This Small Business Innovation Research (SBIR) Phase I project proposes to develop a mobile, easy-to-use, patient oriented, advanced Home Hemodialysis (HD) system that minimizes the use of water and medical wastes, and importantly, minimizes loss of nutrients. End-stage renal disease (ESRD) is a devastating and disabling disease requiring chronic dialysis treatment, which severely limits the mobility and quality of life (QOL) of ESRD patients and their caregivers due to the time and effort required to receive treatment. At dialysis centers, standard hemodialysis treatment, which utilizes massive amounts of highly purified water, results in a significant loss of nutrients. The objectives of this Phase I project are to design and test key units of an HD machine (HDM), to test the efficacy and safety of the system in vitro and to design a light weight (~22 kg) prototype home HD system equipped with high precision components for in vivo studies. Using minimum dialysate (<6L), the developed home HD system will achieve adequate toxin clearance with minimal ion and serum albumin loss, greatly improving the QOL of ESRD patients and their families by allowing for effective and comfortable treatment at home, work, or school or during travel. The broader impact/commercial potential of this project includes reducing the economic burden of end-stage renal disease (ESRD) on patients and Federal healthcare programs. As the number of ESRD patients approaches 3 million globally, it is becoming critical to decrease the cost and resource burden of the chronic dialysis treatment of these patients by drastically decreasing facility costs, use of water and energy in treatment, and to increase patients' quality of life by facilitating greater flexibility in length and place of treatment. The proposed semi-portable hemodialysis machine offers many advantages over currently available dialysis systems. The advantages are based on both the highly efficient dialysis regeneration capability and the light-weight, precisely configured and controlled machine. The savings in raw water costs alone from use of this HD system would be significant. The savings could be even greater in other parts of the world where water costs are significantly higher (i.e. Germany, Great Britain, etc.) and where access to clean water is becoming increasingly difficult (i.e. China, India, Mexico, etc.). The system will enhance the scientific and technical knowledge in the fields of dialysis and sorbent technologies