Optimizing Preservation Solutions for Hypothermic Machine-Perfused Porcine Kidneys

Date

2022

Authors

Ramos, Katherine
Wade, Michael
Williams, Arthur
Yurvati, Albert

ORCID

0000-0002-9022-3552 (Wade, Michael)
0000-0001-7388-9419 (Mallet, Robert T.)
0000-0002-1766-5178 (Yurvati, Albert)

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Abstract

Background: With the mounting incidence of hypertension, type 2 diabetes and other risk factors, end-stage renal disease (ESRD) is increasingly prevalent in the U.S. and worldwide, especially among racial minorities including Hispanics and African Americans. Kidney transplant is the most effective treatment for ESRD, but the supply of transplantable kidneys is inadequate to meet the increasing demand. Before transplantation, kidneys from deceased donors are maintained in a device (LifePort) that pumps ice-cold preservation solution through the organ. Although this hypothermic machine perfusion (HMP) is the most effective kidney preservation method available, kidneys from deceased donors often fail to resume function after transplant, especially when HMP is prolonged. Consequently, any kidneys not transplanted within 30 hours of harvest are discarded. We propose that optimizing the composition of the preservation solution may prevent post-transplant kidney failure and thereby improve kidney transplant outcomes, and potentially extend the useful lifespan of explanted kidneys beyond 30 hours, thereby increasing the pool of available kidneys for transplant. Hypothesis: Hypothermic perfusion of kidneys with solutions containing pyruvate, an energy substrate, anti-oxidant and anti-inflammatory compound, will better maintain perfusion flow and lower vascular resistance, indicating improved stability of the explanted organs. Methods: Kidneys obtained from thirteen anesthetized female Yorkshire pigs were fluid-flushed and then perfused for 72 h with modified, cold (2-4?C) Ringer's solution containing 20 mM glucose, 30 mM mannitol, 50 g/l hydroxyethyl starch ? 20 mM pyruvate in a LifePort organ preservation device while flow and renal vascular resistance were monitored and recorded. Results: Kidneys maintained adequate perfusion for 72 hours despite a 50 ? 4% (mean ? SEM) increase in kidney mass indicating edema. Flows plateaued within the first 6 hours of perfusion and then declined slowly with prolonged perfusion. At 6 h perfusion, flows (ml/min*g) were 0.54 ? 0.06 in kidneys receiving control solution, and 0.61 ? 0.06 in kidneys perfused with pyruvate-enriched solution. At 24 and 72 h, flows were 0.49 ? 0.06 and 0.38 ? 0.04 in the control kidneys, and 0.49 ? 0.03 and 0.37 ? 0.02 in the kidneys perfused with pyruvate enriched solution, respectively. The increases in mass of the control (52?4%) and pyruvate (46?6%) over 72 h perfusion did not differ. Conclusions: Pyruvate augmentation of preservation solution did not affect hypothermic kidney perfusion. The possibilities that pyruvate may affect the kidney's energy and/or antioxidant metabolism without altering organ perfusion or edema, and that measures limiting edema could improve kidney perfusion during HMP, remain to be tested.

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