Optimization of machine perfusion to preserve structure and function of porcine kidney




Wade, Michael
Yurvati, Albert
Williams, Arthur
Hare, Richard
Rayad, Ashraf
Chaudhari, Sarika


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

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Purpose: Improved preservation of explanted kidneys is essential to narrow the supply vs. demand disparity for transplantable human kidneys. This study evaluated whether the use of buffer containing mannitol, a non-toxic osmolyte that minimizes cellular edema, improves kidney preservation during prolonged hypothermic perfusion. Methods: Left kidneys were harvested from anesthetized Yorkshire pigs via laparotomy, followed by cold (2-4°C) machine perfusion for 72 h. Flow rate and resistance were recorded throughout perfusion to assess renal vascular function, then biopsy for histological analysis of hematoxylin and eosin-stained renal cortex and medulla. Results: Kidneys with comparable initial flows and resistances received standard (A) or mannitol-enriched (B) perfusion buffer. Flows (ml/min)/resistances (mm Hg/ml/min) were 65/0.40 (A) vs. 65/0.38 (B) at 5 h, 27/1.03 (A) vs. 54/0.46 (B) at 24 h, and 13/1.99 (A) vs. 49/0.50 (B) at 48 h perfusion. The mass of Kidney A increased by 47%, and that of kidney B by 39%, over 72 h. Histology revealed improved preservation of tubular and glomerular architecture in B vs. A. Conclusion: The addition of mannitol afforded appreciable improvement in renal vascular function during machine perfusion and reduced tubular necrosis when compared to mannitol-free perfusion. Preservation of renal structure using mannitol-enhanced perfusion buffer was superior to the current standard of cold machine perfusion buffer for preserving human kidneys for transplant. By reducing cellular damage and maintaining renal perfusion, the optimization of cold machine perfusion with mannitol holds the potential to increase the availability of kidneys suitable for transplantation.