, β2-MG and albumin on a semi-logarithmic graph as a function of dialysis time t.

  In FIG. 5, the tendency of β2-MG and albumin concentration with time change characteristics is the same as that of urea, and can be divided into an initial stage with a steep slope and a later stage that matches a straight line with a gentler slope. Therefore, since the above formula (4) can be applied to them, the exact removal rate of these waste products can be calculated by using the apparatus of the present invention as in the case of urea.

Claims (6)

A device for determining an initial dissolved mass M _pre in a patient's body fluid from dialysis drainage,
Means for determining the cell membrane clearance K ₁ by measuring the time-varying characteristics of the solute concentration C _D (t) in the dialysis effluent;
Means for determining the initial solute concentration C ₁ (0) in the intracellular fluid from the clearance K _{1 of the} cell membrane;
The initial solute concentration C ₁ (0) in the intracellular fluid, the initial solute concentration C ₂ (0) in the extracellular fluid, the volume V ₁ of the intracellular fluid, and the volume V _{2 of the} extracellular fluid are initialized by the following formula (5). And a device for determining the melting mass M _pre .
[In formula (5), C ₁ (0) is the intracellular fluid initial solute concentration, C ₂ (0) is the extracellular fluid initial solute concentration, V ₁ is the volume of the intracellular fluid, and V ₂ Is the volume of extracellular fluid. ] And means for determining a solute removal amount ΔM from the dialysis drainage flow rate Q _D and the solute concentration C _D (t);
The apparatus of Claim 1 provided with the means to determine a solute removal parameter | index (SRI) by following formula (1).
The means for determining the solute removal amount ΔM uses the solute concentration C _D (t) measured continuously or the solute concentration C _Di measured n times every Δt _i time, according to the following formula (2) or (3). The apparatus according to claim 2, which is means for determining a removal amount ΔM.
The device according to any one of claims 1 to 3, wherein the intracellular fluid initial solute concentration C ₁ (0) is determined by a simultaneous ordinary differential equation of the following formula (4).
[In formula (4), C ₁ is the intracellular fluid solute concentration at time t, C ₂ is the extracellular fluid solute concentration at time t, V ₁ is the volume of the intracellular fluid, and V ₂ is the cell The volume of the external liquid, K ₁ is the clearance of the cell membrane, and K ₂ is the clearance of the dialyzer. ] Apparatus according to any one of claims 1-4 to determine the urea removal rate from the dialysis effluent. Dialysis apparatus provided with a device according to any one of claims 1-5.