Liquid purification or separation – Processes – Liquid/liquid solvent or colloidal extraction or diffusing...
Reexamination Certificate
2000-02-14
2002-07-23
Kim, John (Department: 1723)
Liquid purification or separation
Processes
Liquid/liquid solvent or colloidal extraction or diffusing...
C210S097000, C210S143000, C210S252000, C210S321600, C210S321710, C210S321720, C210S323200, C210S434000, C210S645000, C210S647000, C210S929000, C604S004010, C604S005040
Reexamination Certificate
active
06423231
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to blood cleansing in general and, more particularly, to diafiltration systems.
BACKGROUND OF THE INVENTION
Hemodiafiltration combines standard dialysis and hemofiltration into one process, whereby a dialyzer cartridge containing a high flux membrane is used to remove substances from the blood both by diffusion and by convection. The removal of substances by diffusion is accomplished by establishing a concentration gradient across a semi-permeable membrane by flowing a dialysate solution on one side of the membrane while simultaneously flowing blood on the opposite side of the membrane. To enhance removal of substances using hemodiafiltration, a substitution fluid is continuously added to the blood either prior to the dialyzer cartridge (pre-dilution) or after the dialyzer cartridge (post-dilution). An amount equal to that of the substitution fluid is then ultrafiltered across the dialyzer cartridge membrane carrying with it additional solutes.
Substitution fluid is usually purchased as a sterile
on-pyrogenic fluid contained in large flexible bags or is produced by on-line filtration of a non-sterile dialysate through a suitable filter cartridge rendering it sterile and non-pyrogenic. Such on-line production of substitution fluid is described, inter alia, in D. Limido et al., “Clinical Evaluation of AK-100 ULTRA for Predilution HF with On-Line Prepared Bicarbonate Substitution Fluid. Comparison with HD and Acetate Postdilution HF”,
International Journal of Artificial Organs
, Vol. 20, No.3 (1997), pp. 153-157.
In general, hemodiafiltration schemes use a single dialyzer cartridge containing a high flux semi-permeable membrane. Such a scheme is described, for example, in P. Ahrenholz et al., “On-Line Hemodiafiltration with Pre- and Postdilution: A comparison of Efficiency”,
International Journal of Artificial Organs
, Vol. 20, No.2 (1997), pp 81-90 (“Ahrenholz et al.”). Substitution fluid is introduced into the blood stream either in a pre-dilution mode or in a post-dilution mode relative to the dialyzer cartridge. The preferred mode for maximal removal of both small and large substances from blood is the post-dilution mode, which achieves the highest concentration gradient between the blood and the dialysate fluid. In a typical pre-dilution mode with on-line generation of the substitution fluid, however, the bloodside concentration is lowered relative to the dialysate fluid. As a result, removal (or clearance) of substances can decrease, as described in Ahrenholz et al. This is particularly true for smaller molecules like urea, whereby mass transport is driven more by the diffusion process than by the convection process.
A hemodiafiltration scheme using first and second dialyzer cartridges is described in J. H. Miller et al., “Technical Aspects of High-Flux Hemodiafiltration for Adequate Short (Under 2 Hours) Treatment”, Transactions of American Society of Artificial Internal Organs (1984), pp. 377-380. In this scheme, the substitution fluid is reverse-filtered through a membrane of the second dialyzer cartridge with simultaneous filtration of fluid across a membrane in the first dialyzer cartridge. Counter-current flow of dialysate occurs at both cartridges.
Certain trade-offs exist with respect to removal of different size molecules when comparing pre-dilution diafiltration and post-dilution diafiltration using a single dialyzer cartridge. For example, with on-line pre-dilution diafiltration, one can achieve higher convective filtration rates (compared to on-line post-dilution diafiltration) to enhance removal of large molecules, however, this comes at the expense of reducing the removal of small molecules like urea and creatinine. In on-line post-dilution diafiltration, however, only a limited amount of fluid can be filtered from the blood as it passes through the dialyzer cartridge. The filterable amount is dependent upon several factors, including blood flow rate, blood hematocrit and blood protein concentration. Typically, the filterable amount is 20% to 30% of the incoming blood flow, depending on blood flow rate. For example, at a blood flow rate of 300 ml/min, the filterable amount is limited to about 90 ml/min. Additionally, in on-line pre-dilution or post-dilution diafiltration, there is some loss in clearance due to the lower dialysate flow rate through the diafilter cartridge. For example, at a nominal dialysate flow of 500 ml/min, when 100 ml/min is used as an on-line source of substitution fluid, the resultant dialysate flow into the diafilter cartridge is 400 ml/min.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide a hemodiafiltration method and a device which overcome the limitations associated with convection filtration in existing on-line post-dilution schemes. It is also an object of the present invention to reduce the loss of small molecule clearance associated with on-line pre-dilution diafiltration using a single dialyzer cartridge. In accordance with the present invention, clearance is improved by introducing a non-isosmotic fluid to the dialysate fluid stream and optionally to the substitution fluid stream.
The present invention may be embodied in an improved dialysis machine, e.g., a dialysis machine which is adapted to perform improved hemodiafiltration in accordance with the invention. Alternatively, the hemodiafiltration device of the present invention may be embodied in an “add-on” system which may be used in conjunction with a standard UF controlled dialysis machine to perform improved hemodiafiltration.
A hemodiafiltration device in accordance with an embodiment of the present invention includes at least one dialyzer (e.g., a dialyzer cartridge) for diafiltration, at least one sterility filter (e.g., a sterility filter cartridge) for generating a sterile substitution fluid, a non-isosmotic fluid supply, and a control unit which controls fluid inputs and outputs between the at least one dialyzer, the at least one sterility filter cartridge, the non-isosmotic fluid supply and the dialysis machine.
The dialyzer may contain a semi-permeable membrane which may be embedded within a jacket or housing of a dialyzer cartridge. The membrane separates the dialyzer into a blood compartment and a dialysate compartment. In an embodiment of the present invention, at least first and second dialyzers are used to carry out the diafiltration process. The first and second dialyzers may include first and second dialyzer cartridges or a single cartridge having first and second dialyzer sections. The at least one sterility filter may contain semi-permeable membranes and may be used to remove bacteria, endotoxins, and other particulate from the dialysate, thereby generating a suitable substitution fluid stream on-line. The control unit may contain various pumps, pressure monitoring devices, valves, electronic components, connector fittings, tubing, etc., as required in order to coordinate the operation of the other system components.
Blood enters the bloodside compartment of the first dialyzer, whereby some plasma water is filtered across the semi-permeable membrane into the adjacent dialysate compartment. As the blood leaves the first dialyzer, substitution fluid is added to the blood at a rate higher than the rate at which plasma water is filtered out of the first dialyzer. In accordance with an embodiment of the present invention, the substitution fluid may include a non-isosmotic substitution fluid.
The diluted blood then enters the bloodside compartment of the second dialyzer, whereby additional plasma water (equal to the excess amount of substitution fluid) is filtered across the semi-permeable membrane and into the adjacent dialysate compartment. In this manner, the substitution fluid acts as a post-dilution fluid relative to the first dialyzer as well as a pre-dilution fluid relative to the second dialyzer.
An advantage of this process is that a gain in clearance of small molecular weight substances in the first dialyzer overshadows a loss in clearance of small molecular weight
Collins Gregory R.
Spence Edward C.
Darby & Darby
Kim John
Nephros, Inc.
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