Young Lee1, Sarah M L Steinbach2, David Basile3, Jaipal Singh4,3,5. 1. Indiana Center for Biomedical Innovation, Indianapolis, Indiana, USA, ylee2@iuhealth.org. 2. Department of Veterinary Clinical Sciences, Purdue University, West Lafayette, Indiana, USA. 3. Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine, Indianapolis, Indiana, USA. 4. Indiana Center for Biomedical Innovation, Indianapolis, Indiana, USA. 5. Vasculonics Inc., Indianapolis, Indiana, USA.
Abstract
INTRODUCTION: Blood levels of uremic toxin, asymmetric dimethylarginine (ADMA), are strongly associated with mortality in sepsis, renal failure, and cardiovascular and renal disease patients. METHODS: An extracorporeal approach to reduce pathological ADMA was developed. The dimethylarginine dimethylaminohydrolase (DDAH) was immobilized on agarose beads to prepare a cartridge. The efficacy of cartridge for ADMA lowering in blood was investigated. RESULTS: The DDAH beads and cartridge reduced ADMA from solution or plasma. The magnitude of ADMA removal was dependent on the quantity of DDAH linked to the beads and the flow rate. When tested in association with plasmapheresis, the DDAH-cartridge was highly effective in ADMA removal from the blood and improved the arginine/ADMA ratio in a pig model. CONCLUSION: A new, safe, and effective extracorporeal approach to lower ADMA was developed which may have application in improving outcomes in patients with vascular complications and risk of mortality associated with high ADMA.
INTRODUCTION: Blood levels of uremic toxin, asymmetric dimethylarginine (ADMA), are strongly associated with mortality in sepsis, renal failure, and cardiovascular and renal disease patients. METHODS: An extracorporeal approach to reduce pathological ADMA was developed. The dimethylarginine dimethylaminohydrolase (DDAH) was immobilized on agarose beads to prepare a cartridge. The efficacy of cartridge for ADMA lowering in blood was investigated. RESULTS: The DDAH beads and cartridge reduced ADMA from solution or plasma. The magnitude of ADMA removal was dependent on the quantity of DDAH linked to the beads and the flow rate. When tested in association with plasmapheresis, the DDAH-cartridge was highly effective in ADMA removal from the blood and improved the arginine/ADMA ratio in a pig model. CONCLUSION: A new, safe, and effective extracorporeal approach to lower ADMA was developed which may have application in improving outcomes in patients with vascular complications and risk of mortality associated with high ADMA.
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