Accurate reloading of sorbent materials using patient and session data

Abstract

The present invention relates to devices, systems, and methods for recharging zirconium phosphate and / or zirconium oxide in a reusable sorbent module. The devices, systems, and methods provide for precise recharge of the zirconium phosphate and / or zirconium oxide to avoid the need for excessive recharge solution. The device systems and methods also provide for the calculation of the volume of recharge solution required to fully recharge the zirconium phosphate and zirconium oxide modules.

Description

[0001] This application is a divisional application of the Chinese invention patent application with the application date of March 29, 2019, application number 201910248494.8, and invention name “Precise Refilling of Adsorbent Materials Using Patient and Session Data”.

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application is a continuation-in-part of U.S. Patent Application No. 15 / 364,251, filed on November 29, 2016, which is a continuation-in-part of U.S. Patent Application No. 14 / 722,119, filed on May 26, 2015, and U.S. Patent Application No. 14 / 722,068, filed on May 26, 2015. U.S. Patent Application No. 14 / 722,119 and U.S. Patent Application No. 14 / 722,068 are each a continuation-in-part of U.S. Patent Application No. 14 / 261,651, filed on April 25, 2014, and U.S. Patent Application No. 14 / 642,847, filed on March 20, 2015. U.S. Patent Application No. 14 / 261,651 claims the benefit of and priority to U.S. Provisional Patent Application No. 61 / 941,672 filed on February 19, 2014 and U.S. Provisional Patent Application No. 61 / 909,372 filed on November 26, 2013. U.S. Patent Application No. 14 / 642,847 claims the benefit of and priority to U.S. Provisional Patent Application No. 62 / 016,613 filed on June 24, 2014 and U.S. Provisional Patent Application No. 62 / 077,159 filed on November 7, 2014. Technical Field

[0004] The present invention relates to an apparatus, system and method for recharging zirconium phosphate and / or zirconium oxide in a reusable adsorbent module. The apparatus, system and method provide accurate recharging of zirconium phosphate and / or zirconium oxide to avoid the need for excess recharging solution. The apparatus system and method also provide calculation of the volume of recharging solution required to completely recharge the zirconium phosphate and zirconium oxide module. Background Art

[0005] Zirconium phosphate is used in adsorbent dialysis to remove waste and unwanted solutes, including ammonium, potassium, calcium and magnesium ions, from the dialysate. Zirconium oxide can be used to remove phosphate ions from the dialysate. Zirconium phosphate and zirconium oxide are usually filled in adsorbent boxes. Typically, the adsorbent boxes are discarded and replaced after use. The discarded adsorbent boxes are decomposed and the zirconium phosphate and zirconium oxide are separated from other adsorbent materials. Because zirconium phosphate and zirconium oxide are expensive and refillable, the adsorbent reprocessor treats the recovered materials with chemical solutions. The recycling process requires the material to be transported to a reprocessing facility and involves laborious recycling steps in addition to refilling the adsorbent material. In addition, the adsorbent material cannot be reused immediately and must be added to a new adsorbent box and repackaged for sale. Conventional methods increase costs and infrastructure requirements, and increase complexity and waste.

[0006] Different patients may require different dialysate bicarbonate amounts for effective treatment. For example, patients with alkalosis require less dialysate bicarbonate than other patients. The amount of bicarbonate in the dialysate is usually controlled by adding sodium bicarbonate, which acts as a buffer. The bicarbonate ions in the dialysate are in equilibrium with carbon dioxide. The zirconium phosphate effluent pH is the main driving factor for determining the bicarbonate / carbon dioxide ratio. A lower zirconium phosphate effluent pH will produce more pCO2, which may cause the dialysate to enter the dialyzer at too low a pH, potentially causing hemolysis. High pCO2 may also cause bubbles to form in the dialysate, which may potentially be transferred to the patient. Excess CO2 can be removed by a degasser, such as a membrane contactor degasser, a vacuum degasser, or any other device capable of removing CO2 from a solution. A higher zirconium phosphate effluent pH will cause a higher bicarbonate concentration, requiring less bicarbonate to be added to the dialysate, but may not be used to treat all patients.

[0007] Known recharging systems do not control the volume of chemical solutions used to recharge the zirconium phosphate and zirconium oxide, and instead, simply treat the material with enough recharging chemical to ensure complete recharging. Complete recharging of the adsorbent material is often used to cover the worst case scenario to avoid ammonia breakthrough in patients with high amounts of urea or other ions. In each case, a complete recharge of the adsorbent material is wasteful and more costly than simply recharging the adsorbent material to the point required for a future dialysis session. Recharging the zirconium phosphate or zirconium oxide in this manner results in the use of a larger volume of recharging chemical than might be needed.

[0008] Therefore, there is a need for systems and methods that can refill zirconium phosphate in a zirconium phosphate adsorbent module and / or refill zirconium oxide in a reusable zirconium oxide adsorbent module in an accurate and efficient manner. There is a need for systems and methods that can more accurately match the refilling process for zirconium phosphate and / or zirconium oxide with actual box needs and usage, thereby eliminating additional expenses, time, money and chemical usage. There is also a need for systems and methods that can customize the amount of dialysate bicarbonate by controlling the pH of the zirconium phosphate effluent. There is a further need for systems and methods that can control the zirconium phosphate refilling process to produce a zirconium phosphate module with a desired effluent pH. There is a need to expand to systems and methods for determining the desired zirconium phosphate effluent pH based on the needs of the patient and the system. There is also a need for systems and methods that can calculate the amount of refill solution required to refill the zirconium phosphate and / or zirconium oxide. Summary of the invention

[0009] A first aspect of the invention relates to a method. In any embodiment, the method may include recharging sorbent material within a sorbent module by pumping one or more recharging solutions through the sorbent module; wherein the volume and / or concentration of the one or more recharging solutions are set based on one or more patient parameters and / or one or more dialysis session parameters for a patient and / or dialysis session using the sorbent module.

[0010] In any embodiments, the sorbent module may contain zirconium phosphate; one or more patient parameters may include at least one from the group consisting of: pre-dialysis patient potassium, calcium, magnesium, bicarbonate and urea amounts, patient weight, patient volume, patient residual renal function, patient acidosis status, average number of dialysis sessions per week, and average dialysis session length; and one or more dialysis session parameters may include at least one from the group consisting of: dialysate flow rate, blood flow rate, dialyzer size, dialyzer type, dialysis time, ultrafiltration rate; potassium, calcium, magnesium and bicarbonate dialysis prescription; whether ammonia breakthrough occurs, whether pH alarm occurs, fluid removed during the session, total treatment volume, starting water quality, URR target, URR achieved, clearance, whether blood leakage occurs, and whether hypotensive episodes occur.

[0011] In any embodiments, the sorbent module may contain zirconium oxide; one or more patient parameters may include at least one from the group consisting of: patient weight, patient volume, patient residual renal function, average number of dialysis sessions per week, and average dialysis session length; and one or more dialysis session parameters may include at least one from the group consisting of: dialysate flow rate, blood flow rate, dialyzer size, dialyzer type, dialysis time, ultrafiltration rate; potassium, calcium, magnesium and bicarbonate dialysis prescription; whether ammonia breakthrough occurs, whether pH alarm occurs, fluid removed during the session, total treatment volume, starting water quality, URR target, URR achieved, clearance, whether blood leakage occurs, and whether hypotensive episodes occur.

[0012] In any embodiment, the sorbent module may contain zirconium phosphate, and wherein the one or more patient parameters and / or the one or more dialysis session parameters include total cations and total CO2 pumped through the sorbent module during a previous dialysis session.

[0013] In any embodiment, the total cations and total CO2 pumped through the sorbent module can be obtained from any one or more of the following: (a) direct measurement of the total cations and total CO2 in the dialysate flow path during a previous dialysis session; (b) estimation of the total cations and total CO2 based on patient weight; (c) estimation of the total cations and total CO2 based on the dialysis prescription; (d) estimation of the total cations and total CO2 based on pre-dialysis patient cation measurements and / or pre-dialysis patient total CO2 measurements; (e) estimation of the total cations and total CO2 based on multiple previous dialysis sessions; or (f) a combination thereof.

[0014] In any embodiment, the step of recharging the zirconium phosphate can comprise pumping between 5.0 and 6.0 millimoles of sodium in the one or more recharging solutions per total milliequivalent of total cations pumped through the sorbent module during the previous dialysis session.

[0015] In any embodiment, the step of recharging the zirconium phosphate can include pumping between 0.3 and 1.0 millimoles of acetate in the one or more recharging solutions per millimoles of total CO2 pumped through the sorbent module during the previous dialysis session.

[0016] In any embodiment, the sorbent module may contain zirconium oxide, and the one or more patient parameters and / or the one or more dialysis session parameters may include total phosphate pumped through the sorbent module during a previous dialysis session.

[0017] In any embodiments, the total phosphate pumped through the sorbent module during a previous dialysis session can be obtained from: direct measurement of phosphate in the dialysate flow path during a previous session, estimation based on phosphate removed from the zirconium phosphate used in the previous dialysis session and pre-dialysis patient phosphate measurements; or estimation based on total phosphate pumped through the sorbent box during multiple previous dialysis sessions.

[0018] In any embodiment, the step of recharging the zirconium oxide can include pumping between 6.0 and 7.5 moles of sodium hydroxide in the one or more recharging solutions per mole of phosphate pumped through the sorbent module during the previous dialysis session.

[0019] In any embodiment, the one or more patient parameters and / or the one or more dialysis session parameters may include an estimated duration of the next dialysis session for the patient.

[0020] In any embodiment, the adsorbent module may contain zirconium phosphate and may be prepared using Equation V r =v*Q*t*(C NH4 +C K +C Ca +C Mg +(a*C HCO3 + b)) setting the volume of one or more refilling solutions; wherein Vr is the volume of one or more refilling solutions, Q is the time-averaged volume flow rate into the adsorbent module, t is the session time, C NH4 , C K , C Ca , C Mg and C HCO3 is the average concentration of ammonium, potassium, calcium, magnesium and bicarbonate ions entering the sorbent module, a and b are variables related to the pH of the zirconium phosphate, and v is a variable specific to the recharge process in use.

[0021] Features disclosed as part of the first aspect of the invention may be in the first aspect of the invention alone or in combination, or following a preferred arrangement of one or more of the described elements.

[0022] A second aspect of the present invention relates to a system. In any embodiment, the system may include a refill flow path; the refill flow path includes one or more refill solution sources; the one or more refill solution sources are fluidly connected to an inlet of an adsorbent module containing at least one adsorbent material; and at least one pump for pumping the one or more refill solutions through the adsorbent module from the one or more refill solution sources; and a control system, the control system setting the volume and / or concentration of the one or more refill solutions pumped through the adsorbent module required to refill the adsorbent material in the adsorbent module based on one or more patient parameters and / or one or more dialysis session parameters of the patient and / or dialysis session using the adsorbent module.

[0023] In any embodiment, the sorbent module may contain zirconium phosphate, and the one or more recharge solution sources may include a brine source, a water source, and a disinfectant source.

[0024] In any embodiment, the sorbent module can contain zirconium oxide, and the one or more recharge solution sources can include an alkali source, a water source, and a disinfectant source.

[0025] In any embodiments, the system may include a second refill flow path; the second refill flow path includes one or more refill solution sources, which are fluidly connected to an inlet of a second adsorbent module containing at least one adsorbent material; and at least a second pump for pumping one or more refill solutions through the adsorbent module from the one or more refill solution sources; and a control system that can set the volume and / or concentration of one or more refill solutions pumped through the second adsorbent module required to refill the adsorbent material within the second adsorbent module based on one or more patient parameters and / or one or more dialysis session parameters of the patient and / or dialysis session using the adsorbent module.

[0026] In any embodiments, the sorbent module may contain zirconium phosphate, and the one or more patient parameters may include at least one from the group consisting of: pre-dialysis patient potassium, calcium, magnesium, bicarbonate and urea amounts, patient weight, patient volume, patient residual renal function, average number of dialysis sessions per week, patient acidosis status and average dialysis session length; and the one or more dialysis session parameters include at least one from the group consisting of: dialysate flow rate, blood flow rate, dialyzer size, dialyzer type, dialysis time, ultrafiltration rate; potassium, calcium, magnesium and bicarbonate dialysis prescription; whether ammonia breakthrough occurs, whether pH alarm occurs, fluid removed during the session, total treatment volume, starting water quality, URR target, URR achieved, clearance, whether blood leakage occurs, and whether hypotensive episodes occur.

[0027] In any embodiments, the sorbent module may contain zirconium oxide; one or more patient parameters may include at least one from the group consisting of: patient weight, patient volume, patient residual renal function, average number of dialysis sessions per week, and average dialysis session length; and one or more dialysis session parameters may include at least one from the group consisting of: dialysate flow rate, blood flow rate, dialyzer size, dialyzer type, dialysis time, ultrafiltration rate; potassium, calcium, magnesium and bicarbonate dialysis prescription; whether ammonia breakthrough occurs, whether pH alarm occurs, fluid removed during the session, total treatment volume, starting water quality, URR target, URR achieved, clearance, whether blood leakage occurs, and whether hypotensive episodes occur.

[0028] In any embodiment, the sorbent module may contain zirconium phosphate, and the control system may set the volume and / or concentration of one or more recharge solutions based on the total cations and total CO2 pumped through the sorbent module during a previous dialysis session.

[0029] In any embodiment, the sorbent module may contain zirconium oxide, and the control system may set the volume and / or concentration of one or more recharging solutions based on the total phosphate pumped through the sorbent module during a previous dialysis session.

[0030] Features disclosed as part of the second aspect of the invention may be in the second aspect of the invention alone or in combination, or following a preferred arrangement of one or more of the described elements. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 A recharger for recharging zirconium phosphate modules and / or zirconium oxide modules is shown.

[0032] Figure 2 A graph showing the initial zirconium phosphate effluent pH as a function of the recharge solution pH.

[0033] Figure 3 A graph showing zirconium phosphate effluent pH as a function of the amount of fluid passing through the zirconium phosphate module for recharge solutions having various concentrations of acid, base, and salt.

[0034] Figure 4 A refill flow path for refilling a zirconium phosphate module with two refill solution sources.

[0035] Figure 5 A refill flow path is provided for refilling a zirconium phosphate module with a single source of refill solution.

[0036] Figure 6 Flow chart illustrating the steps in the custom zirconium phosphate recharge process.

[0037] Figure 7 A refill flow path for refilling the zirconium oxide adsorbent module. DETAILED DESCRIPTION

[0038] Unless defined otherwise, all technical and scientific terms used have the same meaning as commonly understood by one of ordinary skill in the art.

[0039] The articles "a" and "an" are used to refer to one or to more than one (ie, to at least one) of the grammatical object of the article. For example, "an element" means one element or more than one element.

[0040] The term "acid concentration" refers to the number of moles of acid dissolved in a given volume of water.

[0041] The term "acid solution" refers to an aqueous solution having a pH of less than 7.

[0042] An "acid source" is a source of fluid or concentrate from which an acid solution can be obtained.

[0043] The term "ammonia breakthrough" refers to ammonia in the fluid exiting the sorbent cartridge.

[0044] The term "amount of cations removed by the zirconium phosphate module in a dialysis session" refers to the total number of moles of potassium, calcium, magnesium, ammonium and other cations adsorbed by the zirconium phosphate in the zirconium phosphate module during dialysis therapy.

[0045] The term "average dialysis session length" refers to the amount of time a patient spends on dialysis in a normal dialysis session.

[0046] The term "average number of dialysis sessions per week" refers to the number of dialysis treatments a patient undergoes during a normal treatment regimen.

[0047] The term "base concentration" refers to the number of moles of base dissolved in a given volume of water.

[0048] The term "alkaline solution" refers to an aqueous solution having a pH greater than 7.

[0049] An "alkali source" is a fluid or concentrate source from which an alkali solution can be obtained.

[0050] "Blood flow rate" refers to the volume of blood pumped through the extracorporeal circuit in a given period of time.

[0051] The term "blood leakage" refers to the passage of the patient's blood across the dialyzer membrane into the dialysate.

[0052] The term "saline source" refers to a source of salt and / or buffer solution containing solutes used to recharge the adsorbent material. In certain embodiments, the saline source may contain sodium salt, acetic acid, sodium acetate, or a combination thereof.

[0053] The term "buffer solution" refers to an aqueous solution containing a weak acid and the conjugate base of the weak acid.

[0054] The term "clearance" refers to the rate at which solutes pass through the dialyzer membrane.

[0055] The term "comprising" includes, but is not limited to, what follows the word "comprising." The use of the term indicates that the listed elements are required or mandatory, but indicates that other elements are optional and may be present.

[0056] The term "concentration" refers to the amount of solute per given volume of solvent.

[0057] The term “consisting of is inclusive of and limited to what follows the phrase “consisting of.” The phrase indicates that the limited elements are required or mandatory, and indicates that other elements may not be present.

[0058] The term "consisting essentially of" includes what follows the term "consisting essentially of" and additional elements, structures, acts, or features that do not affect the basic operation of the device, structure, or method being described.

[0059] The terms “control”, “controlling”, or “controls” refer to the ability of one component to direct the actions of a second component.

[0060] A "control system" may be a combination of components that work together to maintain a system within a desired set of performance specifications. A control system may use processors, memory, and computer components configured to interoperate to maintain desired performance specifications. A control system may also include fluid or gas control components and solute control components as known in the art for maintaining performance specifications.

[0061] The term "desired initial therapy zirconium phosphate effluent pH" refers to the initial zirconium phosphate effluent pH during therapy that is set or determined based at least in part on the needs and capabilities of the system and the patient.

[0062] The terms "determining" or "determine" refer to determining a specific or desired state of a system or one or more variables.

[0063] "Diastate flow rate" refers to the amount of dialysate pumped through the dialysate flow path in a given period of time.

[0064] The term "dialysis prescription" refers to the dialysis parameters intended to be used during a dialysis session. In certain embodiments, a "dialysis prescription" may refer to the expected concentration of one or more solutes in the dialysate used during treatment. For example, a calcium dialysis prescription may refer to the expected calcium concentration of the dialysate during treatment.

[0065] A "dialysis session" is a period of time during which a patient is treated by dialysis, hemodialysis, hemofiltration, ultrafiltration, or other blood fluid removal therapy.

[0066] A "dialysis session parameter" is any data or condition related to a given dialysis session.

[0067] The term "dialysis time" refers to the length of time of a particular dialysis session.

[0068] The term "dialyzer size" refers to the surface area of ​​the dialyzer membrane in the dialyzer.

[0069] The term "dialyzer type" refers to whether a particular dialyzer is a high-flux dialyzer or a low-flux dialyzer. The type may include other features of the dialyzer properties in addition to flux such as efficiency and membrane type. Efficiency properties such as membrane size (surface area), porosity, thickness, internal fiber diameter, and design (wavy, straight fibers) are considered.

[0070] A "disinfectant source" may refer to a source of fluid capable of destroying or removing biological contaminants.

[0071] The term "direct measurement" refers to the use of sensors or other systems to determine one or more parameters.

[0072] The term "duration of the next dialysis session" refers to the estimated length of time between the end of a patient's first dialysis session and the start of the same patient's second dialysis session.

[0073] "Estimated / estimate / estimation" refers to the indirect determination of one or more parameters using one or more variables.

[0074] The term "fluidically connectable" refers to the ability to provide a passage of a fluid, gas, or combination thereof from one point to another. The ability to provide such a passage may be any connection, fastening, or shaping between two points to permit the flow of a fluid, gas, or combination thereof. The two points may be within or between any one or more of any type of compartments, modules, systems, assemblies, and rechargers.

[0075] The term "fluidically connected" refers to a particular state such that a passage of a fluid, gas, or combination thereof is provided from one point to another. A connected state may also include an unconnected state such that two points are disconnected from each other to interrupt flow. It will be further understood that two "fluidically connectable" points as defined above may be from a "fluidically connected" state. Two points may be within or between any one or more of a compartment, module, system, assembly, and recharger (all of any type).

[0076] The term "fluid removed during a session" refers to the total amount of fluid removed from the patient's blood during a dialysis session.

[0077] A "heater" is a component that is capable of raising the temperature of a substance, container, or fluid.

[0078] The terms "heating" or "heat" refer to raising the temperature of a material.

[0079] The term "hypotensive episode" refers to an instance during treatment when a patient experiences hypotension.

[0080] The term "inlet" of an adsorbent module may refer to a portion of an adsorbent module through which a fluid, gas, or combination thereof may be drawn into the adsorbent module.

[0081] The term "initial therapy zirconium phosphate effluent pH" refers to the pH of the fluid exiting the zirconium phosphate sorbent module at or near the start of therapy.

[0082] The term "mixing" generally refers to combining one or more fluids from any source. For example, "mixing" can include laminar or turbulent flow at the location of a fluid line or joint. Another example of "mixing" can include receiving one or more fluids in a component that is configured to receive fluids from one or more sources and mixing the fluids together in the component. In addition, mixing can refer to the dissolution of one or more solids with a fluid, wherein the one or more solids dissolve in the fluid.

[0083] The term "needed to recharge the adsorbent material" refers to the amount of one or more recharging solutions required to produce an adsorbent material having a specified functional capacity. In certain embodiments, the specified functional capacity may be close to 100% or may be lower, depending on the needs of the patient.

[0084] The term "number of previous dialysis sessions" may refer to any number of dialysis sessions of a patient. The number of previous dialysis sessions may be 1, 2, 3 or more dialysis sessions.

[0085] A "patient" or "subject" can be a member of any animal species, preferably a mammalian species, optionally a human. The subject can be an apparently healthy subject, a subject suffering from a disease, or a subject being treated for a disease. In certain embodiments, the patient can be a human, sheep, goat, dog, cat, mouse, or any other animal.

[0086] The term "acidotic state of a patient" refers to the pH value in the patient's blood.

[0087] "Patient parameters" are any data that give relevant information about a patient's health status and therapy requirements.

[0088] "Patient residual renal function" is a measure of how well a patient's kidneys function compared to healthy individuals.

[0089] "Patient volume" refers to the total amount of water in the patient.

[0090] "Patient weight" refers to the mass of the patient.

[0091] The term "pH alarm" refers to an indication that the pH of a fluid is outside a predetermined range.

[0092] The term "pH of zirconium phosphate" refers to the negative logarithm of the concentration of hydrogen ions absorbed onto a given amount of zirconium phosphate.

[0093] "Phosphate blow-off" refers to the amount of phosphate ions initially present in the form of zirconium phosphate that leak into the fluid pumped through the sorbent cartridge.

[0094] "Pre-dialysis patient cation measurement" refers to the determination of the amount of cations in a patient prior to a dialysis session.

[0095] "Pre-dialysis patient total CO2 measurement" refers to a determination of the total CO2 amount in a patient prior to a dialysis session, and may include carbon dioxide amount, bicarbonate amount, and carbonate amount.

[0096] "Pre-dialysis patient phosphate measurement" refers to the determination of the amount of phosphate in a patient prior to a dialysis session.

[0097] When referring to a specific solute or material, the term "pre-dialysis patient amount" refers to the concentration of the solute or material in the patient's blood prior to a dialysis session.

[0098] The term "pump" refers to any device that moves fluids or gases by applying suction or pressure.

[0099] The terms "pumping" or "pumped" or "pump" refer to the use of a pump to move fluids, gases, or a combination thereof.

[0100] The "receiving compartment" is the space within the recharger where the sorbent module to be recharged is placed.

[0101] A "recharge solution" is a solution containing the appropriate ions for recharging a particular adsorbent material. The recharge solution can be a single solution containing all of the necessary ions for recharging the adsorbent material. Alternatively, the recharge solution can contain some of the ions for recharging the adsorbent material, and one or more other recharge solutions can be used to recharge the adsorbent material.

[0102] A "refill solution source" is any source of fluid or concentrate from which a refill solution can be obtained.

[0103] "Refilling" refers to processing an adsorbent material to restore the functional capacity of the adsorbent material so that the adsorbent material can be returned to a state of reuse or use in a new dialysis session. In some cases, the total mass, weight and / or amount of the "refillable" adsorbent material remains unchanged. In some cases, the total mass, weight and / or amount of the "refillable" adsorbent material changes. Without being limited by any one theory of the invention, the refilling process may involve exchanging ions bound to the adsorbent material with different ions, which may increase or decrease the total mass of the system in some cases. However, in some cases, the total amount of adsorbent material will remain unchanged through the refilling process. When the adsorbent material is "refilled", the adsorbent material may be referred to as "refilled".

[0104] A "recharge flow path" is a path through which fluid may travel while recharging the adsorbent material in a reusable adsorbent module.

[0105] As used herein, the term "salt concentration" refers to the number of moles of sodium salt dissolved in a given volume of water.

[0106] "Saline" refers to an aqueous solution containing dissolved sodium and counter ions.

[0107] A "salt source" is a source of fluid or concentrate from which a salt solution can be obtained.

[0108] The term "sequential order" refers to two or more events occurring at different times as opposed to simultaneously.

[0109] The term "session time" refers to the length of time of a dialysis session from the start of a patient's dialysis treatment to the end of the dialysis treatment.

[0110] The term "based at least in part on a setting" or "based on a setting" refers to the calculation of a parameter value where the value is a function of at least one other variable.

[0111] "Sorbent box module" or "sorbent module" means a discrete component of a sorbent box. Multiple sorbent box modules can be assembled together to form a sorbent box having two, three or more sorbent box modules. In some embodiments, a single sorbent box module may contain all the necessary materials for dialysis. In the case, the sorbent box module may be a "sorbent box". A "sorbent box module" or "sorbent module" may contain any material used for sorbent dialysis, and may or may not contain "sorbent material" or adsorbent. In other words, a "sorbent box module" or "sorbent module" generally refers to the use of a "sorbent box module" or "sorbent module" in sorbent-based dialysis such as REDY (recirculating dialysis), rather than a "sorbent material" that must be contained in a "sorbent box module" or "sorbent module".

[0112] The term "sorbent material" refers to a material that is capable of removing a specific solute from a fluid. In certain embodiments, the sorbent material may be zirconium oxide or zirconium phosphate.

[0113] The phrase "specific to the recharging process in use" may refer to one or more variables used to recharge the adsorbent material. In certain embodiments, the variables may include the composition of the recharging solution, the concentration of one or more solutes in the recharging solution, the temperature of the recharging solution, or the flow rate of the recharging solution.

[0114] The term "specified temperature" is a temperature range calculated or measured prior to recharging the zirconium phosphate module.

[0115] The term "starting water quality" may refer to the quality of water used to prepare an initial dialysate for a dialysis session. In certain embodiments, starting water quality may refer to the amount of solutes dissolved in the water used to prepare the initial dialysate.

[0116] A "static mixer" is an assembly configured to accept fluids from one or more sources and mix the fluids together. A static mixer may include components that agitate the fluids to further mix them.

[0117] The term "temperature sensor" refers to a device used to measure the temperature of a gas or liquid in a vessel, container, or fluid line.

[0118] The term "time-averaged volumetric flow rate" may refer to the volume of fluid moved per unit time on average within a dialysis session.

[0119] The term "total cations" may refer to the amount of cations in the dialysate throughout a dialysis session.

[0120] "Total CO2" may refer to the total amount of carbon dioxide, bicarbonate ions, and carbonate ions in the dialysate throughout the dialysis session.

[0121] The term "total phosphate" refers to the total amount of phosphate ions in the dialysate throughout the dialysis session.

[0122] The term "total treatment volume" refers to the total amount of fluid pumped through a sorbent cartridge or sorbent module during a dialysis treatment.

[0123] The term "ultrafiltration rate" refers to the amount of fluid removed from a patient's blood in a given period of time.

[0124] "Urea reduction rate" or "URR" refers to the amount by which a patient's urea level decreases during treatment. The URR can be expressed as 1 minus the ratio of the patient's final urea level to the patient's starting urea level.

[0125] "Achieved URR" refers to the amount of urea reduction actually produced by a dialysis session.

[0126] "URR target" refers to the expected urea reduction rate during a dialysis session.

[0127] A "valve" is a device that can direct the flow of a fluid or gas by opening, closing, or obstructing one or more passages to control whether the fluid or gas travels in a specific path. One or more valves that achieve the desired flow can be configured as a "valve assembly."

[0128] The term "volume" refers to the amount of three-dimensional space occupied by a material.

[0129] A "water source" is a source of fluid from which water can be obtained.

[0130] "Zirconium oxide" is an adsorbent material that can remove anions from a fluid, exchanging the removed anions for different anions. Zirconium oxide may also be referred to as hydrous zirconium oxide.

[0131] "Zirconium phosphate" is an adsorbent material that can remove cations from a fluid, exchanging the removed cations for different cations.

[0132] Zirconium Phosphate Refill

[0133] The present invention relates to systems and methods for recharging and reusing zirconium phosphate and / or zirconium oxide in a reusable sorbent module. Figure 1 A refiller for refilling zirconium phosphate or zirconium oxide in an adsorbent module is described. The refiller includes at least a first receiving compartment 101 for receiving an adsorbent module. The receiving compartment 101 has an adsorbent module inlet and an adsorbent module outlet (not shown) that can be fluidly connected to the inlet and outlet of the adsorbent module (not shown). A door 103 controls the entrance to the receiving compartment 101. A user interface 102 can receive information from a user for controlling the refilling process. The refiller can optionally include a second receiving compartment 104 for receiving a second adsorbent module, which contains the same or different adsorbent materials for simultaneously refilling adsorbent materials. The refiller can include any number of receiving compartments for receiving multiple adsorbent modules or various combinations of adsorbent modules. The refiller can have 1, 2, 3, 4, 5 or more receiving compartments for refilling any number of adsorbent modules. The refiller can be fluidly connected to one or more refill solution sources via a refill flow path. Pumps and valves (not shown) control the movement of fluid from the refill solution source through the zirconium phosphate module.

[0134] The zirconium phosphate is recharged by pumping one or more solutions containing an acid, base, and sodium salt through the zirconium phosphate module. The hydrogen ions and sodium ions in the recharge solution replace potassium, calcium, magnesium, ammonium, and other ions from the dialysate or source water that are bound and adsorbed by the zirconium phosphate during use. The recharge zirconium phosphate with sodium and hydrogen ions can be used during dialysis to remove cationic solutes from the dialysate used. The zirconium oxide can be recharged by pumping one or more solutions containing a hydroxide base through the zirconium oxide adsorbent module. The hydroxide ions can replace the phosphate ions that are bound and adsorbed by the zirconium oxide during use.

[0135] Initial Therapy The pH of the zirconium phosphate effluent depends on the ratio of hydrogen ions to sodium ions on the zirconium phosphate. Figure 2 To illustrate the effect of the refill solution pH on the initial therapy zirconium phosphate effluent pH. Figure 2 The refill solutions in each contained a mixture of sodium chloride, sodium acetate, and acetic acid. The total sodium concentration in each refill solution was 4 M, and the ratio of sodium acetate to acetic acid was varied to control the pH. Figure 2 As described in, the pH of the refill solution controls the initial therapy zirconium phosphate effluent pH. One of ordinary skill in the art will appreciate that the initial therapy zirconium phosphate effluent pH can be controlled by adjusting the pH of the refill solution to produce the desired initial therapy zirconium phosphate effluent pH. The initial therapy zirconium phosphate effluent pH is controlled by changing the ratio of hydrogen ions to sodium ions in the zirconium phosphate. A lower pH refill solution increases the hydrogen ion to sodium ion ratio on the refill zirconium phosphate and decreases the initial therapy zirconium phosphate pH. A higher pH refill solution decreases the hydrogen ion to sodium ion ratio on the refill zirconium phosphate and increases the initial therapy zirconium phosphate effluent pH. The zirconium phosphate effluent pH can be customized based on user needs by controlling the pH of the refill solution.

[0136] Figure 3 The zirconium phosphate effluent pH is shown as a function of the volume of dialysate pumped through the zirconium phosphate module during dialysis. Figure 3 As described in , the initial zirconium phosphate effluent pH is determined by the refill solution used. The pH profile of the zirconium phosphate depends on the quality of the zirconium phosphate and the quality of bicarbonate pumped through the zirconium phosphate module. In the case of high zirconium phosphate quality and low bicarbonate quality pumped through the zirconium phosphate, the initial zirconium phosphate effluent pH can be maintained throughout the therapy session. The zirconium phosphate acts like a buffer, and as more bicarbonate is pumped through the zirconium phosphate, the buffering capacity is exceeded and the pH begins to increase. Without being limited by any theory of the invention, the final pH plateau may be related to the composition and pH of the spent dialysate pumped through the zirconium phosphate module. However, the initial therapy zirconium phosphate effluent pH depends on the pH of the refill solution.

[0137] Table 1 provides non-limiting examples of refill solutions and the resulting initial therapy zirconium phosphate effluent pH. In each case, the refill solution was heated to 80°C prior to use. As shown in Table 1, a higher ratio of sodium acetate to acetic acid resulted in a higher refill solution pH, and therefore a higher initial therapy zirconium phosphate effluent pH. The relative amounts of acid, base, and sodium salt can be set to produce a refill solution with a desired pH.

[0138] Table 1

[0139] Solution TotalNa(M) NaCl(M) NaAce(M) HAce(M) pH Initial effluent pH 1 4.00 4.00 0.00 0.20 2.75 4.40 2 4.00 3.98 0.02 0.20 3.74 5.42 3 4.00 3.88 0.12 0.40 4.23 5.99 4 4.00 3.60 0.40 0.40 4.75 6.58

[0140] Each of the refill solutions in Table 1 is a combination of sodium chloride, sodium acetate, and acetic acid. Those skilled in the art will appreciate that other buffer combinations may be used in place of sodium acetate and acetic acid, including sodium citrate and citric acid, glycolic acid and sodium glycolate, propionic acid and sodium propionate, phosphoric acid and sodium phosphate, or any combination thereof. The relative amounts of sodium chloride and buffer used to achieve the desired initial therapy zirconium phosphate effluent pH will depend on the pKa of the acid used and may vary as desired.

[0141] The zirconium phosphate module effluent pH affects the amount of bicarbonate required during dialysis. Urease in the sorbent box converts urea into carbon dioxide and ammonium ions. The carbon dioxide produced is in equilibrium with the bicarbonate in the dialysate. Before the dialysate enters the dialyzer, carbon dioxide must be removed from the dialysate by a degasser. The degasser can be any type of degasser known in the art for use in dialysis systems. The high zirconium phosphate effluent pH during therapy causes bicarbonate formation to tend toward equilibrium, causing too much bicarbonate in the dialysate for safe treatment. The low zirconium phosphate effluent pH during therapy causes carbon dioxide formation to tend toward equilibrium, requiring the addition of bicarbonate to the dialysate and placing a high burden on the degasser. One type of degasser suitable for removing carbon dioxide is a membrane contactor. The membrane contactor is a dual-chamber device having a hydrophobic microporous membrane separating the chambers. The hydrophobic microporous membrane allows gas transport without allowing transmembrane water transport. A liquid containing gas - in this case CO2 - is passed on one side of the membrane, and an inert gas or vacuum is applied to the chamber on the opposite side of the membrane. CO2 is transported from the liquid by diffusion. Another example of a degasser is a vacuum degasser. A vacuum degasser is a chamber to which a vacuum can be applied and which can be fluidically connected to a liquid containing the gas to be removed. The liquid is sprayed or atomized in the vacuum chamber. High surface area droplets allow for efficient removal of gas. Those skilled in the art will appreciate that any device capable of removing CO2 from the dialysate can be used. The zirconium phosphate effluent pH can be controlled by the pH of the refill solution to meet the needs of the patient and the system. The zirconium phosphate effluent pH is a function of pH, pKa, buffer capacity, amount of sodium chloride, and refill solution temperature. As described, the control system can automatically determine the volume of each component required to achieve the desired initial therapy zirconium phosphate effluent pH based on each of the factors.

[0142] A zirconium phosphate effluent pH of approximately 6.5 allows greater than 95% of patients to be treated with a dialysate bicarbonate concentration of 25 mM. At higher pH, fewer patients can be treated. For example, only about 40% of patients can be treated with a zirconium phosphate effluent pH of 6.9 and a dialysate bicarbonate amount of 25 mM. At very low pH, too much acid is added to the dialysate by the zirconium phosphate, and additional bicarbonate is required to keep the dialysate pH within a safe range, and a degasser is required to remove carbon dioxide. The initial therapy zirconium phosphate effluent pH can be set to any value that produces a safe dialysate, including values ​​between 4.0 and 6.9. Dialysates with lower pH place a higher burden on the degasser.

[0143] Any combination of acids, bases, and sodium salts that can produce a refill solution within the desired pH range can be used to refill the zirconium phosphate. Non-limiting examples of acids and bases include sodium acetate and acetic acid, sodium citrate and citric acid, glycolic acid and sodium glycolate, propionic acid and sodium propionate, phosphoric acid and sodium phosphate, or any combination thereof. Those skilled in the art will appreciate that the relative amounts of acid and base required to produce a refill solution with the desired pH will vary with the pKa of the acid. The relative volumes of acid and base can vary based on the pKa of the specific acid and base used. For example, a refill solution with 3.1 M sodium chloride, 0.9 M sodium acetate, and 0.6 M acetic acid has a pH of 4.6, which will produce a zirconium phosphate effluent pH of 6.5.

[0144] As described, the zirconium phosphate effluent pH during therapy controls the balance between carbon dioxide and bicarbonate in the dialysate. Carbon dioxide and bicarbonate in the dialysate typically come from two sources, namely, the conversion of urea to carbon dioxide and any bicarbonate added to the dialysate. In order to minimize the amount of additional bicarbonate required, the zirconium phosphate effluent pH can be set to a higher value, at least for patients who can be effectively treated with higher amounts of dialysate bicarbonate. The higher zirconium phosphate effluent pH during therapy drives the bicarbonate / carbon dioxide balance toward bicarbonate formation, retaining the bicarbonate produced by urea removed from the patient.

[0145] A control system in the recharger can determine the optimal initial therapy zirconium phosphate effluent pH for the patient based on the patient's pre-treatment bicarbonate and urea amounts. For alkalotic patients, a lower initial therapy zirconium phosphate effluent pH can be selected to minimize the amount of bicarbonate formed from the patient's urea. For other patients, a higher initial therapy zirconium phosphate effluent pH can be selected to produce a higher amount of bicarbonate from the patient's urea, reducing the additional bicarbonate required and minimizing the burden on the degasser. Alternatively, a user interface can be provided in which the user directly enters the desired initial therapy zirconium phosphate effluent pH.

[0146] The control system can be any component capable of monitoring and affecting the state of the refiller. The control system can use processors, memory, and computer components to implement the described functions. The control system is connected to the pumps and valves of the refill flow path, and can control the pumps and valves according to stored instructions. The control system is also connected to various sensors in the refill flow path. The control system receives data from the sensors and controls the pumps and valves of the refill flow path based on the data according to stored instructions. Factors that affect the required initial therapy zirconium phosphate effluent pH, such as the patient's pre-treatment urea and bicarbonate amounts, can be connected to the control system through any components known in the art. The control system can use a mathematical algorithm or a lookup table to automatically determine the optimal refill solution pH, and operate the pumps and valves of the refill flow path to control the refill process.

[0147] Figure 4 A non-limiting example of a refill flow path 401 for customizing a refill solution is described. A zirconium phosphate module 402 can be connected to the refill flow path 401 via a zirconium phosphate inlet 403 and a zirconium phosphate outlet 404. A pump 407 provides a driving force for moving fluid through the refill flow path 401. A salt or brine source 405 containing a salt solution such as sodium chloride or a mixture of sodium chloride and sodium acetate and an acid source 406 containing an acid solution such as acetic acid are fluidly connected to the refill flow path 401. A valve 408 determines the amount of each refill solution entering the refill flow path 401 to produce a refill solution with a specific acid concentration, base concentration, and salt concentration, and can be controlled by a control system. Sodium chloride and / or sodium acetate from the brine source 405 are pumped through the refill flow path 401 to the zirconium phosphate module 402. Acid from an acid source 406 can be pumped into the refill flow path 401 in a ratio with sodium chloride and sodium acetate based on the desired refill solution pH. For example, acetic acid from the acid source 406 may be metered into the sodium chloride and / or sodium acetate in the refill flow path 401 at a specified rate to control the pH of the resulting refill solution. A higher sodium chloride to acid ratio will result in a refill solution at a higher pH, while a lower sodium chloride to acid ratio will result in a refill solution at a lower pH. The control system may automatically control valve 408 to control the ratio of sodium chloride to acid. Alternatively, the acid source 406 may contain a buffer solution such as sodium acetate and acetic acid, and the control system may control the ratio of sodium chloride to buffer to control the refill solution pH. A static mixer 409 may be included to ensure complete mixing of the acid solution and the sodium solution. Alternatively, the acid solution and the sodium solution may be mixed by mixing the two fluid streams in the refill flow path 401. Those skilled in the art will appreciate that different pump and valve arrangements may be used with the refill flow path 401. Figure 4 For example, the saline source 405 and the acid source 406 can be connected to the refill flow path 401 through separate pumps, allowing sodium chloride and acid to be added to the refill flow path 401 at the same time.

[0148] Or, if Figure 4 The described system may have sodium chloride in the first recharge solution source and an alkali solution such as sodium hydroxide in the acid and alkali source. The sodium chloride and acid may be pumped through the zirconium phosphate module and the alkali solution is metered to generate a recharge solution having the desired pH in situ.

[0149] Figure 4The refill flow path 401 in the zirconium phosphate module 402 can also be refilled by adding refill solutions in a sequential order. The acid solution from the acid source 406 can be pumped through the zirconium phosphate module 402 first, followed by the sodium chloride and sodium acetate from the brine source 405. The initial acid solution will produce the zirconium phosphate module 402 at a low pH, and the subsequent addition of sodium chloride and sodium acetate will increase the pH because the sodium ions replace the hydrogen ions initially adsorbed by the zirconium phosphate. The resulting zirconium phosphate effluent pH will depend on the amount of sodium chloride and sodium acetate pumped through the zirconium phosphate module 402 in the second step. The control system can control the addition of sodium chloride and sodium acetate to produce a zirconium phosphate module 402 with a desired initial therapy zirconium phosphate effluent pH. A pH sensor (not shown) can be placed in the zirconium phosphate effluent to determine the zirconium phosphate effluent pH, and sodium chloride can be stopped when the pH sensor reads the desired pH. The concentration and amount of sodium chloride and sodium acetate pumped through the zirconium phosphate module 402 will control the initial therapy zirconium phosphate effluent pH after refilling. Alternatively, the sodium chloride and sodium acetate may be pumped through the zirconium phosphate module 402 first, followed by the acid.

[0150] Figure 5 A refill flow path 501 having a single refill solution source 505 containing a sodium salt and a buffer is illustrated. A zirconium phosphate module 502 can be fluidly connected to the refill flow path 501 via a zirconium phosphate inlet 503 and a zirconium phosphate outlet 504. A pump 506 provides a driving force for moving the fluid through the refill flow path 501. A refill solution source 505 is fluidly connected to the refill flow path 501. A refill solution in the refill solution source 505 at a desired refill solution pH can be pumped through the zirconium phosphate module 502 to refill the zirconium phosphate. In order to change the initial therapy zirconium phosphate effluent pH, the pH of the refill solution can be changed. A user can add a solid or concentrated source of an acid, base, salt, or combination thereof to control the pH of the refill solution to produce a refill solution having a specific acid concentration, base concentration, and salt concentration. The control system can notify the user of the correct amount of acid, base, or salt to be added to the refill solution source 505. Alternatively, a separate acid, base, or salt source may be included in the refill, and the system may automatically add the correct amount to the based refill solution source 505 to produce a refill solution with the desired pH. For example, a refill solution with a pH of 4.6 may be placed in the refill solution source 505 and used for most patients. For patients with severe alkalosis, the system or user may add a predetermined amount of acid to lower the refill solution pH. To reduce the amount of bicarbonate required during therapy, the system or user may add a predetermined amount of base to raise the refill solution pH.

[0151] Figure 7A non-limiting embodiment of a refill flow path 701 for refilling zirconium oxide in a reusable zirconium oxide adsorbent module 702 is illustrated. The zirconium oxide adsorbent module 702 can be fluidly connected to the refill flow path 701 via a zirconium oxide module inlet 703 and a zirconium phosphate module outlet 704. A pump 706 provides a driving force for moving fluid through the refill flow path 701. A refill solution source 705 is fluidly connected to the refill flow path 701 and can be a source of alkali. The refill solution source 705 can contain sodium hydroxide at a specific concentration. A control system (not shown) can set the volume of sodium hydroxide pumped through the zirconium oxide adsorbent module 702 based on one or more patient parameters and / or one or more dialysis session parameters.

[0152] Those skilled in the art will understand that Figure 4-5 The refill flow paths described in and 7 may include additional fluid sources. A water source may provide water for flushing and rinsing the zirconium phosphate module and / or zirconium oxide module before and after refilling. The water source may also provide in-line dilution of any of the refill solutions, allowing the refill solution in the refill solution source to be more concentrated. A disinfectant source may provide a disinfectant solution for disinfecting the zirconium phosphate and / or zirconium oxide module prior to refilling. The disinfectant solution may be any solution capable of disinfecting the zirconium phosphate and / or zirconium oxide sorbent module, including a peracetic acid solution, a citric acid solution, or any other disinfectant.

[0153] The recharger may include multiple recharge flow paths for recharging multiple adsorbent modules. For example, a single recharger may include two or more recharge flow paths for recharging two or more zirconium phosphate adsorbent modules or two or more zirconium oxide adsorbent modules. Additionally, a single recharger may include a zirconium phosphate recharge flow path and a zirconium oxide recharge flow path for recharging the zirconium phosphate adsorbent modules and the zirconium oxide adsorbent modules. One or more recharge solution sources may be shared by two recharge flow paths, or a separate recharge solution source may be used in each flow path.

[0154] The total volume of refill solution required to refill the zirconium phosphate depends on the amount of cations removed by the zirconium phosphate in the previous dialysis session and the amount of total CO2 fed through the zirconium phosphate during the previous dialysis session, which in turn depends on a number of patient and / or dialysis parameters. Patient parameters that affect the amount of cations removed by the zirconium phosphate and the amount of CO2 fed through the zirconium phosphate include pre-dialysis patient potassium, calcium, magnesium, bicarbonate, and urea amounts; patient weight, patient volume, patient residual renal function, average number of dialysis sessions per week, patient acidosis state, and average dialysis session length. Dialysis parameters that affect the amount of cations removed from the zirconium phosphate include dialysate flow rate, blood flow rate, dialyzer size, dialyzer type, dialysis time, ultrafiltration rate; potassium, calcium, magnesium, and bicarbonate dialysis prescriptions; whether ammonia breakthrough occurs, whether pH alarms occur, fluid removed during a session, total treatment volume, starting water quality, URR target, URR achieved, clearance, whether blood leakage occurs, and whether hypotensive episodes occur.

[0155] The total volume of refill solution required to refill the zirconium oxide depends on the amount of phosphate removed by the zirconium oxide in the previous dialysis session, which in turn can depend on a number of patient and / or dialysis parameters. Patient parameters that affect the amount of phosphate removed by the zirconium oxide include patient weight, patient capacity, patient residual renal function, average number of dialysis sessions per week, and average dialysis session length. Dialysis parameters that affect the amount of phosphate removed by the zirconium oxide include dialysate flow rate, blood flow rate, dialyzer size, dialyzer type, dialysis time, ultrafiltration rate; potassium, calcium, magnesium, and bicarbonate dialysis prescription; whether ammonia breakthrough occurs, whether pH alarms occur, fluid removed during the session, total treatment volume, starting water quality, URR target, URR achieved, clearance, whether blood leakage occurs, and whether hypotensive episodes occur.

[0156] Patient use of the zirconium phosphate module and / or zirconium oxide module can be tracked using RFID tags, bar codes, or other tracking devices. The control system can accept any one or more of the patient parameters that affect the amount of refill solution required and determine the required volume of refill solution for refilling the zirconium phosphate module and / or zirconium oxide module. In certain embodiments, the control system can accept patient and dialysis parameters based on the previous use and history of the sorbent box and the patient to determine the required volume of refill solution for refilling the zirconium phosphate module and / or zirconium oxide module. The control system can use all previous history and use of the patient and sorbent module, or can use previous history and use for any specified length of time. In certain embodiments, the control system can use patient and dialysis parameters based on the previous week, month, year, or longer period of time.

[0157] A tracking component such as an RFID tag or bar code can be affixed to the sorbent module and automatically read by the control system at different times, including before dialysis, after dialysis, before refilling, and after refilling. A single reader can read and track the sorbent module at each stage of use, or separate readers and refillers and dialysis systems can be included to track the use of the sorbent module. The tracking system can track the patient using the sorbent module and the dialysis parameters that affect the amount of refill solution required to refill the sorbent module. The parameters can be transmitted to the control system, and the amount of refill solution required can then be determined by a mathematical algorithm, a lookup table, or a combination thereof.

[0158] Typically, about 5.5 millimoles of sodium in the refill solution are required per total milliequivalent of cations (ammonium + potassium + calcium + magnesium) fed through the zirconium phosphate during therapy in order to restore greater than 90% of the original capacity of the zirconium phosphate. Lower moles of sodium are required per mole of cations loaded on the zirconium phosphate for complete refill at elevated temperatures, and less refill solution with a higher refill solution concentration is required. If refilling is performed at room temperature, a higher amount of sodium may be required. The refill solution may have any amount of sodium ions relative to the amount of cations loaded on the zirconium phosphate, including between 5 and 15 times greater sodium ions than the amount of cations loaded on the zirconium phosphate. In certain embodiments, the total millimoles of sodium pumped through the zirconium phosphate module during recharge can be between 5.0 and 15.0 millimoles sodium / millimoles of cations, between 5.0 and 10.0 millimoles sodium / millimoles of cations, between 5.0 and 6.0 millimoles sodium / millimoles of cations, between 7.0 and 12.0 millimoles sodium / millimoles of cations, between 10.0 and 12.5 millimoles sodium / millimoles of cations, or between 10.0 and 15.0 millimoles sodium / millimoles of cations.

[0159] Typically, per mmol of total CO2 (CO2 + HCO3) fed through zirconium phosphate during therapy - +CO3 2- ) requires about 0.6 mmol of total acetate (sodium acetate + acetic acid) in the refill solution in order to achieve the desired effluent pH profile during the next dialysis session. In certain embodiments, the total millimoles of acetate pumped through the zirconium phosphate module during refill can be between 0.3 and 1.0 mmol acetate / mmol total CO2, between 0.3 and 0.5 mmol acetate / mmol total CO2, between 0.5 and 0.7 mmol acetate / mmol total CO2, or between 0.6 and 1.0 mmol acetate / mmol total CO2.

[0160] As described, the patient's acidosis state can be used to determine the desired zirconium phosphate effluent pH for future therapy sessions. For alkalotic patients, a lower initial therapy zirconium phosphate effluent pH can be selected to minimize the amount of bicarbonate formed by the patient's urea. The initial therapy zirconium phosphate effluent pH depends on the concentration and volume of the refill solution used, and can be used by the control system to determine the volume and / or concentration of the refill solution.

[0161] The amount of refill solution required can also depend on the temperature of the refill solution. The described refill flow path can include a heater and an optional heat exchanger for heating the refill solution to a specified temperature before pumping the refill solution through the zirconium phosphate module, as refilling the zirconium phosphate may be more effective at elevated temperatures. A temperature sensor determines the temperature of the refill solution, and the control system can take the temperature into account when determining the total amount of refill solution required. The refill solution can be heated to any specified temperature, including between 60°C-90°C, between 60°C-70°C, between 60°C-80°C, between 75°C-85°C, or between 80°C-90°C. During refill, the control system can use only the volume of refill solution required based on the total amount of cations loaded on the zirconium phosphate, the concentration of the refill solution, and the temperature of the refill solution, saving cost and materials.

[0162] Typically, each mole of phosphate fed through the zirconia module during the previous dialysis session requires about 6.7 moles of sodium hydroxide to recharge the zirconia. In certain embodiments, the total moles of sodium hydroxide pumped through the zirconia module during recharging can be between 5.0 and 8.4 moles of sodium hydroxide / mole of phosphate, between 5.0 and 6.5 moles of sodium hydroxide / mole of phosphate, between 6.0 and 7.0 moles of sodium hydroxide / mole of phosphate, between 6.0 and 8.0 moles of sodium hydroxide / mole of phosphate, or between 6.5 and 8.4 moles of sodium hydroxide / mole of phosphate.

[0163] The total cations and total CO2 pumped through the zirconium phosphate during dialysis can be obtained by direct measurement with one or more sensors in the dialysate flow path during treatment, or estimated. The estimation of total cations and total CO2 can be based on patient weight, dialysate prescription, pre-dialysis patient cation measurement and / or pre-dialysis patient total CO2 measurement or any combination thereof. Similarly, the total phosphate pumped through the zirconium oxide during the dialysis session can be obtained by direct measurement by sensors in the dialysate flow path, or estimated based on phosphate discharged from the zirconium phosphate and pre-dialysis patient phosphate measurement. In certain embodiments, the total cations, total CO2, and total phosphate pumped through the adsorbent material can be estimated based on the number of previous dialysis sessions. The used values ​​or parameters of the patient can be tracked within any number of previous dialysis sessions, and are used to estimate the total cations and total CO2 pumped through the zirconium phosphate in the immediately previous dialysis session. The number of previous dialysis sessions used can be any number n of previous dialysis sessions, where n is 1 or greater. In certain embodiments, the number of previous dialysis sessions can be between 1-5, between 2-10, between 5-10, or more dialysis sessions. The number of previous dialysis sessions can also be set to a length of time, including dialysis sessions over the previous week, month, year, or any other length of time.

[0164] In one non-limiting example, the total urea removed by the zirconium phosphate can be given by EQ(1).

[0165]

[0166] Where Q d is the dialysate flow rate, t is the length of the previous dialysis session, and is the average urea concentration in the dialysate. As described, the average urea concentration of the dialysate can be directly measured by a sensor in the dialysate flow path, or can be estimated.

[0167] EQ (2) provides another method for determining the amount of urea removed by zirconium phosphate.

[0168] Total urea = V 前 *C B尿素，前 –V 后 *C B尿素，后 EQ(2)

[0169] Where V 前 is the patient water volume before the dialysis session, V 后 is the patient water volume after the dialysis session, C B尿素，前 is the amount of urea in the patient's blood before the dialysis session, and C B尿素，后The amount of urea in the patient's blood after the dialysis session. The patient's water volume before the dialysis session can be measured by bioimpedance, or estimated based on the patient's weight. After the dialysis session, the patient's water volume can be measured by bioimpedance, estimated based on body weight, or measured by subtracting the total ultrafiltration volume during the dialysis session from the patient's water volume before the session. The amount of urea in the patient's blood before the dialysis session can be measured directly in the patient's blood, or can be estimated based on a population average, and then adjusted for a specific patient. The amount of urea in the patient's blood before the dialysis session can also be estimated based on the frequency of therapy or a certain day of the week. The amount of urea in the blood after the dialysis session can be measured directly, or estimated based on the amount of urea in the blood before dialysis and the urea reduction rate (URR), wherein the URR is given by EQ (3).

[0170]

[0171] The URR can be estimated based on patient volume, dialyzer clearance, and session length as provided by EQ(4).

[0172] URR=1-e -kt / V EQ(4)

[0173] Where k is the dialyzer clearance, t is the session time, and v is the patient volume. Dialyzer clearance can be determined using EQ(5).

[0174]

[0175] Where Q B is the blood flow rate during the dialysis session, Q D is the dialysate flow rate during the dialysis session, and K o A is the dialyzer mass transfer coefficient, which can be obtained from the dialyzer specification sheet.

[0176] EQ (6) provides a non-limiting equation for determining the total calcium removed by zirconium phosphate.

[0177]

[0178] Where Q d is the dialysate flow rate, t is the length of the previous dialysis session, and is the average calcium concentration in the dialysate entering the sorbent cartridge. The average calcium concentration of the dialysate can be measured directly by a sensor in the dialysate flow path, or can be estimated as the dialysate prescription. The total magnesium removed by the zirconium phosphate can be determined in the same manner as the total calcium. The total potassium removed by the zirconium phosphate can be determined in the same manner as the total calcium, plus additional potassium from the patient, which can be estimated based on patient blood measurements or assumed using pre-therapy potassium blood amounts.

[0179] EQ (7) provides a non-limiting example of an equation for calculating the necessary amount of recharge solution for recharging zirconium phosphate.

[0180] V r =v*Q*t*(C NH4 +C K +C Ca +C Mg +(a*C HCO3 +b))EQ(7)

[0181] Where Vr is the volume of refill solution required to refill the zirconium phosphate, Q is the time-averaged volume flow rate into the zirconium phosphate adsorbent module, t is the session time, and C NH4 , C K , C Ca , C Mg and C HCO3 is the average concentration of ammonium, potassium, calcium, magnesium and bicarbonate entering the zirconium phosphate adsorbent module, a and b are variables related to the pH of the zirconium phosphate and to the amount of hydrogen released from the zirconium phosphate, and v is a variable specific to the recharging process used. In the case of recharging at 80°C with a recharging solution having 4.7 M NaCl, 0.4 M sodium acetate and 0.4 M acetic acid, v = 1.10, a = 0.14 and b = 9.21. Those skilled in the art will appreciate that the values ​​of a, b and v can be readily derived based on the pH of the zirconium phosphate and the specific conditions to be used for recharging.

[0182] The value of the concentration used in EQ (7) can be determined by the basic delivery mode on the dialyzer and the mass balance equation on the dialysate flow path used (equations such as those shown in (1-6) of EQ), and is easily derived by a person skilled in the art. The delivery mode on the dialyzer can include dialysate flow rate, blood flow rate, dialyzer size and koA, patient solute amount before dialysis, solute concentration in the dialysate, patient weight and capacity, and ultrafiltration rate. The mass balance in the dialysate flow path can include the solute concentration in the used dialysate (determined by the dialyzer delivery mode), the volume of the source water used, and the initial water quality (including the solute concentration in the initial water used to produce the initial dialysate). The patient solute amount or the patient's acidosis state before dialysis can be measured with a blood analyzer before treatment, or can be estimated based on the patient's dialysis schedule and typical session parameters such as weekly frequency, session time, patient weight, patient acidosis state, and time since the last session. The method for estimating the concentration from these values ​​can be derived by a person skilled in the art.

[0183] As described, specific alarms or instances during treatment may also affect the concentration and volume of the refill solution required to refill the adsorbent module. Ammonia breakthrough may indicate that the zirconium phosphate is fully loaded with cations, and the refill volume may be increased accordingly. For example, if ammonia breakthrough occurs, 7.0 L of a refill solution having 4.7 M NaCl, 0.4 M sodium acetate, and 0.4 M acetic acid may be used to refill the zirconium phosphate. Alternatively, the total concentration of sodium and acetate in the refill solution may be increased, and the volume of the refill solution may remain unchanged. In certain embodiments, the volume and / or concentration of the refill solution may be increased to exceed the volume and / or concentration required to refill the adsorbent material to ensure complete refilling.

[0184] A pH alarm may indicate that the zirconium phosphate is fully titrated with bicarbonate during treatment, and the refill solution volume or concentration is increased accordingly. For example, 7.0 L of a refill solution having 4.7 M NaCl, 0.4 M sodium acetate, and 0.4 M acetic acid may be used to refill the zirconium phosphate in the event of a pH alarm or an increase in acetate concentration in the refill solution.

[0185] Blood leaks may cause the need to increase the volume of disinfectant solution required to fully disinfect the zirconium phosphate or zirconium oxide or to compensate for inefficiencies due to greater protein exposure of the zirconium phosphate. In certain embodiments, 0.1 L of additional disinfectant solution may be used for each blood leak during treatment, depending on the disinfectant and concentration used.

[0186] In certain embodiments, the estimated duration of the next dialysis session for the patient can be used to set the refill solution volume and / or concentration. If the duration of the next dialysis session is longer, the patient may have a higher amount of urea and a higher amount of phosphate, and a higher capacity required for zirconium phosphate and zirconium oxide at the start of the next dialysis session. In such a case, the volume and / or concentration of the refill solution may be increased to compensate for the expected higher demand in the next dialysis session.

[0187] One of ordinary skill can calculate the total volume of sodium hydroxide required for recharging, taking into account that about 6.7 moles of sodium hydroxide are required to recharge the zirconium oxide per mole of phosphate fed through the zirconium oxide module during the previous dialysis session. For example, if 10 moles of phosphate were fed through the zirconium oxide module during the previous dialysis session, about 67 moles of sodium hydroxide are required for recharging.

[0188] Figure 6A flow chart illustrating the steps of a customized based zirconium phosphate refilling process. In step 601, the required initial therapy zirconium phosphate effluent pH can be determined. As described, the required initial therapy zirconium phosphate effluent pH can be based on one or more patient parameters and system parameters, including the patient's pre-treatment bicarbonate and urea amount and the availability of additional bicarbonate to be added during dialysis and the degassing capacity of the system. The required initial therapy zirconium phosphate effluent pH can be determined by the control system based on patient parameters and / or system parameters, or directly input by the user through the user interface. In step 602, the concentrations of acids, bases, and sodium salts in the refilling solution can be determined. The concentrations described depend on the pKa of the acid or buffer, the buffering capacity, and the temperature of the refilling solution, and can be automatically determined by the control system. In the case of using a single refilling solution source, the control system can automatically notify the user to add a specific amount of acid, base, or salt to the refilling solution. In the case of using two or more refilling solution sources, the control system can determine the relative amount of fluid required for each refilling solution source.

[0189] In step 604, the system can determine the amount of cations removed by the zirconium phosphate module in the previous dialysis session. The amount of cations removed by the zirconium phosphate module depends on the patient's pre-dialysis potassium, calcium, magnesium and urea amounts and patient weight, patient bicarbonate amount, dialysate flow rate, blood flow rate, dialyzer size, dialysis time, ultrafiltration rate, and potassium, calcium, magnesium and bicarbonate dialysis prescriptions. The described patient parameters can be automatically accepted by the control system through a tracking device on the zirconium phosphate module tracking use. Alternatively, the described patient parameters can be directly input by the user based on the patient's medical records or other information. The described patient parameters can also be assumed based on the patient's specifications by the system and based on the patient's blood laboratory by the settings input into the system.

[0190] In step 603, the amounts of acid, base, and sodium salt required to achieve the desired initial therapeutic zirconium phosphate effluent pH can be determined. Using the total volume determined in step 604 and the concentration determined in step 602, the control system can automatically determine the pump rate and / or valve switching required to refill the zirconium phosphate from one or more refill solution sources and control the pumps and valves to produce the refill solution. In step 605, the control system controls the pumps and valves to refill the zirconium phosphate module.

[0191] Those skilled in the art will understand that the Figure 6601 and 602. For example, if the desired initial therapy zirconium phosphate effluent pH of 6.5 will be used for almost all patients, the system can skip steps 601 and 602. The concentrations of acid, base, and salt required to produce a refill solution with the correct pH can be stored in the system memory and used each time. Step 604 can also be eliminated if a specified refill solution volume is used each time.

[0192] Those skilled in the art will appreciate that various combinations and / or modifications and changes may be made in the described systems and methods depending on the specific needs of the operation. In addition, the features illustrated or described as part of aspects of the present invention may be used in aspects of the present invention individually or in combination, or in accordance with a preferred arrangement of one or more of the described elements.

Claims

1. A method comprising the following steps: recharging adsorbent material within an adsorbent module by pumping one or more recharging solutions through the adsorbent module (402, 702); Wherein the volume and / or concentration of the one or more refill solutions is set based on one or more patient parameters and / or one or more dialysis session parameters for a patient and / or dialysis session using the sorbent module.

2. The method of claim 1, wherein the adsorbent module (402) contains zirconium phosphate; wherein the one or more patient parameters include at least one from the group consisting of: pre-dialysis patient potassium, calcium, magnesium, bicarbonate and urea levels, patient weight, patient volume, patient residual renal function, patient acidosis status, average number of dialysis sessions per week, and average dialysis session length; and wherein the one or more dialysis session parameters include at least one from the group consisting of: dialysate flow rate, blood flow rate, dialyzer size, dialyzer type, dialysis time, ultrafiltration rate; potassium, calcium, magnesium and bicarbonate dialysis prescription; whether ammonia breakthrough occurs, whether pH alarm occurs, fluid removed during the session, total treatment volume, starting water quality, URR target, URR achieved, clearance, whether blood leakage occurs, and whether hypotensive episodes occur.

3. The method of claim 1, wherein the adsorbent module (702) contains zirconium oxide; wherein the one or more patient parameters include at least one from the group consisting of: patient weight, patient volume, patient residual renal function, average number of dialysis sessions per week, and average dialysis session length; and wherein the one or more dialysis session parameters include at least one from the group consisting of: dialysate flow rate, blood flow rate, dialyzer size, dialyzer type, dialysis time, ultrafiltration rate; potassium, calcium, magnesium and bicarbonate dialysis prescription; whether ammonia breakthrough occurs, whether pH alarm occurs, fluid removed during the session, total treatment volume, starting water quality, URR target, URR achieved, clearance, whether blood leakage occurs, and whether hypotensive episodes occur.

4. The method of claim 1, wherein the sorbent module contains zirconium phosphate, and wherein the one or more patient parameters and / or one or more dialysis session parameters include total cations and total CO2 pumped through the sorbent module during a previous dialysis session.

5. The method of claim 4, wherein the total cations and total CO2 pumped through the adsorbent module are obtained from any of: a. directly measuring the total cations and total CO2 in the dialysate flow path during the previous dialysis session; b. Estimate total cations and total CO2 based on patient weight; c. Estimate total cations and total CO2 based on the dialysis prescription; d. estimating total cations and total CO2 based on pre-dialysis patient cation measurements and / or pre-dialysis patient total CO2 measurements; e. Estimate total cations and total CO2 based on multiple previous dialysis sessions; or f. Combinations thereof.

6. The method of claim 4, wherein the step of recharging the zirconium phosphate comprises pumping between 5.0 and 6.0 millimoles of sodium in the one or more recharging solutions per total milliequivalent of total cations pumped through the sorbent module during the previous dialysis session.

7. The method of claim 4, wherein the step of recharging the zirconium phosphate comprises pumping between 0.3 and 1.0 mmol of acetate in the one or more recharging solutions per mmol of total CO2 pumped through the sorbent module during the previous dialysis session.

8. The method of claim 1, wherein the sorbent module contains zirconium oxide, and wherein the one or more patient parameters and / or one or more dialysis session parameters include total phosphate pumped through the sorbent module during a previous dialysis session.

9. The method of claim 8, wherein the total phosphate pumped through the sorbent module during the previous dialysis session is obtained from: direct measurement of phosphate in the dialysate flow path during the previous session, estimation based on phosphate removed from zirconium phosphate used in the previous dialysis session and pre-dialysis patient phosphate measurements; or estimation based on total phosphate pumped through the sorbent box during multiple previous dialysis sessions.

10. The method of claim 8, wherein the step of recharging the zirconium oxide comprises pumping between 6.0 and 7.5 moles of sodium hydroxide in the one or more recharging solutions per mole of phosphate pumped through the sorbent module during the previous dialysis session.

11. The method of claim 1 , wherein the one or more patient parameters and / or one or more dialysis session parameters comprise an estimated duration of a next dialysis session for the patient.

12. The method of claim 1, wherein the adsorbent module contains zirconium phosphate, and wherein the volume of the one or more recharge solutions is calculated using Equation V r =v*Q*t*(C NH4 +C K +C Ca +C Mg +(a*C HCO3 + b)) is set; wherein Vr is the volume of the one or more refill solutions, Q is the time-averaged volume flow rate into the adsorbent module, t is the session time, C NH4 , C K , C Ca , C Mg and C HCO3 is the average concentration of ammonium, potassium, calcium, magnesium and bicarbonate ions entering the sorbent module, a and b are variables related to the pH of the zirconium phosphate, and v is a variable specific to the recharging process in use.

13. A system comprising: a refill flow path (401, 701); the refill flow path comprising one or more refill solution sources; the one or more refill solution sources (405, 406, 705) being fluidly connectable to an inlet (403, 703) of an adsorbent module (402, 702) containing at least one adsorbent material; and at least one pump (407, 706) for pumping one or more recharge solutions from the one or more recharge solution sources through the sorbent module; and and a control system that sets the volume and / or concentration of the one or more refilling solutions pumped through the sorbent module required to refill the sorbent material within the sorbent module based on one or more patient parameters and / or one or more dialysis session parameters of the patient and / or dialysis session for which the sorbent module is used.

14. The system of claim 13, wherein the sorbent module (401) contains zirconium phosphate, and wherein the one or more recharge solution sources comprise a brine source (405), a water source, and a disinfectant source.

15. The system of claim 13, wherein the sorbent module contains zirconium oxide (702), and wherein the one or more recharge solution sources include an alkali source (705), a water source, and a disinfectant source.

16. The system of claim 13, further comprising a second recharge flow path; the second recharge flow path comprising one or more recharge solution sources, the sources being fluidly connectable to an inlet of a second adsorbent module containing at least one adsorbent material; and at least a second pump for pumping one or more recharge solutions from the one or more recharge solution sources through the adsorbent module; wherein the control system sets the volume and / or concentration of the one or more refilling solutions pumped through the second sorbent module required to refill the sorbent material within the second sorbent module based on one or more patient parameters and / or one or more dialysis session parameters of the patient and / or dialysis session using the sorbent module.

17. The system of claim 13, wherein the adsorbent module contains zirconium phosphate, wherein the one or more patient parameters include at least one from the group consisting of: Pre-dialysis patient potassium, calcium, magnesium, bicarbonate, and urea levels, patient weight, patient volume, patient residual renal function, patient acidosis status, average number of dialysis sessions per week, and average dialysis session length; and wherein the one or more dialysis session parameters include at least one from the group consisting of: dialysate flow rate, blood flow rate, dialyzer size, dialyzer type, dialysis time, ultrafiltration rate; potassium, calcium, magnesium and bicarbonate dialysis prescription; whether ammonia breakthrough occurs, whether pH alarm occurs, fluid removed during the session, total treatment volume, starting water quality, URR target, URR achieved, clearance, whether blood leakage occurs, and whether hypotensive episodes occur.

18. The system of claim 13, wherein the adsorbent module comprises zirconium oxide, wherein the one or more patient parameters include at least one from the group consisting of: patient weight, patient volume, patient residual renal function, average number of dialysis sessions per week, and average dialysis session length; and wherein the one or more dialysis session parameters include at least one from the group consisting of: dialysate flow rate, blood flow rate, dialyzer size, dialyzer type, dialysis time, ultrafiltration rate; potassium, calcium, magnesium and bicarbonate dialysis prescription; whether ammonia breakthrough occurs, whether pH alarm occurs, fluid removed during the session, total treatment volume, starting water quality, URR target, URR achieved, clearance, whether blood leakage occurs, and whether hypotensive episodes occur.

19. The system of claim 13, wherein the sorbent module contains zirconium phosphate, and wherein the control system sets the volume and / or concentration of the one or more refill solutions based on total cations and total CO2 pumped through the sorbent module during a previous dialysis session.

20. The system of claim 13, wherein the sorbent module contains zirconium oxide, and wherein the control system sets the volume and / or concentration of the one or more recharging solutions based on total phosphate pumped through the sorbent module during a previous dialysis session.

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