Colloid-Enhanced Flush Limits Initial Edema but Exacerbates Subsequent Edema During Hypothermic Machine Perfusion of Porcine Kidneys
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0000-0003-0311-1788 (Mohammad, Moath)
0000-0002-9022-3552 (Wade, Michael)
0000-0002-1766-5178 (Yurvati, Albert)
0000-0001-7388-9419 (Mallet, Robert)
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Abstract
Purpose:
The epidemic of end-stage renal disease (ESRD) has steadily increased demand for transplantable kidneys, and the widening disparity between organ supply and demand is a major public health concern. Hypothermic machine perfusion (HMP) is widely used to preserve deceased donor kidneys for transplantation. Kidneys are harvested and flushed with crystalloid solution before HMP. This study tested the hypothesis that flushing kidneys with solution containing a colloid, hydroxyethyl starch (HES), minimizes edema and improves organ perfusion during subsequent HMP.
Methods:
Kidneys harvested from anesthetized Yorkshire swine were flushed for 15 min with ice-cold Ringer’s solution ± 50 g/l HES, and then either biopsied or installed in a LifePort organ preservation system for 72 h hypothermic (2-4°C) machine perfusion (HMP) before biopsy. ATP contents in renal cortical biopsies were analyzed by UV-Vis spectrophotometry.
Results:
Kidneys gained 49 ± 5% of initial mass during flush with control solution, but only another 3% to 52 ± 5% of initial mass over 72 h HMP. Kidneys flushed with HES-enriched solution gained only 18 ± 3% of initial mass (P<0.001 vs control) during flush, but over 72 h HMP gained another 72% to 90 ± 7% above initial mass (P<0.001 vs. control). Tissue water contents paralleled the respective weight gains (Figure). The HES-flushed kidneys experienced steeper declines in perfusion during HMP than the controls. Cortical ATP content (mmol/g dry mass) fell over 72 h HMP from 2.36 ± 1.40 to 0.44 ± 0.44 (mean ± SD) in control kidneys, and from 1.36 ± 1.31 to 0.38 ± 0.16 in HES-flushed kidneys (both groups: P<0.05, pre- vs. post-HMP).
Conclusion:
Flushing kidneys with HES-enriched solution minimized edema before HMP, but exacerbated edema during subsequent machine perfusion, failed to preserve ATP, and was associated with a steeper decline in organ perfusion during HMP. The mechanisms responsible for edema exacerbation by HES-enhanced flush are under investigation.