Sodium Hydrosulfide Treatment During Porcine Kidney Ex Vivo Perfusion and Transplantation.

IF 1.9 Q3 TRANSPLANTATION Transplantation Direct Pub Date : 2023-10-30 eCollection Date: 2023-11-01 DOI:10.1097/TXD.0000000000001508
Thomas Agius, Julien Songeon, Arnaud Lyon, Justine Longchamp, Raphael Ruttimann, Florent Allagnat, Sébastien Déglise, Jean-Marc Corpataux, Déla Golshayan, Léo Buhler, Raphael Meier, Heidi Yeh, James F Markmann, Korkut Uygun, Christian Toso, Antoine Klauser, Francois Lazeyras, Alban Longchamp
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Abstract

Background: In rodents, hydrogen sulfide (H2S) reduces ischemia-reperfusion injury and improves renal graft function after transplantation. Here, we hypothesized that the benefits of H2S are conserved in pigs, a more clinically relevant model.

Methods: Adult porcine kidneys retrieved immediately or after 60 min of warm ischemia (WI) were exposed to 100 µM sodium hydrosulfide (NaHS) (1) during the hypothermic ex vivo perfusion only, (2) during WI only, and (3) during both WI and ex vivo perfusion. Kidney perfusion was evaluated with dynamic contrast-enhanced MRI. MRI spectroscopy was further employed to assess energy metabolites including ATP. Renal biopsies were collected at various time points for histopathological analysis.

Results: Perfusion for 4 h pig kidneys with Belzer MPS UW + NaHS resulted in similar renal perfusion and ATP levels than perfusion with UW alone. Similarly, no difference was observed when NaHS was administered in the renal artery before ischemia. After autotransplantation, no improvement in histologic lesions or cortical/medullary kidney perfusion was observed upon H2S administration. In addition, AMP and ATP levels were identical in both groups.

Conclusions: In conclusion, treatment of porcine kidney grafts using NaHS did not result in a significant reduction of ischemia-reperfusion injury or improvement of kidney metabolism. Future studies will need to define the benefits of H2S in human, possibly using other molecules as H2S donors.

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猪肾体外灌注和移植过程中的硫化钠治疗。
背景:在啮齿类动物中,硫化氢(H2S)可减少移植后的缺血再灌注损伤并改善肾移植功能。在这里,我们假设H2S的益处在猪身上是保守的,这是一个更具临床相关性的模型。方法:立即或60岁后取出成年猪肾 温缺血(WI)分钟暴露于100µM氢硫化钠(NaHS)(1)仅在低温离体灌注期间,(2)仅在WI期间,以及(3)在WI和离体灌注过程中。用动态增强MRI评价肾脏灌注。MRI波谱进一步用于评估包括ATP在内的能量代谢产物。在不同的时间点收集肾活检以进行组织病理学分析。结果:4次灌注 h用Belzer MPS UW+NaHS的猪肾与单独用UW的灌注相比产生相似的肾灌注和ATP水平。类似地,当在缺血前在肾动脉中施用NaHS时,没有观察到差异。自体移植后,H2S给药后,未观察到组织学损伤或皮质/髓质肾灌注的改善。此外,两组的AMP和ATP水平相同。结论:总之,使用NaHS治疗猪肾移植物并没有显著减少缺血再灌注损伤或改善肾脏代谢。未来的研究需要确定H2S对人体的益处,可能使用其他分子作为H2S供体。
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来源期刊
Transplantation Direct
Transplantation Direct TRANSPLANTATION-
CiteScore
3.40
自引率
4.30%
发文量
193
审稿时长
8 weeks
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