Patent Publication Number: US-2018043081-A1

Title: Peritoneal dialysate purity control system

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation in part of U.S. patent application No. 15/478,569 filed Apr. 4, 2017, which claims benefit of and priority to U.S. Provisional Application No. 62/318,173 filed Apr. 4, 2016, and the disclosures of each of the above-identified applications are hereby incorporated by reference in their entirety. 
    
    
     FIELD OF THE INVENTION 
     The invention relates to devices, systems, and methods for generating a peritoneal dialysate having purity and sterility characteristics suitable for Peritoneal Dialysis (PD). The peritoneal dialysate can be generated from water of variable quality using a purity control system having one or more ultrafilters for sterilization of the peritoneal dialysate Peritoneal dialysate generation system and related methods are described that can generate sterilized peritoneal dialysate and deliver peritoneal dialysis therapy to a patient. 
     BACKGROUND 
     Peritoneal Dialysis (PD), including Automated Peritoneal Dialysis (APD) and Continuous Ambulatory Peritoneal Dialysis (CAPD), can be performed in a clinic or in an at home setting, either by a patient alone or with a care-giver. PD differs from Hemodialysis (HD) in that blood is not removed from the body and passed through a dialyzer, but rather a catheter is placed in the peritoneal cavity and dialysate introduced directly into the peritoneal cavity. Blood is cleaned inside the patient using the patient&#39;s own peritoneum as a type of dialysis membrane. However, because fluid is directly introduced into a human body, the fluid used for peritoneal dialysate is generally required to be free of biological and chemical contaminants. The peritoneal dialysate should also contain specified concentrations of solutes and cations for biocompatibility and for performing membrane exchange. 
     Peritonitis is a serious and common problem in the PD population that results in abdominal pain, fever, and cloudy dialysate. Peritonitis remains a leading complication of PD with around 18% of infection-related mortality in PD patients resulting from peritonitis (Fried et al., “Peritonitis influences mortality in peritoneal dialysis patients,” J. Am. Soc. Nephrol. 1996; 7:2176-2182). Moreover, peritonitis is a contributing factor to death in 16% of deaths on PD, and remains a major cause for patients discontinuing PD and switching to HD. Peritonitis and other peritoneal dialysis complications can often be traced to non-sterile techniques and/or contaminated starting dialysate. 
     The US FDA regulates pre-packaged dialysate for use in PD as a Class II drug if the pre-packaged dialysate is used in either a semi-automatic PD system or an automatic PD system (e.g., cycler system). See 21 C.F.R. Sec. 876.5630. If the peritoneal dialysate is not pre-packaged, the US FDA requires the dialysate be prepared from a dialysate concentrate and “sterile purified water,” which is defined by the FDA in 21 C.F.R. Sec. 165.110(a)(2)(iv) and (vii). Some possible contaminants present in water used to prepare dialysis fluid can be (i) particles, (ii) chemicals, and (iii) microbial contaminants such as bacteria, fungi and yeasts, and microbial derivatives or fragments (e.g., endotoxins released during active growth and lysis of micro-organisms). In additional to meeting purity and sterility requirements, peritoneal dialysate must also contain specific and precise amounts of solutes, such as sodium chloride, sodium bicarbonate, osmotic agents, buffers, and cation infusates. 
     Because traditional peritoneal dialysis systems require FDA-approved, pre-packaged dialysate, the dialysate can be expensive due to high manufacturing, shipping, and storage costs. Shortages can also occur. The problems are not mitigated by on-site dialysate preparation because the source water must still meet high fluid purity and sterility characteristics. Such standards may be difficult to meet, particularly for continuous, automatic peritoneal dialysis machines designed for home use. Further, traditional systems usually require storage of hundreds of liters of dialysate bags, including 300 L or more of peritoneal dialysate and over 300 kg of fluid per month. Storage and shipping of the peritoneal dialysate is expensive, labor intensive, and requires significant storage space. 
     Known systems and methods require significant space to store peritoneal dialysate prior to use. Continuous ambulatory peritoneal dialysis (CAPD) traditionally uses 1-4 exchanges of peritoneal dialysate a day, with an overnight dwell. Because each exchange requires approximately 2-4 L of peritoneal dialysate, use of prepackaged dialysate requires storing about 8-16 L of dialysate per day, or 56-112 L of dialysate per week. Automated peritoneal dialysis uses a cycler to cycle peritoneal dialysis into and out of the peritoneal cavity of the patient, generally at night. APD generally uses 3-5 exchanges daily, requiring up to 20 L of dialysate per day and up to 140 L of dialysate per week. Tidal Peritoneal Dialysis (TPD) is similar to APD with the exception that a between 250 mL to 1000 mL of the peritoneal dialysate is left in the peritoneal cavity of the patient between infusions. The known systems and methods require significant storage space and can deter the adoption of CAPD, APD, or TPD. 
     There is a need for systems and methods that can generate and use peritoneal dialysate using water of varying quality. There is also a need for a system that can generate peritoneal dialysate and use the peritoneal dialysate with an integrated cycler, reducing the number of components necessary for peritoneal dialysis. The need includes peritoneal dialysate having purity and sterility requirements such that patients will not contract an infection due to bacteria or other pathogens in fluid used for peritoneal dialysate. The need is acute for automated fluid generation for continuous dialysis machines for use at home where a water source can be tap water or other non-sterile source. There is also a need for systems and methods that allow for the automated generation of dialysate suitable for peritoneal dialysis that contains the proper amounts of solutes and cations. There is further a need for a system that uses filtration, as opposed to heat, in sterilization of the dialysate, which reduces the generation of glucose degradation products. There is also a need for a system that can generate peritoneal dialysate on demand, or for direct infusion into the patient, reducing the storage time and space requirements, as well as lowering the probability of loss of sterility of the dialysate. 
     SUMMARY OF THE INVENTION 
     The first aspect of the invention relates to a purity and control system for use in an peritoneal dialysis. In any embodiment, the purity and control system can comprise a first fluid line fluidly connected to a peritoneal dialysate generation system and a first ultrafilter; a second fluid line fluidly connecting the first ultrafilter to a second ultrafilter; the peritoneal dialysate generation system comprising at least a water source, an osmotic agent source, an ion concentrate source, and a water purification module fluidly connected to a peritoneal dialysate generation flow path. 
     In any embodiment, the second ultrafilter can be fluidly connected to a control valve; the control valve selectively directing fluid to either the peritoneal dialysate generation system or an integrated cycler. 
     In any embodiment, the control valve can be fluidly connected to the peritoneal dialysate generation system at an infusate line. 
     In any embodiment, the purity control system can comprise a pressure sensor in the first fluid line. 
     In any embodiment, the purity control system can comprise a pressure sensor in a third fluid line fluidly connecting the control valve and the integrated cycler. 
     In any embodiment, the first ultrafilter can be fluidly connected to a fourth fluid line; the fourth fluid line fluidly connected to a waste line. 
     In any embodiment, the waste line can be fluidly connectable to a waste reservoir. 
     In any embodiment, the waste line can be fluidly connectable to a drain. 
     In any embodiment, the second ultrafilter can be fluidly connected to a fifth fluid line; the fifth fluid line fluidly connected to the waste line. 
     In any embodiment, the fourth fluid line can have a valve positioned between the first ultrafilter and the waste line; and the fifth fluid line can have a valve positioned between the second ultrafilter and the waste line. 
     In any embodiment, the system can comprise a second valve positioned on a third fluid line fluidly connecting the second ultrafilter to the integrated cycler. 
     In any embodiment, the system can comprise a control system, the control system controlling a peritoneal dialysate flow rate based on data from the pressure sensor. 
     In any embodiment, the control system can control the peritoneal dialysate flow rate to maintain a pressure of the peritoneal dialysate between −200 mmHg to 500 mmHg, from −50 mmHg to 100 mmHg, from 0 mmHg to 100 mmHg, from −50 mmHg to 200 mm Hg, from 200 mmHg to 500 mmHg, or from 100 mmHg to 400 mmHg. 
     In any embodiment, the system can comprise a control system, the control system controlling a peritoneal dialysate flow rate based on data from the pressure sensor. 
     In any embodiment, the control system can control the peritoneal dialysate flow rate to maintain a pressure of the peritoneal dialysate between −200 mmHg to 500 mmHg, from −50 mmHg to 100 mmHg, from 0 mmHg to 100 mmHg, from −50 mmHg to 200 mm Hg, from 200 mmHg to 500 mmHg, or from 100 mmHg to 400 mmHg. 
     In any embodiment, the water purification module can comprise a sorbent cartridge. 
     The features disclosed as being part of the first aspect of the invention can be in the first aspect of the invention, either alone or in combination, or follow a preferred arrangement of one or more of the described elements. 
     The second aspect of the invention is directed to a method of delivering peritoneal dialysate to a patient comprising the steps of generating peritoneal dialysate with a peritoneal dialysate generation system; pumping the peritoneal dialysate through the purity control system of the first aspect of the invention; and pumping the peritoneal dialysate from the purity control system to the peritoneal dialysate cycler and into a peritoneal cavity of a patient. 
     In any embodiment, the method can comprise the step of measuring a pressure of the peritoneal dialysate upstream of the first ultrafilter, and adjusting a peritoneal dialysate flow rate through the purity control system based on the pressure of the peritoneal dialysate. 
     In any embodiment, the method can comprise the step of measuring a pressure of the peritoneal dialysate downstream of the second ultrafilter, and adjusting a peritoneal dialysate flow rate through the purity control system based on the pressure of the peritoneal dialysate. 
     In any embodiment, the method can comprise the step of generating an alert if the pressure of the peritoneal dialysate upstream of the first ultrafilter is outside of a predetermined range. 
     In any embodiment, the method can comprise the step of generating an alert if the pressure of the peritoneal dialysate downstream of the second ultrafilter is outside of a predetermined range. 
     The features disclosed as being part of the second aspect of the invention can be in the second aspect of the invention, either alone or in combination, or follow a preferred arrangement of one or more of the described elements. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  shows a peritoneal dialysate generation flow path with an integrated cycler. 
         FIG. 2  shows a system for adding concentrates to a peritoneal dialysate generation flow path. 
         FIG. 3  shows an overview of a system for generating and using peritoneal dialysate with a single concentrate source. 
         FIG. 4  shows an overview of a system for generating and using peritoneal dialysate with multiple concentrate sources. 
         FIG. 5  shows an alternative peritoneal dialysate generation flow path with an integrated cycler. 
         FIG. 6  shows a peritoneal dialysate generation flow path with multiple dispensing options. 
         FIGS. 7A-D  show a peritoneal dialysate generation cabinet with a water reservoir and waste reservoir. 
         FIG. 8  shows a peritoneal dialysate generation cabinet connected to a faucet and drain. 
         FIG. 9  shows a peritoneal dialysate generation and delivery system. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Unless defined otherwise, all technical and scientific terms used have the same meaning as commonly understood by one of ordinary skill in the art. 
     The articles “a” and “an” are used to refer to one or to over one (i.e., to at least one) of the grammatical object of the article. For example, “an element” means one element or over one element. 
     The terms “adjusting” or to “adjust” refer to changing a parameter of a fluid, gas, or system. 
     The term “around,” when used in the context of parameter values or ranges, means approximately, or within a certain margin from, the described values or ranges and should be given the broadest interpretation as understood by those of skill in the art. 
     The term “comprising” includes, but is not limited to, whatever follows the word “comprising.” Use of the term indicates the listed elements are required or mandatory but that other elements are optional and may be present. 
     The term “consisting of” includes and is limited to whatever follows the phrase “consisting of.” The phrase indicates the limited elements are required or mandatory and that no other elements may be present. 
     The term “consisting essentially of” includes whatever follows the term “consisting essentially of” and additional elements, structures, acts or features that do not affect the basic operation of the apparatus, structure or method described. 
     The terms “control,” “controlling,” or “controls” refers to the ability of one component to direct the actions of a second component. 
     A “control system” can be a combination of components acting together to maintain a system to a desired set of performance specifications. The control system can use processors, memory and computer components configured to interoperate to maintain the desired performance specifications. The control system can also include fluid or gas control components, and solute control components as known within the art to maintain the performance specifications. 
     A “control valve” can be a valve that selectively controls movement of fluid, gas, or combinations therefore into one or more flow paths, sections, components or sections of a system. 
     The term “delivering peritoneal dialysate” or to “deliver peritoneal dialysate” refer to generating peritoneal dialysate and infusing the peritoneal dialysate. In one non-limiting example, the infusion can be provided to a patient. 
     The term “dialysate” can generally refer to any fluid used in dialysis from which solutes and particles can flow into or out of across a membrane to second fluid. For example, for peritoneal dialysis, solutes can be diffused through a peritoneal membrane of a patient. Dialysate can differ depending on the type of dialysis to be carried out. For example, dialysate for peritoneal dialysis may include different solutes or different concentrations of solutes than dialysate for hemodialysis. 
     The term “downstream” refers to a position of a first component in a flow path relative to a second component wherein fluid, gas, or combinations thereof, will pass by the second component prior to the first component during normal operation. The first component can be said to be “downstream” of the second component, while the second component is “upstream” of the first component. 
     A “drain” is a conduit for carrying waste fluids or gases. 
     The term “fluid” can be any substance without a fixed shape that yields easily to external pressure such as a gas or a liquid. Specifically, the fluid can be water containing any solutes at any concentration. The fluid can also be dialysate of any type including fresh, partially used, or spent. 
     The terms “fluid connection,” “fluidly connectable,” or “fluidly connected” refer to the ability to pass fluid, gas, or combinations thereof from one point to another point. The two points can be within or between any one or more of compartments, modules, systems, and components, all of any type. 
     A “fluid line” can refer to a tubing or conduit through which a fluid, gas, or fluid containing gas can pass. The fluid line can also contain air during different modes of operation such as cleaning or purging of a line. 
     To “generate an alert” or “generating an alert” refer to providing a user with an indication of a state of a system. 
     The terms to “generate peritoneal dialysate,” “generating peritoneal dialysate,” or “peritoneal dialysate generation” refers to creating a peritoneal dialysate solution from constituent parts. 
     The term “infusate line” refers to a fluid line for carrying peritoneal osmotic agents and/or cation infusates into a peritoneal dialysate generation flowpath. 
     An “integrated cycler” can refer a component for movement of fluid into and out of the peritoneal cavity of a patient, wherein the integrated cycler forms a part of an overall system. In one non-limiting example, the integrated cycler can be contained in a housing with other components used for peritoneal dialysis and be in fluid and electrical connection with desired components. 
     An “ion concentrate source” refers to a source of one or more ionic compounds. The ion concentrate source can be in water or solid form. The ion concentrate source can further have one or more ionic compounds that are at a higher ion concentration greater than generally used in dialysis. 
     The term “maintain a pressure” means to control one or more variables to prevent the pressure from exceeding or dropping below predetermined thresholds. 
     The term “measuring” or “to measure” can refer to determining any parameter or variable. The parameter or variable can relate to any state or value of a system, component, fluid, gas, or mixtures of one or more gases or fluids. 
     An “osmotic agent source” refers to a source of osmotic agents in solid and/or solution form. The osmotic agent source can interface with at least one other module found in systems for dialysis. The osmotic agent source can contain at least one fluid pathway and include components such as conduits, valves, filters or fluid connection ports, any of which are fluidly connectable to each other or to a fluid flow path. The osmotic agent source can either be formed as a stand-alone enclosure or a compartment integrally formed with an apparatus for dialysis for containing an osmotic agent source. If the osmotic agent(s) is in solid form, a system as described in the present invention can deliver a fluid, such as a highly purified or sterile water, to dilute the solid osmotic agent. Optional mechanical agitation or other means such as stirring can be used to help dissolve the solid osmotic agent. 
     The term “peritoneal cavity” refers to the space between the parietal peritoneum and visceral peritoneum of a patient. 
     “Peritoneal dialysate” is a dialysis solution to be used in peritoneal dialysis having specified parameters for purity and sterility. Peritoneal dialysate is not the same as dialysate used in hemodialysis although peritoneal dialysate may be used in hemodialysis. 
     The term “peritoneal dialysate flow rate” refers to a rate of a fluid moving through a specified section of a peritoneal dialysate generation system. 
     A “peritoneal dialysate generation flow path” can refer to a path used in generating dialysate suitable for peritoneal dialysis. 
     A “peritoneal dialysate generation system” refers to a collection of components used to generate peritoneal dialysate. 
     “Peritoneal dialysis” is a therapy wherein a dialysate is infused into the peritoneal cavity, which serves as a natural dialyzer. In general, waste components diffuse from a patient&#39;s bloodstream across a peritoneal membrane into the dialysis solution via a concentration gradient. In general, excess fluid in the form of plasma water flows from a patient&#39;s bloodstream across a peritoneal membrane into the dialysis solution via an osmotic gradient. Once the infused peritoneal dialysis solution has captured sufficient amounts of the waste components the fluid is removed. This cycle can be repeated for several cycles each day or as needed. 
     The term “predetermined range” is a range of possible values for a parameter to be set as. 
     The term “pressure sensor” refers to a device for measuring the pressure of a gas or liquid in a vessel, container, or fluid line. 
     The term “pump” refers to any device that causes the movement of fluids or gases by applying suction or pressure. 
     The terms “pumping” or to “pump” refer to moving a fluid or gas through a flow path with a pump. 
     The term “purity control system” refers to a set of components that can sterilize or purify a fluid or gas. 
     “Selectively directing fluid” or to “selectively direct fluid” means to cause a fluid, gas, or combinations thereof to move in a specified flow path. 
     The term “sorbent cartridge” refers to a cartridge containing one or more sorbent materials for removing specific solutes from solution. The term “sorbent cartridge” does not require the contents in the cartridge be sorbent based, and the contents of the sorbent cartridge can be any contents capable of removing solutes from a dialysate. The sorbent cartridge may include any suitable amount of one or more sorbent materials. In certain instances, the term “sorbent cartridge” refers to a cartridge which includes one or more sorbent materials besides one or more other materials capable of removing solutes from dialysate. “Sorbent cartridge” can include configurations where at least some materials in the cartridge do not act by mechanisms of adsorption or absorption. 
     An “ultrafilter” can refer to a semi permeable membrane through which a fluid can pass with removal of one or more solutes or particles from the fluid. 
     The term “upstream” refers to a position of a first component in a flow path relative to a second component, wherein fluid, gas, or a combination thereof, will pass by the first component prior to the second component during normal operation. The first component can be said to be “upstream” of the second component, while the second component is “downstream” of the first component. 
     A “valve” refers to a device capable of directing the flow of fluid or gas by opening, closing or obstructing one or more pathways to allow the fluid or gas to travel in a path. One or more valves configured to accomplish a desired flow can be configured into a “valve assembly.” 
     The term “waste line” refers to a fluid line through which waste fluids, gases, or spent dialysate can be pumped. 
     A “waste reservoir” can refer to a container for collecting and storing used or waste fluids. 
     The term “water purification module” refers to a component or collection of components capable of removing biological or chemical contaminants from water. 
     The term “water source” refers to a source from which water can be obtained. In one non-limiting embodiment, the obtained water is potable. 
     Peritoneal Dialysis Purity Control System 
     The invention relates to systems and methods for generating and using peritoneal dialysate in peritoneal dialysis. A system for generating peritoneal dialysate and delivering peritoneal dialysis therapy to a patient  134  can be configured as illustrated in  FIG. 1 . The system includes a peritoneal dialysate generation flow path  101 . Fluid from a water source, such as water tank  102 , can be pumped into the peritoneal dialysate generation flow path  101 . Additionally, or as an alternative to a water tank  102 , the system can use a direct connection  112  to a water source. System pump  108  can control the movement of fluid through the peritoneal dialysate generation flow path  101 . If a direct connection  112  to a water source is used, a pressure regulator  113  ensures the incoming water pressure is within a predetermined range. The system pumps the fluid from water source through a water purification module  103  to remove chemical contaminants in the fluid in preparation for creating dialysate. 
     The water source can be a source of potable water including a purified water source. Purified water can refer to any source of water treated to remove at least some biological or chemical contaminants. The water tank  102  can alternatively be a non-purified water source, such as tap water, wherein the water from the water tank  102  can be purified by the system as described. A non-purified water source can provide water that has undergone no additional purification, water that has undergone some level of purification, but does not meet the definition of “purified water” provided, such as bottled water or filtered water. The peritoneal dialysate generation flow path  101  can also have a direct connection  112  to a purified or non-purified water source, shown as direct connection  112 . The water source can be any source of water, whether from a tap, faucet, or a separate container or reservoir. 
     The water purification module  103  can be a sorbent cartridge. The sorbent cartridge can include aluminum oxide for removal of fluoride and heavy metals. The sorbent cartridge can have a first layer of aluminum oxide, a second layer of activated carbon and a third layer of an ion exchange resin. The sorbent cartridge can be sized depending on the needs of the user, with a larger sized sorbent cartridge allowing for more exchanges before the sorbent cartridge must be replaced. The sorbent cartridge can also include activated carbon. The activated carbon operates to adsorb non-ionic molecules, organic molecules, and chlorine from the water, along with some endotoxins or bacterial contaminants. In certain embodiments, the sorbent cartridge can include activated carbon, activated alumina, and potentially other components that work primarily by physical and chemical adsorption, combined with one or more ion exchange materials. The ion exchange materials can be any known material in the art, but preferably the ion exchange materials will release hydrogen and hydroxyl ions in exchange for other cations and anions in solution, resulting in water formation by the exchange process. 
     The sorbent cartridge can additionally include a microbial filter and/or a particulate filter. A microbial filter can further reduce the amount of bacterial contaminants present in the fluid from the water tank  102  or direct connection  112 . Optionally, an ultrafilter can be included to remove endotoxins from the fluid. A particulate filter can remove particulate matter from the fluid. The water tank  102  can be any size usable with the system, including between around 12 and around 25 L. A water tank  102  of 20 L can generally generate the necessary peritoneal dialysate for multiple cycles. In certain embodiments, the water purification module  103  can include an optional UV light source for further purification and sterilization of the water prior to adding osmotic agents or ion concentrates. 
     Alternatively, the water purification module  103  can be any component capable of removing contaminants from the water in the water source, including any one or more of a sorbent cartridge, reverse osmosis module, nanofilter, combination of cation and anion exchange materials, activated carbon, activated alumina, silica, or silica based columns. 
     After the fluid passes through the water purification module  103 , the fluid is pumped to a concentrate source  104 , where necessary components for carrying out peritoneal dialysis can be added from the concentrate source  104 . The concentrates in the concentrate source  104  are utilized to create a peritoneal dialysis fluid that matches a dialysis prescription. Concentrate pump  105  and concentrate valve  111  can control the movement of concentrates from the concentrate source  104  to the peritoneal dialysate generation flow path  101  in a controlled addition. Concentrate valve  111  can be replaced with a hose T. A hose T is a fluid connector in a T-shape, with a port at each end for fluid to enter or exit the hose T. The concentrates added from the concentrate source  104  to the peritoneal dialysate generation flow path  101  can include any component prescribed for use in peritoneal dialysate. Table 1 provides non-limiting exemplary ranges of commonly used components of peritoneal dialysate. 
     
       
         
           
               
               
               
             
               
                   
                 TABLE 1 
               
               
                   
                   
               
               
                   
                 Component 
                 Concentration 
               
               
                   
                   
               
             
            
               
                   
                 Sodium chloride 
                  132-134 mmol/L 
               
               
                   
                 Calcium chloride dehydrate 
                 1.25-1.75 mmol/L 
               
               
                   
                 Magnesium chloride hexahydrate 
                 0.25-0.75 mmol/L 
               
               
                   
                 Sodium Lactate 
                   35-40 mmol/L 
               
               
                   
                 Dextrose (D-glucose) monohydrate 
                 0.55-4.25 g/dL 
               
               
                   
                 pH 
                   5-6 
               
               
                   
                 Osmolality 
                  346-485 (hypertonic) 
               
               
                   
                   
               
            
           
         
       
     
     To reduce the glucose degradation products (GDP) formed, some peritoneal dialysate systems use a low GDP formulation. Exemplary peritoneal dialysate concentrations for low GDP formulations are provided in Table 2. Generally, the low GDP peritoneal dialysate is provided in two separate bags, with one bag containing calcium chloride, magnesium chloride and glucose maintained at low pH, and the second bag containing sodium chloride and the buffer components, including sodium lactate and sodium bicarbonate. The two bags are mixed prior to use to generate a peritoneal dialysate with a neutral pH. Alternatively, a two chamber bag can be used to prevent mixing of fluids prior to use wherein, the chambers, can for example, be separated by a wall of a divider of any type. 
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 Low GDP peritoneal dialysate formulations 
               
            
           
           
               
               
               
            
               
                   
                 Component 
                 Concentration 
               
               
                   
                   
               
               
                   
                 Sodium 
                  132-134 mEq/L 
               
               
                   
                 Calcium 
                  2.5-3.5 mEq/L 
               
               
                   
                 Magnesium 
                  0.5-1.0 mEq/L 
               
               
                   
                 Lactate 
                   0-40 mEq/L 
               
               
                   
                 Bicarbonate 
                   0-34 mEq/L 
               
               
                   
                 pH 
                  6.3-7.4 
               
               
                   
                 % glucose (g/dL) 
                  1.5-4.25 
               
               
                   
                   
               
            
           
         
       
     
     One of skill in the art will understand that other components can be used in place of the components listed in Tables 1-2. For example, dextrose as listed in Table 1 is commonly used as an osmotic agent. However, other osmotic agents can be used in addition to, or in place of, the dextrose, including glucose, icodextrin or amino acids, including dialysate with multiple osmotic agents. Although the sources of sodium, calcium, and magnesium listed in Table 1 are chloride salts, other sodium, magnesium, and calcium salts can be used, such as lactate or acetate salts. Peritoneal dialysate may also contain buffers for maintaining pH of the peritoneal dialysate, including bicarbonate buffer, acetate buffer, or lactate buffer. Although not generally used in peritoneal dialysis, potassium chloride can be used for hypokalemic patients who don&#39;t receive sufficient potassium through diet. The concentrate source  104  can contain one or more osmotic agents, as well as one or more ion concentrates, such as concentrated sodium chloride, sodium lactate, magnesium chloride, calcium chloride, and/or sodium bicarbonate. The concentrate source  104  can be a single source of concentrates, including both osmotic agents and ion concentrates, or can include multiple sources of concentrates, with separate sources for the osmotic agents and ion concentrates. The system can have a single concentrate that has all components mixed for a daytime or overnight treatment for use in a home by a single patient. Alternatively, the concentrate source  104  can include separate sources for any solutes to be used in the peritoneal dialysate each with a separate concentrate pump to add each solute. Concentrate pump  105  pumps concentrated solutions from the concentrate source or sources  104  to the peritoneal dialysate generation flow path  101  in a controlled addition. Where more than one concentrate source is used, separate concentrate pumps can move each of the concentrates into the peritoneal dialysate generation flow path  101 , or a single concentrate pump can be used, with valves configured allow individual control over the movement of each of the concentrate solutions to the peritoneal dialysate generation flow path  101 . 
     After addition of solutes from the concentrate source  104 , the fluid in the peritoneal dialysate generation flow path  101  can contain all the necessary solutes for peritoneal dialysis. The peritoneal dialysate should reach a level of sterility for peritoneal dialysis. The level of sterility can be any level that meets an applicable regulatory requirement, such as a sterility assurance level of 10 −6  required by the FDA, meaning that the chance a viable organism is present after sterilization is 1 in 1,000,000. The system can pump the fluid to a sterilization module for sterilization of the peritoneal dialysate. As shown in  FIG. 1 , the sterilization module can include one or more of a first ultrafilter  107 , a second ultrafilter  109 , and an optional UV light source  106 . The sterilization module can be any component or set of components capable of sterilizing the peritoneal dialysate. The sterilization module can be comprised of a single or multiple ultrafilters. The number of ultrafilters can vary from one, two, three, four, and more depending on configuration and usage. A secondary component, such as a UV light source  106  or microbial filter (not shown), can be used in the sterilization module to provide additional sterilization of the peritoneal dialysate. The sterilization module can also include at least two ultrafilters, including second ultrafilter  109  for further sterilization of the fluid and redundancy of the system to protect against sterilization failure. The UV light source  106  can be positioned at any location in the peritoneal dialysate generation flow path  101 , including upstream of ultrafilter  107 , between ultrafilters  107  and  109  or downstream of ultrafilter  109 . The ultrafilters  107  and  109  used in the sterilization module can be replaced as necessary. In one non-limiting embodiment, the ultrafilters  107  and  109  can have a 3-6 month lifetime before replacement. However, no limitation on the lifespan of the ultrafilters is imposed by the system. The ultrafilters  107  and  109  can be any ultrafilter known in the art capable of sterilizing the peritoneal dialysate. A non-limiting example of an ultrafilter is the hollow fiber ForClean ultrafilter, available from Bellco, Mirandola (MO), Italy. In certain embodiments, the sterilization module  106  can use heat sterilization. The sterilization module can include a heater (not shown) to heat the prepared dialysate. Alternatively or additionally, the sterilization module can include a flash pasteurization module (not shown) to sterilize the dialysate through flash pasteurization. The sterilization module can include both heat-based sterilization components and filtration based sterilization components, with a processor, controller, or the user adjusting the mode of sterilization based on the mode of use. For example, a heat based sterilization can be used when the peritoneal dialysate is generated for later use, while a filtration based sterilization can be used when the peritoneal dialysate is generated for immediate use. 
     The generated peritoneal dialysate can be pumped directly to an integrated cycler  110  for immediate infusion into a patient  134 . Alternatively, the dialysate can be pumped to an optional dialysate container  114  as a pre-prepared bolus of solution for storage until ready for use by a patient  134 . Valve  116  can control the movement of fluid to either the integrated cycler  110  or the dialysate container  114 . Stored dialysate in dialysate container  114  can be pumped as needed to the integrated cycler  110  by pump  115  through valve  117 . The dialysate container  114  can include one or more sterilized dialysate bags. The dialysate bags, once filled with peritoneal dialysate, can be stored until needed by the patient  134 . The dialysate container  114  can alternatively be a reusable sterilized container or bag. The reusable container or bag can be cleaned and sterilized daily, or at set time periods. Alternatively, the dialysate container  114  can be any type of storage container, such as a stainless-steel container. The dialysate container  114  can store enough peritoneal dialysate for a single infusion cycle of peritoneal dialysate into the patient  134 , or enough peritoneal dialysate for multiple infusions into a patient  134 . Additional or alternative storage containers can be included at other locations in the peritoneal dialysate generation flow path  101 . A storage container can be included upstream of the sterilization module, and downstream of the water purification module  103 . Before the fluid is utilized in the cycler stage, the fluid can be pumped through the sterilization module to ensure sterility of stored fluid. Further, concentrates can be added to fluid before storing the fluid, or after storage of the fluid but prior to sterilization in the sterilization module. 
     The storage containers can be either upstream or downstream of the concentrate source  104 . The addition of concentrates to the fluid can happen either before storage of the fluid, or after storage of the fluid just before sterilization in the sterilization module. 
     By generating and immediately using the peritoneal dialysate, the dialysate storage time can be reduced, reducing the possibility of bacterial growth. A user interface can be included on the peritoneal dialysis generation machine in communication with the control system, allowing a patient  134  to direct the generation of peritoneal dialysate at a selected time as needed. Additionally, or alternatively, the peritoneal dialysate machine can include a timer, and the timer can cause the peritoneal dialysate machine to generate peritoneal dialysate at predetermined times according to the patient&#39;s  134  peritoneal dialysis schedule. Alternatively, the peritoneal dialysate generation machine can be equipped with wireless communication, such as Wi-Fi, Bluetooth, Ethernet, or any other wireless communication system known in the art. The user can direct the peritoneal dialysis machine to generate peritoneal dialysate at a specified time from any location. By using a timer, user interface, or wireless communication to control the generation of peritoneal dialysate on demand, the peritoneal dialysate storage time can be reduced, lowering the chances of generating significant amounts of degradation products or allowing bacterial growth. 
     The peritoneal dialysate can be generated and used in real time, with direct infusion of the peritoneal dialysate into the patient  134  through the integrated cycler  110 . For real time generation and use of the peritoneal dialysate, the flow rate of fluid through the peritoneal dialysate generation flow path  101  can be between 50 and 300 ml/min. With the online generation of fluid described, a flow rate of 300 ml/min can support an exchange time of between 10 and 15 minutes for a full cycle of draining and filling the peritoneal cavity of a patient  134 . If a dialysate container  114  is used to store generated peritoneal dialysate, the flow rate of fluid through the peritoneal dialysate generation flow path  101  can be any flow rate capable of producing the necessary peritoneal dialysate. In certain embodiments, the flow rate can be at least around 15 mL/min, which can produce around 20 L of peritoneal dialysate in 24 hrs. The integrated cycler  110  can then infuse the generated peritoneal dialysate into the peritoneal cavity of a patient  134 . The integrated cycler  110  and the rest of the system can communicate for the purposes of generation and use of the peritoneal dialysate by any method known in the art, including Bluetooth, Wi-Fi, Ethernet, or direct hardware connections to meet patient or clinic needs. Additional valves and regulators (not shown in  FIG. 1 ) can be included to aid in connection and operation of the peritoneal dialysate generation flow path  101  and integrated cycler  110 . The integrated cycler  110  and the peritoneal dialysate generation flow path  101  can communicate directly, or can each communicate with a control system for control over the generation and use of the peritoneal dialysate. 
     In certain embodiments, the dialysate container  114  can store enough peritoneal dialysate for multiple infusions into the patient  134 , including enough peritoneal dialysate for one day or more of treatment. A timer can be included in the control system and can cause the machine to generate fresh peritoneal dialysate each day or at set times. 
     The integrated cycler  110  can include a metering pump  119  for metering peritoneal dialysate into the peritoneal cavity of the patient  134 . An in-line heater  118  heats the peritoneal dialysate to a desired temperature prior to infusion into the patient  134 . A pressure regulator  120  ensures the peritoneal dialysate pressure is within a predetermined range safe and comfortable for infusion into the patient  134 . The metering pump  119  can use any safe pressure for infusing fluid into the patient  134 . Generally, the pump pressures are on average set at ±10.3 kPa or 77.6 mmHg. If there is no fluid flow, the maximum pressure can increase to ±15.2 kPa or 113.8 mmHg for a short period, such as less than 10 seconds. The peritoneal dialysate is infused into the peritoneal cavity of the patient  134  through infusion line  124 . An additional microbial filter (not shown) may be used to sterilize the peritoneal dialysis fluid immediately before the peritoneal dialysate enters the patient  134 . After a dwell period, the peritoneal dialysate is drained from the patient  134  through drain line  123 . Pump  122  provides a driving force for removing the peritoneal dialysate from the patient  134 . Treatment, other than the first full cycle for a patient in APD, generally begins with drainage of the peritoneal cavity of the patient  134 , prior to infusing the fresh peritoneal dialysate into the patient  134 . An optional waste reservoir  121  can be included to store the used peritoneal dialysate for disposal. Alternatively, the drain line  123  can be directly connected to a drain for direct disposal. A standard waste reservoir  121  is 15 L, however, the waste reservoir  121  can be any size, including between 12 and 20 L. For patients requiring a higher drainage, a drain manifold can be included for connecting multiple waste reservoirs. There is no set rate for draining of peritoneal dialysate from the peritoneal cavity of the patient  134 , and any flow rate can be used with the integrated cycler  110 . 
     Various sensors positioned in the peritoneal dialysate generation and infusion system ensure that the generated fluid is within predetermined parameters. Flow meter  135  ensures the incoming water is at a correct flow rate, while pressure sensor  136  ensures the incoming water is at an appropriate pressure. Conductivity sensor  125  is used to ensure that the water exiting water purification module  103  has been purified to a level safe for use in peritoneal dialysis. Conductivity sensor  126  ensures the conductivity of the dialysate after the addition of concentrates from concentrate source  104  is within a predetermined range. Refractive index sensor  127  ensures that the concentration of the osmotic agents is within a predetermined range. pH sensor  128  ensures the pH of the peritoneal dialysate is within a predetermined range. After passing through the sterilization module including second ultrafilter  109 , pH sensor  129  and conductivity sensor  130  are used to ensure that no changes in the pH or conductivity have occurred during purification or storage of the dialysate in dialysate container  114 . The integrated cycler  110  has flow meter  131 , pressure sensor  132  and temperature sensor  133  to ensure that the dialysate being infused into the patient  134  is within a proper flow rate, pressure, and temperature range. The flow meter  131  can also calculate the volume of solution infused into the patient  134 . The pressure sensor  132  can monitor the pressure in the peritoneal cavity. 
     Overfill, or excessive solution in the peritoneal cavity beyond the target volume may present complications in therapy. Overfill can be caused by many factors, including failing to fully drain the peritoneal cavity prior to infusion of fresh peritoneal dialysate. In any embodiment, the integrated cycler  110  can start therapy with a drain step to ensure that no peritoneal dialysate remains in the peritoneal cavity. Monitoring both pressure and volume of peritoneal dialysate introduced to the patient  134  can avoid overfill. If the pressure rises to a certain point, the system can be programmed to end filling or send an alert to a user to complete filling of the peritoneal cavity at a desired level. The volume of peritoneal dialysate extracted from and introduced to the patient  134  can also be monitored with flow meters to ensure proper volumes of exchanges. Draining the peritoneal cavity can be performed in a similar manner by monitoring the pressure and volume of the drained peritoneal dialysate. 
     As illustrated in  FIG. 1 , the necessary solutes can be added to the peritoneal dialysate generation flow path  101  from a single concentrate source  104 . The solutes can be present in concentrated from within the concentrate source  104  in a fixed ratio for peritoneal dialysis, as shown in Table 1. Using a single concentrate source  104  for all solutes results in peritoneal dialysate having a fixed ratio of each of the solutes. 
     Table 3 provides exemplary non-limiting ranges of solutes that can be added from a single concentrate source  104  to the peritoneal dialysate generation flow path  101 , including the starting concentration of the solutes in the concentrate source, as well as exemplary final volumes of the solutes in the dialysate and the exemplary flow rates of both the solutes and the water in the peritoneal dialysate generation flow path  101  that will achieve those concentrations. The solutes shown in Table  3  are traditional peritoneal dialysate solutes. Table 4 shows exemplary ranges of solutes that can be used as a low GDP formulation. Table 5 shows exemplary ranges of solutes that can be used with icodextrin as the osmotic agent. Icodextrin is sometimes used as an osmotic agent for a long dwell period. If dextrose or glucose is used in a long dwell period, reabsorption of the ultrafiltrate can occur, reducing the net volume of fluid removed. Icodextrin can result in a long sustained ultrafiltration, and can provide improved ultrafiltration efficiency over a long dwell period. One of skill in the art will understand that the concentrations of any of the solutes shown in Tables 3-5 can be altered by altering the flow rates of the system pump  108  or concentrate pump  105 . However, the ratio of the solutes included is fixed if using a single concentrate source  104 . If the ratio of the solutes needs to be altered for any reason, a new concentrate solution may be needed. 
     
       
         
           
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                 Exemplary solutes for addition from  
               
               
                 a single concentrate source 
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                   
                 Solution  
                 Flow  
               
               
                   
                   
                 Concentration  
                 volume 
                 rate 
               
               
                   
                 Component 
                 (g/l) 
                 (ml/L) 
                 (ml/min) 
               
               
                   
                   
               
               
                   
                 Glucose 
                 100-850 
                  50-400 
                 1-18 
               
               
                   
                 Sodium Chloride 
                  13-108 
                  50-400 
                 1-18 
               
               
                   
                 Sodium Lactate 
                 11-90 
                  50-400 
                 1-18 
               
               
                   
                 MgCl 2 •6H 2 O 
                 0.13-1.02 
                  50-400 
                 1-18 
               
               
                   
                 CaCl 2 •2H 2 O 
                 0.6-5.1 
                  50-400 
                 1-18 
               
               
                   
                 Water 
                   
                 600-950 
                  50-1000 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 4 
               
             
            
               
                   
               
               
                 Exemplary solute ranges in a low GDP solution 
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                   
                 Solution  
                   
               
               
                   
                   
                 Concentration 
                 volume 
                 Flow rate 
               
               
                   
                 Component 
                 (g/l) 
                 (ml/L) 
                 (ml/min) 
               
               
                   
                   
               
               
                   
                 Glucose 
                 100-900 
                  50-400 
                 1-18 
               
               
                   
                 Sodium Chloride 
                  13-108 
                  50-400 
                 1-18 
               
               
                   
                 Sodium Lactate 
                 11-90 
                  50-400 
                 1-18 
               
               
                   
                 MgCl 2 •6H 2 O 
                 0.13-1.02 
                  50-400 
                 1-18 
               
               
                   
                 CaCl 2 •2H 2 O 
                 0.6-5.1 
                  50-400 
                 1-18 
               
               
                   
                 Water 
                   
                 600-950 
                  50-1000 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 5 
               
             
            
               
                   
               
               
                 Exemplary solute ranges in icodextrin solution 
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                   
                 Solution  
                   
               
               
                   
                   
                 Concentration 
                 volume 
                 Flow rate 
               
               
                   
                 Component 
                 (g/l) 
                 (ml/L) 
                 (ml/min) 
               
               
                   
                   
               
               
                   
                 Icodextrin 
                 100-850 
                 100-400 
                 2-37 
               
               
                   
                 Sodium Chloride 
                  13-108 
                 100-400 
                 1-18 
               
               
                   
                 Sodium Lactate 
                 11-90 
                 100-400 
                 2-37 
               
               
                   
                 MgCl 2 •6H 2 O 
                 0.13-1.02 
                 100-400 
                 2-37 
               
               
                   
                 CaCl 2 •2H 2 O 
                 0.6-5.1 
                 100-400 
                 2-37 
               
               
                   
                 Water 
                   
                 600-900 
                  50-1000 
               
               
                   
                   
               
            
           
         
       
     
     Although using a single concentrate source  104  in the system requires a fixed ratio of solutes in the generated peritoneal dialysate, a single concentrate source  104  provides certain advantages. Storage requirements are decreased, as only a single concentrate solution needs to be stored for a given dialysate prescription. There is also a lower risk of patient error in adding solutes to the dialysate in the proper amounts. A single concentrate source  104  also requires less supplies, less pumps, and less hardware. Further, because fewer containers are needed, the containers are easier to manage, clean, and disinfect. A higher concentration of solutes in the concentrate source  104  will allow minimization of the container size and maximization of the source water used in PD solution preparation, lowering costs. The limiting factor is mutual solubility of the components, which is generally limited by glucose or icodextrin solubility. The flow rate for the source water can be optimized to adjust the time required to prepare the solution. In the case of on-demand dialysate preparation, a high flow rate is desired to minimize the time needed to prepare the solution. The flow rate limit will be controlled by the metering accuracy of the concentrate pump  105  at the rate required to match the water feed. With a single concentrate source  104 , about 150 ml/exchange can be needed, which corresponds to about 600 ml/day or 4.2 L/week. The concentrate source  104  can be sized depending on the needs of the user, with a larger concentrate source requiring less frequent refilling. 
     The system can also include an additional waste reservoir (not shown in  FIG. 1 ) to collect any waste fluid generated by the water purification module  103  or other components. Alternatively, waste reservoir  121  can also be used to collect any waste fluid generated by the water purification module  103  or other components. The waste reservoir collects effluent generated during disinfection and/or effluent generated by the purification modules, such as a reverse osmosis system. 
     The peritoneal dialysate generation flow path  101  and integrated cycler  110  can be disinfected with a disinfection solution through on-board disinfection if the components of the peritoneal dialysate generation flow path  101  and integrated cycler  110  are to be reused. Disinfection may not be required with a fully disposable peritoneal dialysate generation flow path  101 . The peritoneal dialysate generation flow path  101  and integrated cycler  110  can be configured to form a loop by connecting the portion of the peritoneal dialysate generation flow path  101  that connects to water tank  102  or the direct connection  112  to a water source to the infusion line  124 . The disinfection solution can be introduced into the peritoneal dialysate generation flow path  101  and recirculated through the fluid lines by system pumps  108  and  119 . Alternatively, the peritoneal dialysate generation flow path  101  and integrated cycler  110  can be disinfected separately after disconnection of the integrated cycler  110  from the peritoneal dialysate generation flow path  101 . The disinfection solution can be a citric acid solution, a peracetic acid solution, a bleach solution, or any other disinfection solution known in the art. Disinfectant can be circulated through the flow loop and heated. The disinfectant can be heated to any temperature capable of disinfecting the system, including temperatures of at least 80° C. or greater. The disinfectant can be introduced to the flow loop and recirculated at elevated temperatures to ensure complete disinfection. 
     Solutes can be added to the peritoneal dialysate generation flow path  201  from two or more separate concentrate sources, as shown in  FIG. 2 . The peritoneal dialysate generation flow path  201  can be fluidly connected to a water source and a water purification module upstream of the concentrate sources  202 - 206 , and a sterilization module, an integrated cycler, and optionally a dialysate container downstream of the concentrate sources  202206 , as illustrated in  FIG. 1 . For clarity, these components have been omitted from  FIG. 2 . 
     As illustrated in  FIG. 2 , the concentrate sources  202 - 206  can include one or more ion concentrate sources, such as sodium chloride source  202  containing sodium chloride to be added in a controlled addition to the peritoneal dialysate generation flow path  201  by concentrate pump  207  through valve  212 , sodium lactate source  203  containing sodium lactate to be added in a controlled addition to the peritoneal dialysate generation flow path  201  by concentrate pump  208  through valve  213 , magnesium chloride source  204  containing magnesium chloride to be added in a controlled addition to the peritoneal dialysate generation flow path  201  by concentrate pump  209  through valve  214 , and calcium chloride source  205  containing calcium chloride to be added in a controlled addition to the peritoneal dialysate generation flow path  201  by concentrate pump  210  through valve  215 . One of skill in the art will understand that other ions can be used in formulation of peritoneal dialysate, and each can be contained in a separate ion concentrate source or combined into one or more combined ion concentrate sources. The concentrate source also includes one or more osmotic agent sources, such as dextrose source  206  containing dextrose to be added to the peritoneal dialysate generation flow path  201  by concentrate pump  211  through valve  216 . Any of the concentrate pumps can include flow meters to control the addition of the solutes. A glucose source and/or an icodextrin source can be used in addition to, or in place of, dextrose source  206 . Multiple osmotic agents can be added to the peritoneal dialysate generation flow path  201  from one or more osmotic agent sources. One of skill in the art will understand other solutes can be used alternatively to, or in addition to, the solutes illustrated in  FIG. 2 . A control system in electronic communication with each of the concentrate pumps can control the movement of fluid from the concentrate sources to the peritoneal dialysate generation flow path  201 . The amount of each of the concentrates moved into the peritoneal dialysate generation flow path  201  can be controlled to result in peritoneal dialysate having a prescribed solute concentration, as determined by a doctor or health care provider. The valves  212 - 216  can optionally be replaced with hose T junctions with additional components for preventing backflow into the concentrate source line if that particular line is not being used. Optional sensors  217 ,  218 ,  219 , and  220  ensure the solute concentration in the dialysate is at the correct level after each addition. The sensors  217 - 220  can be any type of sensor appropriate to confirm delivery of the concentrate, such as conductivity sensors. Optional pH sensor  221  can ensure that the pH is a proper level after addition of sodium lactate or other buffer. Optional refractive index meter  222  ensures the dextrose concentration in the dialysate is at the prescribed level. An additional sensor can be included upstream of sodium chloride source  202  for sensing the conductivity of the water prior to addition of concentrates. One of skill in the art will understand that additional sensor arrangements can be used in the described system. Any number of sensors can be included to monitor the peritoneal dialysate concentration, including 1, 2, 3, 4, 5, 6, 7, or more sensors. The concentrate sources can contain the solutes in either solid, powdered, or solution form. A solid or powdered source of solutes can be dissolved by the system by drawing fluid from the peritoneal dialysate generation flow path  201  into the concentrate source to generate a solution with a known concentration, such as a saturated solution of the solutes. During the process of dissolution of the solutes, mechanical, vibration, heating, or other forms of assistance may be used to dissolve the solid or powder solutes. The resulting solution is added to the peritoneal dialysate generation flow path as explained. 
     Although shown as a refractive index meter  222  in  FIG. 2 , one of skill in the art will understand that alternative methods of measuring the osmotic agent concentration can be used, including enzyme based sensors or pulsed amperometric detection. Although illustrated as a single concentrate source in  FIG. 1 , and five separate concentrate sources in  FIG. 2 , one of skill in the art will understand that any number of concentrate sources can generate the peritoneal dialysate, including 1, 2, 3, 4, 5, 6, 7, or more concentrate sources. Any two or more of the separate concentrate sources illustrated in  FIG. 2  can be combined into a single solute source, such as by combining all or some of the ion concentrate sources into a single ion concentrate source where the mixed contents do not cause precipitation of the mixed concentrates. 
     Although each concentrate source is illustrated in  FIG. 2  with a separate concentrate pump and fluid line, one of skill in the art will understand that more than one concentrate source can use a single pump and fluid line, with valves arranged thereon for controlled addition to the peritoneal dialysate generation flow path  201 . 
     The concentrate sources  202 - 206  can be single use concentrate sources or disposable concentrate sources. The disposable concentrate sources are used in a single peritoneal dialysate generation process and then disposed. Multiple use concentrate sources are used repeatedly, and refilled as necessary with the solute. 
     Table 6 provides exemplary, non-limiting, ranges of solutes that can be added to the peritoneal dialysate using a separate osmotic agent source, glucose in Table 6, and a separate ion concentrate source containing sodium chloride, sodium lactate, magnesium chloride, calcium chloride and sodium bicarbonate. Because the glucose is added separately from the ion concentrates, the ratio of glucose to the other solutes can be varied depending on the needs of the patient. 
     
       
         
           
               
             
               
                 TABLE 6 
               
             
            
               
                   
               
               
                 Exemplary ranges of solutes in a  
               
               
                 two-concentrate source system 
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                   
                 Solution 
                   
               
               
                   
                   
                 Concentration  
                 volume 
                 Dialysate 
               
               
                   
                 Component 
                 (g/l) 
                 (ml/L) 
                 composition 
               
               
                   
                   
               
            
           
           
               
               
               
               
               
            
               
                   
                 Part A 
                   
                   
                   
               
               
                   
                 Glucose 
                 850 
                  6-53 
                 0.55-4.5 g/dL 
               
               
                   
                 Part B 
                   
                   
                   
               
               
                   
                 NaCl 
                 269 
                 20 
                  92 mmol/L 
               
               
                   
                 Sodium Lactate 
                 84 
                 20 
                  15 mmol/L 
               
               
                   
                 MgCl 2 •6H 2 O 
                 5 
                 20 
                 0.5 mmol/L 
               
               
                   
                 CaCl 2 •2H 2 O 
                 18 
                 20 
                 2.5 mmol/L 
               
               
                   
                 NaHCO 3   
                 105 
                 20 
                  25 mmol/L 
               
               
                   
                 Water 
                   
                 927-979 
                 56.10 
               
               
                   
                   
               
            
           
         
       
     
     By using multiple concentrate sources, greater individualization and therapy customization can be achieved for each patient. With a single concentrate source, all solutes in the generated peritoneal dialysate must be present in a fixed ratio. By using more than one concentrate source, the ratio of solutes used in the peritoneal dialysate can be altered as the concentration of each of the osmotic agent and ion solutes can be individually controlled. For example, as illustrated by Table 6, with a single ion concentrate source and a single osmotic agent source, peritoneal dialysate with greater or less osmotic agent per concentration of ions can be generated, providing the ability to adjust the tonicity of the peritoneal dialysate solution independently of the electrolyte composition to meet the UF needs of any patient with a single set of solutions and allowing greater control over ultrafiltration. The ultrafiltration rate that results from using the peritoneal dialysate solutions can be altered by altering the concentration of the osmotic agent independently of the ionic solutes, or by changing the osmotic agent used. Because the system is not limited to discrete glucose or other osmotic agent concentrations like known commercial solutions; the system can customize the peritoneal dialysate solutions to meet the ultrafiltration needs of patient as determined by a healthcare provider. As illustrated in Table 6, the glucose level in the peritoneal dialysate solution can be varied from 0.55 g/dL to 4.5 g/dL, while maintaining the electrolytes and buffer components constant, allowing the system to cover the range of glucose formulations currently offered commercially using a single Part A and Part B composition. 
     In certain embodiments, two osmotic agent sources can be used, such as a dextrose source and an icodextrin source. With two osmotic agent sources, one could use dextrose during the daytime exchanges for CAPD and icodextrin during the night dwell to take advantage of the higher UF removal from icodextrin. Conversely, dextrose could be used during the night dwell and icodextrin for the extended daytime dwell in APD systems. 
     By using separate concentrate sources for each solute, complete individualization of the concentrations and ratios of solutes in the peritoneal dialysate can be achieved. Table 7 provides exemplary ranges of solutes that can be used in peritoneal dialysate as made by a system with each solute in a separate concentrate source. An advantage of using separate concentrate sources for each solute is that virtually any peritoneal dialysate solution composition can be prepared from a single set of component formulations. A system with separate concentrate sources for each solute is useful for patients whose prescriptions change periodically due to diet or other factors. Such patients would need to store multiple formulations if using only one or two concentrate sources, and the risk of errors would be increased. 
     
       
         
           
               
             
               
                 TABLE 7 
               
             
            
               
                   
               
               
                 Exemplary dialysate composition from a multi-source system 
               
            
           
           
               
               
               
               
            
               
                   
                   
                 Solution  
                   
               
               
                   
                 Concentration 
                 volume 
                 Dialysate 
               
               
                 Component 
                 (g/l) 
                 (ml/L) 
                 composition 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Part A: Glucose 
                 850 
                  6-53 
                 0.55-4.5 g/dL 
               
               
                 Part B: NaC1 
                 320 
                 15-18 
                  132-134 mmol/L 
               
               
                 Part C: Na Lactate 
                 1000 
                 2-4 
                   15-40 mmol/L 
               
               
                 Part D: MgCl 2 •6H 2 O 
                 500 
                 0.2-0.4 
                  0.5-1.0 mmol/L 
               
               
                 Part E: CaCl 2 •2H 2 O 
                 700 
                 0.5-1.0 
                  2.5-3.5 mmol/L 
               
               
                 Part F: NaHCO3 
                 85 
                  0-34 
                   0-34 mmol/L 
               
               
                 Part G: Icodextrin 
                 1000 
                  0-75 
                   0-7.5 g/dL 
               
               
                 Water 
                   
                 820-971 
                   
               
               
                   
               
            
           
         
       
     
     The one or more concentrate sources can be detachable from the rest of the system for sterilization. The concentrate sources can also be sterilized each time the concentrate sources are filled with new concentrate solutions. Further, the concentrate sources can be sterilized after a set number of uses, or after a set period of time. Moreover, the concentrate sources and the remaining components including the fluid lines of the peritoneal dialysate generation system can be sterilized without any of the components by passing a disinfection solution, such as a citric acid, peracetic acid, or bleach solution, through all of the lines and containers of the system. 
       FIG. 3  illustrates an overview of generating peritoneal dialysate in accordance with the invention. Water from a water source  301  can be purified by a water purification module  302 , as explained. Concentrates from a single concentrate source  303 , which can contain both ion concentrates and one or more osmotic agents, can be added to the purified water to generate a non-sterile peritoneal dialysate solution  304 . The non-sterile peritoneal dialysate solution  304  is sterilized by a sterilization module  305 , which may include an ultrafilter (not shown). As explained, the peritoneal dialysate can be further purified by additional components in the sterilization module  306 , such as by ultrafiltration with a second ultrafilter, by a microbial filter, or by an optional UV light source, to generate a sterilized peritoneal dialysate  307 . The sterilized peritoneal dialysate  307  can be stored or used by any method described herein, including by immediately infusing the peritoneal dialysate into a patient  308 , or dispensing the peritoneal dialysate into a dialysate container for later use in peritoneal dialysis  309 , as illustrated in  FIG. 1 . 
       FIG. 4  illustrates an overview of generating peritoneal dialysate with multiple concentrate sources. Water from a water source  401  can be purified by a water purification module  402 , as explained. Concentrates from an ion concentrate source  403 , which can contain sodium, magnesium, calcium, and bicarbonate, as well as any other ions to be used in peritoneal dialysis, can be added to the purified fluid. An osmotic agent, such as dextrose, can be added from a first osmotic agent concentrate source  404 . A second osmotic agent, such as icodextrin, can be added from a second osmotic agent concentrate source  405 . As illustrated in  FIG. 2 , any number of concentrate sources can be used for further individualization of the peritoneal dialysate, including separate sources for each of the ions used. After addition of the ion and osmotic agent concentrates, the fluid contains all necessary components for use in peritoneal dialysis as non-sterilized peritoneal dialysate  406 . The non-sterile peritoneal dialysate  406  can be sterilized by a sterilization module  407 , which can include an ultrafilter or other sterilization components. The peritoneal dialysate can be further sterilized by the sterilization module  408 , either by ultrafiltration with a second ultrafilter, a microbial filter, or further sterilized with an optional UV light source, to generate a sterilized peritoneal dialysate  409 . The sterilized peritoneal dialysate  409  can be stored or used by any method described herein, including by immediately infusing the peritoneal dialysate into a patient  410 , or dispensing the peritoneal dialysate into a dialysate container for later use in peritoneal dialysis  411 , as illustrated in  FIG. 1 . 
       FIG. 5  illustrates an alternative peritoneal dialysate generation flow path  501  with an integrated cycler  539 . Water from a water source  502  can be pumped through filter  503  by system pump  504 . The filter  503  can remove any particulate matter from the water prior to entering the peritoneal dialysate generation flow path  501 . The water is then pumped through a water purification module, illustrated as a sorbent cartridge  506  in  FIG. 5 . As described, the water purification module can alternatively or additionally include activated carbon, a reverse osmosis module, a carbon filter, an ion exchange resin, and/or a nanofilter. The water enters the sorbent cartridge  506  through sorbent cartridge inlet  507  and exits through sorbent cartridge outlet  508 . Pressure sensor  505  measures the pressure across sorbent cartridge  506 . Filter  509  removes any particulate matter in the fluid after exiting sorbent cartridge  506 . A conductivity sensor  510  determines the conductivity of the fluid exiting sorbent cartridge  506  to ensure the water has been purified. To generate the peritoneal dialysate, concentrates are added from concentrate source  513  through concentrate connector  514  by concentrate pump  515 . Although shown as a single concentrate source  513  in  FIG. 5 , concentrates can be added from any number of separate concentrate sources. Concentrate filter  512  removes any particulate matter from the concentrate before entering the peritoneal dialysate generation flow path  501 . A conductivity sensor  516  determines the conductivity of the generated peritoneal dialysate after addition of the concentrates to ensure the peritoneal dialysate has the correct solute concentrations. Flow sensor  511  determines the flow rate of the fluid after addition of the concentrates. pH sensor  524  determines the pH of the peritoneal dialysate to ensure the peritoneal dialysate has a proper pH. The peritoneal dialysate can be heated to a desired temperature by heater  525 . Temperature sensor  528  ensures the peritoneal dialysate is heated to an appropriate temperature before infusion into the patient  538 . The heater  525  can be placed at any location in the flow path prior to delivery to the patient  538 . In any embodiment, the heater  525  can be located after the exit of the sterilization module, particularly if fluid is stored prior to passing through the sterilization module. The desired temperature of the peritoneal dialysate can be between around 20° C. to around 41° C. As used herein, around 20° C. can include between 19.0° C. and 21.0° C., and around 41° C. can include between 39.0° C. and 41.0° C., or similar as understood by those of skill in the art. In certain embodiments, the desired temperature can be between around 25° C. to around 40° C., around 36.5° C. to around 37.25° C., around 25° C. to around 35° C., or around 30° C. to around 40° C. In a preferred embodiment, the desired temperature can be 37±2° C. 
     As described, the peritoneal dialysate is sterilized by pumping the peritoneal dialysate through a sterilization module, which can include first ultrafilter  518 , and optionally a second ultrafilter  520  and/or an optional UV light source (not shown). Pressure sensor  517  measures the fluid pressure prior to the fluid entering the sterilization module, shown as ultrafilters  518  and  520 , and is used in the control circuit to control the pressure. The fluid passes through first ultrafilter  518 , through valve  519 , and then through second ultrafilter  520 . Connector  523 , three way valve  521 , and valve  519  allow backflushing and disinfection of the ultrafilters  518  and  520 . The fluid is then pumped into the integrated cycler  539  for use in peritoneal dialysis. As described, the system can include a dialysate container (not shown) for storage of the generated peritoneal dialysate until used by the patient  538  at any location, including upstream or downstream of the sterilization module. 
     The integrated cycler  539  includes an infusion line  531  and a drain line  533 . Bubble trap  526  traps air bubbles present in the heated dialysate. The air is vented from the system through bubble trap valve  527 . Pressure sensor  529  ensures the pressure of the fluid is within a predetermined range. The infusion line  531  is connected to a three-way valve  530 , which controls fluid movement between the infusion line  531 , the patient  538 , and the drain line  533 . The three way valve  530  is connected through connector  532  to a catheter inserted into the peritoneal cavity of the patient  538 . A filter  522  can be included between the three-way valve  530  and the catheter for additional cleaning of the peritoneal dialysate prior to entering a patient  538 . In any embodiment, the filter  522  can be a disposable filter. The peritoneal dialysate is infused into the patient  538  and held for a dwell period. After the dwell period, the fluid is pumped out of the peritoneal cavity of the patient  538  by drain pump  536 . The three-way valve  530  is switched to direct fluid into the drain line  533 . Pressure sensor  534  measures the pressure of fluid in the drain line  531  to ensure proper drainage. Flow meter  535  measures the flow rate and volume of fluid removed from the patient  538 . The drain line  531  is connected to a drain or waste reservoir  537  through connector  540  for collection and disposal of the used peritoneal dialysate. 
     For automated disinfection of the system, connector  540  can be connected to connector  523  to form a flow loop. Disinfectant can be circulated through the flow loop and heated. The disinfectant can be heated to any temperature capable of disinfecting the system, including temperatures of at least around equal to 80° C. or greater (≧80) when using citric acid as a disinfectant. Peracetic acid or bleach can be used to disinfect the system at room temperature. The disinfectant can be introduced to the flow loop and recirculated at elevated temperatures to ensure complete disinfection. The disinfectant used can be any suitable disinfectant known in the art, including peracetic acid, citric acid, or bleach. The connectors and components of the system can be gamma and autoclave compatible to resist the high temperatures used during disinfection. The system can be primed by introducing a priming fluid to the peritoneal dialysate generation flow path  501  and integrated cycler  539 . 
       FIG. 6  illustrates an alternative embodiment of the system. Fluid from a water source, such as water tank  602 , can be pumped into the peritoneal dialysate generation flow path  601 . Additionally, or as an alternative to a water tank  602 , the system can use a direct connection to a water source  612 . System pump  608  can control the movement of fluid through the peritoneal dialysate generation flow path  601 . If a direct connection to a water source  612  is used, a pressure regulator  613  can ensure that an incoming water pressure is within a predetermined range. The system pumps the fluid from water source  602  or  612  through a water purification module  603  to remove chemical contaminants in the fluid in preparation for creating dialysate. 
     After the fluid passes through the water purification module  603 , the fluid is pumped to a concentrate source  604 , where necessary components for carrying out peritoneal dialysis can be added from the concentrate source  604 . The concentrates in the concentrate source  604  are utilized to create a peritoneal dialysis fluid that matches a dialysis prescription. Concentrate pump  605  and concentrate valve  611  can control the movement of concentrates from the concentrate source  604  to the peritoneal dialysate generation flow path  601  in a controlled addition. Alternatively, concentrate valve  611  can be a hose T or backflow restricting hose T. The concentrates added from the concentrate source  604  to the peritoneal dialysate generation flow path  601  can include components required for use in peritoneal dialysate. Upon addition of solutes from the concentrate source  604 , the fluid in the peritoneal dialysate generation flow path  601  can contain all the necessary solutes for peritoneal dialysis. The peritoneal dialysate should reach a level of sterility for peritoneal dialysis, as described. As shown in  FIG. 6 , the sterilization module can include one or more of a first ultrafilter  607 , a second ultrafilter  609 , and a UV light source  606 . 
     The generated peritoneal dialysate can be pumped directly to an integrated cycler  610  for immediate infusion into a patient  634 . Alternatively, the dialysate can be pumped to an optional dialysate container  614  as a pre-prepared bolus of solution for storage until ready for use by a patient  634 . Valve  616  can control the movement of fluid to either the dialysate container  614 . Stored dialysate in dialysate container  614  can be pumped as needed to back into the peritoneal dialysate generation flow path  601  by pump  615  through valve  617 . The dialysate container  614  can store enough peritoneal dialysate for a single infusion of peritoneal dialysate into the patient  634 , or enough peritoneal dialysate for multiple or continuous infusions into one or multiple patients. 
     The generated peritoneal dialysate can be pumped to valve  637 . Valve  637  can control movement of the peritoneal dialysate to any of three options. First, the peritoneal dialysate can be pumped to integrated cycler  610 , second diverted for use with a non-integrated external cycler  639 , or third diverted to a dialysate container  640 . All three options can be performed contemporaneously or selectively. If diverted to the non-integrated external cycler  639 , the peritoneal dialysate can be pumped via valve  638 . Valve  638  can control the movement of the peritoneal dialysate through either a direct connection to an external cycler  639  or to a dialysate container  640 . Alternative valve and pump configurations for performing the same functions are contemplated by the present invention. For example, the direct connection to an external cycler  639  can use any type of connector known in the art. The connectors can be single-use or reusable connectors and should provide for sterile transfer of fluids. The connectors should preferably be closed connectors, to avoid contact between the fluids and the external environment. A non-limiting example of a connector that can be used for a direct connection to an external cycler is the INTACT® connectors provided by Medinstill Development LLC, Delaware, US. The dialysate container  640  can be heated with an optional heater  641  and then used in peritoneal dialysis. The connectors to the dialysate container  640  can be any type of connector known in the art. The connectors can be single use or disposable connectors that provide transfer of sterile fluids. A non-limiting example of connectors that can be used with the described system is the Lynx®-Millipore connectors available from Merck KGaA, Darmstadt, Germany. 
     The integrated cycler  610  can include a metering pump  619  for metering peritoneal dialysate into the peritoneal cavity of the patient  634 . A heater  618  heats the peritoneal dialysate to a desired temperature prior to infusion into the patient  634 . A pressure regulator  620  ensures the peritoneal dialysate pressure is within a predetermined range safe for infusion into the patient  634 . The metering pump  619  can use any safe pressure for infusing fluid into the patient  634 . Generally, the pump pressures are on average set at ±10.3 kPa or 77.6 mmHg. If there is no fluid flow, the maximum pressure can increase to ±15.2 kPa or 113.8 mmHg for a short period, such as less than 10 seconds. The peritoneal dialysate is infused into the peritoneal cavity of the patient  634  through infusion line  624 . After a dwell period, the peritoneal dialysate is drained from the patient  634  through drain line  623 . Pump  622  provides a driving force for removing the peritoneal dialysate from the patient  634 . An optional waste reservoir  621  can be included to store the used peritoneal dialysate for disposal. Alternatively, the drain line  623  can be directly connected to a drain for direct disposal. The waste reservoir  621  can be any size, including between around 12 and around 20 L. For patients requiring a higher drainage, a drain manifold can be included for connecting multiple waste reservoirs. 
     Various sensors positioned in the peritoneal dialysate generation and infusion system ensure that the generated fluid is within predetermined parameters. Flow meter  635  ensures the incoming water is at a correct flow rate, while pressure sensor  636  ensures the incoming water is at an appropriate pressure. Conductivity sensor  625  is used to ensure that the water exiting water purification module  603  has been purified to a level safe for use in peritoneal dialysis. Conductivity sensor  626  ensures the conductivity of the dialysate after the addition of concentrates from concentrate source  604  is within a predetermined range. Refractive index sensor  627  insures that the concentration of the osmotic agents is within a predetermined range. pH sensor  628  ensures the pH of the peritoneal dialysate is within a predetermined range. After passing through the sterilization module including second ultrafilter  609 , pH sensor  629  and conductivity sensor  630  are used to ensure that no changes in the pH or conductivity have occurred during purification or storage of the dialysate in dialysate container  614 . The integrated cycler  610  has flow meter  631 , pressure sensor  632  and temperature sensor  633  to ensure that the dialysate being infused into the patient  634  is within a proper flow rate, pressure, and temperature range. 
       FIGS. 7A-D  illustrate a non-limiting embodiment of the peritoneal dialysate generation system arranged as a peritoneal dialysate generation cabinet  801 .  FIG. 7A  illustrates a perspective view of the peritoneal dialysate generation cabinet  801 ,  FIG. 7B  illustrates a front view of the peritoneal dialysate generation cabinet  801 ,  FIG. 7C  illustrates a side view of the peritoneal dialysate generation cabinet  801 , and  FIG. 7D  illustrates a back view of the peritoneal dialysate generation cabinet  801 . 
     A fluid line  805  can connect a water source  804  to the peritoneal dialysate generation cabinet  801 . The fluid line  805  can enter through a connector  828  in a top  806  of the water source  804 . The fluid line  805  connects to the peritoneal dialysate generation flow path as described with reference to  FIGS. 1 and 5-6  through a back of the peritoneal dialysate generation cabinet  801  through connector  832  having a fitting  833  for holding the fluid line  805 , as illustrated in  FIG. 7D . Any of the fluid lines illustrated can be disconnected and removed from the system for cleaning and replacement. A pump (not shown) can provide a driving force for the movement of fluid throughout the peritoneal dialysate generation flow path if required. Water is pumped through the peritoneal dialysate generation cabinet  801  to a water purification module, shown as sorbent cartridge  812  in  FIGS. 7A-B . The water can enter the sorbent cartridge  812  through tubing (not shown) connected to the bottom of the sorbent cartridge  812  within the peritoneal dialysate generation cabinet  801 . The water exits the sorbent cartridge  812  through connector  813  and tubing  814 . An osmotic agent from osmotic agent source  815  and an ion concentrate from an ion concentrate source  817  are added to the fluid as described to generate non-sterilized peritoneal dialysate. The osmotic agent concentrate is added to the fluid through paddle connector  816 . The ion concentrate is added to the fluid through paddle connector  818 . A concentrate pump (not shown) can provide a driving force to move fluid from the concentrate sources into the peritoneal dialysate generation flow path inside of the peritoneal dialysate generation cabinet  801 . As described, the system can use a single ion concentrate source in place of the two sources shown in  FIGS. 7A-B , or more than two concentrate sources. The generated peritoneal dialysate can then be pumped through a sterilization module (not shown), such as an ultrafilter. A second ultrafilter and/or a UV light source can also be included. An integrated cycler (not shown in  FIGS. 7A-D ) can then pump the dialysate into infusion line  819  through connector  820  and into the patient. Fitting  825  allows the infusion line  819  to be removed from the system for cleaning or replacement. Waste fluids can be pumped out of the system through waste line  807 , which connects to the peritoneal dialysate generation cabinet  801  through connector  830  having fitting  831 . A separate waste line for removing used dialysate from the patient (not shown in  FIGS. 7A-D ) can also connect to the peritoneal dialysate generation cabinet  801  and connect to waste line  807 . The waste line  807  enters waste container  808  through a connector  829  in the top  809  of the waste container  808 . Handles  810  and  811  can be included on water source  804  and waste container  808  for easy movement and storage. Although the peritoneal dialysate generation cabinet  801  is illustrated on top of table  826  in  FIGS. 8A-D , the peritoneal dialysate generation cabinet  801  can be used on any stable flat surface. 
     As described, the peritoneal dialysate generation flow path can include various sensors for detection of conductivity, pH, refractive index, or other dialysate parameters. The sensors can be included either inside or outside of the body of the peritoneal dialysate generation cabinet  801 . The fluid lines and valves connecting the components of the peritoneal dialysate generation flow path can likewise be positioned inside of the cabinet body. As described, a top of the peritoneal dialysate generation cabinet  801  can have a graphical user interface  802  including screen  803 . Messages from the control system to the user, or from the user to the control system, can be generated and read through the graphical user interface  802 . The user can direct the generation of peritoneal dialysate through the graphical user interface  802 , and can receive messages from the system through screen  803 . The system can generate alerts to the user, including any problems detected by any of the sensors, as well as the progress of peritoneal dialysate generation. A handle  824  can be included for opening the peritoneal dialysate generation cabinet  801  to allow access to components on the inside of the cabinet. Handles  821  and  823  can be included to hold the fluid lines and power cord when not in use. 
     Disinfection connector  822  illustrated in  FIGS. 7A and 7C  can be included for disinfection of the waste line  807 . During disinfection, the waste line  807  can be disconnected from waste container  808  and connected to disinfection connector  822 . Disinfectant solution from a disinfectant source (not shown in  FIGS. 7A-D ) can then be circulated through the waste line  807  to disinfect the waste line  807 . Disinfection connector  827  can be included for disinfection of fluid line  805 . Fluid line  805  can be connected to disinfection connector  822  and disinfection solution can be circulated through the fluid line  805 . Drain  834  on water source  804  and drain  835  on waste container  808 , allow the water source  804  and waste container  808  to be drained without inverting the containers. 
       FIG. 8  illustrates a peritoneal dialysate generation cabinet  901  using a non-purified water source, faucet  905  in sink  904 . Although illustrated as faucet  905  and sink  904 , one of ordinary skill in the art will understand that any water source can be used. The ability to use municipal or other non-purified sources of water allow the peritoneal dialysate generation system to work at a patient&#39;s home without the need to store large amounts of purified water or dialysate. Fitting  906  connects the water line  907  to the faucet  905  or other water source, allowing the water line  907  to be connected or disconnected as necessary. A pump (not shown) can provide a driving force for the movement of fluid throughout the peritoneal dialysate generation flow path as described with respect to  FIGS. 1 and 5- 6 . The water is pumped through the peritoneal dialysate generation cabinet  901  to a water purification module, shown as sorbent cartridge  911  in  FIG. 8 . The water enters the sorbent cartridge  911  through tubing (not shown) connected to the bottom of the sorbent cartridge  911  within the peritoneal dialysate generation cabinet  901 . The water exits the sorbent cartridge  911  through connector  926  and tubing  912 . An osmotic agent from osmotic agent source  913  and an ion concentrate from an ion concentrate source  914  are added to the fluid as described to generate non-sterilized peritoneal dialysate. The osmotic agent concentrate is added to the fluid through paddle connector  916 . The ion concentrate is added to the fluid through paddle connector  915 . A concentrate pump (not shown) can provide a driving force to move fluid from the concentrate sources into the peritoneal dialysate generation flow path inside of the peritoneal dialysate generation cabinet  901 . As described, the system can use a single ion concentrate source in place of the two sources shown in  FIG. 8 , or more than two concentrate sources. The generated peritoneal dialysate can then be pumped through a sterilization module (not shown), such as an ultrafilter. A second ultrafilter and/or a UV light source can also be included. An integrated cycler (not shown in  FIG. 8 ) can then pump the dialysate into infusion line  917  through connector  918  and into the patient. Fitting  919  allows the infusion line  917  to be removed from the system for cleaning or replacement. Waste fluids can be pumped out of the system through waste line  908 , which can connect to a drain  909  shown in bathtub  910 . A separate drain line (not shown) from the patient can be included to move used dialysate into the drain  909 . Although shown as a bathtub drain  909  in  FIG. 8 , the waste fluids can be conveyed to any type of drain, or alternatively to a waste container as illustrated in  FIGS. 7A-D . Although the peritoneal dialysate generation cabinet  901  is illustrated on top of table  924  in  FIG. 8 , the peritoneal dialysate generation cabinet  901  can be used on any stable flat surface. In certain embodiments, the peritoneal dialysate generation cabinet  901  and the patient can be in the same room as the water source and drain  909 . Alternatively, the patient and/or peritoneal dialysate generation cabinet  901  can be in a separate room, with tubing long enough to reach patient. For longer distances, the tubing should be strong enough to withstand the pressures necessary in pumping fluid over longer distances. 
     As described, a top of the peritoneal dialysate generation cabinet  901  can have a graphical user interface  902  including screen  903 . Messages from the control system to the user, or from the user to the control system, can be generated and read through the graphical user interface  902 . The user can direct the generation of peritoneal dialysate through the graphical user interface  902 , and can receive messages from the system through screen  903 . The system can generate alerts to the user, including any problems detected by any of the sensors, as well as the progress of peritoneal dialysate generation. A handle  920  can be included for opening the peritoneal dialysate generation cabinet  901  to allow access to components on the inside of the cabinet. Handles  921  and  923  can be included to hold the fluid lines and power cord when not in use. 
     Disinfection connector  922  can be included for disinfection of the waste line  908 . During disinfection, the waste line  908  can be disconnected from the drain  909  and connected to disinfection connector  922 . Disinfectant solution from a disinfectant source (not shown in  FIG. 8 ) can then be circulated through the waste line  908  to disinfect the waste line  908 . Disinfection connector  925  can be included for disinfection of water line  907 . The water line  907  can be disconnected from faucet  905  and connected to disinfection connector  925 . Disinfectant solution can be circulated through the water line  907  for disinfection. 
       FIG. 9  illustrates an alternative non-limiting embodiment of a peritoneal dialysate generation flow path  1111 . Water from water source  1101  can be pumped into the peritoneal dialysate generation flow path  1111  by system pump  1103  through connector  1165 . Although shown with screw top  1166  in  FIG. 9 , any method can be used with the water source  1101  to fill and drain the water source  1101 . The water can be pumped through filter  1102  to remove any particulate matter from the water prior to entering the peritoneal dialysate generation flow path  1111 . Alternatively, a dedicated water source, such as a tap or a municipal water source, can be used in place of water source  1101 . Pressure sensor  1104  measures the pressure upstream of sorbent cartridge  1105 . In certain embodiments, an alternative water purification module can be used in place of sorbent cartridge  1105 , including a reverse osmosis module, a nanofilter, a combination of ion and anion exchange materials, activated carbon, silica, or silica based columns. The shading in sorbent cartridge  1105  shows varying layers of sorbent material. However, any order of sorbent material layers can be used, or the sorbent materials can be intermixed. In  FIG. 9 , the sorbent cartridge  1105  has a fluid inlet  1164  and fluid outlet  1163  in a base of the sorbent cartridge  1105 . In certain embodiments, the fluid inlet  1164  and fluid outlet  1163  can instead be on opposite sides of the sorbent cartridge  1105 . A filter  1106  can remove particulate matter in the fluid exiting sorbent cartridge  1105 . 
     A first conductivity sensor  1107  can measure the conductivity of the fluid exiting sorbent cartridge  1105 . One or more infusates can be added from ion concentrate source  1109  through connector  1162  to infusate line  1110  by infusate pump  1112  to the peritoneal dialysate generation flow path  1111  at T-junction  1150 . Filter  1151  can remove any particulate matter from the infusate concentrate prior to reaching the peritoneal dialysate generation flow path  1111 . Alternatively, a valve can be used in place of T-junction  1150 . A second conductivity sensor  1108  can measure the conductivity of the fluid after addition of the infusates to ensure proper concentrations of each infusate. As described, the system can include any number of infusate sources, each with the same or separate infusate pumps and infusate lines. 
     An osmotic agent pump  1115  can add an osmotic agent to the peritoneal dialysate generation flow path  1111  through infusate line  1117  at T-junction  1156 . A filter  1152  can remove any particulate matter from the osmotic agent concentrate. As illustrated in  FIG. 9 , the system can have multiple osmotic agent sources, including dextrose source  1148  fluidly connected to osmotic agent line through connector  1154  and icodextrin source  1114  fluidly connected to osmotic agent line through connector  1160 . Filter  1153  can remove particulate matter from fluid exiting dextrose source  1148  and filter  1161  can remove particulate matter form fluid exiting icodextrin source  1114 . Alternative osmotic agent sources, including an amino acid source or a glucose source, can be used in place of, or in addition to, the dextrose source  1148  and icodextrin source  1114 , allowing customization of the osmotic agents used. Valve  1116  can control the source from which the osmotic agent is obtained. Alternatively, multiple osmotic agent lines and osmotic agent pumps can be started or stopped to prevent and direct flow to a desired flow path or component. A flow sensor  1118  measures the flow rate of fluid through the peritoneal dialysate generation flow path  1111 . A composition sensor  1119  can measure the concentrations of the osmotic agents in the fluid, as well as the infusates. The composition sensor can include a single sensor, or multiple sensors measuring separate fluid parameters. 
     Heater  1120  heats the fluid in the peritoneal dialysate generation flow path  1111  to the patient body temperature. Temperature sensor  1121  measures the temperature of the fluid and can be used to by a control system to control the heater  1120 , heating the fluid to a temperature of between around 20° C. to around 41° C. In a preferred embodiment, the desired temperature can be 37±2° C. or between 36.5° C. to 37.25° C. A control system can monitor the temperature and shut off flow or generate an alarm if the temperature is outside of the desired range. In certain embodiments, the control system can shut off flow if the temperature is equal to greater than around 41° C. Pressure sensor  1122  measures the pressure of the fluid prior to entering a dialysate sterilization module. 
     The dialysate sterilization module can include a first ultrafilter  1123  and a second ultrafilter  1124  fluidly connected by fluid line  1159 . The fluid flows through both ultrafilters to remove any chemical or biological contaminants. Waste fluid can exit the first ultrafilter  1123  through fluid line  1130  and exit the second ultrafilter  1124  through fluid line  1129 . Valves  1149  and  1128  control the movement of fluid between the first ultrafilter  1123  and second ultrafilter  1124  into waste line  1131 , which is fluidly connected to fluid line  1130  at T-junction  1167 . Valves  1149  and  1128  can be used to modulate the fluid movement out of ultrafilters  1123  and  1124  to ensure sufficient pressure for ultrafiltration. If the pressure in ultrafilter  1124  decreases below a necessary value, valve  1128  can be closed, preventing fluid movement from ultrafilter  1123  into fluid line  1130  and increasing the pressure in ultrafilter  1124 . The waste line  1131  is fluidly connected to a waste line  1134  at T-junction  1168  and to waste reservoir  1133  through connector  1169 , or alternatively, to a drain. Although shown with a screw top  1170  and tap  1171 , one of skill in the art will understand that alternative methods for filling and draining waste reservoir  1133  can be used. 
     Fluid exiting the second ultrafilter  1124  passes through optional control valve  1125 . Control valve  1125  can selectively direct fluid into either fluid line  1113  and an integrated cycler or into fluid line  1126  for addition to the dextrose source  1148  and icodextrin source  1114  via T-junction  1155 . The fluid can be added to dextrose source  1148  and icodextrin source  1114  to dissolve solid icodextrin and solid dextrose prior to generating the peritoneal dialysate. 
     Fluid line  1113  can include a pressure sensor  1127  to ensure that the fluid pressure is within predetermined limits prior to entering the integrated cycler. Valve  1135  controls the movement of fluid from the sterilization module. Valve  1136  controls the movement of fluid into and out of the integrated cycler through cycler line  1138 . 
     The cycler line  1138  can include a second temperature sensor  1139  to ensure the proper temperature of the peritoneal dialysate prior to infusion into the patient  1147 . An air detector  1141  is included to detect any air that would otherwise be introduced into the patient  1147 . A bubble trap (not shown) can be included to remove any detected air. A flow sensor  1143  measures the flow rate of fluid in the cycler line  1138  and can be used to control the amount of peritoneal dialysate infused into the patient  1147 . A pressure sensor  1142  can be included to ensure the fluid pressure in cycler line  1138  is within predetermined limits for infusion into the patient  1147 . A catheter  1140  can connect to the cycler line  1138  at connection  1144 . In certain embodiments, a heparin syringe  1146  can be included to add heparin or other medication to the peritoneal dialysate. Filter  1145  removes any particulate matter prior to infusion into the patient  1147 . 
     After a dwell period, the spent peritoneal dialysate can be drained from the patient  1147  through the cycler line  1138 . Drain pump  1132  can provide the driving force for draining the spent peritoneal dialysate. The spent peritoneal dialysate passes through valves  1136  and  1137  and into drain line  1134 , which can fluidly connect to waste reservoir  1133  or to a drain. 
     As illustrated in  FIG. 9 , the peritoneal dialysate generation system can include a purity control system having a first ultrafilter  1123  and second ultrafilter  1124  for sterilization of the peritoneal dialysate, as well as control valve  1125 , valves  1128 ,  1135 , and  1149 , pressure sensors  1122  and  1127 , and fluid lines  1113 ,  1126 ,  1129 ,  1130 ,  1131 , and  1159 , as indicated by dashed box  1173 . The peritoneal dialysate generation system can include the water source  1102 , sorbent cartridge  1105 , peritoneal dialysate generation flow path  1111 , heater  1120  and temperature sensor  1121  as indicated in dashed box  1172 . The second ultrafilter  1124  can be fluidly connected to control valve  1125 , which is fluidly connected to fluid lines  1113  and  1126 . The generated peritoneal dialysate is selectively directed by control valve  1125  to valve  1135  and the integrated cycler for infusion into the patient  1147 . Prior to generation of the peritoneal dialysate, icodextrin source  1114  and dextrose source  1148  can contain solids. Water from water source  1101  can be added to icodextrin source  1114  and dextrose source  1148  to generate dextrose or icodextrin concentrates having a known concentration. To ensure that the icodextrin source  1114  and dextrose source  1148  remain free from chemical or biological contamination, the water can first be passed through the purity control system, including first ultrafilter  1123  and second ultrafilter  1124  prior to addition to the osmotic agent sources. Control valve  1125  can selectively direct the water from the second ultrafilter  1124  through fluid line  1126  and into each of icodextrin source  1114  and dextrose source  1148  via infusate line  1117  to generate osmotic agent concentrates free from contamination. As described, the peritoneal dialysate generation system can include any number of osmotic agent sources, wherein the second ultrafilter  1124  can be fluidly connected to each osmotic agent source. Although not illustrated in  FIG. 9 , the second ultrafilter  1124  can also be fluidly connected to the ion concentrate source  1109  to generate an infusate concentrate free from chemical or biological contamination. Pumping water from the second ultrafilter  1124  to the icodextrin source  1114  and dextrose source  1148  also allows the use of heated water in generating the osmotic agent concentrates. The water can be heated by heater  1120  prior to pumping the water through the purity control system. Using heated water can speed up the dissolution of the osmotic agents to generate osmotic agent concentrates more quickly. By using solid dry powders as the osmotic agent sources, which are then dissolved with sterilized water, the formation of glucose degradation products is reduced, which can preserve peritoneal membrane function and allow patients to remain on peritoneal dialysis for a longer period of time and with higher quality of life, due to fewer complications related to chronic inflammation of the peritoneum. Optional Vibration plate  1157  can agitate the solution in icodextrin source  1114 , and optional vibration plate  1158  can agitate the solution in dextrose source  1148  to further speed dissolution of the osmotic agents. One of skill in the art will understand that alternative means of agitation can be used, including stirrers or other mixers. 
     The purity control system can also include a pressure sensor  1122  in the fluid line fluidly connecting the first ultrafilter  1123  to the peritoneal dialysate generation flow path  1111 . Proper use of the ultrafilters can require a specific pressure range for the fluid flowing through the purity control system. Pressure sensor  1122  can be in communication with a control system that can stop or change the rate of the system pump  1103  to adjust a peritoneal dialysate flow rate if the pressure is outside of the predetermined range. In certain embodiments, the control system can adjust the peritoneal dialysate flow rate to maintain a pressure of between . . . 
     Pressure sensor  1127  measures the pressure of the fluid exiting second ultrafilter  1124 . The pressure of fluid exiting second ultrafilter  1124  must be within a safe range for infusion into the patient  1147 . A control system can control the system pump  1103  to adjust the peritoneal dialysate flow rate and maintain the pressure within a predetermined range exiting the second ultrafilter  1124 . In certain embodiments, the system can automatically generate an alert if the pressure at either or both of pressure sensor  1127  or  1122  is outside of a predetermined range. In certain embodiments, the control system can adjust the peritoneal dialysate flow rate to maintain a pressure of between −200 mmHg to 500 mmHg, from −50 mmHg to 100 mmHg, from 0 mmHg to 100 mmHg, from 31 50 mmHg to 200 mm Hg, from 200 mmHg to 500 mmHg, or from 100 mmHg to 400 mmHg. 
     One skilled in the art will understand that various combinations and/or modifications and variations can be made in the described systems and methods depending upon the specific needs for operation. Moreover, features illustrated or described as being part of an aspect of the invention may be used in the aspect of the invention, either alone or in combination, or follow a preferred arrangement of one or more of the described elements.