Device for extracorporeal blood treatment Device for extracorporeal blood treatment

Abstract

An extracorporeal blood treatment apparatus is provided, comprising: a filtration unit (2) connected to a blood circuit (17) and to a dialysis fluid circuit (32); a control unit (12) arranged to calculate a sodium concentration value for the blood; the estimation of the sodium concentration comprises a sub-step of calculating the sodium concentration value as an algebraic sum of a main contribution based on an iso-ohmolar sodium concentration and of an offset contribution based on a concentration of at least one substance in the dialysis fluid, selected in a group comprising bicarbonate, potassium, acetate, lactate, citrate, magnesium, calcium, sulphate and phosphate.

Description

TECHNICAL FIELD

[0001] The present invention relates to a device for extracorporeal blood treatment and to a method for estimating blood parameters in an extracorporeal blood treatment device.

[0002] In particular, the present invention can allow the determination of blood parameters (e.g. plasma sodium) by means of conductivity measurements after the dialyzer during a hemodialysis, hemofiltration or hemodiafiltration treatment. BACKGROUND

[0003] The kidney fulfils many functions, including the removal of water, the excretion of catabolites (or waste products from metabolism, such as urea and creatinine), the regulation of the concentration of electrolytes in the blood (e.g. sodium, potassium, magnesium, calcium, bicarbonate, phosphate, chloride) and the regulation of the acid / base balance in the body, in particular by removing weak acids and by producing ammonium salts.

[0004] For people who have lost kidney function, the body accumulates water and waste products from metabolism and exhibits excess electrolytes, and generally acidosis, since these excretion and regulation mechanisms no longer work, with the pH of the plasma moving downwards below 7.35 (the blood pH normally varies within a narrow range between 7.35 and 7.45).

[0005] To overcome kidney insufficiency, the traditional treatment method is a blood treatment by extracorporeal circulation through a displacer (dialyzer) having a semi-permeable membrane, in which the patient's blood circulates on one side of the membrane and a dialysate circulates on the other side of the membrane, the dialysate comprising the main electrolytes of the blood at a concentration close to that of a healthy subject.

[0006] In addition, a pressure difference is created between the two compartments of the dialyzer, separated by the semi-permeable membrane, so that a portion of the plasma fluid passes through the membrane by ultrafiltration into the compartment containing the dialysate.

[0007] The blood treatment in the dialyzer involves waste products from metabolism and electrolytes, which are caused by two mechanisms of transfer of molecules through the membrane.

[0008] On the one hand, molecules migrate from a liquid of higher concentration to a liquid of lower concentration. This is a diffusion transfer.

[0009] On the other hand, certain catabolites and certain electrolytes are entrained by the plasma fluid, which filters through the membrane under the action of the pressure difference established between the two compartments of the displacer. This is a convective transfer.

[0010] The three functions of the kidney described above, i.e. removal of water, excretion of catabolites and regulation of the concentration of electrolytes in the blood, are therefore performed in a conventional blood treatment device by a combination of dialysis and hemofiltration, which combination is called hemodialysis.

[0011] Some known dialysis machines provide an option for both ultrafiltration and sodium profiling, trying to improve tolerance to ultrafiltration as dialysis session time becomes shorter. In fact, dialysis time reduction is associated with an increased intolerance of patients to high UF rates.

[0012] Briefly, the UF rate is varied to favor improved vascular refilling. In addition, the sodium content of the dialysis fluid is varied during the treatment, directly affecting the plasma sodium level. The aim is to control the rate of sodium leaving the blood into the dialysate.

[0013] High dialysate sodium concentrations can have negative effects. Sodium can accumulate in the patient, leading to increased thirst after dialysis, weight gain during dialysis and development of hypertension. Sodium profiling has been developed to obtain the benefits of high plasma sodium levels while avoiding unnecessary high sodium uptake during dialysis at the risk of the patient having a related sodium overload. The idea is to minimize side effects during dialysis while eliminating the amount of sodium needed to avoid sodium excess.

[0014] For a hypernatremic or hyponatremic patient, a normal post-dialysis sodium value can be reached. However, monitoring the clinical condition of the patient will indicate whether a normal blood sodium is indicated post-dialysis. For example, a hypernatremic patient is usually stable at a sodium level higher than the post-dialysis level and can suffer side effects if hyponatremic dialysis is performed with the intent to lower its sodium level.

[0015] In the above cases, it is necessary to properly estimate and continuously know and control the plasma sodium elevation.

[0016] From patent document US 5100554 by Polaschegg, a method for in-vivo determination of parameters for hemodialysis is known. For the most efficient and safe performance of hemodialysis, it is necessary to know the dialysis dose depending on the clearance rate of the filtration unit. To be able to determine this in-vivo, the invention provides a method in which the electrolyte transfer of the dialysis fluid is measured by a conductivity meter at two different predetermined dialysis fluid ion concentrations, and based thereon the dialysis rate and the plasma conductivity are determined.

[0017] The patent document EP 547025 by Sternby teaches a method for determining the sodium concentration in the blood of a patient undergoing a dialysis treatment in an artificial kidney and / or the actual dialysis rate of sodium of the artificial kidney. The artificial kidney comprises an extracorporeal blood circuit connected to a filtration unit having a semipermeable membrane defining a first compartment for circulation of blood on one side of the membrane and a second compartment for circulation of the dialysis fluid; the method comprises the steps of circulating in the second compartment of the filtration unit first and second dialysis liquids having different concentrations of sodium in succession, measuring the electrical conductivity upstream and downstream of the filtration unit in the first and second dialysis fluids, and calculating the electrical conductivity of the blood at the inlet of the filtration unit and / or the actual dialysis rate of the artificial kidney by means of the electrical conductivity measured in the first and second dialysis fluids.

[0018] In particular, the electrical conductivity of the blood and the actual dialysis rate are calculated according to the following formulae:

[0019] κ d out = κ d in + (κ b in - κ d in ) x D / Q d

[0020] wherein,

[0021] κ d in = electrical conductivity of the dialysis fluid upstream of the filtration unit;

[0022] κ d out = electrical conductivity of the dialysis fluid downstream of the filtration unit;

[0023] κ b in = electrical conductivity of the blood upstream of the filtration unit;

[0024] D = dialysis rate of the artificial kidney with respect to the electrical conductivity;

[0025] Q d = flow rate of the dialysis fluid.

[0026] The patent documents EP 658352, EP 920877 and EP 1108438 describe further improvements of the above-mentioned method for the calculation of the plasma electrical conductivity.

[0027] The basic principle of the above-mentioned monitoring system is that the outlet dialysis fluid electrical conductivity is measured continuously when the inlet dialysis fluid electrical conductivity is changed by about 1 mS / cm within two minutes. This measurement can be set, for example, every 15 minutes, 30 minutes, 45 minutes or 60 minutes.

[0028] The mathematical modelling of the outlet electrical conductivity allows the calculation of two dialysis process parameters, i.e. the plasma electrical conductivity and the effective ion dialysis rate or ion clearance.

[0029] The plasma conductivity is a reflection of the amount of electrolytes, such as sodium and other physiologically acceptable ions, in the patient's body. This enables to determine whether the patient will leave the clinic with an overload of sodium.

[0030] Although the use of the above method has become widespread today, there are still outstanding problems in attributing a physiological meaning to the result of the blood property.

[0031] Strictly speaking, the "plasma conductivity" does not measure an unambiguous blood property, but is strongly influenced by the measurement itself. It is generally assumed that if the conductivity in the fluid entering the filtration unit is equal to the conductivity leaving the filtration unit, this represents an unambiguous blood property. However, this is an approximation, and it is almost impossible to verify the correctness of the calculation by taking and measuring a blood sample. In the past, attempts have been made to statistically correlate the plasma conductivity with the plasma sodium, but the spread of the data is very large. SUMMARY

[0032] It is an object of the present application to provide an extracorporeal blood treatment apparatus which is capable of properly estimating a blood parameter in extracorporeal blood.

[0033] In particular, it is an object of the present application to provide an extracorporeal blood treatment apparatus which has suitable means for estimating the concentration of at least one substance in blood or a concentration-related parameter of at least one substance in blood.

[0034] It is a further object of the present application to provide an extracorporeal blood treatment apparatus which has a simple model of the ion transport in the filtration unit which contributes to the change in conductivity. This mathematical model allows to calculate the plasma sodium from the conductivity measurement once the blood values of some electrolytes are known or estimated.

[0035] It is a further object of the present application to provide an extracorporeal blood treatment apparatus which is provided to automatically perform a proper automatic setting of the dialysis fluid conductivity based on the determined blood parameter.

[0036] It is a further object of the present application to provide a dialysis apparatus which is capable of providing an automatic transmission and control of the dialysis prescription, in particular in order to restore a proper sodium balance in the patient in each dialysis session.

[0037] It is an object to provide an extracorporeal blood treatment apparatus which is provided to properly estimate the concentration of at least one substance in blood, such as sodium, or a concentration-related parameter of at least one substance in blood, and to run a renal treatment, in any of the hemodialysis (HD), hemofiltration (HF) and hemodiafiltration (HDF) treatment modes.

[0038] At least one of the above mentioned objects is achieved by an apparatus and a corresponding method as defined in one or more of the appended claims, alone or in any arbitrary combination.

[0039] According to a first independent aspect of the application, there is provided an extracorporeal blood treatment apparatus, comprising:

[0040] - a filtration unit (2) having a primary chamber (3) and a secondary chamber (4) separated by a semi-permeable membrane (5);

[0041] - a blood withdrawal line (6) connected to an inlet of the primary chamber (3);

[0042] - a blood return line (7) connected to an outlet of the primary chamber (3), said blood line being arranged for connection to a patient's cardiovascular system;

[0043] - a dialysis supply line (8) comprising at least one infusion line (39) connected to said blood line, optionally the dialysis supply line (8) comprises an inlet line (45) connected to an inlet of the secondary chamber (4) for circulating a dialysis fluid;

[0044] - a dialysis effluent line (13) connected to an outlet of the secondary chamber (4);

[0045] - a control unit (12) arranged to run at least one hemofiltration treatment (HF) or hemodiafiltration treatment (HDF), each of said treatments comprising infusion of a substitution fluid through said infusion line (39), the control unit being arranged for receiving a value representative of a first parameter of isostatic dialysis, said first parameter being selected in the group comprising a concentration of at least one substance, a concentration-related parameter of at least one substance, an electrical conductivity or an electrical conductivity-related parameter, wherein said control unit (12) is arranged for:

[0046] - calculating a value of a second parameter of blood, said second parameter being selected in the group comprising a concentration of at least one substance in blood and a concentration-related parameter of at least one substance in blood; wherein the step of calculating the value of said second parameter is performed according to a main contribution term based on said first parameter and according to an offset contribution term based on a concentration of at least one substance in dialysis fluid, the at least one substance being selected in the group comprising bicarbonate, potassium, acetate, lactate, citrate, magnesium, calcium, sulphate and phosphate; and optionally

[0047] - storing said parameter value in a memory (46) connected to said control unit (12).

[0048] In another independent aspect, there is provided an apparatus for extracorporeal blood treatment, comprising:

[0049] - a filtration unit (2) having a primary chamber (3) and a secondary chamber (4) separated by a semi-permeable membrane (5);

[0050] - a blood withdrawal line (6) connected to an inlet of the primary chamber (3);

[0051] - a blood return line (7) connected to an outlet of the primary chamber (3), said blood line being arranged for connection to a patient's cardiovascular system;

[0052] - a dialysis effluent line (13) connected to an outlet of the secondary chamber (4);

[0053] - a control unit (12) arranged to run at least one hemofiltration treatment (HF) or hemodiafiltration treatment (HDF), each of said treatments comprising the infusion of a substitution fluid through said infusion line (39), the control unit being arranged for receiving a value representative of a first parameter of isostatic dialysis, said first parameter being selected in the group comprising a concentration of at least one substance, a concentration-related parameter of at least one substance, an electrical conductivity or an electrical conductivity-related parameter, wherein the control unit (12) is arranged for:

[0054] - calculating a value of a second parameter of the blood, said second parameter being selected in the group comprising a concentration of at least one substance in the blood and a concentration-related parameter of at least one substance in the blood; wherein the calculation of said parameter value is performed according to a main contribution term based on said first parameter and according to an offset contribution term based on a concentration of at least one substance in the blood, the at least one substance being selected in the group comprising bicarbonate, potassium, acetate, lactate, citrate, magnesium, calcium, sulphate and phosphate; and optionally,

[0055] - storing said second parameter value in a memory (46) connected to the control unit (12), in particular said parameter value is a plasma sodium concentration.

[0056] In another independent aspect, a method for estimating a blood parameter in a device for extracorporeal blood treatment is provided, the device comprising:

[0057] - a filtration unit (2) having a primary chamber (3) and a secondary chamber (4) separated by a semi-permeable membrane (5);

[0058] - a blood withdrawal line (6) connected to an inlet of the primary chamber (3);

[0059] - a blood return line (7) connected to an outlet of the primary chamber (3), said blood line being arranged for connection to a patient's cardiovascular system;

[0060] - a dialysis supply line (8) comprising at least one substitution line (39) connected to the blood line, optionally an inlet line (45) connected to the inlet of the secondary chamber (4) for circulating a dialysis fluid;

[0061] - a dialysis effluent line (13) connected to the outlet of the secondary chamber (4);

[0062] - a control unit (12) arranged to run at least one hemofiltration treatment (HF) or hemodiafiltration treatment (HDF), each of said treatments comprising the infusion of a substitution fluid through the substitution line (39), the control unit being arranged for receiving a value representative of a first parameter of isostatic dialysis, the first parameter being selected in the group comprising a concentration of at least one substance, a concentration-related parameter of at least one substance, an electrical conductivity or an electrical conductivity-related parameter, the method comprising the following steps performed by the control unit:

[0063] - calculating a value of a second parameter of the blood, the second parameter being selected in the group comprising a concentration of at least one substance in the blood and a concentration-related parameter of at least one substance in the blood; wherein the step of calculating the value of the second parameter is performed as a function of a main contribution term based on the first parameter and as a function of an offset contribution term, the offset contribution term being based on a difference, in particular a weighted difference, of the concentration of at least one substance in the dialysis fluid and the concentration of the same substance in the plasma, in particular wherein for HDF predilution treatments and HF predilution treatments, the estimated plasma concentration is a diluted plasma concentration, in particular the diluted plasma concentration is a function of the blood flow rate and the substitution flow rate, optionally the diluted plasma concentration is a function of the dialyzable blood water fraction for the substance in the blood from the patient and the plasma water concentration, in detail the diluted plasma concentration is a function of the concentration of the substance in the substitution fluid;

[0064] - storing the value of the second parameter in a memory (46) connected to the control unit (12).

[0065] In a second aspect according to any one of the preceding aspects, the control unit is arranged to calculate the offset contribution term based on the concentrations of two or more substances in the dialysis fluid selected in the group comprising bicarbonate, potassium, acetate, lactate, citrate, magnesium, calcium, sulphate and phosphate, in particular as a function of the concentrations of at least three of said substances, optionally as a function of the concentrations of bicarbonate, potassium, acetate and citrate in the dialysis fluid, wherein for HDF predilution treatments and HF predilution treatments, the estimated plasma concentration is a diluted plasma concentration, in particular the diluted plasma concentration is a function of the blood flow rate and the substitution flow rate, optionally the diluted plasma concentration is a function of the dialyzable blood water fraction for the substance in the blood from the patient and the plasma water concentration, in detail the diluted plasma concentration is a function of the concentration of the substance in the substitution fluid.

[0066] In a third aspect according to any of the preceding aspects, the control unit is configured to calculate the offset contribution term from a difference, in particular a weighted difference, of the concentration of at least one substance in the dialysis fluid and the concentration of the same substance in the plasma, wherein for HDF pre-dilution treatment and HF pre-dilution treatment the estimated plasma concentration is a diluted plasma concentration, in particular the diluted plasma concentration is a function of the blood flow rate and the infusion flow rate, optionally the diluted plasma concentration is a function of the dialyzable blood water fraction for the substance in the blood from the patient and the plasma water concentration, in detail the diluted plasma concentration is a function of the concentration of the substance in the infusion.

[0067] In a fourth aspect according to any of the preceding aspects, the control unit is configured to calculate the offset contribution term from a difference, in particular a weighted difference, of the concentration of at least one substance in the dialysis fluid and the concentration of the same substance in the plasma, in particular from a difference, in particular a weighted difference, of the concentration of at least two of the substances, optionally from a difference, in particular a weighted difference, of the concentration of bicarbonate, potassium and acetate in the dialysis fluid and the plasma, even more optionally from a difference, in particular a weighted difference, of the concentration of bicarbonate, potassium, citrate and acetate in the dialysis fluid and the plasma, the substance being selected from a group comprising bicarbonate, potassium, acetate, lactate and citrate, wherein for HDF pre-dilution treatment and HF pre-dilution treatment the estimated plasma concentration is a diluted plasma concentration, in particular the diluted plasma concentration is a function of the blood flow rate and the infusion flow rate, optionally the diluted plasma concentration is a function of the dialyzable blood water fraction for the substance in the blood from the patient and the plasma water concentration, in detail the diluted plasma concentration is a function of the concentration of the substance in the infusion.

[0068] In a fifth aspect according to any of the preceding aspects, the value representing the isoelectric dialysis is selected from a group comprising a concentration of at least one substance in the dialysis fluid, a concentration related parameter of at least one substance in the dialysis fluid, a dialysis fluid conductivity, a dialysis fluid conductivity related parameter, a plasma conductivity or a plasma conductivity related parameter, in particular the first parameter is an isoelectric sodium concentration or an isoelectric sodium concentration related parameter.

[0069] In a sixth aspect according to any of the preceding aspects, the second parameter is a concentration of at least one substance in the blood, in particular sodium.

[0070] In a seventh aspect according to any of the preceding aspects, the first parameter is an isoelectric sodium concentration and the second parameter is a sodium concentration in the blood.

[0071] In an eighth aspect according to any of the preceding aspects, the main contribution term is in size a concentration of a substance in the fluid.

[0072] In a ninth aspect according to the preceding aspects, the main contribution term is a concentration value that would run an isoconductance dialysis if used as a dialysis fluid concentration for sodium.

[0073] In a tenth aspect according to any of the preceding aspects, the main contribution term influences the second parameter for at least 80% of the second parameter value, the offset contribution term contributes less than 20% of the second parameter value to the second parameter.

[0074] In an eleventh aspect according to any of the preceding aspects, the sub-step of calculating the second parameter value from the main contribution term and the offset contribution term is a sub-step of calculating at least an algebraic sum, in particular a weighted algebraic sum, of the main contribution term and the offset contribution term, and in particular wherein the offset contribution term is a concentration of a substance in the fluid.

[0075] In a twelfth aspect according to any of the preceding aspects, the main contribution term influences the second parameter for at least 90% of the second parameter value, the offset contribution term contributes less than 10% of the second parameter value to the second parameter.

[0076] In a thirteenth aspect according to any of the preceding aspects, the apparatus comprises a preparation device (9) for preparing a dialysis fluid connected to the supply line (8) and comprising an adjustment device (10) for adjusting a composition of the dialysis fluid, the adjustment device (10) being connected to the control unit (12).

[0077] In a fourteenth aspect according to the preceding aspects, the control unit (12) is configured to set a third parameter value of the dialysis fluid in the dialysis supply line (8) at a setpoint, the third parameter of the dialysis fluid being at least one parameter selected from the group comprising an electrical conductivity of the dialysis fluid, an electrical conductivity related parameter of the dialysis fluid, a concentration of at least one substance in the dialysis fluid, and a concentration related parameter of at least one substance in the dialysis fluid.

[0078] In a fifteenth aspect according to the thirteenth aspect, the control unit (12) is configured to determine a time profile of a third parameter value of the dialysis fluid in the dialysis supply line (8), the third parameter of the dialysis fluid being at least one parameter selected from the group comprising an electrical conductivity of the dialysis fluid, an electrical conductivity related parameter of the dialysis fluid, a concentration of at least one substance in the dialysis fluid, and a concentration related parameter of at least one substance in the dialysis fluid; wherein the control unit drives the adjustment device (10) for adjusting the electrical conductivity or the concentration of at least one substance in the dialysis fluid, the time profile of the third parameter being based on the second parameter.

[0079] In a sixteenth aspect according to any of the preceding aspects, the control unit drives the adjustment device (10) for adjusting the electrical conductivity or the concentration of at least one substance in the dialysis fluid.

[0080] In a seventeenth aspect according to the four preceding aspects, the control unit sets the third parameter value of the dialysis fluid in the dialysis supply line (8) at a set point based on the second parameter.

[0081] In an eighteenth aspect according to the preceding aspects, the adjustment device (10) adjusts the concentration of at least one substance, in particular an ionic substance, in the dialysis fluid, such as sodium.

[0082] In a nineteenth aspect according to the preceding aspects, the control unit drives the adjustment device (10) for adjusting the sodium concentration in the dialysis fluid to set the parameter value of the dialysis fluid in the dialysis supply line (8) to the calculated second parameter value.

[0083] In a twentieth aspect according to any one of the preceding aspects, the control unit is arranged to calculate the offset contribution term from the molar conductivity of at least one substance in the dialysis fluid selected from the group comprising sodium bicarbonate (NaHC03), sodium chloride (NaCI), sodium acetate (NaCH3COO), potassium chloride (KCI), sodium lactate (NaC3H50 ) and trisodium citrate (Na3C6H507), in particular from the molar conductivity of at least two of said substances, more in particular from the molar conductivity of at least three of said substances, optionally from the molar conductivity of at least three substances selected from the group comprising sodium bicarbonate (NaHC03), sodium chloride (NaCI), sodium acetate (NaCH3COO), trisodium citrate (Na3C6H507) and potassium chloride (KCI).

[0084] In a twenty-first aspect according to any one of the preceding aspects, the control unit is arranged to calculate the offset contribution term from the difference between two molar conductivities.

[0085] In a twenty-second aspect according to any one of the preceding aspects, the control unit is arranged to calculate the offset contribution term from the difference between the first molar conductivity of a substance selected from the group comprising sodium bicarbonate (NaHC03), sodium acetate (NaCH3COO), trisodium citrate (Na3C6H507), sodium lactate (NaC3H50 ) and potassium chloride (KCI) and the molar conductivity of sodium chloride (NaCI).

[0086] In a twenty-third aspect according to any one of the preceding aspects, the control unit is arranged to calculate the offset contribution term from the difference between the molar conductivity of sodium bicarbonate (NaHC03) and the molar conductivity of sodium chloride (NaCI).

[0087] In a twenty-fourth aspect according to any one of the preceding aspects, the control unit is arranged to calculate the offset contribution term from the difference between the molar conductivity of sodium acetate (NaCH3COO) and the molar conductivity of sodium chloride (NaCI).

[0088] In a twenty-fifth aspect according to any of the preceding aspects, the control unit is configured to calculate the offset contribution term from the molar conductivity of potassium chloride (KCI).

[0089] In a twenty-sixth aspect according to any of the preceding aspects, the control unit is configured to calculate the offset contribution term from an estimated or measured plasma water concentration of at least one substance, in particular from estimated or measured plasma water concentrations of at least two of the substances, more particularly from estimated or measured plasma water concentrations of at least three of the substances, optionally from estimated or measured plasma water concentrations of bicarbonate, potassium, citrate and acetate, the at least one substance being selected from a group comprising bicarbonate, potassium, acetate, lactate and citrate, in particular, for HDF pre-dilution treatment and HF pre-dilution treatment, the estimated plasma concentration being a diluted plasma concentration, in particular the diluted plasma concentration being a function of blood flow rate and infusion flow rate, optionally the diluted plasma concentration being a function of a dialyzable blood water fraction for the substance and the plasma water concentration in blood from the patient, in detail the diluted plasma concentration being a function of the concentration of the substance in the infusion.

[0090] In a twenty-seventh aspect according to the preceding aspects, the estimated plasma water concentration of at least one substance selected from a group comprising bicarbonate, potassium, citrate and acetate is a pre-dialysis mean value for the respective substance for a large patient population or historical data for the respective substance for an individual patient or a theoretical value for the respective substance or a measured value for the respective substance.

[0091] In a twenty-eighth aspect of any of the twenty-sixth and twenty-seventh preceding aspects, the estimated plasma water concentration is adjusted by a respective fixed offset factor taking into account the Donnan effect.

[0092] In a twenty-ninth aspect according to any of the preceding aspects, the control unit is configured to calculate the offset contribution term as an algebraic sum of at least two components, a first component being a function of a concentration difference, in particular a weighted difference, of at least one substance in the dialysis fluid and the same substance in the plasma, a second component being a function of a concentration difference, in particular a weighted difference, of at least a second substance in the dialysis fluid and the same second substance in the plasma, wherein, for HDF pre-dilution treatment and HF pre-dilution treatment, the estimated plasma concentration is a diluted plasma concentration, in particular the diluted plasma concentration being a function of blood flow rate and infusion flow rate, optionally the diluted plasma concentration being a function of a dialyzable blood water fraction for the substance and the plasma water concentration in blood from the patient, in detail the diluted plasma concentration being a function of the concentration of the substance in the infusion.

[0093] In a thirty-first aspect according to any of the preceding aspects, the control unit is configured to calculate the offset contribution as an algebraic sum of at least two components, a first component being a function of the concentration of at least one substance in the dialysis fluid and / or in the plasma, a second component being a function of the concentration of at least a second substance in the dialysis fluid and / or in the plasma, wherein for HDF pre-dilution treatment and HF pre-dilution treatment the estimated plasma concentration is a diluted plasma concentration, in particular the diluted plasma concentration is a function of the blood flow rate and the infusion flow rate, optionally the diluted plasma concentration is a function of the dialyzable blood water fraction for the substance in the blood from the patient and the plasma water concentration, in detail the diluted plasma concentration is a function of the concentration of the substance in the infusion.

[0094] In a thirty-first aspect according to any of the preceding aspects, the control unit is configured to calculate the offset contribution as an algebraic sum of at least two components, a first component being a function of the concentration of at least one substance in the dialysis fluid and / or in the plasma, a second component being a function of the concentration of at least a second substance in the dialysis fluid and / or in the plasma, wherein for HDF pre-dilution treatment and HF pre-dilution treatment the estimated plasma concentration is a diluted plasma concentration, in particular the diluted plasma concentration is a function of the blood flow rate and the infusion flow rate, optionally the diluted plasma concentration is a function of the dialyzable blood water fraction for the substance in the blood from the patient and the plasma water concentration, in detail the diluted plasma concentration is a function of the concentration of the substance in the infusion.

[0095] In a thirty-first aspect according to any of the preceding aspects, the control unit is configured to calculate the offset contribution as an algebraic sum of at least two components, a first component being a function of the concentration of at least one substance in the dialysis fluid and / or in the plasma, a second component being a function of the concentration of at least a second substance in the dialysis fluid and / or in the plasma, wherein for HDF pre-dilution treatment and HF pre-dilution treatment the estimated plasma concentration is a diluted plasma concentration, in particular the diluted plasma concentration is a function of the blood flow rate and the infusion flow rate, optionally the diluted plasma concentration is a function of the dialyzable blood water fraction for the substance in the blood from the patient and the plasma water concentration, in detail the diluted plasma concentration is a function of the concentration of the substance in the infusion.

[0096] In a thirty-third aspect according to any one of the twenty-ninth to thirty-second preceding aspects, the substance is an ion selected in the group comprising bicarbonate anion (HC03 - ), acetate anion (CH3COO - ), citrate (C6H5O7 3- ) and potassium ion (K + ).

[0097] In a thirty-fourth aspect according to any one of the preceding aspects, the control unit is set to calculate the offset contribution term as a function of at least one flow rate, in particular of the dialysate flow rate at the outlet of the secondary chamber (4).

[0098] In a thirty-fifth aspect according to any one of the preceding aspects, the control unit is set to calculate the offset contribution term as a function of at least an efficiency parameter of the filtration unit (2), in particular of the clearance of the filtration unit (2), optionally of the urea clearance.

[0099] In a thirty-sixth aspect according to any one of the preceding aspects, the control unit is set to calculate the offset contribution term as a function of at least a ratio between one flow rate, in particular of the dialysate flow rate at the outlet of the secondary chamber (4), and an efficiency parameter of the filtration unit (2), in particular of the clearance of the filtration unit (2), optionally of the urea clearance.

[0100] In a thirty-seventh aspect according to any one of the preceding aspects, the control unit is set to calculate the offset contribution term as an algebraic sum of at least two, in particular of three or four or five components, one component being a function of a ratio between one flow rate, in particular of the used dialysate flow rate at the outlet of the secondary chamber (4), and an efficiency parameter of the filtration unit (2), in particular of the clearance of the filtration unit (2), optionally of the urea clearance.

[0101] In a thirty-eighth aspect according to any one of the preceding aspects, the control unit (12) is set for calculating said first parameter value.

[0102] In a thirty-ninth aspect according to any one of the preceding aspects, the control unit (12) is set for receiving said first parameter value as an external input.

[0103] In a fortieth aspect according to any one of the preceding aspects, the control unit (12) is set for storing said first parameter value in a memory (46), said first parameter value not being calculated by the control unit.

[0104] In a forty-first aspect according to any one of the preceding aspects, the offset contribution term has a negative value.

[0105] In a forty-second aspect according to any one of the preceding aspects, the offset contribution term is a function of a residual term (k rest ) that is a conductivity contribution from a less solute, in particular, the less solute is different from sodium, potassium, bicarbonate and acetate, optionally, the less solute is different from sodium, potassium, citrate, bicarbonate and acetate.

[0106] In a forty-third aspect according to any one of the preceding aspects, the offset contribution term is:

[0107] wherein:

[0108]

[0109] In a forty-fourth aspect according to any one of the first to forty-second preceding aspects, the offset contribution term is:

[0110]

[0111] wherein:

[0112]

[0113]

[0114] In a forty-fifth aspect according to any one of the first to forty-second preceding aspects, in the HDF pre-dilution treatment mode and in the HF pre-dilution treatment mode, the offset contribution term is:

[0115]

[0116] wherein:

[0117] In the HF treatment mode, the clearance rate is equal to the dialyzer outlet flow, i.e., K u = Q do ; is the diluted bicarbonate plasma water concentration in the blood entering the filtration unit;

[0118] is the diluted acetate plasma water concentration in the blood entering the filtration unit;

[0119] is the diluted potassium plasma water concentration in the blood entering the filtration unit;

[0120] is the diluted citrate plasma water concentration in the blood entering the filtration unit;

[0121]

[0122] In a forty-sixth aspect according to any one of the preceding aspects, the first parameter is the concentration of at least one substance in the dialysis fluid, in particular sodium.

[0123] In a forty-seventh aspect according to any one of the preceding aspects, the first parameter is the isoconductive substance concentration.

[0124] In a forty-eighth aspect according to any one of the preceding aspects, the first parameter is the plasma conductivity or the dialysis fluid conductivity in isoconductive dialysis.

[0125] In a forty-ninth aspect according to any one of the preceding aspects, the first parameter is a plasma conductivity related parameter, which is the dialysis fluid conductivity in isoconductive dialysis.

[0126] In a fiftieth aspect according to any one of the preceding aspects, the first parameter is an isoconductive sodium concentration related parameter, in particular the plasma conductivity or the dialysis fluid conductivity in isoconductive dialysis.

[0127] In a fifty-first aspect according to any one of the preceding aspects, the first parameter is an isoconductive sodium concentration related parameter, in particular the dialysis fluid conductivity in isoconductive dialysis, and the second parameter is the concentration of sodium in the blood.

[0128] In a fifty-second aspect according to any one of the preceding aspects, immediately after calculating the initial plasma conductivity, the control unit is arranged to drive the adjustment device (10) to change the composition of the dialysis fluid and to set the dialysis fluid sodium to a substantially isoconductive sodium concentration.

[0129] In a fifty-third aspect according to the preceding aspect, after setting the dialysis fluid sodium to a substantially isoconductive sodium concentration, the control unit is arranged to perform a second calculation step, by isoconductive sodium concentration setting, based on the second determined initial conductivity of the dialysis fluid and the second corresponding conductivity of the dialysis fluid in the supply line (8), said calculation of the second estimate being performed to keep the dialysis fluid conductivity substantially constant.

[0130] In a fifty-fourth aspect according to any one of the preceding aspects, after calculating the second estimate of the isoconductive sodium concentration, the control unit is arranged to drive the adjustment device (10) to change the composition of the dialysis fluid and to set the dialysis fluid sodium concentration substantially equal to said second estimate.

[0131] In a fifty-fifth aspect according to any one of the preceding aspects, the control unit (12) is arranged to determine the conductivity of the dialysis fluid both upstream and downstream of said filtration unit (2) for at least two subsequently prepared dialysis fluids having different conductivities, in particular obtained from different concentrations of sodium.

[0132] In a fifty-sixth aspect according to any one of the preceding aspects, the control unit (12) is arranged to store in the memory instructions for setting up the apparatus to run a HD or HDF or HF treatment.

[0133] In a fifty-seventh aspect according to any one of the preceding aspects, the control unit (12) is arranged to use a diluted plasma concentration when calculating the second parameter of the blood.

[0134] In a fifty-eighth aspect according to any one of the preceding aspects, the diluted plasma concentration is dependent on the infusion flow rate of an infusion fluid into the blood circuit upstream of the filtration unit in the direction of blood circulation.

[0135] Further characteristics and advantages of the present application will be better apparent from the detailed description of at least one embodiment of the present application, illustrated by way of non-limiting example in the accompanying drawings of the present specification. BRIEF DESCRIPTION OF DRAWINGS

[0136] Reference will now be made to the accompanying drawings, which are provided by way of non-limiting example, and in which:

[0137] Figure 1 An extracorporeal blood treatment apparatus manufactured according to an example embodiment is schematically shown. DETAILED DESCRIPTION

[0138] Figure 1 An extracorporeal blood treatment apparatus 1 in an embodiment of the present application is shown.

[0139] One example of a hydraulic circuit 100 is schematically shown, but it should be noted that the specific structure of the hydraulic circuit 100 is not relevant to the purpose of the present application, and therefore other circuits and circuits different from those specifically shown in the figures can be used, due to the functional and design needs of each single medical apparatus. Figure 1 The specific structure of the hydraulic circuit 100 is not relevant to the purpose of the present application, and therefore other circuits and circuits different from those specifically shown in the figures can be used, due to the functional and design needs of each single medical apparatus.

[0140] The hydraulic circuit 100 establishes a dialysis fluid circuit 32 having at least one dialysis supply line 8. The dialysis supply line 8 can take different hydraulic circuit line configurations, according to the specific apparatus treatment mode, or can not take different hydraulic circuit line configurations.

[0141] In a hemodialysis (HD) treatment mode, the supply line 8 is arranged to convey dialysis fluid from at least one source 14 towards a treatment station 15, where one or more filtration units 2 or dialyzers are operated. The dialysis fluid and the blood are mainly displaced through a semi-permeable membrane in the filtration units 15 by a diffusion process.

[0142] In the hemofiltration (HF) treatment mode, the supply line 8 comprises an infusion line 39 arranged to convey infusate from at least one source 14 to the blood circuit. The infusion line 39 can comprise an ultrafilter 44 to additionally filter fluid received upstream of the infusion point into the blood circuit. By using a large amount of ultrafiltration, simultaneously with reinfusion of sterile replacement fluid in the blood circuit, removal of waste products from the blood is achieved.

[0143] In the hemodiafiltration (HDF) treatment mode, the supply line 8 is arranged to convey dialysis fluid from the source 14 to the treatment station 15 and further comprises an infusion line 39 to convey infusate from the source 14 to the blood circuit 17. HDF is a combination of hemodialysis and hemofiltration.

[0144] Generally, although not necessarily, the source 14 of the supply line 8 and the infusion line 39 is the same (i.e. the dialysis fluid preparation device 9). Of course, different sources can also be used.

[0145] Furthermore, the supply line 8 is generally branched into the infusion line 39 of infusate in the blood circuit 17 and into an inlet line 45 leading fluid to the treatment station 15. With reference to Figure 1 , the branching point is indicated by reference numeral 46.

[0146] Although different hydraulic circuits 100 can be used to provide HF, HD and HDF treatment with exclusively the relevant lines for the specific treatment (e.g. no infusion line 39 for HD treatment, no inlet line 45 for HF treatment), the hydraulic circuit 100 is generally of the type shown in Figure 1 and comprises both the infusion line 39 and the inlet line 45, subsequently, the device control unit 12 can control the passage of fluid through said lines according to the selected treatment, e.g. by means of suitable valves or clamps.

[0147] The dialysis fluid circuit 32 further comprises at least one dialysis effluent line 13 for conveying dialysate (used dialysate and liquid ultrafiltrated from the blood through the semi-permeable membrane 5) from the treatment station 15 towards an evacuation zone schematically represented by 16 in Figure 1 .

[0148] The hydraulic circuit cooperates with the blood circuit 17, which is also schematically represented in Figure 1 as its basic components. With reference to the present application, the specific structure of the blood circuit is also not essential. Therefore, with reference to Figure 1 , a possible embodiment of the blood circuit is briefly described, however, the blood circuit is provided by way of non-limiting example only.

[0149] Figure 1The blood circuit 17 comprises a blood withdrawal line 6 designed to remove blood from the vascular access 18 and a blood return line 7 designed to return treated blood to the vascular access 18.

[0150] Figure 1 The blood circuit 17 also comprises the primary chamber 3, or blood chamber, of the blood filtration unit 2, the secondary chamber 4 of which is connected to the hydraulic circuit 100.

[0151] More in detail, the blood withdrawal line 6 is connected at the inlet of the primary chamber 3, while the blood return line 7 is connected at the outlet of the primary chamber 3.

[0152] In turn, the dialysis supply line 8 is connected at the inlet of the secondary chamber 4, while the dialysis effluent line 13 is connected at the outlet of the secondary chamber 4.

[0153] The filtration unit 2, for example a dialyzer or a plasma filter or a hemofilter or a hemodialysis filter, comprises (as mentioned above) two chambers 3 and 4 separated by a semipermeable membrane 5, for example of the hollow-fiber type or of the plate type.

[0154] The blood circuit 17 can also comprise one or more air separators 19: in the example shown in the figure, an air separator 19 is included in the blood return line 7 upstream of the safety valve 20. Figure 1

[0155] Of course, other air separators can also be present in the blood circuit, for example provided along the blood withdrawal line 6.

[0156] The safety valve 20 can be activated to close the blood return line 7, for example for safety reasons, it being necessary to stop the return of blood to the vascular access 18.

[0157] The extracorporeal blood treatment apparatus 1 can also comprise one or more blood pumps 21, for example positive displacement pumps such as peristaltic pumps; in the example shown in the figure, a blood pump 21 is included on the blood withdrawal line 6. Figure 1

[0158] The apparatus of the above-described embodiments can also comprise a user interface 22, for example a graphical user interface or GUI, and a control unit 12, i.e. a settable / settable control unit connected to the user interface.

[0159] For example, the control unit 12 can comprise one or more digital microprocessor units or one or more analog units or other combinations of analog and digital units. For example, in relation to the microprocessor units, once the unit has executed a specific program (for example a program from the outside or directly integrated on the microprocessor card), the unit is set to define a plurality of functional blocks which constitute means respectively designed to perform the corresponding operations which will be better described in the following description.​​

[0160] In combination with one or more of the above features, the medical device can further comprise a closing device operating, for example, in the blood circuit 17 and / or in the dialysis fluid circuit 32 and commandable between a first operating condition, in which the closing device allows the flow of liquid towards the filtration unit 2, and a second operating condition, in which the closing device blocks the passage of liquid towards the filtration unit 2.

[0161] In this case, if an alarm condition has been detected, the control unit 12 can be connected to the closing device and set to drive the closing device from the first operating condition to the second operating condition.

[0162] In Figure 1 In this case, as mentioned above, the closing device comprises a safety valve 20 (for example, an electromagnetic valve) controlled by the unit 12. Obviously, it is possible to use a valve with other characteristics, for example, a shut-off pump or other means configured to selectively prevent and enable the passage of fluid.

[0163] Optionally or in addition to the safety valve 20, the closing device can comprise a bypass conduit 23 connecting the dialysis fluid supply conduit 8 and the dialysis effluent conduit 13 for bypassing the dialyzer and one or more fluid check means 24 connected to the control unit 12 for selectively opening and closing the bypass conduit 23. The assembly (bypass conduit 23 and fluid check means 24) can replace or supplement the presence of the safety valve 20, indicated by the dashed line in Figure 1 In the case in which the closing device comprises the safety valve 20 and the bypass conduit 23 and the fluid check means 24, the control unit 12 can be configured to drive the safety valve 20 and the fluid check means 24 in such a way as to selectively enable or prevent the passage of fluid through the filtration unit 2.

[0164] The check means 24, under the command of the control unit, close the passage of fluid towards the treatment zone and directly connect the source 14 with the dialysis effluent conduit 13 through the bypass conduit 23.

[0165] Again, in order to control the passage of liquid towards the filtration unit 2, the dialysis fluid pump 25 and the dialysate pump 26 can be included, respectively, on the dialysis fluid supply conduit 8 and on the dialysis effluent conduit 13 and are operatively connected to the control unit 12.

[0166] The device further comprises a dialysis fluid preparation device 9, which can be of any known type, for example, comprising one or more sources of concentrate 27, 28 and respective concentrate pumps 29, 30 for delivery, and at least one conductivity sensor 35.

[0167] Of course, other kinds of dialysis fluid preparation device 9 can be used equivalently, with a single or further sources of concentrate and / or a single or more pumps.

[0168] Since the dialysis apparatus can comprise various liquid sources 14 (for example one or more water sources, one or more concentrate sources 27 and 28, one or more disinfectant sources 33) connected to the dialysis supply line 8 by respective delivery lines 36, 37 and 38, the apparatus can establish at each delivery line a respective check member (not all shown) and, for example, comprising valve members 31 and 34 and / or occlusion pumps.

[0169] The preparation apparatus 9 can be any known system configured to prepare, on-line, a dialysis fluid from water and concentrates.

[0170] The dialysis supply line 8 fluidically connects the preparation apparatus 9 for preparing a dialysis fluid to the filtration unit 2 and / or to the blood circuit 17. For example, the preparation apparatus 9 can be the apparatus described in US patent No. 6123847, the contents of which are incorporated herein by reference.

[0171] As shown, the dialysis supply line 8 connects the preparation apparatus 9 for preparing a dialysis fluid to the filtration unit 2 and comprises a main line 40, the upstream end of which is intended for connection to a source 14 of tap water.

[0172] The delivery lines 36 / 37 are connected to the main line 40, the free end of which is intended for fluid communication (for example, immersion) in containers 27, 28 of concentrated saline solutions containing, respectively, sodium chloride and / or calcium chloride and / or magnesium chloride and / or potassium chloride.

[0173] The concentrate pumps 29, 30 are arranged in the delivery lines 36 / 37, allowing the metered mixing of water and concentrate solutions in the main line 40. The concentrate pumps 29, 30 are driven on the basis of a comparison between: 1) a target conductivity value of the liquid mixture formed at the point of junction of the main line 40 with the delivery lines 36 / 37, (2) a value of the conductivity of the mixture measured by a conductivity sensor 35 arranged in the main line 40, immediately downstream of the junction between the main line 40 and the delivery lines 36 / 37.

[0174] Thus, as mentioned above, the dialysis fluid can contain ions of, for example, sodium, calcium, magnesium and potassium, while the preparation apparatus 9 can be set to prepare the dialysis fluid on the basis of a comparison between the target conductivity value and the actual conductivity value of the dialysis fluid measured by the conductivity sensor 35 of the apparatus 9.

[0175] The preparation apparatus 9 comprises a conditioning apparatus 10 (i.e. the concentrate pumps 29, 30) of known type, set to condition the concentration of specific substances, in particular ionic substances, in the dialysis fluid. In general, it is advantageous to control the concentration of sodium of the dialysis fluid.

[0176] The dialysis supply line 8 forms an extension of the main line 40 of the preparation device 9 for preparing the dialysis fluid. On this dialysis supply line, in the direction of circulation of the liquid, there is a first flow meter 41 and a dialysis fluid pump 25.

[0177] The supply line 8 branches (at branch point 46) into an infusion line 39, in Figure 1 In the example, this infusion line is directly connected to the blood return line 7, in particular to the air separator 19 via a post-infusion conduit 47b (solid line).

[0178] Optionally, the infusion line 39 can infuse an infusion solution in the blood withdrawal line 6, in particular downstream of the blood pump 21 at a pre-infusion point 48 via a pre-infusion conduit 47a (dashed line).

[0179] One embodiment also comprises an infusion line 39 branching into a pre-infusion branch 47a and a post-infusion branch 47b directing an infusion solution in the blood withdrawal line 6 and the blood return line 7, respectively, such an embodiment being also within the scope of the present description.

[0180] One or more infusion pumps 43 can be used to pump a desired infusion flow into the blood circuit. The infusion pump 43 can be a positive displacement pump (e.g. a peristaltic pump as illustrated), but also any other pump suitable for transferring an infusion solution (e.g. a volumetric pump).

[0181] The dialysis effluent line 13 can be provided with a dialysis fluid pump 26 and a second flow meter 42. The first and second flow meters 41, 42 can be used (in a known manner) to control the liquid balance of the patient connected to the blood circuit 17 during a dialysis session.

[0182] The dialysis effluent line 13 is provided with a sensor 11, immediately downstream of the filtration unit 2, to measure a parameter value of the dialysis fluid in the dialysis effluent line.

[0183] In detail, the parameter of the dialysis fluid measured by the sensor 11 is at least one parameter selected in the group comprising the conductivity of the dialysis fluid, a conductivity-related parameter of the dialysis fluid, the concentration of at least one substance in the dialysis fluid and a concentration-related parameter of at least one substance in the dialysis fluid.

[0184] In detail, the sensor 11 is a conductivity sensor connected to the dialysis effluent line 13 and arranged to detect the conductivity value of the dialysis fluid downstream of the filtration unit 2.

[0185] Optionally (or in combination), the sensor 11 can comprise a concentration sensor arranged to measure the concentration of at least one substance in the dialysis fluid, such as the sodium concentration.

[0186] Accordingly, the sensor 35 on the dialysis fluid supply line can not be a conductivity sensor and can differently comprise a concentration sensor for measuring the concentration of at least one substance in the dialysis fluid, such as the sodium concentration.

[0187] Figure 1 The control unit 12 of the dialysis apparatus shown in Fig. 1 can be connected to a (graphical) user interface 22 through which the control unit can receive instructions, e.g. target values, such as the blood flow rate Q b , the dialysis fluid flow rate Q di , the infusion flow rate Q inf (pre-infusion and / or post-infusion), the patient weight loss WL. The control unit 12 can also receive values detected by sensors of the apparatus, e.g. the above-mentioned flow meters 41, 42, the (e.g. conductivity) sensor 35 of the preparation apparatus 9 and the (e.g. conductivity) sensor 11 in the dialysis effluent line 13. Based on the received instructions and the set operating mode and algorithms, the control unit 12 drives actuators of the apparatus, such as the blood pump 21, the above-mentioned dialysis fluid and dialysate pumps 25, 26, the preparation apparatus 9 and the infusion pump 43.

[0188] As mentioned before, the described embodiments are intended to provide non-limiting examples. In particular, Figure 1 The blood circuit of Fig. 1 should not be interpreted as limiting or restrictive, as the apparatus in the present invention can comprise further components or alternative components than the ones described.

[0189] For example, an ultrafiltration line can be comprised, wherein at least one corresponding pump is connected to the dialysis effluent line 13.

[0190] Figure 1 The blood circuit of Fig. 1 is for double-needle treatment; however, this is one non-limiting example of a blood line apparatus.

[0191] In fact, the apparatus can be set to perform single-needle treatment, i.e. the patient is connected to the extracorporeal blood circuit through a single needle, and then the extracorporeal blood line from the patient is split into a withdrawal line and a return line, using e.g. a 'Y-shaped' connector. During single-needle treatment, blood withdrawal phases, in which blood is removed from the patient, alternate with blood return phases, in which blood is returned to the patient.

[0192] Furthermore, one or more apparatuses for measuring the concentration of a specific substance can be implemented on the dialysis fluid side or (and) on the blood side of the hydraulic circuit (or both). It can be desirable to know the concentration of calcium, potassium, magnesium, bicarbonate and / or sodium.

[0193] Finally, the above-mentioned one or more pumps and all the other necessary temperature, pressure and concentration sensors can operate on the dialysis supply line 8 and / or on the dialysis effluent line 13, so as to monitor the preparation and flow of the liquids in the hydraulic circuit.

[0194] In view of the above description of possible embodiments of the extracorporeal blood treatment apparatus, the specific working of the apparatus and the algorithm of the setting control unit are subsequently described.

[0195] Definitions

[0196] We define "dialysis fluid" as the fluid prepared and, where appropriate, introduced into the second chamber (4) of the filtration unit (2), dialyzer (for example, HD and HDF), based on the selected treatment. The dialysis fluid can also be indicated as "fresh dialysis fluid".

[0197] We define "dialysate" as the liquid coming from the outlet of the second chamber (4) of the filtration unit (2), dialyzer. The dialysate is a used dialysis fluid, including uremic toxins removed from the blood.

[0198] We define "infusion" as the fluid prepared and infused in the blood circuit (17), in the blood withdrawal line (6) or in the blood return line (7), or in both blood lines (6, 7).

[0199] We define 'isoconductive dialysis' as a dialysis treatment in which the electrical conductivity of the dialysis fluid does not change before and after the filtration unit (2), K di = K do .

[0200] We define 'plasma conductivity' as the electrical conductivity of the dialysis fluid in isoconductive dialysis.

[0201] We define 'hemodialysis treatment mode' (HD) as a dialysis treatment in which fresh dialysis fluid is directed to the filtration unit 2 and no substitution fluid is infused into the blood circuit.

[0202] We define 'hemofiltration treatment mode' (HF) as a treatment in which substitution fluid is directed into the blood circuit 17 and no fresh dialysis fluid is directed to the filtration unit 2.

[0203] We define 'hemofiltration treatment mode' (HF post-dilution) as a treatment in which substitution fluid is directed into the blood circuit 17 downstream of the filtration unit (no substitution fluid is directed into the blood circuit upstream of the filtration unit).

[0204] We define 'hemofiltration treatment mode' (HF pre-dilution) as a treatment in which substitution fluid is directed into the blood circuit 17 upstream of the filtration unit (no substitution fluid is directed into the blood circuit downstream of the filtration unit).

[0205] We define the 'hemodiafiltration treatment mode' (HDF) as a treatment in which both substitution fluid is directed into the blood circuit 17 downstream of the filtration unit 2 and fresh dialysis fluid is directed into the filtration unit 2.

[0206] We define the 'post-dilution hemodiafiltration treatment mode' (HDF post-dilution) as a treatment in which both substitution fluid is directed into the blood circuit 17 downstream of the filtration unit 2 and fresh dialysis fluid is directed into the filtration unit 2 (without substitution fluid being directed into the blood circuit upstream of the filtration unit).

[0207] We define the 'pre-dilution hemodiafiltration treatment mode' (HDF pre-dilution) as a treatment in which both substitution fluid is directed into the blood circuit 17 upstream of the filtration unit 2 and fresh dialysis fluid is directed into the filtration unit 2 (without substitution fluid being directed into the blood circuit downstream of the filtration unit).

[0208] We define the 'isoconductive substance concentration' as the concentration of a substance in the dialysis fluid in isoconductive dialysis.

[0209] We define the 'isoconductive sodium concentration' as the sodium concentration in the dialysis fluid in isoconductive dialysis.

[0210] In the present application, the term "citrate" and the term "Cit" mean that the ingredient is in the form of a salt of citric acid, such as its sodium, magnesium, calcium or potassium salt. Citric acid (denoted as C6H8O7) is stepwise deprotonated, and thus, citrate includes all different forms of citrate (denoted as C6H5O7 3- , hydrogen citrate (denoted as C6H6O7 2- ) and dihydrogen citrate (denoted as C6H7O 7- ).

[0211] The term "citrate" or "total citrate" means the total amount of citric acid and any of its salts, such as its sodium, magnesium, calcium or potassium salt.

[0212] In other words, "total citrate" refers to the sum of free citrate ions and citrate containing complexes and ion pairs.

[0213] Glossary of terms

[0214] The following terms are used consistently in all equations provided in the following description of the detailed work of the extracorporeal blood treatment device.

[0215]

[0216]

[0217]

[0218]

[0219]

[0220]

[0221]

[0222]

[0223] The Donnan effect adjusts the electrical effect of the ions, ensuring that the electrical neutrality is maintained on the membrane. To estimate the Donnan factor, reference is made to Trans Am Soc Artif Intern Organs, 1983; 29; 684-7, "Sodium Fluxes during hemodialysis", Lauer A., Belladonne M., Saccaggi A., Glabman S., Bosch J.

[0224] To implement the method for estimating the plasma sodium during hemodialysis, a model of ion transfer in the filtration unit has been developed. In fact, if the blood values of certain electrolytes are known or estimated, the plasma sodium can be calculated from the conductivity measurements by means of a simple model of the filtration unit.

[0225] According to the developed method, one term, called c di,Na,isocond , is the isoconductivity sodium concentration of the dialysis fluid, and one term, called C di,Na,offset , is the term for obtaining the plasma sodium concentration.

[0226] For two dialysis fluid settings, indicated with indices 1 and 2, respectively (for example, different conductivity and / or concentration of at least one solute), the first term can be calculated by means of the following expression:

[0227] For HD, HDF post-dilution and HF post-dilution treatment modalities, the term for obtaining the plasma sodium concentration can be calculated by means of the following expression:

[0228]

[0229]

[0230] The plasma sodium is related to the plasma water as follows:

[0231] c p,Na = f pw *c pw,Na (III)

[0232] where the plasma water fraction (fpw ) is typically about 0.93:

[0233] f pw ≈0.93

[0234] Given the above calculations, it follows that:

[0235]

[0236] For HDF pre-dilution and HF pre-dilution treatment modalities, the term used to obtain the plasma sodium concentration can be calculated by the following expression:

[0237]

[0238] In HF treatment modalities, this clearance is equal to the dialyzer outlet flow, i.e., K u = Q do .

[0239] Solution proposal

[0240] The technical solution described here can be applied to HD, HDF and HF treatment modalities, in particular with concentrates having acetate and / or citrate.

[0241] The above model is very useful in determining blood parameters of interest. Even if not explicitly stated, the various steps of the proposed method that will be described below are intended to be performed by the control unit 12 of the extracorporeal blood treatment device 1.

[0242] In particular, the treatment process is started, preferably but not necessarily, as a double-needle hemodialysis treatment.

[0243] The user will input the prescription values through the user interface 22. For example, set values for the total weight loss WL and the total treatment time T are provided, as well as the blood flow rate Q b and the fresh dialysis flow rate Q di . If needed, also the infusion flow rate Q inf , or the total accumulated infusion volume (V inf ) is provided.

[0244] Other parameters can be input through the user interface, such as the bag type, the sodium user limit, etc.

[0245] Before starting the treatment, the operator needs to further input the 'bicarbonate' setting.

[0246] The control unit 12 receives, or optionally calculates, the initial dialysate conductivity or the initial concentration of at least one solute (e.g., sodium) in the dialysate from the prescription.

[0247] In this respect, it is worth noting that, in the following detailed description, reference is made to a regulation device which controls the concentration of ionic species (in particular the sodium concentration) in the preparation of the dialysis fluid, in order to obtain the desired conductivity of the dialysis fluid.

[0248] However, regulation devices which directly regulate the overall conductivity of the dialysis fluid are also included in the spirit of the present description, or, in any case, the present description also includes regulation devices which modify the concentration of different ionic species.

[0249] The haemodialysis or haemodiafiltration or haemofiltration treatment is then started.

[0250] The isoconductance sodium concentration is provided to the control unit 12. In more detail, the isoconductance sodium concentration can be calculated according to expression I.

[0251] Alternatively, an isoconductance sodium concentration related parameter can be provided to the control unit 12; the isoconductance sodium concentration related parameter can be the plasma conductivity. In fact, the isoconductance sodium concentration is related to the plasma conductivity; the isoconductance sodium concentration knowing the plasma conductivity can be derived in a manner known to the person skilled in the art and vice versa; of course, the composition of the dialysis fluid should be known. In fact, the conductivity of a solution can be calculated as the sum of several terms; each term represents a salt contained in the solution and each term is built as the product of the molar conductivity and the concentration of the salt. The concentration of sodium can be calculated from the conductivity according to the same relationship. In this case, the plasma conductivity (subsequently used to obtain the isoconductance sodium concentration) can be calculated by conventional methods, for example according to any one of the methods in patent documents EP547025, US5100554, EP658352, EP920877 or EP1108438.

[0252] As mentioned above, when the isoconductance sodium concentration (or the isoconductance sodium concentration related parameter) is not known, different methods can be used to determine the related parameter.

[0253] In the HD treatment mode, in order to calculate the isoconductance sodium concentration (or the isoconductance sodium concentration related parameter), the conductivity upstream and downstream of the filtration unit is measured for the dialysis fluid flowing through the filtration unit.

[0254] Then, in the same HD treatment mode, a regulated dialysis fluid is prepared having a different solute (for example, sodium) concentration and the conductivity upstream and downstream of the filtration unit is again measured for the regulated dialysis fluid; for example, the two dialysis fluids can differ by about 10 mmol / L.

[0255] In other words, the basic principle of the monitoring system described above is that the outlet dialysate conductivity is measured continuously when the inlet dialysate conductivity is changed, for example, by 1 mS / cm during, for example, two (or more) minutes.

[0256] Alternatively, the control unit 12 receives the iso-oncotic sodium concentration or the plasma conductivity directly as an input. This applies to all HD / HDF / HF treatment modes. For example, the physician or the nurse can receive the laboratory analysis and can provide the data to the machine via the user interface of the dialysis monitor; the control unit 12 is arranged to store the iso-oncotic sodium concentration or the plasma conductivity used for the subsequent dialysis fluid parameter adjustment in the memory 46.

[0257] Furthermore, for all HD / HDF / HF treatment modes, the iso-oncotic sodium concentration or the plasma conductivity can be estimated using different formulas, which do not explicitly require two dialysis fluids of different sodium concentrations. This is particularly the case for the HDF and HF treatment modes. The following approach can also be employed for the HD treatment mode.

[0258] For example, according to another embodiment, which can be employed for HD / HDF and HF treatment modes, the control unit 12 is arranged to calculate the initial plasma conductivity based on the sum of at least the initial conductivity of the dialysate plus the difference between the inlet and outlet conductivities at the filtration unit or dialyzer, weighted by a factor of the dialysate flow rate. In more detail, the difference between the inlet and outlet conductivities of the filtration unit is also weighted by a factor of the blood flow rate in the blood line.

[0259] In particular, according to this another embodiment, the control unit 12 is arranged to calculate the plasma conductivity using the following formula:

[0260]

[0261] The meaning of the above-mentioned symbols is given in the glossary.

[0262] It is worth emphasizing that, during the calculation of the initial plasma conductivity (formula (VI)), in the HD and HDF treatment modes, the dialysis fluid is circulated through the secondary chamber 4, keeping the dialysis fluid parameter values substantially constant.

[0263] In the HF and HDF treatment modes, the dialysis fluid / infusion fluid is circulated through the infusion line 39, again keeping the dialysis fluid parameter values substantially constant.

[0264] In a further embodiment, the control unit 12 is arranged to calculate the initial plasma conductivity based on the sum of at least the initial conductivity of the fresh dialysis fluid plus the difference between the inlet and outlet conductivities at the filtration unit, weighted by a factor of the dialysate flow rate. In more detail, the difference between the inlet and outlet conductivities of the filtration unit or dialyzer is also weighted by a factor of the filtration unit clearance.

[0265] In particular, according to this further embodiment, the control unit 12 is arranged to calculate the plasma conductivity using the following formula:

[0266]

[0267] The meaning of the above symbols and constants is given in the glossary.

[0268] It is worth emphasizing that during the calculation of the initial plasma conductivity (formula (VII)), the dialysis fluid is circulated through the secondary chamber 4, keeping the dialysis fluid parameter values substantially constant, both in the HD and in the HDF treatment mode.

[0269] In the HF and HDF treatment modes, the dialysis fluid / infusate is circulated through the infusate line 39, again keeping the dialysis fluid parameter values substantially constant.

[0270] Of course, both formulas (VI) and (VII) for the estimation of the plasma conductivity can be applied iteratively, meaning that the estimated value of the newly calculated PC(k p,1 ) is applied to the dialysis fluid and, once a steady state is reached, a new estimated value is calculated again after measuring the conductivity at the filter inlet and outlet.

[0271] Estimation of the dialyzer clearance

[0272] Since the filter unit (dialyzer) clearance K u is unknown (see, for example, formula (VII) above for the clearance K u ), it is necessary to estimate it. For the purpose of the estimation, it is assumed that all ions have the same dialyzer clearance, which is equal to the urea clearance.

[0273] In HDF treatment, it is important to distinguish the dialyzer clearance, which is related to the transfer across the membrane, from the treatment (patient) clearance, which describes the removal of the substance from the patient. The patient clearance has clinical interest, while the interest for the purpose of the calculation of the initial set point lies in the dialyzer characteristics. Therefore, when referring to the clearance in this document, it is the filter unit / dialyzer clearance, unless otherwise stated.

[0274] In the calculation of the clearance, the ultrafiltration flow through the membrane must be taken into account. The total ultrafiltration flow Q u is the sum of the weight loss flow rate Q wl and the infusate flow rate Q inf :

[0275] Q u = Q wl + Q inf (VIII) In the HD treatment mode, the infusate flow rate Q inf is zero.

[0276] In general, the infusate flow rate Q infis the sum of the pre-infusion flow rate (i.e. the flow of fluid infused into the blood circuit 17 upstream of the filtration unit 2) and the post-infusion flow rate (i.e. the flow of fluid infused into the blood circuit 17 downstream of the filtration unit 2).

[0277] The dialyzer inlet fluid flow rate is:

[0278] Q di = Q d - Q inf (IX) where Q d is the total dialysis fluid flow rate, i.e. the total flow rate of dialysis fluid prepared by the preparation device 9 and subsequently divided (if appropriate) into the flow rate of fluid to the filtration unit (Q di ) and the flow rate of fluid to be infused into the blood circuit (Q inf ).

[0279] In the HF treatment mode, the dialyzer inlet fluid flow rate Q di is zero, since Q d = Q inf .

[0280] The dialyzer outlet fluid flow rate Q do may be calculated as:

[0281] Q do = Q di + Q u (X)

[0282] The clearance K u may be calculated using the following equation:

[0283]

[0284] where

[0285]

[0286] k m A is the modified mass transfer coefficient:

[0287]

[0288] and k0A is the mass transfer coefficient of the dialyzer.

[0289] k0A can be derived with information about the dialyzer used, for example the device can receive information from the user or by reading specific composition identification data. Alternatively, the control unit 12 can assume a standard dialyzer, which has (for example) k0A = 1100 ml / min as a fixed value. In this latter case, the error of the calculated K u will be within ±10% for all commonly used dialyzers.

[0290] Pe is also known as the Peclet number, which is defined as

[0291]

[0292] Q bwi is the dialyzer inlet blood water flow, which can be calculated as:

[0293] Q bwi = f bw Q b (XV)

[0294] Conversely, in HDF predilution, the dialyzer inlet blood water flow must include the infusion flow:

[0295] Q bwi = f bw Q b + Q inf (XVI)

[0296] In this equation, Q b is the actual (arterial) blood flow rate and f bw is the dialyzable blood water fraction, which can be calculated using the following equation:

[0297] f bw = f cw · γ cw,u · Hct + f pw · (1 - Hct) (XVII)

[0298] Where the meaning of the symbols used is clarified in the glossary section.

[0299] Using the above reference values, for example, in normal conditions of hemodialysis, the dialyzable blood water fraction f bw for urea will be 0.89.

[0300] The dialyzer outlet blood water flow can be calculated from the following equation

[0301] Q bwo = Q bwi - Q u (XVIII)

[0302] Estimation of the dialyzer clearance - HF treatment.

[0303] In HF treatment mode, since the clearance is equal to the dialyzer outlet flow, the clearance calculation is simple:

[0304] K u = Q do = Q u = Q inf + Q wl (XIX)

[0305] By definition, in HF, Q di = 0.

[0306] Estimation of citrate clearance

[0307] For citrate, the free ion Cit 3- does not govern its complexation and ion pair. Depending on the pH in plasma and dialysis solution, there is a substantial fraction of CaCit 2- , MgCit - , and NaCit - along with some HCit 2- .

[0308] We approximate that the individual clearance values are close to the individual values called .

[0309] This clearance is used to calculate the actual flow rate, using a mass transfer coefficient value of k0A Cit = 0.212 · k0Afor K u equations (4), (5), (6).

[0310] Estimation of plasma water fraction

[0311] Post-HD and post-HDF / HF dilution

[0312] The plasma water fraction depends on the total plasma protein concentration c p,tp and can be estimated as:

[0313] f pw = 1 - 0.00107 · c p,tp (XX) where c p,tp is the plasma protein concentration. In case of normal plasma protein concentration c p,tp = 70 g / L, the plasma water fraction is f pw = 0.925.

[0314] HDF / HF predilution

[0315] In HDF and HF predilution mode, the dilution of blood and the corresponding reduction of total protein concentration must be taken into account to calculate the plasma water fraction of blood in the dialyzer.

[0316] This is done using the following equation:

[0317]

[0318] f pw = 1 - 0.00107 · c pi,tp (XXII) The meaning of the symbols used is clarified in the glossary section.

[0319] Estimation of the Donnan factor alpha

[0320] Post-HD and post-HDF / HF dilution

[0321] The transfer of charged, permeable dialyzer membrane substances is influenced by the charged plasma proteins. This influence is quantified by the Donnan factor alpha.

[0322] If the plasma protein concentration c p，tp is known, the Donnan factor alpha for a single charged cation can be estimated using the following equation:

[0323]

[0324] In the case of a normal plasma total protein concentration of c p，tp = 70 g / L, the Donnan factor in the conditions typical for hemodialysis is alpha = 0.95.

[0325] HDF / HF predilution

[0326] In the HDF and HF predilution mode, the dilution of the blood and the corresponding reduction of the total protein concentration must be taken into account when calculating the Donnan factor of the blood in the dialyzer.

[0327] This is done using the following equation:

[0328]

[0329]

[0330] Where the meaning of the used symbols is clarified in the glossary paragraph.

[0331] Estimation of the sodium concentration in the blood (second blood parameter)

[0332] As mentioned above, according to an aspect of the innovation, the control unit 12 receives a value of a parameter. This parameter can be the isoconductive sodium concentration or a parameter related to the isoconductive sodium concentration.

[0333] As mentioned above, the control unit 12 is arranged for calculating a value of a second parameter of the blood.

[0334] The second parameter is selected between a concentration of a substance in the blood and a parameter related to the concentration of a substance in the blood.

[0335] According to specific needs, it can be determined the sodium content (or the content of different electrolytes) in the blood.

[0336] The step of calculating the value of the second parameter of the blood is performed as a function of a main contribution term based on / according to the isoconductive sodium concentration and as a function of an offset contribution term (i.e. a term that takes into account the transport driving gradients of certain specific substances).

[0337] The main contribution term can account for (can contribute to) at least 80% of the sodium concentration reaching the same parameter value (in particular at least 90% of the same parameter value), i.e. the general value of the sodium concentration in the plasma depends mainly on the isoconductive sodium concentration.

[0338] More in detail, the offset contribution term can contribute less than 20% (or even less than 15%) to the sodium concentration in the blood (and in particular less than 10% to the same parameter value).

[0339] The calculation is a weighted algebraic sum of at least the main contribution term (c di,Na,isocond ) and the offset contribution term (c di,Na,offset ), according to the following general formula:

[0340]

[0341] In order to estimate the blood sodium content, i.e. c p,Na , an offset factor C di,Na,offset needs to be applied to the isoconductive sodium concentration, i.e. C di,Na,isocond .

[0342] The main contribution term (C di,Na,isocond ) is a concentration value that, if used as dialysis fluid concentration for sodium, would perform an isoconductive dialysis; we define "isoconductive dialysis" as a dialysis treatment in which the conductivity of the dialysis fluid does not change from before to after the filtration unit 2, i.e. K di = K do .

[0343] As shown in formula (XXVI), the concentration of sodium in the plasma is a weighted sum of C di,Na,isocond and C di,Na,offset . In particular the algebraic sum of the two terms is multiplied by a factor f pw / a (i.e. the plasma water fraction divided by the Tonnens factor).

[0344] Although not necessary, since the calculation can also be based on the conductivity, the main contribution term and the offset contribution term are in size the concentrations of the substances (e.g. sodium) in the fluid.

[0345] The Applicant has understood that certain specific substances present in the dialysis fluid, i.e. bicarbonate, potassium, acetate and citrate, have a major role that should be taken into account when expecting to estimate the blood sodium content from the measurement of the isoconductive sodium concentration. Of course other substances also play a role, such as lactate, magnesium and calcium.

[0346] In addition, the difference in concentration between the same substances in the blood and in the dialysis fluid also affects the mentioned estimation.

[0347] In view of the above, the Applicant has also realized that certain parameters having a weight in determining the excess of sodium are known at the time of calculating the offset contribution term and depend on the machine settings (e.g. concentrate used) or on the patient's prescription (e.g. dialysate flow rate). Other parameters depend on the patient undergoing the treatment and therefore can be directly measured (e.g. laboratory analysis) or estimated (e.g. based on a large population or patient history).

[0348] The offset contribution term assumes a negative value in all or almost all the main dialysis settings, i.e. it reduces the main contribution term, which is the concentration value that would allow an isoconductive treatment if used as the concentration of sodium in the dialysis fluid.

[0349] In fact, the main contribution term takes into account the effect of all the ions on the isoconductive sodium concentration; the offset contribution term modifies this value to determine only the concentration of sodium (or another substance).

[0350] More in detail, the control unit is configured to calculate the offset contribution term based on the concentration of at least one substance in the dialysis fluid selected in the group comprising bicarbonate, potassium, acetate, lactate and citrate; in particular, the calculation is made as a function of the concentration of at least two of said substances, more in detail as a function of the concentration of bicarbonate, potassium, acetate and / or citrate and lactate in the dialysis fluid.

[0351] As mentioned above, the control unit is configured to calculate the offset contribution term as a function of the weighted difference between the concentration of at least one of the above-mentioned substances in the dialysis fluid and the concentration of the same substance in the plasma.

[0352] In the case of HDF pre-dilution and HF pre-dilution treatment modes, for example, the estimated plasma water concentration of the specific substance (i) of potassium, bicarbonate, potassium, acetate and citrate is replaced with the corresponding diluted blood concentration, to take into account the dilution caused by the pre-infusion.

[0353] Furthermore, the control unit calculates the offset contribution term as a function of the molar conductivity of at least one substance in the dialysis fluid; in detail, said substance can be selected in the group of acids or salts comprising bicarbonate, chloride, acetate, citrate, phosphate and sulphate, wherein said salts are formed with sodium, potassium, calcium and magnesium.

[0354] More in detail, the calculation takes into account the molar conductivity of at least two, in particular at least three, of said substances, in particular sodium bicarbonate (NaHC03), sodium chloride (NaCl), sodium acetate (NaCH3COO), trisodium citrate (Na3C6H5O7) and potassium chloride (KC1).

[0355] Further, the offset contribution term is a function of the difference between the first molar conductivity of a substance selected in the group comprising sodium bicarbonate (NaHCO3), sodium acetate (NaCH3COO), trisodium citrate (Na3C6H5O7) and potassium chloride (KCI), and the molar conductivity of sodium chloride (NaCI).

[0356] Alternatively, the offset contribution term is a function of the difference between the first molar conductivity of a substance selected in the group comprising sodium bicarbonate (NaHCO3), trisodium citrate (Na3C6H5O7) and potassium chloride (KCI), and the molar conductivity of sodium chloride (NaCI).

[0357] The control unit is further arranged to calculate the offset contribution term from the estimated plasma water concentration of at least one substance selected in the group comprising bicarbonate, potassium, acetate, lactate and citrate; in particular based on the estimated plasma water concentration of at least two, three or four of said substances; in one specific example of the present specification, the offset contribution term is a function of the estimated plasma water concentration of bicarbonate, potassium and acetate. In another specific example, citrate is also taken into account.

[0358] In HD, HDF post-dilution and HF post-dilution, the estimated plasma water concentrations of bicarbonate, potassium, citrate and acetate are the pre-dialysis average values of the respective substances for a large patient population. As previously mentioned, the estimated plasma water concentrations of bicarbonate, potassium and acetate can optionally be based on other statistically prepared values, or historical values for a specific patient, or direct measurements made prior to the treatment.

[0359] With respect to HDF pre-dilution and HF pre-dilution, the estimated plasma water concentration in the blood entering the dialyzer takes into account the dilution of the blood caused by the substitution fluid upstream of the dialyzer.

[0360] In HDF pre-dilution and HF pre-dilution mode, the estimated plasma water concentration is a function of the blood flow rate Q b and the infusion flow rate Q inf . Further, it is a function of the dialyzable blood water fraction (calculated from hematocrit - Hct and cell water fraction) of the selected substance and the plasma water concentration in the blood from the patient (i.e. upstream of the pre-dilution infusion point); the estimated plasma water concentration is also a function of the infusion concentration of the same substance.

[0361] Note that in the specific formula, the estimated plasma water concentration can optionally be adjusted by a respective (preferably but not necessarily fixed) offset factor. The numerical value can be e.g. 0.95 (a) or 1.05 (a -1 ), but other values can also be used (typically depending on protein content and ion charge).

[0362] More specifically, the offset factor is a function of the charged plasma proteins, in particular of the transthyretin. In the HD, HDF post-dilution and HF post-dilution modalities, the offset factor is the transthyretin a or the inverse a -1 In the HDF pre-dilution and HF pre-dilution modalities, the offset factor should take into account the decrease in total protein concentration due to the pre-dilution infusion. Therefore, in this latter case, the offset factor is a function of the dilution protein concentration affected by the blood flow Q b , the infusion flow Q inf and the red blood cell fraction of the blood Hct (see, for example, equation (XXV)).

[0363] The offset contribution term is an algebraic sum of a plurality of components, a first component being a function of the concentration difference, in particular of the weighted difference, of at least one substance in the dialysis fluid and the same substance in the plasma, a second component being a function of the concentration difference, in particular of the weighted difference, of at least a second substance in the dialysis fluid and the same second substance in the plasma, a third component being a function of the concentration difference, in particular of the weighted difference, of at least a third substance in the dialysis fluid and the same third substance in the plasma.

[0364] The substances can be selected in a group comprising the bicarbonate anion (HC03 - ), the acetate anion (CH3COO - ), the citrate anion (C6H5O7 3- ) and the potassium ion (K + ), in addition to lactate.

[0365] Furthermore, in the case of HDF pre-dilution and HF pre-dilution treatment modalities, the estimated plasma water concentration of the specific substance (i) of sodium, bicarbonate, potassium, acetate and citrate, for example, is replaced with the corresponding diluted blood concentration, in order to take into account the dilution caused by the pre-infusion. Therefore, the above difference is the difference between the diluted blood concentration and the concentration of the same substance in the dialysis fluid.

[0366] The above general considerations are reflected in specific and non-limiting implementation formulas, which allow to determine the precise sodium concentration in the blood when the isoconductive sodium concentration is known.

[0367] Of course, different formulas can be optionally used, including one or more of the above general principles / substances.

[0368] As mentioned above, in order to estimate the sodium content in the blood, i.e. c p,Na , it is necessary to apply to the calculated isoconductive sodium concentration an offset factor C di,Na,offset :

[0369]

[0370] HD treatment modality

[0371] In the case of HD treatment mode:

[0372]

[0373] Or, if the influence of other substances is also taken into account, the offset factor can be calculated with a similar formula in which another term is included in the algebraic sum.

[0374] This other term is the fourth component in the sum, which depends at least on the ratio between one flow rate (in particular the flow rate of dialysis liquid at the outlet of the secondary chamber 4) and an efficiency parameter of the filtration unit 2 (in particular the clearance of the filtration unit 2, optionally the urea clearance).

[0375] In this case, the formula is written as:

[0376]

[0377]

[0378] The factor K (i.e. K = 1 - K rest ) defines the influence on the conductivity due to other components of the dialysis fluid different from the components already treated and included in the respective formula. Thus, the effect of salts containing calcium, magnesium, lactate, phosphate and sulphate can have an impact on the conductivity. The effect produced by these components is generally small and does not vary significantly between one dialysis treatment and another.

[0379] In the case of citrate is taken into account, the formula can be written as:

[0380]

[0381] is an approximate clearance value of citrate. The clearance is referred to the use of the respective K u The K0A Cit = 0,212 * K0A Urea value of the mass transfer of the actual flow rate calculation.

[0382] HDF post-dilution treatment mode

[0383] In the case of post-dilution of HDF treatment mode, the same equations (XXVIII-XXX) are applied as for HD treatment mode, but with the clearance K u (see equations (XI-XVI)) calculated for the HDF treatment case (taking into account the substitution flow rate).

[0384] HDF pre-dilution treatment mode.

[0385] The equations for HDF pre-dilution are similar to those for HDF post-dilution, but we must take into account the dilution of blood before it enters the dialyzer.

[0386] The dilution of the plasma water concentration of the substance I in the pre-dilution mode is described by equation (XXXI), which for the sake of understanding is reported here:

[0387]

[0388] The offset factor is calculated as follows:

[0389]

[0390] In the case where the effect of other substances is also taken into account, the offset factor can be calculated with a similar equation in which another term is included in the algebraic sum.

[0391] This other term is the fourth component of the sum, which depends at least on the ratio between one flow rate (in particular the flow rate of dialysis liquid at the outlet of the secondary chamber 4) and an efficiency parameter of the filtration unit 2 (in particular the clearance of the filtration unit 2, optionally the urea clearance K u ). Of course, the dilution of the blood caused by the pre-infusion of replacement fluid is also taken into account.

[0392] HF pre-dilution treatment mode

[0393] The equation for HF pre-dilution is the same as for HDF pre-dilution, but in which the filtration unit clearance is equal to the flow rate of dialysis liquid at the outlet of the filtration unit, i.e. K u = Q do .

[0394] HF post-dilution treatment mode

[0395] The equation for HF post-dilution is the same as for HD, but in which the filtration unit clearance is equal to the flow rate of dialysis liquid at the outlet of the filtration unit, i.e. K u = Q do .

[0396] Once the sodium concentration in the blood has been calculated, the control unit can drive the adjustment device 10 to adjust the conductivity or concentration of the substance in the fresh dialysis fluid and set the third parameter value of the dialysis fluid in the dialysis fluid feed line 8 at the calculated set point on the basis of the estimated blood sodium content. The third parameter can be the sodium concentration or the conductivity in the dialysis fluid or the same dialysis fluid.

[0397] Of course, it is also possible to use the estimated blood sodium content to create a sodium profile in real time to be applied to a specific patient in order to control the sodium balance throughout the dialysis treatment.

Claims

1. A device for extracorporeal blood treatment, comprising: - a blood circuit comprising a filtration unit (2), a blood withdrawal line (6) and a blood return line (7), wherein, the filtration unit (2) has a primary chamber (3) and a secondary chamber (4) separated by a semipermeable membrane (5), the blood withdrawal line (6) is connected to an inlet of the primary chamber (3), the blood return line (7) is connected to an outlet of the primary chamber (3), said blood withdrawal line and said blood return line being arranged for connection to a patient's cardiovascular system; - a dialysis supply line (8) comprising at least one infusion line (39) connected to said blood circuit; - a dialysis effluent line (13) connected to an outlet of the secondary chamber (4); - a control unit (12) arranged to run at least one hemofiltration treatment (HF) or hemodiafiltration treatment (HDF), each of said treatments comprising infusion of a substitution fluid through said infusion line (39), the control unit (12) being arranged for receiving a value of a first parameter indicative of isostatic dialysis, said first parameter being selected in a group comprising a concentration of at least one substance, a concentration-related parameter of at least one substance, an electrical conductivity or an electrical conductivity-related parameter; - a preparation device (9) for preparing a dialysis fluid connected to said supply line (8) and comprising conditioning means (10) for conditioning a composition of the dialysis fluid, the conditioning means (10) being connected to the control unit (12); wherein said control unit (12) is arranged for: - calculating a value of a second parameter of the blood, said second parameter being selected in a group comprising a concentration of at least one substance in the blood and a concentration-related parameter of at least one substance in the blood; wherein the step of calculating the value of said second parameter is performed according to a main contribution term based on said first parameter and according to an offset contribution term based on a difference between a concentration of at least one substance in the dialysis fluid and a concentration of the same substance in the plasma, wherein the concentration of said substance in the plasma is estimated and, for a pre-dilution treatment of hemodiafiltration (HDF) and hemofiltration (HF), the estimated concentration of said substance in the plasma is a concentration of said substance in the plasma diluted, said substance in the dialysis fluid being selected in a group comprising bicarbonate, potassium, acetate, lactate, citrate, magnesium, calcium, sulphate and phosphate; - storing the value of said second parameter in a memory (46) connected to the control unit (12); - setting a value of a third parameter of the dialysis fluid in said dialysis supply line (8) at a setpoint based on the second parameter, the third parameter of the dialysis fluid being at least one parameter selected in a group comprising an electrical conductivity of the dialysis fluid, an electrical conductivity-related parameter of the dialysis fluid, a concentration of at least one substance in the dialysis fluid and a concentration-related parameter of at least one substance in the dialysis fluid; - driving the conditioning means (10) for conditioning the electrical conductivity of the dialysis fluid or the concentration of at least one substance in the dialysis fluid at said setpoint, wherein the infusion line (39) comprises an ultrafilter (44) to additionally filter the fluid received upstream of an injection point into the blood circuit.

2. The apparatus of claim 1, wherein, The control unit is arranged to calculate the offset contribution term based on a difference between concentrations of two or more substances in the dialysis fluid selected from the group comprising bicarbonate, potassium, acetate, lactate, citrate, magnesium, calcium, sulphate and phosphate and concentrations of the same substances in blood plasma.

3. The apparatus of claim 1, wherein, The control unit is arranged to calculate the offset contribution term based on a difference between concentrations of at least three substances in the dialysis fluid selected from the group comprising bicarbonate, potassium, acetate and citrate and concentrations of the same substances in blood plasma.

4. The apparatus of any one of claims 1 to 3, wherein, The control unit is arranged to calculate the offset contribution term from weighted concentration differences of at least the substances in the dialysis fluid and the same substances in blood plasma, the substances being selected from the group comprising bicarbonate, potassium, acetate, lactate and citrate.

5. The apparatus of any one of claims 1 to 3, wherein, The diluted blood plasma concentration is a function of the blood flow rate and the infusion flow rate.

6. The apparatus of any one of claims 1 to 3, wherein, The diluted blood plasma concentration is a function of the dialysable blood water fraction of the substance in blood from the patient and the plasma water concentration.

7. The apparatus of any one of claims 1 to 3, wherein, The diluted blood plasma concentration is a function of the concentration of the substance in the infusion.

8. The apparatus of any one of claims 1-3, wherein, The control unit is arranged to calculate the offset contribution term from weighted concentration differences of at least three substances in the dialysis fluid and in blood plasma, the substances being selected from the group comprising bicarbonate, potassium, acetate and citrate.

9. The apparatus of any one of claims 1-3, wherein, The first parameter is an isoconductive sodium concentration or an isoconductive sodium concentration related parameter and the second parameter is a concentration of at least one substance in blood, the substance being sodium.

10. The apparatus of any one of claims 1-3, wherein, The main contribution term is in magnitude a concentration of a substance in a fluid, wherein the main contribution term is a concentration value at which an isoconductive dialysis would run if used as a dialysis fluid concentration for sodium.

11. The apparatus of any one of claims 1-3, wherein, The main contribution term accounts for at least 80% of the second parameter value, the offset contribution term accounts for less than 20% of the second parameter value, and wherein the sub-step of calculating the second parameter value from the main contribution term and the offset contribution term is a sub-step of calculating a weighted algebraic sum of at least the main contribution term and the offset contribution term, wherein the offset contribution term is in magnitude a concentration of a substance in a fluid.

12. The apparatus of any one of claims 1-3, wherein, The control unit (12) is arranged for determining a time profile of a third parameter value of a dialysis fluid in the dialysis supply line (8), the third parameter of the dialysis fluid being at least one parameter selected from the group comprising an electrical conductivity of the dialysis fluid, an electrical conductivity related parameter of the dialysis fluid, a concentration of at least one substance in the dialysis fluid and a concentration related parameter of at least one substance in the dialysis fluid; wherein the control unit drives the regulating device (10) for regulating an electrical conductivity or a concentration of at least one substance in the dialysis fluid, the time profile of the third parameter being based on the second parameter.

13. The apparatus of any one of claims 1-3, wherein, The control unit is configured to calculate the offset contribution as an algebraic sum of at least two components, a first component being a function of a concentration difference of at least a first substance in the dialysis fluid and the same substance in the blood plasma, and a second component being a function of a concentration difference of at least a second substance in the dialysis fluid and the same substance in the blood plasma, wherein the first substance and the second substance are selected from a group comprising bicarbonate anions (HCO3 - ), acetate anions (CH3COO - ), citrate (C6H5O7 3- ) and potassium ions (K + ).

14. The apparatus of any one of claims 1-3, wherein, The control unit is configured to calculate the offset contribution as an algebraic sum of at least two components, a first component being a function of a weighted concentration difference of at least a first substance in the dialysis fluid and the same substance in the plasma, and a second component being a function of a weighted concentration difference of at least a second substance in the dialysis fluid and the same second substance in the plasma, wherein the first substance and the second substance are selected from a group comprising bicarbonate anions (HCO3 - ), acetate anions (CH3COO - ), citrate (C6H5O7 3- ), and potassium ions (K + ).

15. The apparatus of claim 14, wherein, The control unit (12) is arranged to calculate an isoconductive sodium concentration from a dialysis fluid conductivity upstream of the filtration unit (2), a dialysis fluid conductivity downstream of the filtration unit (2), a dialysis fluid flow rate at the inlet of the secondary chamber (4) and an efficiency parameter of the filtration unit (2) or a blood flow rate.

16. The apparatus of claim 14, wherein, Said control unit (12) is set to determine an iso-conductance sodium concentration from at least two conductivity values determined respectively upstream and downstream of said filtration unit (2) in at least two subsequently prepared dialysis fluids having different sodium concentrations.

17. An apparatus for extracorporeal blood treatment, comprising: a blood circuit comprising a filtration unit (2), a blood withdrawal line (6) and a blood return line (7), wherein the filtration unit (2) has a primary chamber (3) and a secondary chamber (4) separated by a semi-permeable membrane (5), the blood withdrawal line (6) is connected to an inlet of the primary chamber (3), the blood return line (7) is connected to an outlet of the primary chamber (3), said blood withdrawal line (6) and said blood return line (7) being set for connection to a patient's cardiovascular system; - a dialysis supply line (8) comprising at least one infusion line (39) connected to said blood circuit; - a dialysis effluent line (13) connected to an outlet of the secondary chamber (4); - a control unit (12) set to run at least one hemofiltration treatment (HF) comprising the infusion of a substitution fluid through said infusion line (39), said control unit (12) being set to receive a value of a first parameter for iso-conductance dialysis, said first parameter being selected in a group comprising a concentration of at least one substance and a conductivity; - a preparation device (9) for preparing a dialysis fluid connected to said supply line (8) and comprising a conditioning device (10) for conditioning the composition of the dialysis fluid, the conditioning device (10) being connected to the control unit (12), wherein said control unit (12) is set to: - calculate a value of a second parameter of the blood, said second parameter being a concentration of at least one substance in the blood; wherein the step of calculating said second parameter value is performed according to a main contribution term based on said first parameter and according to an offset contribution term; wherein said main contribution term accounts for at least 80% of the second parameter value and said offset contribution term contributes less than 20% of the second parameter value; and wherein the sub-step of calculating the second parameter value from said main contribution term and said offset contribution term is a sub-step of calculating an algebraic sum of at least said main contribution term and said offset contribution term, wherein said control unit is set to calculate said offset contribution term from a difference between a concentration of at least one substance in the dialysis fluid and a concentration of the same substance in the plasma, said substance being selected in a group comprising bicarbonate, potassium, acetate, lactate and citrate, - store said second parameter value in a memory (46) connected to the control unit (12); - set a third parameter value of the dialysis fluid in said dialysis supply line (8) at a set point based on the second parameter, said third parameter of the dialysis fluid being at least one parameter selected in a group comprising a conductivity of the dialysis fluid, a conductivity related parameter of the dialysis fluid, a concentration of at least one substance in the dialysis fluid and a concentration related parameter of at least one substance in the dialysis fluid, wherein the infusion line (39) comprises an ultrafilter (44) to additionally filter the fluid received upstream of an injection point into the blood circuit.

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