PRIORITY CLAIM

The present application is a National Phase of International Application No. PCT/EP2017/077566, filed Oct. 27, 2017, which claims priority to Swedish Application No. 1651540-5, filed Nov. 25, 2016, the entire contents of each of which are incorporated herein by reference and relied upon.

TECHNICAL FIELD

The present invention relates to an apparatus for extracorporeal blood treatment and a method for controlling the extracorporeal blood treatment apparatus.

In particular, the invention may be used for regulating the conductivity of a dialysis liquid during a hemodialysis, a hemofiltration or hemodiafiltration treatment.

In more detail, the apparatus and the method are particularly adapted for properly regulating the concentration of sodium in the dialysis liquid, particularly to run an isotonic or an isonatric or an isonatrikalemic dialysis treatment.

BACKGROUND OF THE INVENTION

The kidneys fulfil many functions, including the removal of water, the excretion of catabolites (or waste from the metabolism, for example urea and creatinine), the regulation of the concentration of the electrolytes in the blood (e.g. sodium, potassium, magnesium, calcium, bicarbonates, phosphates, chlorides) and the regulation of the acid/base equilibrium within the body, which is obtained in particular by the removal of weak acids and by the production of ammonium salts.

In individuals who have lost the use of their kidneys, since these excretion and regulation mechanisms no longer work, the body accumulates water and waste from the metabolism and exhibits an excess of electrolytes, as well as, in general, acidosis, the pH of the blood plasma shifting downwards, below 7.35 (the blood pH normally varies within narrow limits of between 7.35 and 7.45).

In order to overcome renal dysfunction, resort is conventionally made to a blood treatment involving extracorporeal circulation through an exchanger having a semipermeable membrane (dialyzer) in which the patient's blood is circulated on one side of the membrane and a dialysis liquid, comprising the main electrolytes of the blood in concentrations close to those in the blood of a healthy subject, is circulated on the other side.

Furthermore, a pressure difference is created between the two compartments of the dialyzer which are delimited by the semipermeable membrane, so that a fraction of the plasma fluid passes by ultrafiltration through the membrane into the compartment containing the dialysis liquid.

The blood treatment which takes place in a dialyzer as regards waste from the metabolism and electrolytes results from two mechanisms of molecular transport through the membrane.

On the one hand, the molecules migrate from the liquid where their concentration is higher to the liquid where their concentration is lower. This is diffusive transport.

On the other hand, certain catabolites and certain electrolytes are entrained by the plasma fluid which filters through the membrane under the effect of the pressure difference created between the two compartments of the exchanger. This is convective transport.

Three of the abovementioned functions of the kidney, namely the removal of water, the excretion of catabolites and the regulation of the electrolytic concentration of the blood, are therefore performed in a conventional blood treatment device by the combination of dialysis and blood filtration (this combination is referred to as hemodialysis).

As regards the regulation of the acid/base equilibrium inside the body, the approach adopted to overcome renal deficiency is to act on a mechanism by which the acid/base equilibrium inside the body is regulated, this mechanism consisting of the buffer systems of the blood, the main one of which comprises carbonic acid, as a weak acid, associated with its alkali salt, bicarbonate. This is why, in order to correct acidosis in a patient suffering from renal insufficiency, he is administered with bicarbonate via the vascular route, directly or indirectly, during a hemodialysis session.

Moreover, it must be underlined that sodium is the main ionic solute of extracellular volume. From literature search and according to the main opinion leaders in the dialysis field, the determination of dialysis fluid sodium concentration to be used during the dialysis treatment appears as one of the major challenges of dialysis prescription.

The dialysis fluid sodium concentration significantly affects the sodium balance and the intracellular hydration of the patient with implications on hemodialysis tolerance and also long term patient survival.

Hypertonic dialysis fluid sodium prescription will result in a positive sodium balance followed by a water shift from the intracellular to extracellular compartment. The intracellular dehydration increases vasopressin release and provokes thirst with the consequence of a greater inter-dialytic weight gain and hypertension.

On the contrary, a dialysis fluid sodium concentration that is too low (i.e., hypotonic) will provoke a negative sodium gradient with a water shift in the intracellular compartment, which is responsible for intra-dialytic cramps, headache, hypovolemia and risk of hypotension.

One of current opinions is the idea that sodium balance should be maintained null during a dialysis treatment: this is based on the so-called “sodium set point” theory, according to which both healthy subjects and dialysis patients tend to maintain a stable extra-cellular sodium concentration.

As above mentioned, sodium is removed during dialysis through convection and/or diffusion. The main sodium removal process during dialysis is convective. If we assume that the ultrafiltrate fluid is basically isotonic, convection does not change the tonicity of the extracellular fluid.

There is a need to help the physician to prescribe a “physiological” dialysis fluid composition to treat the patient.

Moreover, a second need is to have a bio-sensing-based therapy which is easy to use and designed also for operators not very skilled or working in crowded and very busy dialysis rooms.

To at least partly solve the above mentioned drawbacks, document U.S. Pat. No. 4,508,622 teaches a dialysis device in which the electrolyte composition of the untreated and treated fluids routed through the dialyzer may be determined and the composition of the dialysis solution adapted to the patient's requirements.

A first electrolyte detector (conductivity cell) is provided upstream of the dialyzer and a second electrolyte detector (conductivity cell) is provided downstream of the dialyzer. Each detector is coupled to a readout element through which both of the values of the dialysis solution may be observed and eventually controlled. In more detail, the apparatus according to U.S. Pat. No. 4,508,622 consists essentially of a unit for production of the dialysis solution and a dialyzer connected to the unit and followed downstream by a pump to produce a vacuum in the dialyzer on the side of the dialysis fluid. The detector mounted upstream of the dialyzer, and connected with a control unit, measures the conductivity of the total dialysis solution.

A second detector is mounted downstream of dialyzer and is connected with a comparator which is, in turn, connected to a differentiation unit. A control signal is provided by the differentiation unit to control unit if there is a difference in the differentiation unit that deviates from the predetermined nominal value.

During dialysis fluid circulation, if detector generates a signal to the evaluation unit and subsequently to the differentiation unit which deviates by a certain amount from the signal generated by detector, i.e., a difference in value appears which deviates from the predetermined value for differentiation unit, the difference unit activates the control unit, which in turn switches concentrate pump on or off as a function of the higher or lower concentration in the dialysis solution to be produced. A treatment in which the dialysis fluid has the same conductivity of the blood and of the spent dialysis fluid, is one of the described implementations.

However, the dialysis fluid and the blood reach the same conductivity after a certain time lapse which clearly affects the pre-dialytic plasma sodium content. Therefore, the method described in U.S. Pat. No. 4,508,622 in not properly an ‘isoconductive’ dialysis treatment.

In any case, ‘isoconductive’ dialysis has been shown to lead to undesired sodium loading in the patient.

Moreover, the prior art devices include dialysis apparatus wherein the conductivity of dialysis fluid is controlled in order to reach a desired post-dialysis plasmatic conductivity, i.e. conductivity (or sodium concentration) of the patient's blood at the end of the dialysis treatment.

It is known, for example from EP 1389475, a dialysis apparatus provided with a conductivity system that computes the dialysis fluid conductivity (corresponding to the dialysis fluid sodium concentration) from periodic measurements of the sodium blood concentration allowing the sodium level of the patient to reach a prescribed end-of-session value.

This dialysis apparatus includes a bag and a pump for infusing a patient with an infusion solution containing sodium at a determined and known concentration.

A structure for determining the sodium concentration [Na+]dialof the dialysis liquid is also provided so that the patient's body tends towards a desired sodium concentration [Na+]des, as a function of the dialysance D for sodium of the dialyser, of the desired sodium concentration [Na+]desinside the patient's body, of the infusion flow rate and of the sodium concentration [Na+]solof the infusion solution.

A control unit drives the pump for regulating the sodium concentration of the dialysis liquid such that this concentration is equal (tends towards) to the determined concentration [Na+]dial.

As previously mentioned, one of the problems of the dialysis apparatus of the discussed prior art is presently the choice of the appropriate post-dialysis plasmatic conductivity target.

EP 2377563 discloses a dialysis apparatus comprising a blood treatment unit with an online preparation device for preparing a dialysis fluid containing sodium and comprising a dialysis preparation section for regulating the concentration of sodium in the dialysis fluid. The blood circuit is configured to circulate extracorporeal blood through the blood chamber; control means determines a value representative of the sodium concentration in the blood and are programmed for driving the dialysis preparation section as a function of the determined plasma sodium value, such that the substance concentration in the dialysis fluid tends towards the substance concentration in the blood.

The plasma sodium content is determined by measuring the inlet and outlet conductivities of the dialysis fluid upstream and downstream the dialyzer, by then changing the conductivity upstream the filter by a prefixed step and measuring a second time the inlet and outlet conductivities of the dialysis fluid upstream and downstream the dialyzer with the modified conductivity value.

With the methods described, for example in EP 547025 or in EP 920877, it is possible to determine the plasma conductivity and thereby to properly regulate the dialysis fluid preparation section.

The described system however changes the blood conductivity and tonicity since the dialysis fluid enters into contact and exchange significantly with blood before a plasma conductivity calculation; the effect on plasma conductivity is in an amount proportional to the difference between blood and dialysis fluid conductivities.

Finally, document U.S. Pat. No. 8,182,692 describes a dialysis apparatus providing a treatment in which a dialysis fluid having a sodium concentration substantially equal to the estimated current sodium concentration in the patient's blood is performed by placing the dialysis fluid in communication with the patient's blood across the semi-permeable membrane to perform a dialysis treatment on the patient's blood without substantially altering the sodium concentration of the patient's blood during the performance of the dialysis treatment.

In more detail, a solution supply device, containing a conductivity-testing solution, is selectively placed in communication with dialyzer and the blood flowing therein.

According to this patent, any subject, including hemodialysis patients, has a set level of sodium in his body, referred to as the “set point.” The set point of a subject tends to remain relatively constant, and sodium levels deviating too far from the set point may cause discomfort to the subject. Given the above, the method of the prior art includes causing blood to flow through blood conduit of the dialyzer and flowing the conductivity-testing solution in the opposite direction through the dialyzer.

Conductivity detectors measure the conductivity of conductivity-testing solution as the solution enters and exits dialyzer. Conductivity-testing solution is formulated such that electrically conductive solutes other than sodium in the patient's blood have little or no effect on the conductivity measurements of conductivity-testing solution.

According to U.S. Pat. No. 8,182,692, due to the closely matched concentrations of electrically conductive solutes, such as phosphate, sulfate, bicarbonate, potassium, calcium, and magnesium, in conductivity-testing solution and in the patient's blood, little diffusion of those electrically conductive solutes occurs across membrane. Consequently, the conductivity measurements of conductivity-testing solution is closely correlated with the level of sodium in the patient's blood.

Therefore, conductivity-testing solution is exclusively used to accurately determine the level of sodium in the patient's blood as a function of the change in conductivity across dialyzer of the conductivity-testing solution.

Control unit then determines the level of sodium in the patient's blood as a function of the measured conductivity values.

After determining the concentration of sodium in the patient's blood, dialysis fluid may be prepared to include a concentration of sodium that is substantially equal to the concentration of sodium determined to exist in the patient's blood.

Moreover, US2012/018379 discloses an apparatus and a method for the determination and regulation of the concentration of one dissolved substance (e.g. sodium) in a dialysis fluid circuit of a hemodialysis machine.

The user presets the sodium regulation range before the start of the dialysis using an estimated value for the dialysis fluid sodium required to achieve the isonatric state or a lab measurement of the patient sodium or a value determined by the regulation from earlier treatments. In addition, the distribution volume of the patient is input for the application of the model for the correction of the diffusive balance. Furthermore, the initial concentrations of bicarbonate and potassium in the patient are set. They come from an analysis by means of a blood gas analyzer before the start of the dialysis treatment.

After the start of the treatment, the dialysis fluid flow and the conductivity are determined upstream and downstream of the dialyzer and a calculation of the updated current bicarbonate and potassium concentration in the patient takes place with it being assumed that the potassium clearance corresponds to the sodium clearance and that the bicarbonate clearance corresponds to 70% of the sodium clearance. The sodium clearance from the blood flow is estimated until the presence of the first clearance measurement.

The calculation of the conductivity balance and of the correction term for the ion exchange and thus for the sodium balance then takes place from these data.

The conductivity of fluids measured upstream and downstream, the sodium balance and the correction term for the dialysis fluid conductivity downstream of the dialyzer are then the input values for the sodium regulation. The desired conductivity thus determined is finally converted into a desired value for the dialysate sodium while taking account of the composition of the dialysis concentrate and this preset value is transmitted to a metering unit for dialysis fluid preparation.

SUMMARY

An aim of the present invention is providing an extracorporeal blood treatment apparatus able to automatically perform a proper setting of the dialysis fluid content of a substance, particularly an ionic substance, present in the blood as well.

In detail it is an aim of the present invention to provide an extracorporeal blood treatment apparatus with a proper tool helping the physician to prescribe a “physiological” dialysis fluid composition, particularly to run an isotonic, isonatric or isonatrikalemic dialysis treatment.

A further aim of the invention is to make available an extracorporeal blood treatment apparatus provided with a selectable biosensing-based therapy which is easy to use and designed for not skilled operators or users working in crowded and busy dialysis rooms.

It is an object to provide an extracorporeal blood treatment apparatus configured to run an isotonic, isonatric or isonatrikalemic dialysis treatment in any of hemodialysis (HD), hemofiltration (HF) and hemodiafiltration (HDF) treatment modes.

It is an aim of the invention to provide an extracorporeal blood treatment machine configured to automatically perform a proper automatic setting of the dialysis fluid conductivity.

A further aim of the invention is to make available a dialysis apparatus able to provide an automated delivery and control of the dialysis prescription, particularly in order to restore at each dialysis session the proper sodium-water equilibrium to the patient.

At least one of the above-indicated aims is attained by an apparatus and a corresponding method as in one or more of the appended claims, taken singly or in any combination.

According to a first independent aspect of the invention an extracorporeal blood treatment device is provided includinga filtration unit (2) having a primary chamber (3) and a secondary chamber (4) separated by a semi-permeable membrane (5);a blood withdrawal line (6) connected to an inlet of the primary chamber (3),a blood return line (7) connected to an outlet of the primary chamber (3), said blood lines being configured for connection to a patient cardiovascular system;a dialysis supply line (8) including at least an infusion line (39) connected to said blood circuit;a dialysis effluent line (13) connected to an outlet of the secondary chamber (4);a preparation device (9) for preparing a dialysis fluid connected to said dialysis supply line (8) and comprising regulating means (10) for regulating the composition of the dialysis fluid,a sensor (11) for measuring a parameter value of the dialysate in the dialysis effluent line (13), said parameter of the dialysate being at least one chosen in a group consisting of conductivity of the dialysate, a conductivity-related parameter of the dialysate, concentration of at least a substance in the dialysate and a concentration-related parameter of at least a substance in the dialysate;a control unit (12) configured to run at least a hemofiltration treatment (HF) or a hemodiafiltration treatment (HDF), each of said treatment including an infusion of substitution fluid through said infusion line (39), the control unit (12) being connected to the sensor (11) for receiving said parameter value of the dialysate, said control unit (12) being also connected to the regulating means (10) and programmed for calculating a value representative of the plasma conductivity, wherein said control unit (12) is configured for:setting a parameter value for the dialysis fluid in the dialysis supply line (8) at an initial set point, said parameter of the dialysis fluid being at least one chosen in a group consisting of conductivity of the dialysis fluid, a conductivity-related parameter of the dialysis fluid, concentration of at least a substance in the dialysis fluid and a concentration-related parameter of at least a substance in the dialysis fluid;after setting the dialysis fluid parameter value at the initial set point, circulating the dialysis fluid through the infusion line (39) so as to inject fluid in the blood;circulating blood through the primary chamber (3) of the filtration unit (2);measuring at least an initial value of said parameter of the dialysate downstream of said secondary chamber (4) at the beginning of the treatment,calculating, based on the measured initial parameter value of the dialysate and on the corresponding parameter value of the dialysis fluid in the supply line (8), the value of the initial plasma conductivity.

According to a further independent aspect of the invention a method for setting the parameters in an apparatus for extracorporeal blood treatment is provided, the apparatus comprising:a filtration unit (2) having a primary chamber (3) and a secondary chamber (4) separated by a semi-permeable membrane (5);a blood withdrawal line (6) connected to an inlet of the primary chamber (3),a blood return line (7) connected to an outlet of the primary chamber (3), said blood lines being configured for connection to a patient cardiovascular system;a dialysis supply line (8) including at least an infusion line (39) connected to said blood circuit;a dialysis effluent line (13) connected to an outlet of the secondary chamber (4);a preparation device (9) for preparing a dialysis fluid connected to said supply line (2) and comprising regulating means (10) for regulating the composition of the dialysis fluid,a sensor (11) for measuring a parameter value of the dialysate in the dialysis effluent line (13), said parameter of the dialysate being at least one chosen in a group consisting of conductivity of the dialysate, a conductivity-related parameter of the dialysate, concentration of at least a substance in the dialysate and a concentration-related parameter of at least a substance in the dialysate;a control unit (12) configured to run at least a hemofiltration treatment (HF) or a hemodiafiltration treatment (HDF), each of said treatment including an infusion of substitution fluid through said infusion line (39), said control unit (12) being connected to the sensor (11) for receiving said parameter value of the dialysate, said control unit (12) being also connected to the regulating means (10) and programmed for calculating a value representative of the plasma conductivity of the blood in said blood lines (6,7), the method comprising the following steps performed by the control unit:setting a parameter value for the dialysis fluid in the dialysis supply line (8) at an initial set point, said parameter of the dialysis fluid being at least one chosen in a group consisting of conductivity of the dialysis fluid, a conductivity-related parameter of the dialysis fluid, concentration of at least a substance in the dialysis fluid and a concentration-related parameter of at least a substance in the dialysis fluid;after setting the dialysis fluid parameter value at the initial set point, circulating the dialysis fluid through the infusion line (39) so as to inject fluid in the blood;circulating blood trough the primary chamber (3) of the filtration unit (2);measuring at least an initial value of said parameter of the dialysate downstream of said secondary chamber (4) at the beginning of the treatment,calculating, based on the measured initial parameter value of the dialysate and on the corresponding parameter value of the dialysis fluid in the dialysis supply line (8), the value of the initial plasma conductivity.

In a second aspect, according to the previous aspects, the regulating means (10) modify the dialysis fluid composition by changing conductivity of the dialysis fluid and/or by changing the concentration of at least one substance in the dialysis fluid.

In a 3rdaspect, according to the previous aspects, the preparation device (9) prepares a dialysis fluid containing at least a substance, said substance being present in the blood too, said regulating means (10) regulating the concentration of at least said substance in the dialysis fluid, said substance being an ionic substance, in particular said substance being sodium.

In a 4thaspect according to the previous aspects, the dialysis supply line (8) further includes an inlet line (45) connected to an inlet of the secondary chamber (4), particularly in an HDF treatment mode, the control unit being configured to circulate the dialysis fluid through the secondary chamber (4) of the filtration unit (2) so as to exchange with blood, said circulating the dialysis fluid through the dialysis supply line (8) up to measuring the initial value of said parameter of the dialysate downstream of said secondary chamber used for the calculating of the initial plasma conductivity, being performed maintaining the dialysis fluid parameter value substantially constant.

In a 5thaspect according to anyone of the previous aspects, the control unit is configured to set the parameter value for the dialysis fluid at the initial set point so that a dialysis fluid conductivity matches a first estimate of the plasma conductivity of the blood.

In a 6thaspect according to anyone of the previous aspects, the parameter value is a concentration value of at least a substance of the dialysis fluid, in particular said substance being sodium.

In a 7thaspect according to anyone of the previous aspects, the control unit (12) is configured for calculating the initial set point of a substance concentration in the dialysis fluid, a regulation of the dialysis fluid conductivity in the supply line (8) deriving from said calculated set point of said substance.

In an 8thaspect according to the 7thaspect, the control unit is configured to calculate the initial set point of the substance concentration to be set in the dialysis fluid as a function of the difference in concentration of at least a further substance in the dialysis fluid and the same further substance in the plasma, the substance, whose concentration is to be set, being different from the further substance, in particular for HDF pre-dilution treatment and HF pre-dilution treatment, said plasma concentration is a diluted plasma concentration, in particular the diluted plasma concentration being function of the blood flow rate and of the infusion flow rate, optionally the diluted plasma concentration being function of a dialyzable blood water fraction for said substance and the plasma water concentration in blood from patient, in detail the diluted plasma concentration being function of a concentration of said substance in the infused fluid.

In a 9thaspect according to the 7thor 8thaspects, the control unit is configured to calculate the initial set point of the substance in the dialysis fluid as a function of the concentration of at least a further substance in the dialysis fluid, the substance, whose concentration is to be set, being different from the further substance, optionally the further substance being chosen in the group including bicarbonate, potassium, calcium, magnesium, acetate, lactate, citrate, phosphate and sulphate, in particular as a function of the concentration of at least two of said substances, optionally as a function of the concentration of bicarbonate, potassium, acetate, and/or citrate, in the dialysis fluid.

In a 10thaspect according to anyone of the previous aspects from the 7thto the 9th, the control unit is configured to calculate the initial set point of the substance in the dialysis fluid as a function of the difference in concentration of at least a further substance in the dialysis fluid and in the plasma, the substance, whose concentration is to be set, being different from the further substance, said further substance being chosen in the group including bicarbonate, potassium, calcium, magnesium, acetate, lactate, phosphate, sulphate, and citrate, in particular as a function of the difference, in particular a weighted difference, in concentration of at least two of said substances, optionally as a function of the difference, in particular a weighted difference, in concentration of bicarbonate, potassium, citrate, and/or acetate in the dialysis fluid and plasma, in particular for HDF pre-dilution treatment and HF pre-dilution treatment, said plasma concentration of the substance is a diluted plasma concentration, in particular the diluted plasma concentration being function of the blood flow rate and of the infusion flow rate, optionally the diluted plasma concentration being function of a dialyzable blood water fraction for said substance and the plasma water concentration in blood from patient, in detail the diluted plasma concentration being function of a concentration of said substance in the infused fluid.

In an 11thaspect according to anyone of the previous aspects from the 7thto the 10th, the control unit is configured to calculate the initial set point of the substance in the dialysis fluid as a function of the molar conductivities of at least a substance in the dialysis fluid chosen in the group including acids and salts of bicarbonate (HCO3−), chloride (Cl−), acetate (CH3COO−), lactate (C3H5O3−), citrate (C6H5O73−), phosphate (PO43−), and sulphate (SO42−), wherein the salts are formed with sodium, potassium, calcium, or magnesium, in particular as a function of the molar conductivities of at least two of said substances, in more detail as a function of the molar conductivities of at least three of said substances, optionally as a function of the molar conductivities of the four of said substances, for example sodium bicarbonate (NaHCO3), sodium chloride (NaCl), sodium acetate (NaCH3COO), and potassium chloride (KCl), or sodium bicarbonate (NaHCO3), sodium chloride (NaCl), trisodiumcitrate (NaC6H5O7), and potassium chloride (KCl).

In a 12thaspect according to anyone of the previous aspects from the 7thto the 11th, the control unit is configured to calculate the initial set point of the substance in the dialysis fluid as a function of an estimated plasma concentration of at least a substance chosen in the group including sodium, bicarbonate, potassium, acetate, and citrate, in particular as a function of the estimated plasma concentration of at least two of said substances, in more detail as a function of the estimated plasma concentration of at least three of said substances, optionally as a function of the estimated plasma concentration of at least four of said substances included in the group consisting of sodium, potassium, calcium, magnesium, bicarbonate, acetate, lactate, citrate, phosphate, and sulphate,

in particular for HDF pre-dilution treatment and HF pre-dilution treatment, said estimated plasma concentration is a diluted plasma concentration, in particular the diluted plasma concentration being function of the blood flow rate and of the infusion flow rate, optionally the diluted plasma concentration being function of a dialyzable blood water fraction for said substance and the plasma water concentration in blood from patient, in detail, the diluted plasma concentration being function of a concentration of said substance in the infused fluid.

In a 13thaspect according to the 12thaspect, the estimated plasma concentration of at least a substance chosen in the group including sodium, bicarbonate, potassium, acetate, lactate, and citrate is the mean pre-dialysis values of the corresponding substance for large patient populations, or historical data of the corresponding substance for the individual patient or theoretical values of the corresponding substance or measured values of the corresponding substance.

In a 14thaspect according to anyone of the previous aspects from the 7thto the 13th, the control unit is configured to calculate the initial set point of the substance in the dialysis fluid as a function of at least one flow rate, in particular the dialysate flow rate at the outlet of the secondary chamber (4).

In a 15thaspect according to anyone of the previous aspects from the 7thto the 14th, the control unit is configured to calculate the initial set point of the substance in the dialysis fluid as a function of at least an efficiency parameter of the filtration unit (2), in particular a clearance of the filtration unit (2), optionally the urea clearance and/or the citrate clearance.

In a 16thaspect according to anyone of the previous aspects from the 7thto the 15th, for a HDF pre-dilution treatment mode and/or for a HF pre-dilution treatment mode, the control unit is configured to calculate the initial set point of sodium concentration in the dialysis fluid using the following relationship:

cdi,Na,start=αbi·Qb·fNa·cpw,artNaQb·fNa+(1-αbi)·Qinf++⁢1MκNaCl⁢((MκNaHCO3-MκNaCl)⁢(1αbi·Qb·fHCO3·cpw,art⁢HCO3+Qinf·cdi,HCO3Qb·fHCO3+Qinf-cdi,HCO3)++⁢(MκNaAc-MκNaCl)⁢(1αbi·Qb·fAc·cpw,artAc+Qinf·cdi,AcQb·fAc+Qinf-cdi,Ac)++⁢MκKCl·(αbi·Qb·fK·cpw,artK+Qinf·cdi,KQb·fK+Qinf-cdi,K)++⁢Kb,CitKu·(MκNa3⁢Cit-3)⁢((0.167αbi-3+0.125αbi-2+0.706αbi-1)··Qb·fCit·cpw,artCit+Qinf·cdi,CitQb·fCit+Qinf-cdi,Na3⁢Cit))++⁢QdoKu⁢κrest⁢3)·Qb·fNa+QinfQb·fNa+(1-αbi)·Qinf(I)

wherein:

in HF treatment mode, the clearance being equal to the dialyzer outlet flow, i.e. Ku=Qdo;

Qb·fNa·cpw,artNaQb·fNa+(1-αbi)·Qinf
is a diluted plasma water concentration of sodium in blood entering the filtration unit;

Qb·fHCO3·⁢cpw,artHCO3+Qinf·cdi,HCO3Qb·fHCO3+Qinf
is a diluted plasma water concentration of bicarbonate in blood entering the filtration unit;

Qb·fAc·cpw,artAc+Qinf·cdi,AcQb·fAc+Qinf
is a diluted plasma water concentration of acetate in blood entering the filtration unit;

Qb·fK·cpw,art⁢K+Qinf·cdi,KQb·fK+Qinf
is a diluted plasma water concentration of potassium in blood entering the filtration unit;

Qb·fCit·cpw,artCit+Qinf·cdi,CitQb·fCit+Qinf
is a diluted plasma water concentration of citrate in blood entering the filtration unit;

MκNaHCO3Is the molar conductivity of sodium bicarbonate (NaHCO3)MκNaClIs the molar conductivity of sodium chloride (NaCl)MκNaAcIs the molar conductivity of sodium acetate (NaCH3COO)MκKClIs the molar conductivity of potassium chloride (KCl)κrest3Is the conductivity contribution from lesser solutes 3cdi,HCO3Dialysis fluid concentration of bicarbonate as set by theoperator;cdi,KDialysis fluid concentration of potassium ions (K+) asdetermined by the used concentrate;cdi,AcDialysis fluid concentration of acetate as determined by theused concentrate;cdi,Na3CitDialysis fluid concentration of total citrate as determined bythe used concentrate;QdoIs the dialysate flow rate at dialyzer outletKuIs the dialyzer clearance for ureaαbiDonnan factor in HF/HDF pre-dilution mode;

In a 17thaspect according to anyone of the previous aspects from the 7thto the 15th, the control unit is configured to calculate the initial set point of sodium concentration in the dialysis fluid using the following relationship:

cdi,Na,start=α·cpwNa+++⁢1MκNaCl⁢((MκNaHCO3-MκNaCl)·(α-1·cpwHCO3--cdHCO3-)++⁢MkKCl·(α·cpwK+-cdK+)++⁢(MκNaAc-MκNaCl)·(α-1·cpwAc--cdAc-)++⁢KbCitKb·(MκNa3⁢Cit-3⁢MκNaCl)·((0.167α-3+0.125α-2+0.706α-1)·cpwNa3⁢Cit-cdNa3⁢Cit)++⁢QdoKb·κrest⁢3)(II)

wherein:

MκNaHCO3Is the molar conductivity of sodium bicarbonate (NaHCO3)MκNaClIs the molar conductivity of sodium chloride (NaCl)MκNaAcIs the molar conductivity of sodium acetate (NaCH3COO)MκKClIs the molar conductivity of potassium chloride (KCl)Mκ,Na3CitIs the molar conductivity of trisodium citrate (Na3C6H5O7)κrest3Is the conductivity contribution from lesser solutes 3cdi,HCO3Is the dialysis fluid concentration of bicarbonatecdi,KIs the dialysis fluid concentration of potassiumcdi,AcIs the dialysis fluid concentration of acetatecdi,Na3CitIs the dialysis fluid concentration of total citratecpw,NaIs the estimated or measured pre-dialysis concentration ofsodium ions (Na+) in plasma watercpw,HCO3Is the estimated or measured pre-dialysis concentration ofbicarbonate anions (HCO3−) in plasma watercpw,AcIs the estimated or measured pre-dialysis concentration ofacetate anions (CH3COO−) in plasma watercpw,KIs the estimated or measured pre-dialysis concentration ofpotassium ions (K+) in plasma watercpw,Na3CitIs the estimated or measured pre-dialysis concentration oftotal citrate in plasma waterQdoIs the dialysate flow rate at dialyzer outletKuIs the dialyzer clearance for ureaKbCitIs the dialyzer clearance for citrateαIs the Donnan factor

In a 18thaspect according to anyone of the previous aspects, the sensor (11) is configured to measure a conductivity of the dialysate.

In an 19thaspect according to anyone of the previous aspects, the control unit is configured to estimate at least the initial value of the parameter value of the dialysate representative of the conditions prevailing after the exchange process has reached stable conditions, said estimate being based on at least one measurement of the parameter value in the dialysate.

In a 20thaspect according to anyone of the previous aspects, the control unit (12) is configured to measure at least the initial value of the parameter value of the dialysate in the dialysis effluent line (13) downstream of the secondary chamber (4) as soon as the exchange process in the filtration unit (2) reaches stable conditions.

In a 21staspect according to the previous aspect, the control unit (12) is configured to determine reaching of stable conditions for the exchange process in case one or more of the following conditions occurs:a first derivative of the median or of the average value of the conductivity of the dialysate is lower in size than a first threshold for a specified time window;a first derivative of the value of conductivity of the dialysate is lower in size than a first threshold for a specified time window;a first derivative of the filtered value of conductivity of the dialysate is lower in size than a first threshold for a specified time window, the filtered value being a value filtered either by a median filter or a linear filter, either a finite impulse response filter, or an infinite impulse response filter;a second derivative of the median value of the conductivity of the dialysate is lower in size than a second threshold for a specified time window;a second derivative of the value of conductivity of the dialysate is lower in size than a first threshold for a specified time window;a second derivative of the filtered value of conductivity of the dialysate is lower in size than a first threshold for a specified time window;a change or a relative change of the value of conductivity of the dialysate or a filtered version of the value of the conductivity since a fixed previous point in time is below a first threshold;a change or the relative change of the value of conductivity of the dialysate or a filtered version of the value of the conductivity since a fixed time interval backwards is below a first threshold;a prefixed time has lapsed after starting circulation of both blood and dialysis fluid in the filtration unit, in particular said pre-fixed time being not more than 15 minutes;a variable time has lapsed after starting circulation of both blood and dialysis fluid in the filtration unit, said variable time being function of at least a parameter of the apparatus.

In a 22ndaspect according to the previous aspect, the at least one parameter is chosen in the group including a volume of the secondary chamber (4) of the filtration unit (2), dialysis fluid flow rate, blood flow rate, filtration unit permeability.

In a 23rdaspect according to the previous 21stor 22ndaspects, during the step of determining reaching of stable conditions, the control unit (12) is configured to prevent changes in the dialysis fluid flow rate, particularly the control unit (12) is also configured to prevent changes in the blood flow rate and/or in the ultrafiltration rate.

In a 24thaspect according to anyone of the previous aspects, the control unit (12) is configured to measure a conductivity value of the dialysate and to compensate the measured initial conductivity value of the dialysate for the effect of the electrically neutral substance, in particular said electrically neutral substances include urea and glucose.

In a 25thaspect according to the previous aspect, the control unit (12) is configured to compensate the measured initial conductivity value of the dialysate as a function of the concentration of at least a substance in the dialysis fluid, said substance being particularly glucose.

In a 26thaspect according to the previous 24thor 25thaspects, the control unit is configured to compensate the measured initial conductivity value of the dialysate as a function of at least one flow rate, in particular the dialysate flow rate at the outlet of the secondary chamber (4).

In a 27thaspect according to anyone of the previous aspects from the 24thto the 26th, the control unit is configured to compensate the measured initial conductivity value of the dialysate as a function of at least an efficiency parameter of the filtration unit (2), in particular a clearance of the filtration unit (2), optionally the urea clearance.

In a 28thaspect according to anyone of the previous aspects from the 24thto the 27th, the control unit is configured to compensate the measured initial conductivity value of the dialysate as a function of an estimated plasma concentration of at least a substance chosen in the group including glucose and urea, in particular as a function of the estimated plasma concentration of both glucose and urea.

In a 29thaspect according to anyone of the previous aspects from the 24thto the 28th, the control unit is configured to compensate the measured initial conductivity value of the dialysate using the following formula (III):

κ0,do=κdo(1-γg(cdi,g+fg,KB⁢KuQdo⁢(cp,gfpw-cdi,g))⁢(1-γu⁢KuQdo⁢cp,ufpw)(III)

wherein:

Dialysate conductivity after filtration unit;QdoDialysate flow rate at the filtration unit outlet;KuFiltration unit clearance for urea;cdi,gDialysis fluid concentration of glucose;cp,gPre-dialysis concentration of glucose in plasma;cp,uPre-dialysis concentration of urea in plasma;fpwPlasma water fraction, i.e. the part of plasma that is pure water;fg,KBGlucose clearance fraction, i.e. the relative glucose clearancecompared to urea clearance;Dialysate fluid conductivity at the filtration unit outletfor a pure electrolyte solution (with conductivitycompensated for the influence of glucose and urea);γgConductivity correction term for glucose;γuConductivity correction term for urea;

In a 30thaspect according to anyone of the previous aspects, the control unit (12) is configured to compensate an initial conductivity of the dialysis fluid for the effect of the electrically neutral substances, in particular said electrically neutral substances include glucose.

In a 31staspect according to the previous aspect, the control unit (12) is configured to compensate the initial conductivity of the dialysis fluid as a function of the concentration of at least a substance in the dialysis fluid, said substance being particularly glucose.

In a 32ndaspect according to anyone of the previous 30thor 31staspects, the control unit is configured to compensate the initial conductivity of the dialysis fluid using the following formula (IV):

κ0,di=κdi1-γg⁢cdi,g(IV)

wherein:

Dialysis fluid conductivity upstream the filtration unit;cdi,gDialysis fluid concentration of glucose;Dialysis fluid conductivity at the filtration unit inlet fora pure electrolyte solution (with conductivitycompensated for the influence of glucose, if present);γgConductivity correction term for glucose;

In a 33rdaspect according to anyone of the previous aspects, once the diffusion process in the filtration unit (2) reaches stable conditions, the control unit (12) is configured to determine at least an initial conductivity of the dialysis fluid upstream said secondary chamber (4), said determining being executed either by receiving the dialysis fluid conductivity set value or by receiving a signal from a sensor for measuring a conductivity-related value of the dialysis fluid in the dialysis fluid supply line (8).

In a 34thaspect according to the previous aspect, the control unit (12) is configured to determine the initial conductivity of the dialysis fluid and the initial conductivity of the dialysate substantially at the same time.

In a 35thaspect according to anyone of the previous aspects, the control unit is configured to calculate the plasma conductivity as a function of at least one flow rate, in particular said flow rate being chosen in the group including the dialysate flow rate at the outlet of the secondary chamber (4) and the blood flow rate in the blood lines (6,7).

In a 36thaspect according to the previous aspect, the control unit is configured to calculate the plasma conductivity as a function of the dialysate flow rate at the outlet of the secondary chamber (4) and the blood flow rate in the blood lines (6,7).

In a 37thaspect according to anyone of the previous aspects, the control unit is configured to calculate the plasma conductivity as a function of at least an efficiency parameter of the filtration unit (2), in particular a clearance of the filtration unit (2), optionally the urea clearance.

In a 38thaspect according to anyone of the previous aspects from the 24thto 29th, the control unit is configured to calculate the plasma conductivity as a function of at least a compensated initial conductivity of the dialysate.

In a 39thaspect according to anyone of the previous aspects from the 30thto 32nd, the control unit is configured to calculate the plasma conductivity as a function of at least a compensated conductivity of the dialysis fluid in the dialysis supply line (8).

In a 40thaspect according to anyone of the previous aspects, the control unit is configured to calculate the plasma conductivity according to the following formula (V):

κp,1′=κ0,do+QdoQBset⁢(κ0,do-κ0,di)(V)

wherein:

Plasma conductivity first estimate;QdoDialysate flow rate at the filtration unit outlet;QbsetSet blood flow rate at the filtration unit inlet;Dialysis fluid conductivity at the filtration unitinlet for a pure electrolyte solution;Dialysate conductivity at the filtration unit outletfor a pure electrolyte solution;

In a 41staspect according to anyone of the previous aspects, the control unit is configured to calculate the plasma conductivity according to the following formula (VI):

κp,1″=κ0,di+QdoKu⁢(κ0,do-κ0,di)(VI)

wherein:

Plasma conductivity first estimate;QdoDialysate fluid flow rate at the filtration unit outlet;KuFiltration unit clearance for urea;Dialysis fluid conductivity at the filtration unit inletfor a pure electrolyte solution;Dialysate conductivity at the filtration unit outletfor a pure electrolyte solution;

In a 42ndaspect according to anyone of the 37thor 41staspect, the control unit is configured to calculate the urea clearance as a function of one or more flow rates chosen in the group including the dialyzer inlet blood water flow rate, the dialyzer outlet blood water flow rate, the ultrafiltration flow rate and the dialysis fluid flow rate at the outlet of the secondary chamber (4).

In a 43rdaspect according to the previous aspect, the control unit is configured to calculate the urea clearance for HD and HDF treatment modes according to the following formulas (VII):

Ku=Qbwi·1-QbwoQbwi·ψ1-Qbwoqdo·ψ(VIIa)

where ψ is:

ψ=QdoQdi·(Qbwo·QdoQbwi·Qdi)Km⁢AQu(VIIb)

where kmA is:

km⁢A=PeePe-1*k0⁢A(VIIc)

where Pe is:

Pe=Quk0⁢A(VIId)

wherein:

QdiDialysis fluid flow rate at the filtration unit inlet;QbwiDialyzer inlet blood water flow rate;QbwoDialyzer outlet blood water flow rate;QdoDialysate flow rate at filtration unit outlet (i.e., Qdi+ Quf);KuFiltration unit clearance for urea;K0AUrea mass transfer coefficient of the filtration unit;QuTotal ultrafiltration flow rate;PePeclet number;kmAModified mass transfer coefficient;

In a 44thaspect according to anyone of the previous aspects, after calculating the initial plasma conductivity, the control unit is configured to drive the regulating means (10) to change the composition of the dialysis fluid to reach a dialysis fluid conductivity substantially equal to the calculated initial plasma conductivity.

In a 45thaspect according to anyone of the previous aspects, immediately after calculating the initial plasma conductivity, the control unit is configured to drive the regulating means (10) to change the composition of the dialysis fluid and to set the dialysis fluid conductivity substantially equal to the calculated plasma conductivity.

In a 46thaspect according to the previous aspect, after setting the dialysis fluid conductivity substantially equal to the calculated plasma conductivity, the control unit is configured to execute a second calculating step, based on a second determined initial conductivity of the dialysate and on a second corresponding conductivity of the dialysis fluid in the supply line (8), of a second estimate of the initial plasma conductivity, said calculating the second estimate being performed maintaining the dialysis fluid conductivity substantially constant and substantially equal to the calculated plasma conductivity.

In a 47thaspect according to anyone of the previous aspects, after calculating the second estimate of the initial plasma conductivity, the control unit is configured to drive the regulating means (10) to change the composition of the dialysis fluid and to set the dialysis fluid conductivity substantially equal to said second estimate.

In a 48thaspect according to anyone of the previous 46thor 47thaspects, the calculation of the second estimate of the plasma conductivity is executed according to anyone of the aspects from the 35thto 43rd.

In a 49thaspect according to anyone of the previous aspects, the control unit is configured to drive the regulating means as a function of the calculated plasma conductivity to change the dialysis fluid conductivity.

In a 50thaspect according to anyone of the previous aspects, the control unit is programmed to allow selection of at least one treatment mode chosen in the group including HD treatment mode, HDF treatment mode and HF treatment mode, additionally, the control unit is programmed to allow selection of at least one treatment mode chosen in the group including isotonic dialysis, isonatric dialysis, and isonatrikalemic dialysis, the control unit is configured to drive the regulating means as a function of the calculated plasma conductivity and of the chosen treatment mode to set either a desired dialysis fluid inlet conductivity or a desired dialysis fluid inlet substance concentration, in particular said substance being sodium.

In a 51staspect according to the previous aspect, the control unit is programmed to keep the desired dialysis fluid inlet conductivity substantially constant throughout the remainder of the treatment.

In a 52ndaspect according to the 5thaspect, the parameter value is a conductivity value of the dialysis fluid.

In a 53rdaspect according to anyone of the previous aspects, the setting of the parameter value in the dialysis fluid includes the sub-step of calculating the parameter value as a function of a main contribution term based on a blood parameter and as a function of an adjustment contribution term based on a concentration of at least a substance in the dialysis fluid chosen in the group including bicarbonate, potassium, acetate, lactate, citrate, magnesium, calcium, and phosphate, said blood parameter being the plasma conductivity or a plasma conductivity-related of the blood in the extracorporeal blood circuit.

In a 54thaspect according to the previous aspect, the control unit is configured to calculate the adjustment contribution term based on the concentration of two or more substances in the dialysis fluid chosen in the group including bicarbonate, potassium, acetate, lactate, citrate, in particular as a function of the concentration of at least three of said substances, optionally as a function of the concentration of bicarbonate, potassium, and acetate in the dialysis fluid.

In a 55thaspect according to the 53rdor 54thaspect, the control unit is configured to calculate the adjustment contribution term as a function of the difference in concentration of at least a substance in the dialysis fluid and the same substance in the blood plasma, wherein for HDF pre-dilution treatment and HF pre-dilution treatment, said plasma concentration is a diluted plasma concentration, in particular the diluted plasma concentration being function of the blood flow rate and of the infusion flow rate, optionally the diluted plasma concentration being function of a dialyzable blood water fraction for said substance and the plasma water concentration in blood from patient, in detail the diluted plasma concentration being function of a concentration of said substance in the infused fluid.

In a 56thaspect according to anyone of the previous aspects from the 53rdto the 55th, the control unit is configured to calculate the adjustment contribution term as a function of the difference in concentration of at least a substance in the dialysis fluid and the same substance in the plasma, said substance being chosen in the group including bicarbonate, potassium, acetate, lactate, and citrate, in particular as a function of the difference in concentration of at least two of said substances, optionally as a function of the difference in concentration of bicarbonate, potassium, citrate, and acetate in the dialysis fluid and plasma, wherein for HDF pre-dilution treatment and HF pre-dilution treatment, said plasma concentration is a diluted plasma concentration, in particular the diluted plasma concentration being function of the blood flow rate and of the infusion flow rate, optionally the diluted plasma concentration being function of a dialyzable blood water fraction for said substance and the plasma water concentration in blood from patient, in detail the diluted plasma concentration being function of a concentration of said substance in the infused fluid.

In a 57thaspect according to anyone of the previous aspects from the 53rdto the 56th, the blood parameter is the plasma conductivity, or the concentration of at least a substance in the blood, said substance being in particular sodium.

In a 58thaspect according to anyone of the previous aspects from the 53rdto the 57th, the parameter of the dialysis fluid is the conductivity of the dialysis fluid, or the concentration of at least a substance in the dialysis fluid, said substance being in particular sodium.

In a 59thaspect according to anyone of the previous aspects from the 53rdto the 58th, the blood parameter is the plasma conductivity and the parameter of the dialysis fluid is the conductivity of the dialysis fluid.

In a 60thaspect according to anyone of the previous aspects from the 53rdto 59th, the blood parameter is the concentration of at least a substance in the blood, said substance being in particular sodium, and the parameter of the dialysis fluid is the concentration of at least a substance in the dialysis fluid, said substance being in particular sodium.

In a 61staspect according to anyone of the previous aspects from the 53rdto the 60th, the blood parameter is the concentration of at least a substance in the blood, and the parameter of the dialysis fluid is the concentration of at least the same substance in the dialysis fluid.

In a 62ndaspect according to anyone of the previous aspects from the 53rdto the 61st, the main contribution term is dimensionally a concentration of a substance in a fluid.

In a 63rdaspect according to anyone of the previous aspects from the 53rdto the 62nd, the main contribution term is a dialysis fluid concentration of sodium at an isoconductive state, i.e. when the dialysis fluid conductivity substantially matches the plasma conductivity.

In a 64thaspect according to anyone of the previous aspects from the 53rdto the 63rd, the main contribution term affects the dialysis fluid parameter value for at least 80% of the parameter value, the adjustment contribution term contributes to the dialysis fluid parameter value for less than 15% of the parameter value.

In a 65thaspect according to anyone of the previous aspects from the 53rdto the 64th, the sub-step of calculating the parameter value as a function of the main contribution term and the adjustment contribution term is a sub-step of calculating an algebraic sum of at least the main contribution term and the adjustment contribution term and particularly the adjustment contribution term is dimensionally a concentration of a substance in a fluid.

In a 66thaspect according to anyone of the previous aspects from the 53rdto the 65th, the adjustment contribution term is the sodium concentration set point adjustment relative to an isoconductive state to provide a treatment chosen in the group including isotonic dialysis, isonatric dialysis, and isonatrikalemic dialysis.

In a 67thaspect according to anyone of the previous aspects from the 53rdto the 66th, the main contribution term affects (contributes to) the dialysis fluid parameter value for at least 90% of the parameter value, the adjustment contribution term contributing to the dialysis fluid parameter value for less than 10% of the parameter value.

In a 68thaspect according to anyone of the previous aspects from the 53rdto the 67th, the control unit drives the regulating means (10) for regulating the conductivity or the concentration of at least a substance in the dialysis fluid, the control unit setting the parameter value for the dialysis fluid in the dialysis supply line (8) at the calculated set point.

In a 69thaspect according to anyone of the previous aspects from the 53rdto the 68th, the regulating means (10) regulates the concentration of at least a substance in the dialysis fluid, in particular an ionic substance, such as sodium.

In a 70thaspect according to anyone of the previous aspects from the 53rdto the 69th, the control unit drives the regulating means (10) for regulating the sodium concentration in the dialysis fluid to set the parameter value for the dialysis fluid in the dialysis supply line (8) at the calculated set point.

In a 71staspect according to anyone of the previous aspects from the 53rdto the 70th, the control unit is configured to calculate the adjustment contribution term as a function of the molar conductivities of at least a substance in the dialysis fluid chosen in the group including sodium bicarbonate (NaHCO3), sodium chloride (NaCl), sodium acetate (NaCH3COO), potassium chloride (KCl), lactate, and trisodium citrate (Na3C6H5O7), in particular as a function of the molar conductivities of at least two of said substances, in more detail as a function of the molar conductivities of at least three of said substances, optionally as a function of the molar conductivities of sodium bicarbonate (NaHCO3), sodium chloride (NaCl), sodium acetate (NaCH3COO), trisodium citrate (Na3C6H5O7), and potassium chloride (KCl).

In a 72ndaspect according to anyone of the previous aspects from the 53rdto the 71st, the control unit is configured to calculate the adjustment contribution term as a function of a difference between two molar conductivities.

In a 73rdaspect according to anyone of the previous aspects from the 53rdto the 72nd, the control unit is configured to calculate the adjustment contribution term as a function of a difference between a first molar conductivity of a substance chosen in the group including sodium bicarbonate (NaHCO3), sodium acetate (NaCH3COO), trisodium citrate (Na3C6H5O7), and potassium chloride (KCl), and a molar conductivity of sodium chloride (NaCl).

In a 74thaspect according to anyone of the previous aspects from the 53rdto the 73rd, the control unit is configured to calculate the adjustment contribution term as a function of a difference between a molar conductivity of sodium bicarbonate (NaHCO3), and a molar conductivity of sodium chloride (NaCl).

In a 75thaspect according to anyone of the previous aspects from the 53rdto the 74th, the control unit is configured to calculate the adjustment contribution term as a function of a difference between a molar conductivity of sodium acetate (NaCH3COO), and a molar conductivity of sodium chloride (NaCl).

In a 76thaspect according to anyone of the previous aspects from the 53rdto the 75th, the control unit is configured to calculate the adjustment contribution term as a function of a difference between a molar conductivity of trisodium citrate (Na3C6H5O7), and a molar conductivity of sodium chloride (NaCl).

In a 77thaspect according to anyone of the previous aspects from the 53rdto the 76th, the control unit is configured to calculate the adjustment contribution term as a function of a difference between a molar conductivity of potassium chloride (KCl), and a molar conductivity of sodium chloride (NaCl).

In a 78thaspect according to anyone of the previous aspects from the 53rdto the 77th, the control unit is configured to calculate the adjustment contribution term as a function of an estimated plasma water concentration of at least a substance chosen in the group including bicarbonate, potassium, acetate, lactate, and citrate, in particular as a function of the estimated plasma water concentration of at least two of said substances, in more detail as a function of the estimated plasma water concentration of at least three of said substances, optionally as a function of the estimated plasma water concentration of bicarbonate, potassium, citrate, and acetate, wherein for HDF pre-dilution treatment and HF pre-dilution treatment, said estimated plasma concentration is a diluted plasma concentration, in particular the diluted plasma concentration being function of the blood flow rate and of the infusion flow rate, optionally the diluted plasma concentration being function of a dialyzable blood water fraction for said substance and the plasma water concentration in blood from patient, in detail the diluted plasma concentration being function of a concentration of said substance in the infused fluid.

In a 79thaspect according to anyone of the previous aspects from the 53rdto the 78th, the estimated plasma water concentration of at least a substance chosen in the group including bicarbonate, potassium, citrate, and acetate is the mean pre-dialysis values of the corresponding substance for large patient populations or historical data of the corresponding substance for the individual patient or theoretical values of the corresponding substance or measured values of the corresponding substance.

In a 80thaspect according to the 78thor 79thaspects, the estimated plasma water concentration or the diluted plasma water concentration is adjusted by a respective, preferably fixed, adjusting factor taking account of the Donnan effect.

In a 81staspect according to anyone of the previous aspects from the 53rdto the 80th, the control unit is configured to calculate the adjustment contribution term as an algebraic sum of at least two components, a first component being function of the difference, in particular weighted difference, in concentration of at least a substance in the dialysis fluid and the same substance in the blood plasma, the second component being function of the difference, in particular weighted difference, in concentration of at least a second substance in the dialysis fluid and the same second substance in the blood plasma, wherein for HDF pre-dilution treatment and HF pre-dilution treatment, said plasma concentration is a diluted plasma concentration, in particular the diluted plasma concentration being function of the blood flow rate and of the infusion flow rate, optionally the diluted plasma concentration being function of a dialyzable blood water fraction for said substance and the plasma water concentration in blood from patient, in detail the diluted plasma concentration being function of a concentration of said substance in the infused fluid.

In an 82ndaspect according to anyone of the previous aspects from the 53rdto the 81st, the control unit is configured to calculate the adjustment contribution term as an algebraic sum of at least three components, a first component being function of the difference, in particular weighted difference, in concentration of at least a substance in the dialysis fluid and the same substance in the blood plasma, the second component being function of the difference, in particular weighted difference, in concentration of at least a second substance in the dialysis fluid and the same second substance in the blood plasma, the third component being function of the difference, in particular weighted difference, in concentration of at least a third substance in the dialysis fluid and the same third substance in the blood plasma, wherein for HDF pre-dilution treatment and HF pre-dilution treatment, said plasma concentration is a diluted plasma concentration, in particular the diluted plasma concentration being function of the blood flow rate and of the infusion flow rate, optionally the diluted plasma concentration being function of a dialyzable blood water fraction for said substance and the plasma water concentration in blood from patient, in detail the diluted plasma concentration being function of a concentration of said substance in the infused fluid.

In an 83rdaspect according to anyone of the previous aspects from the 53rdto the 82nd, the control unit is configured to calculate the adjustment contribution term as an algebraic sum of at least two components, a first component being function of a concentration of at least a substance in the dialysis fluid and/or in the blood plasma, a second component being function of a concentration of at least a second substance in the dialysis fluid and/or in the blood plasma, wherein for HDF pre-dilution treatment and HF pre-dilution treatment, said plasma concentration is a diluted plasma concentration, in particular the diluted plasma concentration being function of the blood flow rate and of the infusion flow rate, optionally the diluted plasma concentration being function of a dialyzable blood water fraction for said substance and the plasma water concentration in blood from patient, in detail the diluted plasma concentration being function of a concentration of said substance in the infused fluid.

In an 84thaspect according to anyone of the previous aspects from the 53rdto the 83rd, the control unit is configured to calculate the adjustment contribution term as an algebraic sum of at least three components, a first component being function of a concentration of at least a substance in the dialysis fluid and/or in the blood plasma, a second component being function of a concentration of at least a second substance in the dialysis fluid and/or in the blood plasma, a third component being function of a concentration of at least a third substance in the dialysis fluid and/or in the blood plasma.

In an 85thaspect according to anyone of the previous aspects from the 81stto the 84th, said substance is chosen in the group including bicarbonate anions (HCO3−), acetate anions (CH3COO−), citrate anions (C6H5O73−), and potassium ions (K+).

In an 86thaspect according to anyone of the previous aspects from the 53rdto the 85th, the control unit is configured to calculate the adjustment contribution term as a function of at least one flow rate, in particular the spent dialysis fluid flow rate at the outlet of the secondary chamber (4).

In an 87thaspect according to anyone of the previous aspects from the 53rdto the 86th, the control unit is configured to calculate the adjustment contribution term as a function of at least an efficiency parameter of the filtration unit (2), in particular a clearance of the filtration unit (2), optionally the urea clearance and/or the citrate clearance.

In an 88thaspect according to anyone of the previous aspects from the 53rdto the 87th, the control unit is configured to calculate the adjustment contribution term as a function of at least a ratio between one flow rate, in particular the spent dialysis fluid flow rate at the outlet of the secondary chamber (4), and an efficiency parameter of the filtration unit (2), in particular a clearance of the filtration unit (2), optionally the urea clearance and/or the citrate clearance.

In an 89thaspect according to anyone of the previous aspects from the 53rdto the 88th, the control unit is configured to calculate the adjustment contribution term as an algebraic sum of at least two, and particularly three or four or five, components, one component being a function of at least a ratio between one flow rate, in particular the spent dialysis fluid flow rate at the outlet of the secondary chamber (4), and an efficiency parameter of the filtration unit (2), in particular a clearance of the filtration unit (2), optionally the urea clearance and/or the citrate clearance.

In a 90thaspect according to anyone of the previous aspects from the 53rdto the 89th, the control unit (12) is programmed for calculating the blood parameter.

In a 91staspect according to anyone of the previous aspects from the 53rdto the 90th, the control unit (12) is programmed for receiving as an input the blood parameter.

In a 92ndaspect according to anyone of the previous aspects from the 53rdto the 91st, the control unit (12) is programmed for storing in a memory said value representative of the parameter of the blood in said blood lines, said value representative of the parameter of the blood being not calculated by the control unit.

In a 93rdaspect according to anyone of the previous aspects from the 53rdto the 92nd, the adjustment contribution term has a negative value.

In a 94thaspect according to anyone of the previous aspects from the 53rdto the 93rd, for a HDF pre-dilution treatment mode and/or for a HF pre-dilution treatment mode, the adjustment contribution term is:

cdi,Na,isotonic,⁢adj=-1MκNaCl⁢((MκNaHCO3-MκNaCl)⁢(1αbi·Qb·fHCO3·cpw,artHCO3+Qinf·cdi,HCO3Qb·fHCO3+Qinf-cdi,HCO3)++⁢(MκNaAc-MκNaCl)⁢(1αbi·Qb·fAc·cpw,artAc+Qinf·cdi,AcQb·fAc+Qinf-cdi,Ac)++⁢(MκKCl-MκNaCl)·(αbi·Qb·fK·cpw,artK+Qinf·cdi,KQb·fK+Qinf-cdi,K)++⁢Kb,CitKu·(Mκ⁢⁢Na3⁢Cit-MκNaCl)⁢((0.167⁢⁢αbi-3+0.125⁢⁢αbi-2+0.706⁢⁢αbi-1)··Qb·fCit·cpw,artCit+Qinf·cdi,CitQb·fCit+Qinf-cdi,Na3⁢Cit))++⁢QdoKu⁢(κrest⁢⁢1+κrest⁢⁢2)(VIII)

wherein:

in HF treatment mode, the clearance being equal to the dialyzer outlet flow, i.e. Ku=Qdo;

Qb·fHCO3·cpw,artHCO3+Qinf·cdi,HCO3Qb·fHCO3+Qinf
is a diluted plasma water concentration of bicarbonate in blood entering the filtration unit;

Qb·fAc·cpw,artAc+Qinf·cdi,AcQb·fAc+Qinf
is a diluted plasma water concentration of acetate in blood entering the filtration unit;

Qb⁣·fK·cpw,artK+Qinf·cdi,KQb·fK+Qinf
is a diluted plasma water concentration of potassium in blood entering the filtration unit;

Qb·fCit·cpw,artCit+Qinf·cdi,CitQb·fCit+Qinf
is a diluted plasma water concentration of citrate in blood entering the filtration unit;

cdi,Na,isotonic,adjSodium set point adjustment (relative to isoconductive state)required to provide isotonic dialysis;MκNaHCO3Is the molar conductivity of sodium bicarbonate (NaHCO3)MκNaClIs the molar conductivity of sodium chloride (NaCl)MκNaAcIs the molar conductivity of sodium acetate (NaCH3COO)MκKClIs the molar conductivity of potassium chloride (KCl)κrest1Is the conductivity contribution from lesser solutes 1κrest2Is the conductivity contribution from lesser solutes 2cdi,HCO3Dialysis fluid concentration of bicarbonate as set by theoperator;cdi,KDialysis fluid concentration of potassium ions (K+) asdetermined by the used concentrate;cdi,AcDialysis fluid concentration of acetate as determined by theused concentrate;cdi,Na3CitDialysis fluid concentration of total citrate as determined bythe used concentrate;QdoIs the dialysate flow rate at dialyzer outletKuIs the dialyzer clearance for ureaαbiDonnan factor in HF/HDF pre-dilution mode;

In a 95thaspect according to anyone of the previous aspects from the 53rdto the 93rd, for a HDF pre-dilution treatment mode and/or for a HF pre-dilution treatment mode, the adjustment contribution term is:

cdi,Na,isoNa,⁢adj=-1MκNaCl⁢((MκNaHCO3-MκNaCl)⁢(1αbi·Qb·fHCO3·cpw,artHCO3+Qinf·cdi,HCO3Qb·fHCO3+Qinf-cdi,HCO3)++⁢(MκNaAc-MκNaCl)⁢(1αbi·Qb·fAc·cpw,artAc+Qinf·cdi,AcQb·fAc+Qinf-cdi,Ac)++⁢MκKCl·(αbi·Qb·fK·cpw,artK+Qinf·cdi,KQb·fK+Qinf-cdi,K)++⁢Kb,CitKu·(Mκ⁢⁢Na3⁢Cit-3⁢MκNaCl)⁢((0.167⁢⁢αbi-3+0.125⁢⁢αbi-2+0.706⁢⁢αbi-1)··Qb·fCit·cpw,artCit+Qinf·cdi,CitQb·fCit+Qinf-cdi,Na3⁢Cit))++⁢QdoKu⁢κrest⁢⁢3(IX)

wherein:

Qb·fHCO3·cpw,artHCO3+Qinf·cdi,HCO3Qb·fHCO3+Qinf
is a diluted plasma water concentration of bicarbonate in blood entering the filtration unit;

Qb·fAc·cpw,artAc+Qinf·cdi,AcQb·fAc+Qinf
is a diluted plasma water concentration of acetate in blood entering the filtration unit;

Qb·fK·cpw,artK+Qinf·cdi,KQb·fK+Qinf
is a diluted plasma water concentration of potassium in blood entering the filtration unit;

Qb·fCit·cpw,artCit+Qinf·cdi,CitQb·fCit+Qinf
is a diluted plasma water concentration of citrate in blood entering the filtration unit;

cdi,Na,isoNa,adjSodium set point adjustment (relative to isoconductive state)required to provide isonatremic dialysis;MκNaHCO3Is the molar conductivity of sodium bicarbonate (NaHCO3)MκNaClIs the molar conductivity of sodium chloride (NaCl)MκNaAcIs the molar conductivity of sodium acetate (NaCH3COO)MκKClIs the molar conductivity of potassium chloride (KCl)κrest3Is the conductivity contribution from lesser solutes 3cdi,HCO3Dialysis fluid concentration of bicarbonate as set by theoperator;cdi,KDialysis fluid concentration of potassium ions (K+) asdetermined by the used concentrate;cdi,AcDialysis fluid concentration of acetate as determined by theused concentrate;cdi,Na3CitDialysis fluid concentration of total citrate as determined bythe used concentrate;QdoIs the dialysate flow rate at dialyzer outletKuIs the dialyzer clearance for ureaαbiDonnan factor in HF/HDF pre-dilution mode;

In a 96thaspect according to anyone of the previous aspects from the 53rdto the 93rd, for a HDF pre-dilution treatment mode and/or for a HF pre-dilution treatment mode, the adjustment contribution term is:

cdi,Na,isoNaK,⁢adj=-1MκNaCl⁢((MκNaHCO3-MκNaCl)⁢(1αbi·Qb·fHCO3·cpw,artHCO3+Qinf·cdi,HCO3Qb·fHCO3+Qinf-cdi,HCO3)++⁢(MκNaAc-MκNaCl)⁢(1αbi·Qb·fAc·cpw,artAc+Qinf·cdi,AcQb·fAc+Qinf-cdi,Ac)++⁢(MκKCl-MκNaCl)·(αbi·Qb·fK·cpw,artK+Qinf·cdi,KQb·fK+Qinf-cdi,K)++⁢Kb,CitKu·(Mκ⁢⁢Na3⁢Cit-3⁢MκNaCl)⁢((0.167⁢⁢αbi-3+0.125⁢⁢αbi-2+0.706⁢⁢αbi-1)··Qb·fCit·cpw,artCit+Qinf·cdi,CitQb·fCit+Qinf-cdi,Na3⁢Cit))++⁢QdoKu⁢κrest⁢⁢3(X)

wherein:

Qb·fHCO3·cpw,artHCO3+Qinf·cdi,HCO3Qb·fHCO3+Qinf
is a diluted plasma water concentration of bicarbonate in blood entering the filtration unit;

Qb·fAc·cpw,artAc+Qinf·cdi,AcQb·fAc+Qinf
is a diluted plasma water concentration of acetate in blood entering the filtration unit;

Qb·fK·cpw,artK+Qinf·cdi,KQb·fK+Qinf
is a diluted plasma water concentration of potassium in blood entering the filtration unit;

Qb·fCit·cpw,artCit+Qinf·cdi,CitQb·fCit+Qinf
is a diluted plasma water concentration of citrate in blood entering the filtration unit;

cdi,Na,isoNa+K,adjSodium set point adjustment (relative to isoconductivestate) required to provide isonatremic dialysis;MκNaHCO3Is the molar conductivity of sodium bicarbonate (NaHCO3)MκNaClIs the molar conductivity of sodium chloride (NaCl)MκNaAcIs the molar conductivity of sodium acetate (NaCH3COO)MκKClIs the molar conductivity of potassium chloride (KCl)κrest3Is the conductivity contribution from lesser solutes 3cdi,HCO3Dialysis fluid concentration of bicarbonate as set by theoperator;cdi,KDialysis fluid concentration of potassium ions (K+) asdetermined by the used concentrate;cdi,AcDialysis fluid concentration of acetate as determined bythe used concentrate;cdi,Na3CitDialysis fluid concentration of total citrate as determinedby the used concentrate;QdoIs the dialysate flow rate at dialyzer outletKuIs the dialyzer clearance for ureaαbiDonnan factor in HF/HDF pre-dilution mode;

In a 97thaspect according to anyone of the previous aspects from the 53rdto the 93rd, for a HD treatment mode, HDF post-dilution treatment mode and/or for a HF post-dilution treatment mode, the adjustment contribution term is:

cdi,Na,isotonic,adj=-1⁢((MκNaHCO3-MκNaCl)⁢(1α*cpw,HCO3-cdi,HCO3)+(MκNaAc-MκNaCl)⁢(1α*cpw,Ac-cdi,Ac)++⁢(MκKCl-MκNaCl)⁢(α*cpw,K-cdi,K)++⁢KbCitKu⁢(MNa3⁢Cit-MκNaCl)⁢((0.167α-3+0.125α-2+0.706α-1)*cpw,Na3⁢Cit-cdi,Na3⁢Cit)++⁢QdoKu⁢(κrest⁢1+κrest⁢2))(XI)

wherein:

cdi,Na,isotonic,adjSodium concentration set point adjustment (relative toisoconductive state) required to provide isotonic dialysisMκNaHCO3Is the molar conductivity of sodium bicarbonate (NaHCO3)MκNaClIs the molar conductivity of sodium chloride (NaCl)MκNaAcIs the molar conductivity of sodium acetate(NaCH3COO)MκKClIs the molar conductivity of potassium chloride (KCl)Mκ,Na3CitIs the molar conductivity of trisodium citrate(Na3C6H5O7)κrest1Is the conductivity contribution from lesser solutes 1κrest2Is the conductivity contribution from lesser solutes 2cdi,HCO3Is the dialysis fluid concentration of bicarbonatecdi,KIs the dialysis fluid concentration of potassiumcdi,AcIs the dialysis fluid concentration of acetatecdi,Na3CitIs the dialysis fluid concentration of total citratecpw,HCO3Is the estimated or measured pre-dialysis concentrationof bicarbonate anions (HCO3−) in plasma watercpw,AcIs the estimated or measured pre-dialysis concentration( of anions CH3COO−) in plasma watercpw,KIs the estimated or measured pre-dialysis concentrationof potassium ions (K+) in plasma watercpw,Na3CitIs the estimated or measured pre-dialysis concentrationof total citrate in plasma waterQdoIs the dialysate flow rate at dialyzer outletKuIs the dialyzer clearance for ureaKbCitIs the dialyzer clearance for citrateαIs the Donnan factor

In a 98thaspect according to anyone of the previous aspects from the 53rdto the 93rd, for a HD treatment mode, HDF post-dilution treatment mode and/or for a HF post-dilution treatment mode, the adjustment contribution term is:

cdi,Na,isoNa,adj=-1⁢((MκNaHCO3-MκNaCl)⁢(1α*cpw,HCO3-cdi,HCO3)+(MκNaAc-MκNaCl)⁢(1α*cpw,Ac-cdi,Ac)++⁢KbCuKu⁢(MNa3⁢Cit-3⁢MκNaCl)⁢((0.167α-3+0.125α-2+0.706α-1)*cpw,Na3⁢Cit-cdi,Na3⁢Cit)++⁢MκQdoKu⁢κrest⁢3)(XII)

wherein:

Cdi,Na,isoNa,adjSodium concentration set point adjustment (relative toisoconductive state) required to provide isonatric dialysisMκNaHCO3Is the molar conductivity of sodium bicarbonate (NaHCO3)MκNaClIs the molar conductivity of sodium chloride (NaCl)MκNaAcIs the molar conductivity of sodium acetate (NaCH3COO)MκKClIs the molar conductivity of potassium chloride (KCl)MNa3CitIs the molar conductivity of trisodium citrate (Na3C6H5O7)κrest3Is the conductivity contribution from lesser solutes 3cdi,HCO3Is the dialysis fluid concentration of bicarbonatecdi,KIs the dialysis fluid concentration of potassiumcdi,AcIs the dialysis fluid concentration of acetatecdi,Na3CitIs the dialysis fluid concentration of total citratecpw,HCO3Is the estimated or measured pre-dialysis concentration ofbicarbonate anions (HCO3−) in plasma watercpw,AcIs the estimated or measured pre-dialysis concentration ofanions (CH3COO−) in plasma watercpw,KIs the estimated or measured pre-dialysis concentration ofpotassium ions (K+) in plasma watercpw,Na3CitIs the estimated or measured pre-dialysis concentration oftotal citrate in plasma waterQdoIs the dialysate flow rate at dialyzer outletKuIs the dialyzer clearance for ureaKbCitIs the dialyzer clearance for citrateαIs the Donnan factor

In a 99thaspect according to anyone of the previous aspects from the 53rdto the 93rd, for a HD treatment mode, HDF post-dilution treatment mode and/or for a HF post-dilution treatment mode, the adjustment contribution term is:

cdi,Na,isoNa+K,adj=-1⁢((MκNaHCO3-MκNaCl)⁢(1α*cpw,HCO3-cdi,HCO3)+(MκNaAc-MκNaCl)⁢(1α*cpw,Ac-cdi,Ac)++⁢KbCuKu⁢(MNa3⁢Cit-3⁢MκNaCl)⁢((0.167α-3+0.125α-2+0.706α-1)*cpw,Na3⁢Cit-cdi,Na3⁢Cit)++⁢(MκKCl-MκNaCl)⁢(a*cpw,K-cdi,K)+QdoKu⁢κrest⁢3)(XIII)

wherein:

cdi,Na,isoNa+K,adjSodium concentration set point adjustment (relative toisoconductive state) required to provide isonatrikalemicdialysisMκNaHCO3Is the molar conductivity of sodium bicarbonate (NaHCO3)MκNaClIs the molar conductivity of sodium chloride (NaCl)MκNaAcIs the molar conductivity of sodium acetate (NaCH3COO)MκKClIs the molar conductivity of potassium chloride (KCl)MNa3CitIs the molar conductivity of trisodium citrate(Na3C6H5O7)κrest3Is the conductivity contribution from lesser solutes 3cdi,HCO3Is the dialysis fluid concentration of bicarbonatecdi,KIs the dialysis fluid concentration of potassiumcdi,AcIs the dialysis fluid concentration of acetatecdi,Na3CitIs the dialysis fluid concentration of total citratecpw,HCO3Is the estimated or measured pre-dialysis concentration ofbicarbonate anions (HCO3−) in plasma watercpw,AcIs the estimated or measured pre-dialysis concentration ofanions (CH3COO−) in plasma watercpw,KIs the estimated or measured pre-dialysis concentration ofpotassium ions (K+) in plasma watercpw,Na3CitIs the estimated or measured pre-dialysis concentration oftotal citrate in plasma waterQdoIs the dialysate flow rate at dialyzer outletKuIs the dialyzer clearance for ureaKbCitIs the dialyzer clearance for citrateαIs the Donnan factor

In a 100thaspect according to the previous aspects, the setting of the second parameter value in the dialysis fluid includes the sub-step of calculating the parameter value as a function of the main contribution term, the adjustment contribution term and a compensation contribution term.

In a 101staspect according to the previous aspect, the compensation contribution term is dimensionally a concentration of a substance in a fluid.

In a 102ndaspect according to the previous two aspects, the sub-step of calculating the parameter value as a function of the main contribution term, the adjustment contribution term and the compensation contribution term is a sub-step of calculating an algebraic sum of at least the main contribution term, the adjustment contribution term, and the compensation contribution term.

In a 103rdaspect according to the previous three aspects, the compensation contribution term is a sodium compensation term to compensate for occurred unwanted sodium transfers during treatment.

In a 104thaspect according to the previous four aspects, the compensation contribution term is a sodium compensation term to compensate for unwanted sodium transfers occurred during calculation of said value representative of the parameter of the blood in said blood lines, particularly at the start of the treatment.

In a 105thaspect according to the previous aspect, the compensation contribution term has generally a negative value.

In a 106thaspect according to the previous six aspects, the control unit (12) is further configured, during a monitoring phase, to re-determine the blood parameter, the monitoring phase occurring a predetermined number of times during the treatment, at each monitoring phase an unwanted net transfer of a substance, e.g. sodium, occurs through the semipermeable membrane (5), the compensation contribution term is a sodium compensation term to compensate for occurred unwanted sodium transfers during the monitoring phase.

In a 107thaspect according to the previous seven aspects, the compensation contribution term for the unwanted substance transfer is calculated for distributing a compensation for the substance during the remaining treatment time.

In a 108thaspect according to the previous eight aspects, the compensation contribution term is a function of the remaining treatment time, i.e. total treatment time (T) minus elapsed treatment time (ti), in particular is a function of 1/(T−ti).

In a 109thaspect according to the previous nine aspects, the compensation contribution term is a function of the difference between the calculated substance, e.g. sodium, set point (cdi,Na,set,isotonic; cdi,Na,set,isoNa; cdi,Na,set,isoNa+K) and the actual dialysis fluid same substance, e.g. sodium, concentration set point (cdi,Na,set,actual) used during treatment.

In a 110thaspect according to the previous ten aspects, the compensation contribution term is calculated according to the following formula:

∑t1T-ti⁢∫titi+Δ⁢ti(Cdi,Na,set-Cdi,Na,actual,i)⁢dt(XIV)

wherein

cdi,Na,set,actualis the actual dialysis fluid sodium concentration set point used during the treatment;

cdi,Na,set, is the calculated sodium set point which may correspond to either dialysis fluid concentration of sodium ions (Na+) to provide isotonic dialysis cdi,Na,set,isotonicor dialysis fluid concentration of sodium ions (Na+) to provide isonatric dialysis cdi,Na,set,isoNaor dialysis fluid concentration of sodium ions (Na+) to provide isonatrikalemic dialysis cdi,Na,set,isoNa+K;

T is the total treatment time; and

tiis the elapsed treatment time.

In a 111thaspect according to the previous eleven aspects, the second parameter value in the dialysis fluid is calculated according to the following relation:

cdi,Na,set,compensated=cdi,Na,set+∑i1T-ti⁢∫titi+Δ⁢ti(cdi,Na,set-cdi,Na,actual,i)⁢dt(XV)

wherein

cdi,Na,set,actualis the actual dialysis fluid sodium concentration set point used during the treatment;

cdi,Na,set, is the calculated sodium set point which may correspond to either dialysis fluid concentration of sodium ions (Na+) to provide isotonic dialysis cdi,Na,set,isotonicor dialysis fluid concentration of sodium ions (Na+) to provide isonatric dialysis cdi,Na,set,isoNaor dialysis fluid concentration of sodium ions (Na+) to provide isonatrikalemic dialysis cdi,Na,set,isoNa+K;

T is the total treatment time; and

tiis the elapsed treatment time.

In a 112thaspect according to anyone of the previous aspects, the control unit (12) is not configured to run an HD treatment mode.

In a 113thaspect according to anyone of the previous aspects, in HDF pre-dilution mode and/or in HF pre-dilution mode, the control unit (12) is configured to calculate a diluted plasma water concentration of one or more substances due to pre-infusion flow, the substance being chosen in the group including bicarbonate, potassium, acetate, lactate, citrate.

In a 114thaspect according to anyone of the previous aspects, said circulating the dialysis fluid through the infusion line (39) up to measuring the initial value of said parameter of the dialysate downstream of said secondary chamber used for the calculating of the initial plasma conductivity (e.g. up to a first estimate of plasma conductivity), is performed maintaining the dialysis fluid parameter value substantially constant.

In a 115thaspect according to anyone of the previous aspects, once a first estimate of the initial plasma conductivity is calculated, the dialysis fluid parameter value of the substitution fluid in the infusion line (39) is changed to match the first estimate and a second estimate is calculated.

In a 116thaspect according to anyone of the previous aspects, in HF and HDF treatment modes, once an identification phase for determining the dialysis fluid parameter value of the substitution fluid in the infusion line (39) is ended, the dialysis fluid parameter value is preferably maintained substantially constant throughout the remaining treatment time.

Further characteristics and advantages of the present invention will better emerge from the detailed description that follows of at least an embodiment of the invention, illustrated by way of non-limiting example in the accompanying figures of the drawings.

