C. Kensinger1, J. Groszek2, S. Karp1, D. Laneve1, P. Williams1, R. Kant3, T. Yeager3, S. Roy3, W. Fissell2 1Vanderbilt University Medical Center,Department Of General Surgery,Nashville, TN, USA 2Vanderbilt University Medical Center,Department Of Medicine,Nashville, TN, USA 3University Of California – San Francisco,Department Of Bioengineering And Therapeutic Sciences,San Francisco, CA, USA
Introduction: Patents with end-stage renal disease (ESRD) have high mortality and morbidity rates on dialysis. Transplantation offers the best treatment option but is limited by organ availability. An implantable artificial kidney using silicon nanoporous membranes is in development to address this problem. A key challenge is the long-term blood patency of the hemofilter with respect to thrombosis formation and membrane fouling from plasma protein adsorption. These experiments assess the long-term biocompatibility of an implantable artificial kidney.
Methods: Single-channel, polycarbonate parallel-plate hemofilters (membrane area 0.72 cm2) are designed using computational fluid dynamics to minimize turbulence and stasis through the device flow path. Two ultrathin membranes with highly controlled pores made by sacrificial silicon oxide techniques, which allows size selective sieving, define the parallel plates along the flow path. Hemofiltration results from the hydrostatic pressure gradient across the membrane.
Seven millimeter polytetrafluoroethylene grafts are anastomosed to the common iliac artery and vein to be used as inflow and outflow conduits to the hemofiltration device. Heparin is administered intra-operatively. Effluent collection reservoirs are placed in the upper abdomen. Access ports are connected to the reservoirs and brought through the abdominal wall into the subcutaneous tissue. This allows post-operative monitoring of hemofilter function and filtration rates. Following the operation, the animals are housed without restrictions. The grafts are serially assessed post-operatively with a doppler ultrasound to ensure patent flow through the devise.
Results: Fourteen pre-clinical canine surgeries have been performed. Hemofilter patency rates were 67% (8/12) prior the initiation of post-operative Warfarin treatment. With adequate systemic anticoagulation, patency rates have been 100% (2/2). Intra-operative filtration rates have averaged 0.41 microliters/minute with an expected filtration rate of 0.42 microliters/min based on membrane characteristics. Blood flow through the device has averaged 300cc/minute at the time of hemofilter implant and explant.
Conclusion: These experiments highlight successful surgical technique and manufacturing biocompatibility providing the foundation for further preclinical experiments aimed towards the future realization of an implantable artificial kidney.