Hydroxyethyl Starch-Enhanced Flush Initially Minimizes but Ultimately Exacerbates Edema of Machine Perfused Porcine Kidneys

Hydroxyethyl Starch-Enhanced Flush Initially Minimizes but Ultimately Exacerbates Edema of Machine Perfused Porcine Kidneys. Michael Wade, Katherine Ramos, Casey Horani, Ashraf Reyad, Arthur G. Williams Jr., Albert H. O-Yurvati, Robert T. Mallet. PURPOSE: Improved preservation of explanted kidneys is essential to narrow the supply vs. demand disparity for transplantable human kidneys. Edematous expansion of the explanted organ may make explanted kidneys unsuitable for transplant. This study evaluated the impact of initial flushing of porcine kidneys with a solution containing hydroxyethyl starch (HES), an osmolyte commonly used in preservation solutions for kidney transplantation, on edema during subsequent hypothermic machine perfusion METHODS: This study utilized kidneys from Yorkshire swine due to the anatomical and functional similarities of porcine and human kidneys. Left kidneys were harvested from isoflurane-anesthetized pigs via laparotomy. The renal artery was cannulated and the organ was flushed for 10 min with 400 mL of control Ringer's solution (group A) or with Ringer's solution containing 50 g/L hydroxyethyl starch (group B). Kidneys then underwent hypothermic machine perfusion (2-4°C) for 21-72 hr in a LifePort organ preservation system, with flow rates and resistance recorded throughout perfusion. The kidneys were weighed before and after flush of the organ, weighed again after machine perfusion, and then biopsied for histological analysis of renal cortex and medulla. RESULTS: Group A kidney mass increased by 49 ± 13% (mean ± standard deviation) during initial flush (n =7) and by 52 ± 14% after flush and 72 h machine perfusion (n=8); thus, 95% of the organ expansion occurred during the initial flush. In contrast, Group B kidney mass increased by 19 ± 9% during initial organ flush (n=6), a 60% reduction vs. Group A (P < 0.001), but total weight gain was 83 ± 21% after machine perfusion (n=3). Machine perfusion of 2 of the 3 Group B kidneys failed at 21 hr and 23 hr perfusion, and only 1 was perfused for the entire 72 hours. In both groups, histology revealed preserved tubular and glomerular architecture, but appreciable cellular edema following machine perfusion. Accumulation of debris in the tubular lumina and vacuolization of tubular epithelial cells was evident in Group B, but not Group A. CONCLUSION: In explanted kidneys flushed with colloid-free Ringer's and machine-perfused for 72 h, almost the entire increase in mass occurred during the initial organ flush. As hypothesized, the addition of HES colloid sharply lowered the initial organ expansion, but unexpectedly exacerbated organ expansion during subsequent hypothermic machine perfusion, such that the HES-flushed kidneys gained more mass than the controls flushed without HES. Thus, the potential benefit of including HES in the initial flush solution was lost during machine perfusion. Arguably, the excessive expansion may have contributed to the impaired machine perfusion of these kidneys. Animal Use Protocol: IACUC-2020-0011