Normothermic Machine Perfusion of Kidneys: Optimization of Perfusate

• Author / Creator

  Wu, Yilun

• Chronic kidney disease and end-stage renal disease (ESRD) are becoming increasingly prevalent in the world. The World Health Organization estimates that in 2015, 1.2 million people died from kidney failure, an increase of 32% from a decade ago. An estimated 2 million people worldwide are currently receiving lifesaving renal replacement therapy; however, the true prevalence of end-stage renal disease is estimated to be significantly higher. Two forms of renal replacement therapy currently exist: dialysis or transplantation. Kidney transplantation has demonstrated significant improvements in quality of life, survival, and cost-savings over dialysis. However, there are major drawbacks facing kidney transplantation, such as the availability and quality of donor grafts. With an ever-increasing demand for kidney allografts, it is necessary to improve the preservation, evaluation, and intervention of the recovered donor graft prior to transplantation. Traditional methods of kidney preservation rely upon hypothermia to reduce ischemic injury, but its lack of metabolic activity does not allow the evaluation of renal function or injury metrics prior to implantation. A novel method of normothermic ex situ machine perfusion (NMP) may be able to provide the metabolic support and re-establish renal function (waste removal and electrolyte homeostasis). Kidney NMP can offer a metabolically active environment that allows improved evaluation and intervention opportunities before the graft is transplanted. However, due to its relative immaturity as a clinical intervention, kidney NMP lacks an established gold standard perfusate composition and protocol. This research project investigates the effects of different perfusate components and their effects on proposed evaluation metrics during kidney NMP. The first study establishes hypothermic and normothermic machine perfusion protocols using a porcine kidney model and investigates perfusion dynamics and urine and perfusate compositions. The second study investigates the
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  effects of two oncotic agents on kidney NMP metrics. And the last study investigates the effects of two oxygen carriers on kidney NMP metrics. Research within this thesis aims to elucidate the efficacy of different perfusate components and their effects on various perfusion, inflammatory, and injury metrics within kidney NMP. With the optimization of perfusate composition and evaluation methods, normothermic kidney perfusion could improve clinical outcomes of kidney transplant recipients and improve the utilization of donor grafts.

• Subjects / Keywords

  • Machine Perfusion
  • Ex Situ Perfusion
  • Ex Vivo Perfusion
  • Perfusate
  • Whole Blood
  • Dextran
  • Kidney transplantation

• Graduation date

  Spring 2020

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-jq3p-v976

• License

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