Deterioration of Endothelial and Smooth Muscle Cell Function in DCD Kidneys After Static Cold Storage in IGL-1 or UW

Background

Kidneys obtained from donors after cardiac death are damaged by the combination of warm and cold ischemia. Although the parenchymal damage of these kidneys is well studied, little is known about the functional effects of warm and cold ischemia on the renal vascular bed. We compared kidney preservation using the new extracellular-type cold storage solution from Institut Georges Lopez (IGL-1) with the University of Wisconsin solution (UW) and focused on vasomotor functions.

Methods

The influence of warm and cold ischemia on vasomotor functions was studied in an isolated perfused kidney model. Six groups of donation after cardiac death donor kidneys were studied with warm ischemia of 0, 15, and 30 min followed by 0 or 24 h cold storage preservation in IGL-1 or UW at 4°C. Endothelial dependent vasodilation was studied using acetylcholine, smooth muscle cell (SMC) constriction was assessed using phenylephrine, and finally endothelial independent relaxation was tested using papaverine-sulfate.

Results

SMCs were significantly affected by cold ischemia showing a 50% reduction of phenylephrine mediated constriction after preservation. Additional warm ischemia did not affect SMCs. After UW preservation endothelial dependent vasodilation was only significantly reduced when the combination of warm and cold ischemia was present. IGL-1 preserved kidneys showed a reduction in endothelial dependent vasodilation after isolated warm ischemia. Both preservation solutions rendered equal results after 24 h preservation.

Conclusion

Vasomotor functions are negatively influenced by the combination of warm and cold ischemia. Both IGL-1 and UW performed equally in preserving vasomotor functions. The interesting finding of the rapid decline of SMC function might point at the first step toward intimal hyperplasia as seen in late transplant dysfunction.

Key Words: vasomotor function, preservation, donation after cardiac death, warm ischemia, kidney transplantation, isolated perfused kidney