JPH11218536A - Method for computing production speed of creatinine by using hemodialytic data - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a useful index regarding the muscle amount, the protein nutrition state or the like of a dialyzed patient by using only hemodialytic data by using a specific formula. SOLUTION: In the method, the production speed of creatinine is computed by using only hemodialytic data while Formula I is used. In the formula, g (24 h) represents the production speed of creatinine (in g/kg/d), Cs represents the concentration of the creatinine before a first or second dislysis per week (in mg/d(), and A represents a numerical value which is found by Formula II in the case of the first dislysis per week and by Formula III in the case of the second dialysis per week. In the Formula II and Formula III, Td represents the time for a dialysis (in h), and Ce represents the concentration of the creatinine after the first or second dialysis per week. Thereby, by using an analyzed result by a blood sampling method which is performed usually in a dialysis center and by using dialysis recorded data which is recorded usually, the production speed of the creatinine of a patient is found, and a useful index regarding the muscle amount, the protein nutrition state or the like of the pateint can be obtained.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel method for calculating creatinine production rate using hemodialysis data.

[0002]

BACKGROUND OF THE INVENTION It has been reported that urinary excretion of creatinine, which roughly correlates with creatinine production, reflects muscle mass. Recently Keshaviah (J. Am.
Soc. Nephrol 1994; 4: 1475-85) et al.
It was shown that the rate of creatinine production in hemodialysis patients, which was determined based on the amount of creatinine excreted in the dialysate, also correlated with muscle mass. Since about half of the total protein in the body forms muscle, creatinine production rate may be a useful indicator of protein nutritional status. The creatinine production rate can be easily determined from the creatinine concentration at the end of dialysis and the creatinine concentration before the next dialysis. However,
Blood collection for biochemical analysis in almost all dialysis centers is performed before and after one dialysis. Therefore, it was impossible to determine the creatinine production rate by the above method based on the analysis results obtained by ordinary blood sampling.

[0003]

SUMMARY OF THE INVENTION In view of the above-mentioned problems of the prior art, it is an object of the present invention to provide a method for producing creatinine using the results of analysis by a blood collection method usually performed in a current dialysis center. It is to provide a method by which can be calculated. In the present invention, it is an object of the present invention to provide a useful index relating to the muscle mass, protein nutritional status, and the like of a dialysis patient by using this method.

[0004]

The present inventors have developed an equation for determining the rate of creatinine production from the measured creatinine concentration before dialysis and the creatinine concentration after dialysis. In development, the inventor states that 1) the patient receives dialysis treatment three times a week on one of the following days of the week: Monday, Wednesday, Friday or Tuesday, Thursday or Saturday; 2) little residual renal function; 3) Gastrointestinal creatinine clearance 0.04 l / k
g / day is constant, 4) gastrointestinal creatinine clearance during dialysis can be ignored, 5) serum creatinine concentration is measured only before and after the first or second dialysis weekly, 6) the patient is in a stable state, 7) With the addition of seven assumptions that the ratio of the creatinine distribution volume (liter) to the ideal body weight (kg) is 0.49, a method for calculating the creatinine production rate using the hemodialysis data of the present invention was obtained.

That is, the present invention is a method for calculating a creatinine production rate using hemodialysis data, characterized by using the equation (1). g (24h) = 7056Cs / A (1) Here, g (24h) is a creatinine production rate (g / k).
g / d), Cs is the creatinine concentration (mg / dl) before the first or second week of dialysis, A is the formula (2) for the first dialysis of the week, and the formula is 2 for the second dialysis of the week. The numerical value obtained by using (3) is shown. In Equations (2) and (3), Td is the dialysis time (h), and Ce is 1 of the week.
Creatinine concentration (mg / mg) after the second or second dialysis
dl) and Cs indicate the creatinine concentration (mg / dl) before the first or second dialysis in the same manner as described above.

[0006]

(Equation 3)

[0007]

(Equation 4)

In the formulas shown in the present invention, the significant figures of the coefficients are displayed to the lower digits, but may be omitted as long as the significant figures of the numbers obtained as the calculation result can be accurately calculated to two digits. . Preferred significant figures are three digits.

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be described below in more detail. In the present invention, creatinine distribution volume (liter)
The ratio of to the ideal body weight (kg) is 0.49,
It was determined as follows. The present inventor measured the creatinine distribution volume V (liter) after dialysis rebound of 36 patients using the following equation (4). V = (E−Cs · ΔBW) / (Cs−Cr) (4) where Cs is the creatinine concentration before dialysis (mg / l),
Cr is the rebound creatinine concentration (mg /
l), ΔΒW is the weight loss by dialysis (kg), E is the amount of creatinine removed into the dialysate by dialysis (mg)
It is.

In the present invention, the ideal body weight IBW (kg)
Was determined by the following equation (5). IBW = 0.9 (H-100) (5) Here, H is height (cm). The ratio of the creatinine distribution volume thus determined to the ideal body weight is 0.49.
± 0.06 (mean ± standard deviation) and the coefficient of variation is 1
2%.

(Calculation of creatinine production rate) From the analysis of the one pool model and the variable volume model of dialysis urea kinetics, the present inventor found that the value (Kt / V) obtained by dividing the product of creatinine clearance and dialysis time by the creatinine distribution volume was obtained. It has been found that the creatinine concentration Cs before the dialysis in the stable period is proportional to the value (g / V) obtained by dividing the creatinine production rate by the creatinine distribution volume, if it is constant. Cs = a · g / V (6) Note that Kt / V of creatinine is simply referred to as Kt / V hereinafter.
It is described.

The slope a of this linear equation changes depending on the value of Kt / V and on the dialysis time. Therefore, in the range of 0.4 to 1.1, Kt / V and 15 in increments of 0.05
The slope a was determined for the dialysis time in 15-minute increments in the range from 0 to 330 minutes. To determine the slope a at each Kt / V, g / V is 4.25 × 10 ⁻⁵ mg / g
C at ml / min (≒ 30 mg / kg / day)
s (mg / dl) was calculated using a computer, and Cs · V / g (= a) was calculated using this. as a result,
When the dialysis time was in the range of 150 to 330 minutes, little change in Cs · V / g was observed regardless of Kt / V.

Thus, the correlation between Cs versus g / V and Kt / V at a dialysis time of 240 minutes was determined. That is,
Cs versus g / V was plotted as a function of Kt / V, which was equationed using a Levenberg-Marquardt algorithm and using a nonlinear least-squares curve approximation. As a result, the following equation (7) was obtained as the equation that best fits the data (r> 0.
9999).

[0014]

(Equation 5) (In the formula, Cs, g / V, and Kt / V are used in the same meaning as described above. The same applies hereinafter.)

Next, the relationship between Kt / V and Ce / Cs was determined in order to replace Kt / V with Ce / Cs in equation (7).
It is known that creatinine balance during hemodialysis is represented by the following equation (8).

[0016]

(Equation 6)

The following equation (9) is obtained from the equations (7) and (8).

[0018]

(Equation 7)

In the formula, Td is the dialysis time (min).

Here, the relationship between In (Ce / Cs) and Kt / V is shown in FIG. As shown in FIG. 1, when Td is constant, the logarithmic value of Ce / Cs calculated from Expression (9), that is, the relationship between ln (Ce / Cs) and Kt / V is a linear relationship. Therefore, in order to express the relationship between In (Ce / Cs) and Kt / V by a linear equation of the form y = ax + b, Td in 15-minute intervals in the range of 120 minutes to 360 minutes
The value of ln (Ce / Cs) was calculated at two values of Kt / V (0.4 and 1.1). Where x is ln
(Ce / Cs), and y is Kt / V. When plotting the slope a of the line of ln (Ce / Cs) versus Kt / V obtained as a function of Td, it was found that the relationship between a and Td was also a linear relationship. Therefore, Td and a
Is expressed by the following equation (10) (r> 0.99)
9), a = −0.000316Td−0.99925 (10)

Similarly, plotting the intercept of a straight line of In (Ce / Cs) versus Kt / V as a function of Td gives b and Td
Is also a linear relationship, and the regression equation is expressed by the following equation (11) (r> 0.999). b = 0.0000611Td−0.0021816 (11) As a result, Kt / V is represented by the following equation (12). Kt / V = − (0.000316Td + 0.999) ln (Ce / Cs) + (0.0000611Td−0.00219) (12) Here, Kt / V calculated from the equation (12) is substituted into the equation (7), and creatinine is obtained. Taking into account that the volume of distribution is 490 ml / kg, an equation for determining the creatinine production rate in the present invention is obtained.

(Correction of the formula for determining the creatinine production rate in the present invention by the change in the creatinine distribution volume) Since the change in the creatinine distribution volume is ignored here, the g / V obtained here is small. Therefore, if the g / V obtained here is corrected for the change in weight by the following method, a more accurate g / V can be obtained. The creatinine balance between the third dialysis and dialysis in the previous week can be calculated by the equation (1) if the change in the creatinine distribution volume is ignored.
3), which is expressed by equation (14) when the change in the creatinine distribution volume is considered. g · Ti-E _i3 = V · Cs ₁ −V · Ce ₃ (13) G · Ti-E _i3 = (V + ΔV) · Cs ₁ −V · Ce ₃ (14)

Here, Ti is the length (min) between the third dialysis and the last dialysis in the previous week, that is, between the end of the third dialysis in the previous week and the start of the first dialysis in this week. The length of E
_i3 is the amount (mg) of creatinine degraded in the gastrointestinal tract during the third dialysis between the previous week and _Ce3 is the creatinine concentration (mg / m3) at the end of the third dialysis of the previous week.
l), G is the creatinine production rate (mg / mg) in a creatinine kinetic model in which the creatinine distribution volume is a variable.
min) and g are the creatinine production rate (m) in a creatinine kinetic model in which the creatinine distribution volume is a constant.
g / min), V is the volume of distribution (volume at the end of dialysis in models with volume change) (ml), ΔV is the volume of creatinine distribution between the third dialysis of the previous week and the first dialysis of this week (Ml).

From equations (13) and (14), the following equation (15) for correcting g / V is obtained.

[0025]

(Equation 8)

Where IBW is the ideal weight (kg), ΔBW
Is the weight loss (kg) during the first dialysis of the week.

As another method of correcting the creatinine production rate by a change in the creatinine distribution volume, there is a method in which the creatinine concentration before dialysis is corrected in advance by a change in the creatinine distribution volume. The amount of creatinine in the body before dialysis
If there is no weight gain between dialysis and no weight gain, then the following equation holds. Cs × V = Cs ′ (V × ΔV) where Cs is the creatinine concentration before dialysis when there is no weight gain, Cs ′ is the creatinine concentration before dialysis when there is weight gain, V is the creatinine distribution volume, and ΔV is the creatinine distribution. The change in volume (= weight gain) is shown.

Therefore, the creatinine concentration before dialysis can be corrected using the following equation (16), and the creatinine production rate calculated using the creatinine concentration before dialysis corrected in this way is the same as the creatinine distribution volume. Has been corrected.

[0029]

(Equation 9)

(Estimation of Rebound Creatinine Concentration after Dialysis) In the present invention, the existence of a difference in intracellular and extracellular creatinine concentration at the end of dialysis due to creatinine transfer resistance of the cell membrane is neglected. If a more accurate creatinine production rate is determined, the post-dialysis rebound creatinine concentration estimated by the following method is used instead of the post-dialysis creatinine concentration. The magnitude of post-dialysis rebound of creatinine concentration is thought to be related to the rate of creatinine removal during dialysis. In order to estimate the post-dialysis rebound creatinine concentration, the correlation between parameters reflecting the rate of creatinine removal and various parameters reflecting the magnitude of the rebound of creatinine concentration was examined for 18 dialysis patients.

The average patient weight was 53.1 ± 2.5 kg and the average blood flow was 211 ± 8 ml / min. All patients were urinary free and the dialysis time was 4 hours for 13 and 4.5 hours for 5 patients. Fifteen patients had internal shunts and three had external shunts. In 9 of the 15 internal shunts, extracorporeal blood was returned to the vein instead of the shunt. Blood collection at the end of dialysis was performed without decreasing the blood flow in patients who returned extracorporeally circulated blood to the vein and those in the external shunt. In the remaining six patients, the blood flow was reduced to 50 ml / min one minute before blood collection at the end of dialysis. One hour after completion of dialysis, blood was collected to measure the rebound creatinine concentration after dialysis.

In the present invention, the concentration of rebound creatinine (mg / ml) after adialysis actually measured for aCr, aC
When s and aCe are the creatinine concentration (mg / ml) before and after dialysis actually measured, respectively, aCr / a
Ce, (aCs-aCr) / (aCs-aCe) and (aCr-aCe) / (aCs-aCe) were used as parameters indicating the magnitude of rebound after dialysis, and K / V was used as a parameter for creatinine removal rate. . K /
V was calculated by the following equations (17) and (18) using aCs, aCe, and dialysis time Td (min). (Kt / V) = In (aCs / aCe) (17) (K / V) = (Kt / V) / Td (18)

The correlation coefficients are K / V and aCr / aC, respectively.
e is 0.775, K / V and (aCs-aCr) /
0.274 between (aCs-aCe), K / V and (a
-0.2 between (Cr-aCe) / (aCs-aCe)
74. Therefore, to estimate the post-dialysis rebound creatinine concentration, a regression equation between K / V and aCr / aCe expressed by the following equation (19) can be used.

[0034]

(Equation 10)

Based on the above correlation, the following equation (20) for estimating the post-dialysis rebound creatinine concentration eCr (mg / ml) is obtained.

[0036]

[Equation 11]

In order to examine the validity of the method for estimating the rebound creatinine concentration after dialysis, the rebound creatinine concentration after dialysis actually measured for another 17 patients and the formula (20)
Was compared with the concentration determined in the above. The average weight of these patients was 55.1 ± 3.5 kg and the average blood flow was 213 ±
It was 6 ml / min. All patients were urinary free and the dialysis time was 4 hours for 14 people and 4.5 hours for 3 people. All patients were internal shunts, and 5 of 17 returned extracorporeally circulated blood to the vein instead of the shunt. In all patients, blood was collected in the same manner as in the study to determine the relationship between the rate of creatinine removal and the magnitude of the rebound in creatinine concentration. FIG. 2 shows the relationship between the post-dialysis riband creatinine concentration thus estimated and the actually measured value.
It was shown to. As shown in FIG. 2, the post-dialysis rebound creatinine concentration estimated in this way was substantially equivalent to the actually measured concentration.

[0038]

EXAMPLE The creatinine production rate of 14 urinary stable urinary stable hemodialysis patients with the method of the present invention and conventional dialysis.
It was calculated by a method based on a creatinine kinetic model during dialysis, and the two were compared. The result is shown in FIG. The x-axis is the result calculated using the present invention (corrected by the change in the creatinine distribution volume and the rebound after dialysis), and the y-axis is the creatinine concentration measured one hour after the end of dialysis (that is, the rebound concentration after dialysis) and the next time. It is the result by the conventional method calculated from the creatinine concentration before dialysis. The equation for the regression line is shown in the following equation (21). y = 0.963x + 0.200 (21) It can be seen that the result according to the present invention and the result according to the conventional method are in good agreement.

[0039]

According to the present invention, it is possible to determine the creatinine production rate of a patient only by using the analysis results obtained by a blood collection method usually performed in a dialysis center and the data of a normally recorded dialysis record. Thus, useful indices concerning the muscle mass, protein nutritional status, and the like of the patient can be obtained.

[Brief description of the drawings]

FIG. 1 is a graph showing the relationship between ln (Ce / Cs) and Kt / V.

FIG. 2 is a graph showing a relationship between an estimated post-dialysis rebound creatinine concentration and an actually measured value.

FIG. 3 is a graph showing the creatinine production concentration of the example.

Claims (1)

[Claims] 1. A method for calculating a creatinine production rate using hemodialysis data, wherein equation (1) is used. g (24h) = 7056Cs / A (1) Here, g (24h) is a creatinine production rate (g / kg).
/ D), Cs is the creatinine concentration (mg / dl) before the first or second week of dialysis, A is the formula (2) for the first dialysis of the week, and the formula (2) for the second dialysis of the week. The numerical value obtained by using 3) is shown. In Equations (2) and (3), Td is the dialysis time (h), and Ce is 1 of the week.
Creatinine concentration (mg / mg) after the second or second dialysis
dl) and Cs indicate the creatinine concentration (mg / dl) before the first or second dialysis in the same manner as described above. (Equation 1) (Equation 2)