Abstract
Cold preservation is the standard of care for renal grafts. However, research on alternatives like perfusion at higher temperatures and supplementing preservation solutions with hydrogen sulfide (H2S) has gained momentum. In this study, we investigated whether adding H2S donor AP39 to porcine blood during subnormothermic perfusion at 21 °C improves renal graft outcomes. Porcine kidneys were nephrectomized after 30 min of clamping the renal pedicles and treated to 4 h of static cold storage (SCS) on ice or ex vivo subnormothermic perfusion at 21 °C with autologous blood alone (SNT) or with AP39 (SNTAP). All kidneys were reperfused ex vivo with autologous blood at 37 °C for 4 h. Urine output, histopathology and RNAseq were used to evaluate the renal graft function, injury and gene expression profiles, respectively. The SNTAP group exhibited significantly higher urine output than other groups during preservation and reperfusion, along with significantly lower apoptotic injury compared to the SCS group. The SNTAP group also exhibited differential pro-survival gene expression patterns compared to the SCS (downregulation of pro-apoptotic genes) and SNT (downregulation of hypoxia response genes) groups. Subnormothermic perfusion at 21 °C with H2S-supplemented blood improves renal graft outcomes. Further research is needed to facilitate the clinical translation of this approach.
Highlights
We investigate whether subnormothermic perfusion at 21 ◦ C with hydrogen sulfide (H2 S) donor AP39 improves donation after cardiac death (DCD) porcine renal graft outcomes compared to static cold storage (SCS) and subnormothermic perfusion without AP39, using ex vivo pulsatile perfusion for preservation and reperfusion
To investigate whether subnormothermic perfusion with AP39-supplemented blood can improve ex vivo DCD renal graft function, porcine kidneys were assigned to four h of cold storage or subnormothermic perfusion with non-stressed blood at 21 ◦ C, with or without AP39
DCD kidneys perfused with AP39-supplemented blood (SNTAP group) exhibited significantly higher (p < 0.05) urine output than the kidneys perfused with blood on their own (SNT group) (Figure 2A)
Summary
Over the past 25 years, hydrogen sulfide (H2 S) has become known as the third gasotransmitter, following nitric oxide and carbon monoxide, and the body of literature about its roles in all cells and tissues continues to expand [1,2,3]. One interesting therapeutic application of H2 S is its use in kidney graft preservation to improve renal transplant outcomes. Renal transplantation is the preferred treatment for end stage renal disease, because it enhances the quality of life and survival compared to hemodialysis [4]. The demand for transplantable kidneys, outweighs the supply. Kidneys obtained via donation after cardiac death (DCD) are being used more often in transplant centers across the globe [5]. DCD kidneys typically exhibit higher rates of delayed graft function (DGF)
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