The Monsanto Polyacrylonitrile Hollow Fiber Artificial Kidney

Summary

Advantages of a hollow-fiber hemodialyzer have been well described.^1–3 The goal of this program was to provide a working model of a noncellulosic hollow fiber artificial kidney with nonthrombogenic blood-contacting surfaces, low blood-priming volume and low pressure drop, a satisfactory rate of urea transport, and high rate of ultrafiltration of water. Also, the reliability and utility of these devices was to be demonstrated through clinical evaluation.

To define materials for hollow fibers, preliminary studies were conducted with various membrane compositions including polyvinyl alcohol, ethylene vinyl alcohol copolymers, ethylene/acrylate copolymers, nylon, and polyacrylonitrile (PAN). Membranes of modified PAN gave urea resistance values, in vitro, of 15 min/cm. In vivo testing, by medical collaborators at Peter Bent Brigham Hospital, Boston, Mass.,gave resistance values of 17 min/cm, which compared to a value of 19 min/cm for Bemberg Cuprophane. Ultrafiltration rates could be regulated up to 300 ml/min/m² using a transmembrane pressure differential of only 25 mm Hg.

Using the results of our membrane research and our background knowledge of the spinnability of various polymeric materials, a modified PAN was selected as the prime candidate for development as a dialyzing hollow fiber. This material could readily be rendered nonthrombogenic by quaternizing groups in the polymer followed by ionic coupling with heparin.

Three multiple-bundle, parallel-flow dialyzing subscale artificial kidneys incorporating the modified PAN hollow fibers were prepared and tested in vitro and in vivo. Urea transport of the fiber was significantly lower than that observed in the membrane. However, the high rate of water ultrafiltration and the nonthrombogenic properties were confirmed.

To obtain greater simplicity and lower cost 1/6-scale single bundle dialyzers were then designed, fabricated, and tested. The units consisted of approximately 2000 modified PAN fibers having inside diameters of ∿300 microns, and 15-cm dialyzing length, which were encased in a disposable cartridge with nonthrombogenic blood-contacting surfaces. This sterilizable, disposable cartridge design is low in cost and lends itself to the ease of handling and operation necessary for patients on home dialysis.

Two of these single-bundle, hollow fiber prototype artificial kidney units were tested in vivo in patients suffering from chronic renal failure by Drs. Merrill, Hampers and Lowrie at Peter Bent Brigham Hospital. These units were used independent of any other dialyzers, and demonstrated that the modified PAN hollow fiber kidneys were truly nonthrombogenic, provided a permeability of 0.01 to 0.015 cm/min (urea clearance of 34 ml/min), exhibited very high ultrafiltration (which was adjustable over any desired clinical range), and were of clinical utility.

Scale-up of the current design indicates that a full-size kidney of present fiber composition would require ∿12,000 fibers. With foreseeable improvements in the fiber dialysis characteristics, as indicated from membrane data, a practical full-scale hemodialyzer could evolve from the prototype 2000-fiber unit.