Abstract:
A method for renal replacement therapy includes priming a fluid circuit and recirculating the sterile fluid during priming to permit gas to float out of the sterile fluid into a fluid reservoir. The fluid is preferably either warmed during circulation or vibrated to promote the removal of gas.

Description:
REFERENCE TO RELATED APPLICATIONS 
     This is a divisional application Ser. No. 10/650,935, filed Aug. 27, 2003, now U.S. Pat. No. 7,214,312, which is a continuation-in-part of Ser. No. 09/905,246, filed Jul. 12, 2001, now U.S. Pat. No. 6,649,063, the entireties of which are hereby incorporated by reference. 
    
    
     FIELD OF THE INVENTION 
     The present invention relates generally to medical devices and methods for renal replacement therapy and also to various safety features, particularly related to ensuring a low rate of pyrogenic material in infusible fluids. 
     BACKGROUND OF THE INVENTION 
     Patients undergoing hemofiltration, hemodialysis, hemodiafiltration, ultrafiltration, or other form of renal replacement therapy need replacement fluid, dialysate, or infusate which is free of biological contaminants. Given the large amount of purified fluid needed by such therapies and the current method of spiking multiple bags of replacement fluid, dialysate, or infusate, there is a risk of touch contamination resulting in the introduction of biological contaminants into the fluids. Making the appropriate connections, then filtering the fluid greatly reduces this risk to the patient. It would be advantageous if the same equipment used in renal replacement therapy, such as hemofiltration, could be reconfigured for on-line decontamination of prepackaged solutions such as dialysate to produce the large volumes of purified replacement fluid required for the therapy. 
     Presently methods to produce volumes of dialysate from tap water are known, but require complex water purification/standardization equipment, since impurities and cleaning additives such as chlorine vary greatly in tap water from municipality to municipality and within a municipality over time. (See Twardowski U.S. Pat. Nos. 6,146,536 and 6,132,616.) 
     Moreover, dialysate solution, whether prepared online or prepackaged, while of the proper concentration for use as a purified replacement fluid, is not deemed to be sufficiently free of pathogenic contaminants to allow the injection of such a fluid into a patient. In hemodialysis, the dialysate never enters the patient&#39;s body, but instead flows past a semipermeable membrane that permits impurities in the blood to osmose through the membrane from the higher concentration blood to the lower concentration dialysate. Thus dialysate, intended for extracorporeal use only, is less expensive than solutions prepared as replacement fluids, which will be injected into a patient. 
     Attempts to render dialysate sufficiently purified for use as a replacement fluid in hemofiltration and hemodiafiltration have focused on a continuous sterilization process that requires a separate dialysate filtration/purification apparatus that must be periodically purged and verified to provide sufficient constant flow of purified replacement fluid required for hemofiltration. (See Chavallet U.S. Pat. Nos. 6,039,877 and 5,702,597.) Such devices are necessarily complicated and require separate pumping systems for the sterilization process. 
     At least one prior art reference U.S. Pat. No. 6,280,632B1 shows purified replacement fluid being created during dialysis treatment by filtering the dialysate online. However, the technique shown requires a filter for this purpose. Since it is desirable, for safety reasons to make as much of the purified part of the fluid circuit used in blood treatment disposable and since filters are expensive, the need for an additional filter is a cost concern. 
     SUMMARY OF THE INVENTION 
     The present invention provides devices and methods for producing purified replacement fluid in a unit that is subsequently used for renal replacement therapy on a patient. The system can be used both to purify non-purified fluid and to further purify sterile fluid contaminated (e.g., by touch contamination) during connection due to improper technique. In a first embodiment, a system is provided to perform a method that includes the steps of providing a renal replacement therapy unit that has a filter with a membrane separating a waste side of the filter from a clean side. The membrane has a pore size smaller than the non-purified and pyrogenic material to be filtered. The renal replacement therapy unit also includes a first container of a solution of suitable concentration for use as a replacement fluid that may include the pyrogenic material or otherwise sterile fluid which has been contaminated (e.g., by touch contamination) during connection due to improper technique. The first container is in fluid communication with the waste side of the filter. The unit also includes a second container that is adapted to hold purified replacement fluid. The second container is in fluid communication with the clean side of the filter. A pump, generally the ultrafiltrate pump, is in fluid communication with the first container and the second container. The pump is capable of switching between a first direction that pumps fluid out of the first container and a second direction that removes waste from blood. A second pump, called a replacement fluid pump, pumps fluid out of the second container. The method further includes the step of running the pump in the first (reverse) direction to pump the solution of suitable concentration from the first container into the waste side of the filter. The solution from the first container is filtered through the membrane of the filter to trap the pyrogenic material on the waste side of the filter and produce purified replacement fluid in the clean side of the filter. The purified replacement fluid that flows from the clean side of the filter is collected in the second container. During therapy the pump switches to run in the second (forward) direction to pump waste from the blood. The purified replacement fluid is pumped from the second container into the blood by a second pump. The purified replacement fluid is used to perform renal replacement therapy on a patient. 
     Another embodiment is a pre-connected, purified fluid management kit for use in presterilizing replacement fluids prior to renal replacement therapy. The kit includes various disposable components of a renal replacement therapy unit. In one embodiment, the kit includes a fluid pumping and balancing system, a purified fluid reservoir, a plurality of tubes conventionally used in a renal replacement therapy, and a replacement fluid container. Each of the plurality of tubes has a first end in fluid communication with the fluid pumping and balancing system and a second end releasably coupled to and in fluid communication with the purified fluid reservoir. The replacement fluid container tube has a first end coupled to the fluid pumping and balancing system and a second end adapted to couple to a replacement fluid container. The kit is sterilized and packaged in a container at the time of manufacturing to prevent contamination prior to use in a renal replacement therapy unit. 
     Another embodiment is a system for batch sterilization of replacement fluid and renal replacement therapy using the purified fluid. The system includes a renal replacement therapy unit adapted to releasably receive a sterilized kit and a sterilized kit having preconnected disposable elements of the renal replacement therapy unit. The kit includes a fluid pumping and balancing system, a plurality of connectors, each having a first end coupled to the fluid pumping and balancing system and a second end adapted to releasably couple to the renal replacement therapy unit, a purified replacement fluid container releasably coupled to the fluid pumping and balancing system through a plurality of tubes, and a tube having a first end coupled to the fluid pumping and balancing system and a second end adapted to releasably couple to a container of solution to be purified. 
     Another embodiment is a method for producing purified replacement fluid in a renal replacement therapy unit. The method includes the steps of providing a renal replacement therapy unit, a sterilized kit that includes certain disposable elements of the unit, and a container of solution of suitable concentration for use as a replacement fluid. The unit is adapted to releasably receive the sterilized kit. The kit includes a plurality of tubes adapted to releasably couple to the renal replacement therapy unit, a preconnected purified replacement fluid container and a tube having an end adapted to releasably couple to the solution container. The method further includes the steps of releasably coupling the sterilized kit to the renal replacement therapy unit, releasably coupling the tube to the container of a solution of suitable concentration for use as a replacement fluid, pumping the solution through the renal replacement therapy unit to sterilize it, and capturing the purified solution in the purified replacement fluid container for use in renal replacement therapy. 
     Another embodiment includes a purified disposable fluid circuit with no connections that are exposed for contamination. Replacement fluid can be generated using the fluid circuit in a manner that safeguards against touch contamination. The embodiment may use a double lumen access spike that is permanently bonded to the fluid circuit as described in U.S. patent application Ser. No. 10/393,209, for “Blood Circuit with Leak-Safe Features” and filed Mar. 20, 2003, hereby incorporated by reference as if fully set forth in its entirety herein. An automatically sealing connector may be provided to allow the access needle to be used for filtering replacement fluid, priming, and treatment. 
     Another embodiment demonstrates how filtering of replacement fluid by using the same filter as used for dialysis allows the saving of a filter while still ensuring against contamination risk. 
     According to an embodiment, a method is disclosed for performing renal replacement therapy with a treatment device that employs a fluid circuit with liquid and blood fluid circuits separated by a membrane, the membrane having a pore size effective to block the passage of pyrogenic material. The method comprises: connecting a source of electrolytically-balanced fluid to the liquid fluid circuit; ensuring sterility of the electrolytically-balanced fluid by passing the same through the membrane to produce sterile fluid and storing the sterile fluid in a reservoir; warming and maintaining a temperature of the sterile fluid until a treatment time; recirculating the sterile fluid through the reservoir to permit gas to be purged from the sterile fluid and prime a first portion of the fluid circuit; priming a further portion of the fluid circuit. 
     In a variation, the priming a further portion is executed after the recirculating. The methods may include conveying blood from a patient through the blood fluid circuit during a treatment cycle and removing waste from the blood from the blood circuit through the membrane to the liquid fluid circuit. The method may further include using the sterile fluid from reservoir in the process of performing a blood waste removing process on a patient. The methods may further include ensuring sterility includes ensuring a rate of endotoxins below a predetermined level by filtering with a membrane with a pore size effective to limit endotoxins. The predetermined level may be 3 EUs/ml. or less. The methods may further include vibrating the reservoir to aid in the removal of gas. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  depicts an embodiment of a hemofiltration unit performing the therapy. 
         FIG. 2A  is a schematic of the embodiment of  FIG. 1 , performing hemofiltration therapy. 
         FIG. 2B  is a schematic of the embodiment of  FIG. 3  performing solution sterilization. 
         FIG. 3  is an embodiment of a hemofiltration unit operating in the reverse pumping mode used for solution sterilization 
         FIG. 3A  depicts an embodiment of a hemofiltration unit used to mix dialysate. 
         FIG. 4  is another embodiment of a disposable unit adapted to couple to a hemofiltration unit for solution sterilization, priming, and subsequent hemofiltration therapy. 
         FIG. 5  is an embodiment of a hemofiltration unit performing solution sterilization demonstrating the fluid flow paths. 
         FIG. 6  is an embodiment of a hemofiltration unit in priming mode. 
         FIG. 7A  is an embodiment of a renal replacement therapy system (without tubing) showing the installation of a fluid management kit in a hemofiltration unit adapted to receive the kit. 
         FIG. 7B  shows the embodiment of the system of  FIG. 7A  with the kit fully installed (without tubing). 
         FIG. 8A  illustrates a hemofiltration system without waste fluid bypass configured for generation of purified replacement fluid. 
         FIG. 8B  illustrates a hemofiltration system without waste fluid bypass configured for priming with purified replacement fluid. 
         FIG. 8C  illustrates a hemofiltration system without waste fluid bypass configured for treatment. 
         FIG. 9A  illustrates a fluid circuit with a double lumen access needle permanently attached to the venous line. 
         FIG. 9B  illustrates some details of the device of  FIG. 9A  in a use context. 
         FIG. 10  illustrates details of the embodiment of  FIGS. 9A and 9B . 
         FIG. 11A  illustrates a first embodiment of an automatically-self sealing connector. 
         FIG. 11B  illustrates a second embodiment of an automatically-self sealing connector with a combined double lumen access needle. 
         FIG. 11C  illustrates the use of the embodiment of  FIG. 11B  with a fluid circuit during replacement fluid preparation. 
         FIG. 11D  illustrates the use of the embodiment of  FIG. 11B  with a fluid circuit during priming. 
         FIGS. 11E and 11F  illustrate mechanisms for ensuring that bubbles are given an opportunity to settle out of a priming flow. 
         FIG. 11G  illustrates the use of the embodiment of  FIG. 11B  with a fluid circuit during treatment. 
         FIG. 12A  illustrates a dialysis system embodiment of the prior art. 
         FIG. 12B  illustrates a dialysis fluid circuit configured for replacement fluid preparation. 
         FIG. 12C  illustrates a dialysis fluid circuit configured for treatment. 
         FIG. 13  is a flow chart illustrating an example of a control procedure for preparing replacement fluid and priming a fluid circuit of a hemofiltration system. 
         FIG. 14A  is a diagram of a preferred embodiment of a fluid circuit set with a cartridge and filter in which a replacement fluid line is permanently attached to a replacement fluid reservoir. 
         FIG. 14B  is a diagram of a preferred embodiment of a fluid circuit set with a cartridge and filter in which a replacement fluid line is permanently attached to a replacement fluid reservoir and blood lines are permanently attached to a preconnected patient access needle. 
         FIG. 15  illustrates the use of a heat source to supply heat to a portion of a fluid circuit according to various embodiments of the invention. 
         FIG. 16  illustrates the use of a vibration source to supply vibration to a fluid reservoir according to various embodiments of the invention. 
     
    
    
     DETAILED DESCRIPTION 
     A hemofiltration device  1  is depicted in  FIG. 1 . In a conventional forward pumping hemofiltration mode, a draw blood line  20  carries blood, for example arterial blood, from the patient  92  to a filter  30 . A membrane in the filter  30  allows waste products such as urea and other undesirable metabolic byproducts that are blood contaminants together with water to pass through the filter membrane to the waste side of the filter  30  and out a side port  40  into a waste line  50 . The waste line  50  drains the waste filtrate  61  into a waste container  60 . The filter membrane does not permit blood cells and higher molecular weight proteins to pass through with the waste filtrate and thus concentrated, purified blood passes out the filter top port  70 . The fluid volume lost as waste filtrate during the hemofiltration process must now be replaced in the concentrated, purified blood to return the blood to its proper physiologic concentration. Accordingly, a measured volume of purified replacement fluid (“RF”)  81  from a purified fluid reservoir  80  is added to the filtered blood in an amount equal to the volume of waste filtrate removed during the hemofiltration process. A fluid balancing system (not shown in  FIG. 1 ) that measures the waste filtrate removed and then dispenses the proper volume of replacement fluid needed is located inside the hemofiltration unit  1 . Systems and devices for fluid balancing have been described in U.S. patent application Ser. No. 09/513,773, filed Feb. 25, 2000, the contents of which are incorporated herein in their entirety by reference. The replacement fluid flows from the replacement purified fluid reservoir  80 , through the replacement fluid line  10 , to the balancing system in the hemofiltration unit  1 . The reconstituted blood, now consisting of the concentrated, purified blood and the measured amount of replacement fluid, is returned via the return blood line  90 , for instance a venous line, to the patient  92 . 
       FIG. 2A  shows a schematic representation of the hemofiltration process. A draw blood line  20  carries blood from the patient to the filter  30 . The blood pump  25  pushes the blood through the filter, and the pressure differential due to the positive pressure of the blood drives the blood across the membrane. A balancing system  48  meters the waste or blood, water, and contaminants through the membrane  35  of the filter  30 , metering out the blood, water, and contaminants into the waste side  33  of the filter and allowing concentrated purified blood to pass out the clean side  37  of the filter and into the filter top port.  70 . The waste filtrate exits the waste port  40  of the filter  30  and passes into the balancing system  48 . Purified replacement fluid flows from the purified replacement fluid reservoir  80  through the replacement fluid line  10  to the balancing system  48  where a measured amount of purified replacement fluid equal to the amount of waste filtrate passed through the balancing system  48  is allowed to combine with the concentrated blood in the return line  90  and return to the patient. The waste filtrate that has passed through the balancing system passes through the waste line  50  and into the waste container  60 . 
     If the therapy requires hemofiltration and ultrafiltration, then an ultrafiltration pump  45  removes excess fluid from the patient&#39;s blood and dumps the excess fluid into the waste container  60 . This excess fluid removed by the ultrafiltration pump  45  does not pass through the balancing system and thus is not matched by an equal amount of replacement fluid. The system may use additional pumps such as a waste pump and a replacement fluid pump as part of the fluid balancing system to assist the proper fluid flow through the system. 
       FIG. 3  shows an embodiment of the present invention prior to connection to the patient  92  to perform therapy. The hemofiltration unit  1  is configured to convert a solution of suitable electrolyte concentration for use as a replacement fluid  82 , for example dialysate, in a container  62  to purified replacement fluid  81  that is pumped to a container adapted to hold the purified fluid, such as a purified fluid reservoir  80 , via a filtration sterilization process. While the solution  82  to be converted will have the proper electrolyte concentration required of replacement fluids, there is a concern that the solution will include pyrogenic material, for example pathogens such as bacteria, endotoxins, and thus not be sufficiently pure to be injected into a patient as a replacement fluid. Thus, the hemofiltration unit can be used to filter the solution to remove pyrogens and to prepare safe replacement fluid for a subsequent hemofiltration procedure by running the appropriate pump in the hemofiltration unit in reverse of the pumping mode used for conventional hemofiltration. In a preferred embodiment, the hemofiltration unit is adapted to receive certain disposable components including a fluid pumping and balancing system as more fully explained herein. 
       FIG. 2B  shows the fluid sterilization process schematically. A pump in fluid communication with the fluid container  62 , for instance an ultrafiltration pump  45 , is run in reverse of the direction that the pump is conventionally run during ultrafiltration therapy to draw fluid from the container  62  up through the waste line  50  and into the waste side  33  of the filter  30  via the waste port  40 . The pump  45  forces the fluid through the filter membrane  35  into the clean side  37  of the filter. Because the pyrogenic material in the fluid, for instance bacteria and endotoxins, are mostly larger than the pore size of the filter membrane  35 , such material in the fluid remains on the waste side  33  of the filter. The filtered fluid, now rendered safe, emerges as purified replacement fluid from the top port  70  of the filter and flows through the return blood line  90  into the purified replacement fluid reservoir  80 . Preferably, the filter is one that reduces the rate of endotoxins to very low levels. For example, for hemofiltration, an endotoxin rate of 0.03 EUs/ml. is preferred. 
     In other methods, the user mixes the dialysate and then sterilizes it as shown in  FIG. 3A . A first container  82  of concentrated electrolytes, e.g., any one or more of sodium lactate, potassium, calcium, magnesium chloride, sodium chloride, bicarbonate and/or other appropriate salts, and/or other elements, is connected to Y-connector  84 . A second container  83  of water, ringers lactate, or saline is also connected to the Y-connector. The two solutions are then mixed as they pass through Y-connector  84  and then pass through the filter. 
     The hemofiltration unit automatically primes the remainder of the fluid pathway when all of the replacement fluid is transformed into purified replacement fluid. The priming process is described more fully herein. 
     Once the fluid pathway is primed, the hemofiltration unit is ready to be connected to the patient for renal replacement therapy. Referring again to  FIGS. 1 and 2A , the blood pump  25  pumps the patient&#39;s blood through the filter  30 , the balancing system  48  meters fluid from the purified fluid reservoir  80 , and the trapped bacteria on the waste side  33  of the filter pass into the container  60  along with waste blood water. In a preferred embodiment, the now-empty container  60  previously containing the solution  82  can now be used as a waste container for the hemofiltration therapy. A system using more than one filter can also be employed. Further, the system can be used to mix a concentrate solution with another solution. 
     While the embodiments shown are described for hemofiltration therapy, the devices and methods can be used for blood processing, infusive therapies, or any renal replacement therapy, for instance hemodiafiltration, and can also be used for hemodialysis. Moreover, while the hemofiltration unit described is a volumetric system, this method can be readily employed with active flow balancing control such as mass-metric systems that use scales instead of balance chambers or flow meters or purely mechanical systems based on weight or volume. 
     In a preferred embodiment, the fluid pumping and balancing system and optionally other elements may be preconnected, prepackaged, sterilized and sealed by the manufacturer into a disposable unit such as a kit to reduce touch contamination that can be introduced during set-up of the fluid sterilization process. A renal therapy unit is adapted to receive the kit, which is releasably coupled to the unit, to form a system for batch sterilization of replacement fluid and subsequent renal replacement therapy using the purified fluid. Following therapy, the kit may be removed and discarded and a new kit can be installed for a subsequent fluid sterilization and therapy procedure. 
       FIG. 4  shows an embodiment of a pre-connected, disposable fluid management kit  100 . The embodiment includes a filter  300 , for example a hemofilter, and a purified fluid reservoir  800  connected to a fluid pumping and balancing system  12  through various tubes or lines  900 ,  10 ,  200 . A first end  901 ,  101 ,  201  of each tube  900 ,  10 ,  200  is coupled to the fluid pumping and balancing system  12  and a second end  902 ,  102 ,  202  of each tube  900 ,  10 ,  200  is releasably coupled to the purified fluid reservoir  800  via connectors  93 ,  11 ,  21 . Manual clamps  94  may also be used to control fluid flow when disconnecting lines. A waste line  500  has a first end  501  coupled to the fluid pumping and balancing system  12  and a second end  502  removably sealed by a cap  52 . In the embodiment of  FIG. 4 , the fluid management kit includes a filter  300  in fluid communication with the pumping and balancing system.  12 . The pre-coupled, disposable components of the fluid management kit are sterilized by the manufacturer and sealed in a suitable container  130  to guard against contamination. The container  130  may be a poly bag, TYVEK™, paper or other suitable material. The sterilization process used by the manufacturer may be of any conventional method used for sterilizing medical equipment such as gamma irradiation, chemical sterilant such as ethylene oxide, steam, e-beam or the like. The fluid pumping and balancing system  12  of the embodiment of  FIG. 4  includes a blood pump  250 , an ultrafiltrate pump  450 , a fluid balancing system  480 , and a venous air detector  515 . The fluid balancing system  480  illustrated in the embodiment is a volumetric system, however it could also be gravimetric flow meters or other means of fluid balancing. The components of the fluid management kit may be connected to form a fluid pathway in any conventional structure used for hemofiltration and ultrafiltration such as the structures shown in the embodiments of  FIGS. 1-3 . Similarly, the hemofiltration filter  300  may be integrated into the fluid pathway in any conventional structure. In certain embodiment, the hemofiltration filter is not part of the disposable kit. 
     In the embodiment of  FIG. 4 , the purified fluid reservoir  800  is releasably coupled to the fluid pumping and balancing system  12  through a blood return line  900 , a purified replacement fluid line  10  and a draw blood line  200  through connectors  93 ,  11 , and  21 . The connectors  93 ,  11 , and  21  can be Luer connectors, proprietary connectors or any other connectors that will provide a hermetic seal that can be decoupled by a user. The purified fluid reservoir  800  may be of any size required by the therapy, but preferably between 1 and 75 liters and most preferably between 5 and 50 liters, generally approximately 20 liters. The replacement fluid container line  500  can later be used as a waste line during hemofiltration. 
     Use of the pre-packaged, sterilized fluid management kit greatly reduces the risk of touch contamination. For instance, in the embodiment of  FIG. 4 , the only connection that must be made by the user during set up is the connection of the replacement fluid container to the waste line  500 . Replacement fluid is commonly provided in one-liter bags, thus requiring up to 50 of more connections to sterilize a sufficient amount of fluid depending on the prescribed therapy. In the embodiment of  FIG. 4 , all of these connections are made on the waste side of the filter, and accordingly any contamination introduced by the connection procedure is filtered out as the solution moves through the system to the purified fluid reservoir  800  during batch sterilization. 
       FIG. 5  shows a schematic of the fluid flow of the fluid management kit  100  of the embodiment of  FIG. 4  in use in a system for batch sterilization of replacement fluid and subsequent renal replacement therapy, where the system includes the hemofiltration unit fitted with a disposable fluid management kit. The system is best seen in  FIGS. 7A and 7B , where the system  1000  for batch sterilization of replacement fluid and renal replacement therapy using the purified fluid includes a renal replacement therapy unit  1100  adapted to releasably receive a sterilized fluid management kit and a purified fluid management kit  1200  (tubing and bags not shown).  FIG. 7A  shows the installation of the kit  1200  into the unit  1100 . Returning now to  FIG. 5 , the fluid flow illustrates the batch sterilization process. The second end  502  of the waste line  500  has been releasably coupled to the replacement fluid containers  600 . All of the other fluid connectors  93 ,  11 ,  21  have been preconnected by the manufacturer and thus are not a source of touch contamination during set-up. Only one pump  450  runs during filtration. All other pumps and the balancing system are dormant during filtration. Filtration continues until the entire batch has been processed. 
     During replacement fluid sterilization, the pump  450 , which in this embodiment is the ultrafiltration pump, runs in reverse (a second direction) of its conventional therapeutic pumping direction (a first direction) through filter  300  until the containers  600  of replacement fluid are empty. The emptying of the container results in air pumped into the filter, which is sensed by the venous air detector  515 , best seen in  FIG. 4 . When the venous air detector  515  senses the presence of air, software in the hemofiltration system triggers the pump  450  to reverse the pumping direction to the first direction and to prime the system including the filter. Alternatively, the pump  450  may be stopped and the balancing system turned on. This pumps fluid first direction pumps fluid from the purified fluid replacement reservoir  800 . This priming process is shown in  FIG. 6 . Since the blood return line  900 , the draw line  200  and the replacement fluid line  10  are all connected to the purified replacement fluid reservoir  800 , fluid can-be drawn out and air pushed into the reservoir  800  where it floats out of solution. The pump  250  rotates in the forward, or first, pumping direction, metering fluid from the bag  800  and forcing air into the bag  800  from the return line  900 . Fluid is drawn-through the replacement fluid line  10  and into the fluid balancing system  480  forcing air out into the venous return line  900 . Purified replacement fluid is pushed back across the filter  300  to the waste side of the filter and dumping a minimum of fluid into the former replacement fluid containers, now the waste containers  570 . Because the reservoir  800  of purified replacement fluid acts as a bubble trap, the hemofiltration system, exclusive of the bag, is primed and free of air. 
     An integrity test can be performed on the filter to verify that the replacement fluid was properly filtered during sterilization. The test, substantially similar to that used in manufacture of the filter itself, measures the partial pressure of the wet filter using the air from the arterial line as the test medium. The replication of the manufacturer&#39;s test assures that the filter is leak free and thus the filtered fluid is purified and safe to use as a replacement fluid. 
     In certain embodiments, a blood leak detector  516  can be incorporated into the fluid pumping and balancing system and used as a redundant test of filter integrity. If the filter demonstrates a leak after the patient has been connected, the blood leak detector will alarm. 
     Once a test of filter integrity is successfully performed and the system has been primed as previously described, the unit is ready for renal replacement therapy, for instance hemofiltration or hemodiafiltration. The second end of each of the draw and return lines is decoupled from the purified replacement fluid reservoir and each is releasably coupled to the appropriate vascular access of the patient and renal replacement therapy is initiated. The vascular access can be a native fistula, a synthetic graft, a catheter a subcutaneous port or other conventionally used method. 
     Referring to  FIG. 8A , in a hemofiltration embodiment where no ultrafiltrate pump is available or where it is preferred to use a pump other than an ultrafiltrate pump, a waste fluid pump  334  is used to convey raw replacement fluid through a filter  324  for preparation of a batch of purified replacement fluid. Note that in this embodiment, a balancing mechanism  310  must be one that permits a negative pressure to be transmitted through it to the source fluid container  314  in order for this to work. For example, the balancing mechanism  310  may incorporate an internal bypass to permit the waste pump  334  to draw raw fluid through the balancing mechanism  310  waste side  310 A. Alternatively, a six-way valve or set of valves may be used to reverse flow such that positive pressure is always applied to the balance mechanism or, if not required, a simple flow direction reversal. A connector  330 A is provided to permit connection of the raw fluid reservoir  314 . The waste fluid pump  334  pumps in the direction shown to convey fluid through the filter  324  then through any and/or all of the lines  311 A,  311 B, and  311 C via junctions  332  and couplings  318 / 319  and  320 / 321 . Purified replacement fluid is collected in a replacement fluid container  312 . As in previous embodiments, preferably, all connections are permanent except couplings  318 / 319  and  320 / 321 , which are only uncoupled momentarily for connection to a patient access, and  330 A/ 330 B. The circuit guards against contamination because the latter coupling is isolated from the replacement fluid container  312  and all the lines  311 A,  311 B, and  311 C which might introduce contaminants into the patient bloodstream. 
     A pressure sensor  331  may be provided upstream of the filter  324  and downstream of the pump  334 . The pump  334 A may be operated during preparation of replacement fluid and halted intermittently while a controller  331 A records a pressure relaxation profile output by the pressure sensor  331 . Any changes in the shape of the curve may be determined by suitable calibration procedures to correspond to a possible loss of integrity of the filter  324 . If a change in the pressure relaxation curve goes beyond some suitable limit, an alarm may be activated and the replacement fluid preparation operation halted by the controller  331 A. One example of a parameter for monitoring is to provide a programmable controller to fit each real time data set to an exponential to generate a decay constant, which may be stored to create a stored record. The record may be queried to detect any changes in the decay constant or change in a rate of change if the decay constant that may be used as an indication of a loss of integrity. The integrity check may also server to ensure the integrity of the waste portion of the fluid circuit as well. 
     Note that if pumps  316  and  322  are of a type that can selectively permit the free backflow of fluid, fluid may pass through all of the lines  311 A,  311 B, and  311 C during purified fluid preparation. Alternatively, the pumps  316  and  322  may be bypassed and fluid passed through line  311 B alone. 
     Referring now to  FIG. 8B , the embodiment similar to that of  FIG. 8A , is illustrated as it operates during a priming mode. As explained earlier, no connections are newly made or broken in going from preparation mode of the previous figure and priming mode as in the present figure. Purified fluid is now pumped by a replacement fluid pump  316  through the balancing mechanism  310  replacement fluid side  310 B. At the same time, blood pump  322  draws purified fluid and pumps it through the purified side  328  of the filter  324  where part goes into the waste side  326  and part runs through junction  332  back to the replacement fluid container  312 . The waste pump  334  may be run at a slow rate to permit a small amount of fluid to be metered through the waste side and into the waste receptacle  314 , which during preparation mode of  FIG. 8A  served as the raw replacement fluid container. Note that during priming, the waste pump  334  runs in a direction opposite that used during preparation. In an alternative embodiment, the waste pump  334  may be such that it allows passive flow either selectively or permanently. Permanent passive flow capability may be provided by ensuring that the waste pump  334  provides less than a 100% seal. Selective passive flow capability may be provided by providing a controllable actuator to back an internal platen (used in peristaltic pumps) slightly away from the pump rollers of the peristaltic pump that is usually employed in medical systems. 
     Referring now to  FIG. 8C , the hemofiltration system of the foregoing embodiments is shown in a treatment mode. The connections  318 / 319  and  320 / 321  are broken and connected to connectors  335  of a patient access  336 . Before beginning operation of the pumps  316 ,  322 , and  334 , lines  311 A and  311 B are clamped to prevent fluid leaking or contamination. To treat, pumps  316 ,  322 , and  334  all operate in the same directions as in the previous embodiment. Blood is drawn from the patient access  336  and flows through the filter  324  where waste is drawn by waste pump  334 . For each unit of waste passing through the balancing mechanism  310 , an equal unit of replacement fluid is pumped into junction  332  and ultimately into the patient access for reinfusion. To draw down a net volume of fluid in a patient in this type of system which lacks a bypass, the balancing mechanism may be configured to negatively bias the flow of replacement fluid appropriately by some other means such as numerical control, mechanical means, etc. A number of such means are known. Also, the waste pump  334  may be run for a period of time after stopping the replacement fluid pump  316  and placing the balancing mechanism in configuration that permits passive flow through it. For example, this may be done by opening the balancing chamber valves in the waste fluid circuit in the balancing mechanism disclosed in U.S. Pat. No. 6,554,789, which is hereby incorporated by reference as fully set forth in its entirety herein. 
       FIG. 9A  illustrates a fluid circuit portion  210  in the form of a cartridge and  FIG. 9B  shows the embodiment of  FIG. 9A  in use in a blood treatment machine  183 . Examples are illustrated in U.S. patent application Ser. No. 09/513,773, which is hereby incorporated by reference as if fully set forth in its entirety herein. 
     In the field of extracorporeal blood treatment, it is the general practice to provide connectors for connecting and disconnecting the venous line from the access device. Thus, the embodiment of  FIGS. 9A and 9B  shows a consumable component that may be provided for treatment in which a permanent connection exists between the venous line  206  and a venous channel of the access device  205  of a consumable fluid circuit or portion thereof. An arterial line  207  may or may not be connected to the needle  205  by a detachable connector.  FIG. 9A  illustrates a cartridge portion  210 , but the consumable device of  FIG. 9  may be packaged in a form other than a cartridge, as is known. 
     Referring now also to  FIG. 10 , the venous line  206  is permanently connected to a body  215  by, for example, adhesive bonding, thermal welding, mechanical lock or some other means. In a preferred embodiment, the permanent connection runs at least to a point of the air sensor  178  in the blood treatment machine  245 . Referring now particular to  FIG. 9A , the permanent connection between the needle or catheter  205  may be ensured by providing the permanent arrangement as part of a fluid circuit  209  with a main portion  210  permanently attached to the venous line  206 . Referring now particularly to  FIG. 9B , the permanent connection is preferably continuous up to and including a pump portion of the circuit  175  and a first air sensor  170  ordinarily part of the blood treatment machine  183 . This ensures that if any connections are improperly made, they can only happen in such a way as to cause air to be drawn in. Referring to  FIG. 10 , thus, a fluid circuit  250  defines a continuous and permanent connection from an entry point  223  up to an air sensor  178 . The circuit may include various portions  245  which may include a filter  180  and other components for a blood treatment. Thus, the filter  180  (shown in  FIG. 9B  and embedded in portion  245  in  FIG. 10 ), in a preferred configuration, is permanently attached and supplied with the fluid circuit  250 . 
     Note that preferably the needle or catheter  205  is of such design that if the needle pulls out, there is no practical possibility that the venous line  206  could allow blood loss without air being sucked into the arterial line. The permanent connection is a part of this, but if the venous cannula extends further than the arterial cannula, this can be assured. In an alternative embodiment, both the venous  206  and arterial  207  lines are permanently connected to the double lumen access needle  215  thereby ensuring further against touch contamination. 
     Referring now to  FIG. 11A , a connector  605  which disconnects a male luer  618  from a female  630  when a clamp  625  is pinched as indicated by arrows  602 . The connector  605  may be used for connections  318 / 319  and  320 / 321  of  FIGS. 8A-8C . When pinched, ridges  616  of the clamp  625  engage and compress a tube  626  passing through an opening  628  in clamp  625 . Spines  614  and  618  pivot about living hinges  636  withdrawing hooks  610  from engagement with male luer  618 . Thus, the male luer  618  cannot be disconnected from the female  630  without pinching off tube  626 . To keep tube  626  pinched off, a tongue and pawl mechanism  624  and  622 , such as commonly used in tubing clamps and common plastic wire ties may be used prior to disconnection, the tube  612  is preferably clamped to prevent leakage. Once disconnected, male luer  618  may be connected with a female luer connector (not shown) of a patient access (not shown). This ensures that there is no chance of air or pyrogens making their way into the RF container. 
     Referring to  FIG. 11B , another connector  401  is configured to ensure a tube  419  is blocked prior to disconnection in preparation for treatment. The connection includes a double lumen access needle  407  which may be configured as discussed with reference to  FIGS. 9A ,  9 B, and  10 . The needle  425  fits snugly within a channel  430  inside a casing section  411 . The needle is guided by vanes  427  which project axially such that the needle  425  is supported at the center of the casing section  411 . The vanes permit fluid to flow around the needle  425 . The casing section  411  is permanently attached to a casing section  415  which houses a cap  423  fitted over the end of needle  425 . A tube connector  421  has a spring  417  that is positioned to help keep the cap in place when connector  421  is attached permanently to channel section  415 . A tube  419  is permanently attached to the connector  421 . 
     The needle  407  has a male luer  429  fitting that is inserted into a female luer fitting  428  in the casing section  411 . The male and female luers  429  and  428  are held together by a peel-away compression band  409  that wraps over projecting portions  444  and  445  of the dual lumen access needle  407  and casing section  411 , respectively. When the band  409  is peeled away from the projecting portions  444  and  445 , the dual lumen access needle  407  may be withdrawn from the casing section  411 . 
     The cap  423  has radial projections  423 P that center the needle  425  within the cap  423  but allow fluid to flow from the end of the needle  425  and out of the cap  423 . Thus, fluid may flow from either tube  403  or  405  through the needle  425 , through an interior of the cap  423  through casing sections  411  and  415  and out through the tube  419  as indicated by arrows  446 . Preferably, before the dual lumen access needle  407  is withdrawn from the casing section  411 , the tubes  403  and  405  are clamped to prevent leaking. The dual lumen access needle  407  may be inserted into a patient access immediately after withdrawal from casing section  411 . 
     The cap  423  has a male luer type fitting portion  423 L at a base thereof. A female luer type fitting portion  411 L receives the male luer type fitting portion  423 L when the dual lumen access needle  407  is withdrawn from the casing section  411  of the connector  413  and the cap is pulled off the needle  425 . As a result the  415 C is plugged by the cap  423 . 
     The embodiments of  FIGS. 11A and 11B  may help to guard against contamination by preventing any backflow of fluid into the replacement fluid reservoir (e.g.  312  of  FIGS. 8A-8C ) of any of the foregoing embodiments. This is illustrated in  FIGS. 11C and 11D  which show the configuration of a representative embodiment of hemofiltration system in fluid preparation and treatment modes. During fluid preparation, the double lumen access needle  425  is inserted in the connector  413  and only ultrafiltrate pump  350  may be operated while the replacement fluid pump  316 , the waste pump  334 , and the blood pump  322  are idle. Raw fluid flows from a waste container  314  through connector  330 A/ 330 B through a junction  360 , through an ultrafiltrate pump  350  running in reverse, through a junction  362 , through a filter  324 , through junction  332 , through the double lumen access needle  425  and the connector  413 , through the common line  311 D, and into the replacement fluid container  312 . As discussed above, the replacement fluid is purified and preferably left with an endotoxin level below 3 EU/ml. by the properties of the media provided in the filter  324 . 
     Referring now to  FIG. 11D , in priming mode, the replacement fluid pump  316  pumps fluid in a reverse direction into the replacement fluid container  312  while the blood pump  322  draws replacement fluid from the replacement fluid container  312  through the line  311 D, through the connector  413 , through the double lumen access needle  425 , through the blood pump  322  through the filter  324 , through the junction  332 , through the replacement fluid side  310 B of the balancing mechanism  310 , to the replacement fluid pump  316 . At the same time waste pump  334  draws fluid from the filter  324  via the junction  362  and pumps it through the balancing mechanism  310  waste side  310 A and into the waste container  314  while the ultrafiltrate pump draws fluid from the junction  362  and pumps it through the junction  360  into the waste container  314 . As discussed above, a continuous circulation through the replacement fluid container  312  provides a flow of substantial rate and duration to eliminate most of the air in the purified replacement fluid by allowing it to settle in the RF container  312 . This is also discussed in U.S. Patent Application Ser. No. 60/386,483, entitled: “Last-chance quality check and/or air/pathogen filter for infusion systems,” which is hereby incorporated by reference as if fully set forth in its entirety herein. The present and other embodiments in the present specification may also be configured to provide heating to the replacement fluid at some point to permit the replacement fluid to evolve any dissolved gases which will settle out into the replacement fluid container  312  as the fluid circulates. 
     As described,  FIG. 15  illustrates the use of a heat source  1020  to supply heat (indicated at  1030 ) to a portion of a fluid circuit  1010  according to various embodiments of the invention.  FIG. 16  illustrates the use of a vibration source  1050  to supply vibration (indicated at  1060 ) to a fluid reservoir  1040  according to various embodiments of the invention. 
     The flow in the fluid circuit waste side may be established after purging air from the replacement fluid side by continuous recirculation for a period of time. The flush of the waste side may be merely sufficient to push any air out of the waste side of the filter  324  and up to the balancing mechanism  310  and pump  350 . A volume sufficient for that purpose would be optimal and the replacement fluid pump  316 , the waste pump  334 , the blood pump  322 , and the ultrafiltrate pump  350  may be controlled by an automatic controller (not shown) accordingly. 
     Note that a venous branch  361  may be purged of air bubbles by appropriately regulating the relative speeds of the replacement fluid pump  316 , the waste pump  334 , the blood pump  322 , and the ultrafiltrate pump  350 . The pump speeds may be changed such that a substantial flow is established in the venous line  361  at a point in time after replacement fluid has been recirculated for a time. This may be done by changing the relative speeds from a state where the flow generally bypasses the venous line  361  to one where a substantial flow passes through it. For example, the latter may be obtained by halting the blood pump  322  and running the replacement fluid pump  316  in the forward direction (opposite the direction depicted in  FIG. 11D ) so that fluid flow toward the replacement fluid container  312  in line  311 D from the venous line  361 . 
     The following comments apply to all the above embodiments, not just that of  FIG. 11D . Referring to  FIGS. 11E and 11F , it is important in recirculating flow through the replacement fluid container  312  to ensure that bubbles have the opportunity to settle out. The accesses to the interior of a replacement fluid container  825 A and  825 B is preferably such that the opportunity for mixing of the incoming  827 A,  827 B and outgoing  829 A,  829 B flows is minimal. This prevents short-circuiting which would interfere with gas settling out of the flow, As indicated in  FIG. 11E , this may be done by placing an incoming flow&#39;s  827 A jet direction and location remote from the corresponding outgoing flow&#39;s  829 A. Alternatively, or in addition, a barrier  831  may be used to separate the incoming  827 A and outgoing  829 A flows. An alternative is illustrated in  FIG. 11F  and discussed in U.S. application Ser. No. 10/393,185 filed Mar. 20, 2003 entitled “Dual Access Spike for Infusate Bags,” which is hereby incorporated by reference as if fully set forth in its entirety herein. Referring to  FIG. 11F , incoming  827 B and outgoing  829 B flows pass through a double-access spike that helps to prevent mixing of incoming  827 B and outgoing  829 B flows by ensuring the incoming flow  827 B is propelled away from the zone of suction of the outgoing flow  829 B. 
     In addition to causing gases to settle out in the replacement fluid container  312 , imperfectly mixed electrolyte may also be better mixed by the process of pumping through the replacement fluid container  312 . The uniformity may be monitored by means of a fluid quality sensor  317  which may be, for example, an inductive conductivity cell or wetted resistance sensor. 
     Referring now to  FIG. 11G , prior to treatment, the venous  361  and arterial  362  lines are clamped with typical tubing claims (not shown) and the double lumen access needle  425  removed from the connector  413 . The connector automatically seals the line  311 D as discussed above. The needle may then be inserted in a patient access  336 . The replacement fluid pump  316 , the waste pump  334 , the blood pump  322 , and the ultrafiltrate pump  350  may be activated and treatment begun. During treatment, blood circulates through the filter  324  urged by the blood pump  322  while waste is drawn off by the waste pump  334  and the ultrafiltrate pump  350 . The balancing mechanism meters a flow of replacement fluid from the replacement fluid container  312 , urged by the replacement fluid pump  316  and the resulting flow is added to the venous flow of blood returned via the double lumen access needle  425  into the patient. 
     Referring to  FIG. 12A , a dialysis system according to an embodiment of the prior art has a dialysate pump  706  which draws dialysis fluid from a raw dialysate source  702  and pumps it through a balancing mechanism  726 , through a first stage purification filter  714 , and into a second stage purification filter  716  where most of the flow bypasses the second stage filter  716  and flows into a dialyzer  722 . Blood is circulated through the dialyzer  722  by a pump  724  and returned to the patient along with a small amount of fluid from the secondary filter  716  that passes through the junctions  718  and  723  to join with the flow of blood. The rate of flow of replacement fluid may be regulated using control valves or metering pumps (not shown) according methods known in the art. Most of the spent dialysate passes through the balancing mechanism  726 , but part is bypassed by the utrafiltrate pump  708  such that a net fluid loss may be provided for maintaining the fluid balance of the patient according to known treatment methods. 
       FIGS. 12B and 12C  illustrate how the use of the inventive method and apparatus permits the second stage filter  716  to be eliminated. In  FIG. 12B , replacement fluid is filtered by a first stage filter  714  and a dialyzer  722  providing first and second stage filtering as in the embodiment of  FIG. 12A  without the need for a separate filter  716 . This is achieved by employing the dialyzer  722  as a purification filter to prepare a batch of replacement fluid prior to treatment. During a fluid preparation phase, as shown in  FIG. 12B , raw dialysate is pumped from a source  702  by a pump  706  through a balancing mechanism  726 , through a purification filter  714  while a control valve  733  is held closed. The filtered dialysate is thus filtered again as it passes through the membrane of the dialyzer  722 , through a junction  723  and into the replacement fluid container  740  thereby filling it. After enough purified-filtered replacement fluid has been stored, the dialysis system is placed in treatment mode as illustrated in  FIG. 12C . 
     Referring now also to  FIG. 12C , the lines  737  are clamped as indicated at  345  and connectors  735  are disconnected and new connections  739  made to a patient access  720 . As the dialysis treatment is initiated, replacement fluid is drawn from the replacement fluid container  740  and its flow metered by a replacement fluid pump  742 . The rate of flow of replacement fluid may be determined by means of a flow measurement using known numerical, calibration, and control techniques that are well known and need not be delineated here. In other respects, the dialysis treatment proceeds as discussed with reference to  FIG. 12A . As in previous embodiments, it should be clear from inspection that the fluid circuit may guard against touch contamination by providing a hermetically sealed system except for connections  739 . 
     Referring now primarily to  FIG. 13  but also to  FIGS. 11C ,  11 D, and  11 G, a representative control procedure for preparing replacement fluid and priming a fluid circuit begins with simultaneous execution of two parallel processes  780  and  790 . The process  790  is a looping process that may continue throughout the execution of the  780  process as illustrated. Process  780  begins at step S 10  with the initiation of the ultrafiltrate pump  350  in a reverse direction in the embodiments  FIGS. 5 and 11C  (or the waste pump in the embodiment of  FIG. 8A ). Immediately afterward at step S 20 , a replacement fluid heater (discussed in U.S. Patent Application Ser. No. 60/386,483 incorporated by reference above) may be activated to warm the replacement fluid captured in the replacement fluid container  312 . Control flow loops through step S 25  until some condition establishes that sufficient replacement fluid has been filtered. This condition may-be determined in various ways such as by weighing the filtered replacement fluid (filled RF container  312 ) or unfiltered replacement fluid (empty source container  314 ), by cumulating a measured mass flow rate of replacement fluid (by direct flow rate measurement or by pump shaft speed, for example), by cumulative pumping time, by detection of air in the line, etc. 
     Once the replacement fluid has been filtered, control branches to step S 30  where a user may be alerted. Control loops through step S 35  permitting a user to begin the priming process by generating a command at step S 35  causing control to branch to step S 40 . Alternatively steps S 30  and S 35  may be omitted and priming may begin immediately with the execution of step S 40 . At step S 40 , the blood pump  322  may be started to begin pumping purified replacement fluid through the blood and replacement fluid circuits  351 B and  311 D. In the present embodiment, the priming flow in step S 40  helps to carry any air away from the filter membrane and allow any bubbles to settle out of solution in the RF container  312 . During this phase, a small amount of flow through the filter membrane may be permitted to ensure that bubbles are not later allowed into the primed blood and replacement fluid circuits. Control loops through step S 45  for an interval sufficient to ensure that the-circuit is primed, the end of which may be determined by various means. For example, a bubble detector or fluid quality sensor  317  may be monitored until a signal from it falls below a threshold level. Alternatively, or in addition, the passage of a specified interval of time or the flow of a cumulative quantity of fluid may be detected. Control may also loop through step S 45  waiting for the further condition of uniform fluid quality indicated by sensor  323 . That is, an additional requirement of a constant fluid quality signal from that sensor may be required. This would be particularly advantageous if electrolytes were mixed with water at the treatment site. 
     After the above interval, at step S 50 , the waste, ultrafiltrate, and replacement fluid pumps  334 ,  350 , and  316  may be started to purge and prime those lines. To purge the branch  361  in the embodiment of  FIGS. 11C ,  11 D, and  11 G, the replacement fluid pump  316  may be run at a much higher rate than the blood pump  322  during at least a portion of step S 50 . Various differences in the relative rates or sequencing of the waste, ultrafiltrate, and replacement fluid pumps  334 ,  350 , and  316  may be provided to ensure the various lines are primed with relatively bubble-free replacement fluid. One such alternative is illustrated at steps S 60  and S 65  which may be substituted for steps S 40 , S 45 , and S 50 . In step S 60 , all the pumps are started and run, but their relative speeds are governed to ensure that air is purged as in the foregoing embodiments. 
     The continuously looping process  790  intermittently stops a pump, for example ultrafiltrate pump  350  while closing any relevant valves and stopping other pumps that may interfere, in order to gather data for testing filter membrane integrity. The process may be conducted during any of the steps of procedure  780  or all of them. The procedure may begin with a pause after which one or more pumps are halted together or in sequence such that a pressure relaxation trend may be recorded S 3  using a pressure sensor (e.g.,  331  in  FIGS. 8A-8C ) and a controller  331 A. The relaxation curve may be compared to a template or to previously recorded curves to determine if the membrane is intact S 4 . If the test of S 4  is passed, control passes to step S 5  where the pumps are restarted (valves opened as required) to continue the current process. Otherwise in step S 6  an alarm may be generated and other automatic actions taken as needed. Note that testing of backpressure may not require the stopping of pumps so the steps S 2  and S 5  may be omitted. IN such case, the continuous or intermittent pressure signal relative to the pump rate may be monitored as the pump (e.g., pump  334 ) operates. 
     Note that bubble traps may be used in the fluid circuit at various points and the RF container  312  may be provided with an air escape valve or membrane as discussed in system according to U.S. Pat. No. 6,572,641 entitled “Devices for warming fluid and methods of use” and filed Apr. 9, 2001, which is hereby incorporated by reference as if fully set forth in its entirety herein. 
     Referring to  FIG. 14A , a disposable fluid circuit with a filter  458  are partly supported by a cartridge  460  orienting for installation various components including balancing chambers  480 , access points  515 ,  453 ,  454   456   455  and others for pressure, fluid quality, etc. measurement of blood, waste, dialysate and/or replacement fluid lines. Pumping regions  450 ,  451 ,  452 , and  457  are also provided. The illustration is for a hemofiltration circuit but a similar structure would provide for hemodialysis or other blood treatments. Arterial  202  and venous  463  blood lines are preconnected by selective connectors  471  and  475  and permanent attachments  473  and  474  to replacement fluid container  800 . A waste line  500  is capped and may be fitted with a connector for connecting to a waste bag or dump (not shown). The replacement fluid line  10  is permanently connected by attachment  472  to the replacement fluid container  800 . All connections are such that the blood side of the filter is completely sealed and the only access required for preparation of purified replacement fluid is the waste line  500 . The connectors  471  and  475  must be undone to connect to a patient access after sterilizing the replacement fluid which fills the container  800 . 
     Referring to  FIG. 14B , in an alternative embodiment of a fluid circuit, similar to that of  FIG. 14A , the replacement fluid line  10  is, again, permanently connected to the replacement fluid container  800 . A common permanent connection  484  is provided to attach to the connector  413  which has, received therein, the dual lumen access needle  425 . All connections are such that the blood side of the filter is completely sealed and the only access required for preparation of purified replacement fluid is the waste line  500 . Only the connector  425 / 413  need be undone and in doing so, the connector  413  is automatically sealed as discussed above. In other respects, the embodiment of  FIG. 14B  is similar to that of  FIG. 14A . 
     Although the foregoing invention has, for the purposes of clarity and understanding, been described in some detail by way of illustration and example, it will be obvious that certain changes and modifications may be practiced that will still fall within the scope of the appended claims. For example, the devices and methods of each embodiment can be combined with or used in any of the other embodiments. Although the fluid circuit examples described above included hemofiltration and hemodialysis circuits employing generic and volumetric balancing, it is possible to employ features of the embodiments with other kinds of balancing systems such as those described in U.S. Patent Application Ser. No. 60/440,176 filed Jan. 15, 2003 entitled “Waste balancing for extracorporeal blood treatment,” hereby incorporated by reference as if fully set forth in its entirety herein. Also, further variations and details on preparation of replacement fluid are provided in the following application which is hereby incorporated by reference as if fully set forth in its entirety herein: U.S. Patent Application Ser. No. 60/438,567 filed Jan. 7, 2003 entitled “Preparation of replacement fluid by means of batch filtration prior to treatment.”