Method to form a dialysis composition comprising citrate, calcium and magnesium

Abstract

A method to form a dialysis composition includes determining for a patient a prescribed calcium concentration for a dialysis fluid to be administered to the patient. The determination is made based on a non-citrate containing calcium dialysis fluid. 0.5 to 3 mM citrate and 1 to 5 mM total calcium are introduced to the dialysis fluid. The total calcium results in a calcium concentration that is 0.1 to 0.2 mM per 1 mM citrate greater than the prescribed calcium concentration. 0 to 1.5 mM total magnesium is introduced to the dialysis fluid.

Claims

1. A method to form a dialysis composition, the method comprising: determining for a patient a prescribed calcium concentration for a dialysis fluid to be administered to the patient, wherein the determination is made based on a non-citrate containing calcium dialysis fluid; introducing 0.5 to 3 mM citrate to the dialysis fluid, introducing 1 to 5 mM total calcium to the dialysis fluid, wherein the total calcium results in a calcium concentration that is 0.1 to 0.2 mM per 1 mM citrate greater than the prescribed calcium concentration; and introducing 0 to 1.5 mM total magnesium to the dialysis fluid.

2. The method of claim 1, wherein the concentration of calcium is 0.12 to 0.18 mM per 1 mM citrate greater than the prescribed calcium concentration.

3. The method of claim 1, wherein the introduction of the total calcium provides a constant calcium mass transport irrespective of a level of the citrate.

4. The method of claim 1, wherein the determination of the prescribed calcium concentration determines the prescribed calcium concentration to be selected from the group consisting of 1.00 mM, 1.25 mM, 1.50 mM, and 1.75 mM.

5. The method of claim 4, wherein the prescribed calcium concentration selected from the group consisting of 1.00 mM, 1.25 mM, 1.50 mM, and 1.75 mM results in a blood outlet total calcium value selected from the group consisting of 1.94 mM, 2.17 mM, 2.40 mM, and 2.62 mM, respectively.

6. The method of claim 1, wherein the concentration of calcium is 1.1 to 1.2 mM per 1 mM citrate.

7. The method of claim 1, wherein the concentration of calcium is 1.12 to 1.18 mM per 1 mM citrate.

8. The method of claim 1, wherein the determination of the prescribed calcium concentration is based on at least one of calcium concentration and calcium mass transport for the patient.

9. The method of claim 1 comprising determining a prescribed concentration of total magnesium for the dialysis fluid, wherein the introduction of the total magnesium results in a concentration of magnesium that is 0.04 to 0.10 mM per 1 mM citrate greater than the prescribed concentration of total magnesium.

10. The method of claim 9, wherein the determination of the prescribed magnesium concentration determines the prescribed magnesium concentration to be selected from the group consisting of 0.50 mM, 0.6 mM, and 0.75 mM.

11. The method of claim 10, wherein the prescribed magnesium concentration selected from the group consisting of 0.50 mM, 0.6 mM, and 0.75 mM results in a blood outlet total magnesium value of 0.87 mM, 0.95 mM, and 1.07 mM, respectively.

12. The method of claim 1, wherein the introduction of the total magnesium provides a constant magnesium mass transport irrespective of a level of the citrate.

Description

BRIEF DESCRIPTION OF THE FIGURES

(1) FIG. 1 shows the concentration of total calcium needed in the dialysis fluid as a function of the citrate concentration to keep the same total calcium concentration in the blood outlet, i.e. to get a constant transport of calcium irrespectively of the citrate level.

(2) FIG. 2 shows the concentration of total magnesium needed in the dialysis fluid as a function of the citrate concentration to keep the same total magnesium concentration in the blood outlet, i.e. to get a constant transport of magnesium irrespectively of the citrate level.

DETAILED DESCRIPTION

Definitions

(3) The term “dialysis composition” means the composition of dialysis fluids for hemodialysis, hemodiafiltration, hemofiltration, and peritoneal dialysis, fluids for dialysis within renal intensive care, fluids for substitution or infusion normally containing buffering substances.

(4) The term “citrate” means that the component may be added as citric acid or any salt thereof, such as its sodium, magnesium, calcium or potassium salt thereof, i.e. citrate, to the dialysis composition. However, after mixing thereof with the remaining components including the buffer, citric acid is normally converted into citrate within the fluid.

(5) The term “total citrate” refers to the total amount of citrate present in a fluid, thus representing the sum of citrate present as ionized citrate and complex bound citrate.

(6) The term “total calcium concentration” refers to the total amount of calcium present in a fluid, thus representing the sum of calcium present as ionized calcium, and complex bound calcium including protein bound calcium (mostly albumin bound).

(7) The term “total magnesium concentration” refers to the total amount of magnesium present in a fluid, thus representing the sum of magnesium present as ionized magnesium, and complex bound magnesium including protein bound magnesium (mostly albumin bound).

(8) The term “ordinary prescribed calcium concentration” means the calcium concentration that is prescribed to the patient when a non-citrate containing dialysis fluid is used. This concentration is normally 1.00 mM, 1.25 mM, 1.5 mM, or 1.75 mM, dependent on calcium concentration and calcium mass transport for that specific patient. This is individual and depends on food intake, different type of medication, such as calcium containing phosphate binders and Vitamin D and so forth, since last dialysis session and the imbalance already summoned during earlier dialysis and food intake.

(9) The term “ordinary prescribed magnesium concentration” means the magnesium concentration that is prescribed to patient when a non-citrate containing dialysis fluid is used. This concentration is normally 0.5 mM, 0.6 mM or 0.75 mM, dependent on magnesium concentration and magnesium mass transport for that specific patient.

(10) The term [cit] means the total citrate concentration within the dialysis composition as defined above.

(11) The term [Ca].sub.new means the total calcium concentration to be used in the dialysis composition according to the invention.

(12) The term [Ca].sub.norm means the ordinary prescribed calcium concentration, see above for further definition.

(13) The term k.sub.Ca means the amount (mM) calcium that needs to be added to the citrate containing dialysis composition per 1 mM citrate in addition to the ordinary prescribed calcium concentration, [Ca].sub.norm.

(14) The term [Mg].sub.new means the total magnesium concentration to be used in the dialysis composition according to the invention.

(15) The term k.sub.Mg norm means the ordinary prescribed magnesium concentration, see above for further definition.

(16) The term k.sub.Mg means the amount (mM) magnesium that needs to be added to the citrate containing dialysis composition per 1 mM citrate in addition to the ordinary prescribed magnesium concentration, [Mg].sub.norm.

(17) As stated above, when using citrate within dialysis compositions, one specific effect has to be taken into account, namely its ability to form a complex with, in particular, divalent electrolytes like calcium and magnesium.

(18) When some plasma calcium, i.e. the calcium ionized within the patient's blood, is complex bound to citrate, the level of free ionized calcium will decrease, and some calcium will then be released from albumin. The fraction of total calcium that is bound to albumin will then decrease. Both the free ionized calcium and the calcium citrate complexes are able to pass the dialyzer membrane, and there will thus be an increased force driving calcium from the blood to the dialysate. In order to maintain the same calcium balance in the patient with citrate as with acetate in the dialysis composition it is necessary to increase the calcium level in the dialysis fluid if the citrate level is increased.

(19) The transport rate of various substances across the semipermeable membrane in the dialyzer is quantified by a clearance value, which is defined as the transport rate divided by the blood inlet concentration. For solutes that are present also in the dialysis fluid the term dialysance is used instead of clearance, and the driving force for the transport is the concentration difference. For small, uncharged, water soluble compounds like urea or creatinine it has been known since long how to theoretically calculate clearance/dialysance in hemodialysis from the blood and dialysis fluid flow rates and dialyzer characteristics, the so called mass transfer area coefficient koA. These formulas were later extended to hemodiafiltration, where significant ultrafiltration takes place. Based on a theory of the additional effects of electrical forces on charged particles in membrane transport new formulas have been derived for clearance/dialysance of charged substances when the electrical potential across the membrane (membrane potential) is known. If required such a potential arises to maintain electroneutrality. In order to quantify the membrane potential we use the formulas to calculate all transports of charged substances with a guessed potential. The membrane potential is then adjusted in an iterative manner until the total transports of positive and negative charges across the membrane are equal. This illustrates that all charged substances, both complex bound substances and ions, act together. It is not possible to calculate the isolated transport for just one ion.

(20) It is also necessary to handle the complex binding. The transport of each complex across the membrane is governed by the forces discussed above, just as for other substances. But when the complex leaves one side of the membrane its concentration will decrease, and this will affect the equilibrium between the complex and its components. The corresponding is true on the other side of the membrane when the concentration of the complex increases. These changes in the equilibriums will also affect the transport across the membrane, and it is necessary to include the equilibrium equations in the calculation of the transports.

(21) The mass transfer area coefficients of the various substances are also needed in the calculations. The value for urea is obtained from the clearance values given by the dialyzer manufacturer. The value for potassium is derived to 70% of the urea value by comparing clearances for urea and potassium at blood flow of 200 ml/min and dialysis fluid flow of 500 ml/min. For a large number of other substances data may be found in literature relating their mobility to the mobility of potassium. The mass transfer area coefficients are proportional to the mobility, and the mass transfer area coefficient for other substances may therefore be derived from that of potassium. Values for substances that could not be found in literature may be found by interpolation from substances with similar molecular weight.

(22) One important substance in blood is albumin, which binds several other substances like sodium, calcium, magnesium and hydrogen ions. Each albumin molecule has the ability to bind a large number of these ions (pH dependent) with different equilibrium constants. Both calcium and magnesium ions may bind also to bicarbonate and citrate. These equilibrium constants were also found in literature.

(23) To calculate the complex transport across a semipermeable membrane in a dialyzer, the dialyzer is divided into a number (5-20) of subdialyzers along its entire length. In each subdialyzer the transport of each substance and each complex are considered separately, but using a membrane potential to maintain electroneutrality. With the given inlet concentrations for each substance the outlet concentrations are calculated from the transports. The total concentrations of each basic compound are then calculated by summing their free concentrations and the concentrations of all the complexes where they appear. These total concentrations are then used to calculate a new distribution between free concentrations and the relevant complexes according to the respective equilibrium constants. These recalculated concentrations are then used as input to the next subdialyzer. About 30 iterations along the whole dialyzer are needed to reach a steady state situation.

(24) When citrate is added to the dialysis fluid and transfers into the blood stream in the dialyzer it will bind to calcium and this will cause more calcium to be released from albumin as explained above. The level of ionized calcium is therefore deranged in the blood in the dialyzer. But when this blood is returned to the patient and meets the large blood volume there, a new equilibrium will be established. In contrast to the dialyzer blood, the citrate level in the patient will still be low, and very little calcium will be bound to citrate. The complexes in the blood from the dialyzer will be diluted in the large blood volume in the patient, and this will change the equilibrium so that most of the calcium is released. Since the level of ionized calcium thus changes quite a lot as soon as the blood is returned to the patient it is not possible to base the calcium level in the dialysis fluid on the concentration of ionized calcium.

(25) On the contrary, the total calcium level will not change if the citrate level changes. Our assumption is therefore that the total concentration of calcium (i.e. the sum of free calcium, complex bound and albumin bound calcium) in the blood returned to the patient should be independent of the amount of citrate in the dialysis fluid. What this means is evaluated by simulating treatments with varying levels of citrate in the dialysis fluid.

(26) The calculations were first performed with blood inlet total calcium concentration of 2.4 mM. The blood flow rate was 300 ml/min, the dialysis fluid flow rate 500 ml/min, koA of the dialyzer (for urea) was 1000 ml/min. The dialysis fluid inlet calcium values without citrate were chosen to 1, 1.25, 1.5 and 1.75 mM which gave blood outlet values for total calcium of 1.94, 2.17, 2.40 and 2.62 mM, respectively. Next the dialysis fluid inlet calcium values necessary to maintain the same blood outlet total calcium values (thus maintaining the same calcium transport across the membrane) were determined for citrate levels of 0-2 mM in steps of 0.25 mM.

(27) In FIG. 1 the concentration of total calcium needed in the dialysis fluid is shown as a function of the citrate concentration to keep the same total calcium concentration in the blood outlet, i.e. to get a constant transport of calcium irrespectively of the citrate level. Results are shown for four different levels of calcium transfer between blood and dialysis fluid, all with a total calcium of 2.4 mM at the blood inlet.

(28) It turns out that the need for calcium in the dialysis fluid increases almost linearly with the citrate level, and the slopes are almost equal for the different initial calcium levels, about 0.15 mM calcium for each mM of citrate. These results are shown in FIG. 1, displaying the required total calcium levels in the dialysis fluid as functions of the citrate level for the four different calcium levels at zero citrate. Noted in the end of each line are the resulting total calcium levels at the blood outlet.

(29) These calculations were then repeated for blood flow rates between 200-400 ml/min, for a dialysis fluid flow rate of 800 ml/min and for koA (urea)=700 ml/min. The total calcium levels in the blood outlet became different in the different cases, but interestingly enough, in all cases the requirement for the calcium level in the dialysis fluid still increases with about 0.15 mM per mM of citrate.

(30) Thus, when citrate is added to the dialysis fluid, the calcium level needs to be increased by about 0.10 to 0.2 mM for each 1 mM of citrate, or 0.12 to 0.18 mM for each 1 mM citrate, or 0.15 mM for each mM of citrate.

(31) The citrate added to the dialysis fluid and transferred into the blood stream in the dialyzer will also bind to magnesium and the same situation as with calcium will apply with magnesium.

(32) The calculations with magnesium were performed in a similar manner, and were first performed with blood inlet total magnesium concentration of 0.96 mM. The blood flow rate was 300 ml/min, the dialysis fluid flow rate 500 ml/min, koA of the dialyzer (for urea) was 1000 ml/min. The dialysis fluid inlet magnesium values without citrate were chosen to 0.5, 0.6, and 0.75 mM which gave blood outlet values for total magnesium of 0.87, 0.95, and 1.07 mM, respectively. Next the dialysis fluid inlet magnesium values necessary to maintain the same blood outlet total magnesium values (thus maintaining the same magnesium transport across the membrane) were determined for citrate levels of 0-2 mM in steps of 0.25 mM.

(33) In FIG. 2 the concentration of total magnesium needed in the dialysis fluid is shown as a function of the citrate concentration to keep the same total magnesium concentration in the blood outlet, i.e. to get a constant transport of magnesium irrespectively of the citrate level. Results are shown for three different levels of magnesium transfer between blood and dialysis fluid, all with a total magnesium of 0.96 mM at the blood inlet.

(34) It turns out that the need for magnesium in the dialysis fluid also increases almost linearly with the citrate level, and the slopes are almost equal for the different initial magnesium levels, about 0.07 mM magnesium for each mM of citrate. These results are shown in FIG. 2, displaying the required total magnesium levels in the dialysis fluid as functions of the citrate level for the three different magnesium levels at zero citrate. Noted in the end of each line are the resulting total magnesium levels at the blood outlet.

(35) Thus, when citrate is added to the dialysis fluid the magnesium level needs to be increased by about 0.04 to 0.10 mM for each 1 mM of citrate, or 0.06 to 0.08 mM for each 1 mM citrate, or 0.07 mM for each 1 mM of citrate.

EXAMPLES

(36) By way of example, and not limitation, the following examples identify a variety of dialysis compositions pursuant to embodiments of the present invention.

Example 1

(37) In table 1a electrolyte concentrations within different acetate containing dialysis fluid are given, one row for each dialysis fluid (Examples 1a:1-1a:25).

(38) In table 1b electrolyte concentrations within corresponding citrate containing dialysis fluids are given, wherein the same row shows the corresponding electrolyte concentration needed to keep the patient's calcium mass balance unchanged in comparison when using a dialysis fluid not containing any citrate (Examples 1b:1-1b:25).

(39) However, all these dialysis fluids, both acetate and citrate containing dialysis fluids, further contain about 130-150 mM sodium, 135-145 mM sodium or 140 mM sodium, and 20-40 mM bicarbonate, 25-35 mM bicarbonate or 34 mM bicarbonate, and chloride determined by electro-neutrality.

(40) TABLE-US-00001 TABLE 1a Electrolyte concentrations in acetate dialysis fluids K.sup.+ Ca.sup.2+ Mg.sup.2+ Acetate Gluc. Example: mM mM mM mM g/l 1a:1 1 1.00 0.5 3 1 1a:2 1 1.25 0.5 3 1 1a:3 1 1.50 0.5 3 1 1a:4 1 1.75 0.5 3 1 1a:5 2 1.00 0.5 3 1 1a:6 2 1.25 0.5 3 1 1a:7 2 1.50 0.5 3 1 1a:8 2.5 1.25 0.5 3 1 1a:9 2.5 1.50 0.5 3 1 1a:10 2 1.75 0.5 3 1 1a:11 3 1.25 0.5 3 1 1a:12 3 1.50 0.5 3 1 1a:13 3 1.75 0.5 3 1 1a:14 4 1.25 0.5 3 1 1a:15 4 1.50 0.5 3 1 1a:16 4 1.75 0.5 3 1 1a:17 0 1.50 0.5 3 0 1a:18 1 1.25 0.5 3 0 1a:19 1 1.50 0.5 3 0 1a:20 2 1.25 0.5 3 0 1a:21 2 1.50 0.5 3 0 1a:22 2 1.75 0.5 3 0 1a:23 3 1.25 0.5 3 0 1a:24 3 1.50 0.5 3 0 1a:25 3 1.75 0.5 3 0

(41) TABLE-US-00002 TABLE 1b Electrolyte concentrations in corresp. citrate dialysis fluids K.sup.+ Ca.sup.2+ Mg.sup.2+ Citrate Gluc. Example: mM mM mM mM g/l 1b:1 1 1.20 0.5 1 1 1b:2 1 1.45 0.5 1 1 1b:3 1 1.60 0.5 1 1 1b:4 1 1.87 0.5 1 1 1b:5 2 1.15 0.5 1 1 1b:6 2 1.40 0.5 1 1 1b:7 2 1.65 0.5 1 1 1b:8 2.5 1.37 0.5 1 1 1b:9 2.5 1.60 0.5 1 1 1b:10 2 1.90 0.5 1 1 1b:11 3 1.45 0.5 1 1 1b:12 3 1.60 0.5 1 1 1b:13 3 1.87 0.5 1 1 1b:14 4 1.40 0.5 1 1 1b:15 4 1.65 0.5 1 1 1b:16 4 1.85 0.5 1 1 1b:17 1 1.70 0.5 1 0 1b:18 1 1.43 0.5 1 0 1b:19 1 1.65 0.5 1 0 1b:20 2 1.45 0.5 1 0 1b:21 2 1.62 0.5 1 0 1b:22 2 1.85 0.5 1 0 1b:23 3 1.43 0.5 1 0 1b:24 3 1.62 0.5 1 0 1b:25 3 1.85 0.5 1 0

Example 2

(42) In table 2a electrolyte concentrations within different acetate containing dialysis fluids are given, one row for each dialysis fluid (Examples 2a:1-2a:25).

(43) In table 2b electrolyte concentrations within corresponding citrate containing dialysis fluids are given, wherein the same row shows the corresponding electrolyte concentration needed to keep the patient's calcium and magnesium mass balance unchanged in comparison when using a dialysis fluid not containing any citrate (Examples 2b:1-2b:25).

(44) Again, as indicated above, both acetate containing and citrate containing fluids further contain sodium, bicarbonate and chloride as indicated above.

(45) TABLE-US-00003 TABLE 2a Electrolyte concentrations in acetate dialysis fluids K.sup.+ Ca.sup.2+ Mg.sup.2+ Acetate Gluc. Example: mM mM mM mM g/l 2a:l 1 1.00 0.5 3 1 2a:2 1 1.25 0.5 3 1 2a:3 1 1.50 0.5 3 1 2a:4 1 1.75 0.5 3 1 2a:5 2. 1.00 0.5 3 1 2a:6 2. 1.25 0.5 3 1 2a:7 2 1.50 0.5 3 1 2a:8 2.5 1.25 0.5 3 1 2a:9 2.5 1.50 0.5 3 1 2a:10 2. 1.75 0.5 3 1 2a:11 3 1.25 0.5 3 1 2a:12 3 1.50 0.5 3 1 2a:13 3 1.75 0.5 3 1 2a:14 4 1.25 0.5 3 1 2a:15 4 1.50 0.5 3 1 2a:16 4 1.75 0.5 3 1 2a:17 0 1.50 0.5 3 0 2a:18 1 1.25 0.5 3 0 2a:19 1 1.50 0.5 3 0 2a:20 2 1.25 0.5 3 0 2a:21 2 1.50 0.5 3 0 2a:22 2 1.75 0.5 3 0 2a:23 3 1.25 0.5 3 0 2a:24 3 1.50 0.5 3 0 2a:25 3 1.75 0.5 3 0

(46) TABLE-US-00004 TABLE 2b Electrolyte concentrations in corresp. citrate dialysis fluids K.sup.+ Ca.sup.2+ Mg.sup.2+ Citrate Gluc. Example: mM mM mM mM g/l 2b:l 1 1.20 0.57 1 1 2b:2 1 1.45 0.56 1 1 2b:3 1 1.60 0.54 1 1 2b:4 1 1.87 0.54 1 1 2b:5 2 1.15 0.60 1 1 2b:6 2 1.40 0.58 1 1 2b:7 2 1.65 0.57 1 1 2b:8 2.5 1.37 0.58 1 1 2b:9 2.5 1.60 0.58 1 1 2b:10 2 1.90 0.56 1 1 2b:11 3 1.45 0.54 1 1 2b:12 3 1.60 0.58 1 1 2b:13 3 1.87 0.57 1 1 2b:14 4 1.40 0.57 1 1 2b:15 4 1.65 0.58 1 1 2b:16 4 1.85 0.60 1 1 2b:17 1 1.70 0.54 1 0 2b:18 1 1.43 0.54 1 0 2b:19 1 1.65 0.57 1 0 2b:20 2 1.45 0.54 1 0 2b:21 2 1.62 0.58 1 0 2b:22 2 1.85 0.60 1 0 2b:23 3 1.43 0.54 1 0 2b:24 3 1.62 0.54 1 0 2b:25 3 1.85 0.58 1 0

Example 3

(47) In table 3 electrolyte concentrations within different citrate containing dialysis fluids are given, wherein the column [Ca].sub.norm shows ordinary prescribed calcium concentrations, while the column [Ca].sub.new shows the total calcium concentration to be used in the citrate containing dialysis fluid.

(48) The dialysis fluids according to Examples 3:1 to 3:24 further contain about 130-150 mM sodium, 135-145 mM sodium or 140 mM sodium, and 20-40 mM bicarbonate, 25-35 mM bicarbonate or 34 mM bicarbonate, 0-4 mM potassium, 0-2 g/L glucose and chloride determined by electroneutrality.

(49) TABLE-US-00005 TABLE 3 [Ca].sub.norm Citrate [Ca].sub.new mmol/L mmol/L mmol/L Example: (mM) (mM) (mM) 3:1 1.0 0.5 1.07 3:2 1.25 0.5 1.32 3:3 1.5 0.5 1.57 3:4 1.75 0.5 1.82 3:5 1.0 0.8 1.12 3:6 1.25 0.8 1.37 3:7 1.5 0.8 1.62 3:8 1.75 0.8 1.87 3:9 1.0 1.5 1.22 3:10 1.25 1.5 1.47 3:11 1.5 1.5 1.72 3:12 1.75 1.5 1.97 3:13 1.0 2.0 1.3 3:14 1.25 2.0 1.55 3:15 1.5 2.0 1.8 3:16 1.75 2.0 2.05 3:17 1.0 2.5 1.37 3:18 1.25 2.5 1.62 3:19 1.5 2.5 1.87 3:20 1.75 2.5 2.12 3:21 1.0 3.0 1.45 3:22 1.25 3.0 1.7 3:23 1.5 3.0 1.95 3:24 1.75 3.0 2.2

Example 4

(50) In table 4 electrolyte concentrations within different citrate containing dialysis fluids are given, wherein the column [Ca].sub.norm shows ordinary prescribed calcium concentrations and the column [Mg].sub.norm shows ordinary prescribed magnesium concentration, while the column [Ca].sub.new shows the total calcium concentration to be used in the citrate containing dialysis fluid and the column [Mg].sub.new shows the total magnesium concentration to be used in the citrate containing dialysis fluid.

(51) The dialysis fluids according to Examples 4:1 to 4:36 further contain about 130-150 mM sodium, 135-145 mM sodium or 140 mM sodium, and 20-40 mM bicarbonate, 25-35 mM bicarbonate or 34 mM bicarbonate, 0-4 mM potassium, 0-2 g/L glucose and chloride determined by electroneutrality.

(52) TABLE-US-00006 TABLE 4 [Ca].sub.norm [Mg].sub.norm Citrate [Ca].sub.new [Mg].sub.new mmol/L mmol/L mmol/L mmol/L mmol/L Example: (mM) (mM) (mM) (mM) (mM) 4:1 1.0 0.75 0.5 1.07 0.78 4:2 1.25 0.60 0.5 1.32 0.63 4:3 1.5 0.50 0.5 1.57 0.53 4:4 1.75 0.75 0.5 1.82 0.78 4:5 1.0 0.50 0.8 1.12 0.56 4:6 1.25 0.60 0.8 1.37 0.66 4:7 1.5 0.75 0.8 1.62 0.81 4:8 1.75 0.75 0.8 1.87 0.81 4:9 1.0 0.50 1.25 1.19 0.59 4:10 1.25 0.60 1.25 1.44 0.69 4:11 1.5 0.75 1.25 1.69 0.84 4:12 1.75 0.75 1.25 1.94 0.84 4:13 1.0 0.75 1.5 1.22 0.85 4:14 1.25 0.60 1.5 1.47 0.70 4:15 1.5 0.50 1.5 1.72 0.60 4:16 1.75 0.75 1.5 1.97 0.85 4:17 1.0 0.75 1.75 1.26 0.87 4:18 1.25 0.60 1.75 1.51 0.72 4:19 1.5 0.50 1.75 1.76 0.62 4:20 1.75 0.75 1.75 1.91 0.87 4:21 1.0 0.50 2.0 1.3 0.64 4:22 1.25 0.60 2.0 1.55 0.74 4:23 1.5 0.75 2.0 1.8 0.89 4:24 1.75 0.75 2.0 2.05 0.89 4:25 1.0 0.60 2.5 1.37 0.77 4:26 1.25 0.50 2.5 1.62 0.67 4:27 1.5 0.75 2.5 1.87 0.92 4:28 1.75 0.50 2.5 2.12 0.67 4:29 1.0 0.50 2.25 1.34 0.66 4:30 1.25 0.60 2.25 1.59 0.76 4:31 1.5 0.75 2.25 1.84 0.91 4:32 1.75 0.75 2.25 2.09 0.91 4:33 1.0 0.75 3.0 1.45 0.96 4:34 1.25 0.60 3.0 1.7 0.81 4:35 1.5 0.50 3.0 1.95 0.71 4:36 1.75 0.50 3.0 2.2 0.71

(53) When increasing the amount of total citrate within the dialysis fluid, the amount of bicarbonate has to be adjusted towards the lower end if the ranges given above.

(54) While the invention has been described in connection with what is presently considered to be the most practical and preferred embodiments, it is to be understood that the invention is not to be limited to the disclosed embodiments, but on the contrary, is intended to cover various modifications and equivalent arrangements included within the spirit and the scope of the appended claims.