Department of Renal Medicine, Aarhus University Hospital, Aarhus N, Denmark.
Department of Biomedicine, Aarhus University, Aarhus C, Denmark.
PLoS One. 2021 Aug 11;16(8):e0255930. doi: 10.1371/journal.pone.0255930. eCollection 2021.
Reduced free thiols in plasma are indicative of oxidative stress, which is an important contributor to ischaemia-reperfusion injury (IRI) in kidney transplantation leading to kidney damage and possibly delayed graft function (DGF). In a post-hoc, exploratory analysis of the randomised controlled CONTEXT trial, we investigated whether higher (i.e. less oxidised) plasma levels of free thiols as a biomarker of reduced oxidative stress are associated with a better initial graft function or a higher GFR.
Free thiol levels were measured in plasma at baseline, 30 and 90 minutes after reperfusion of the kidney as well as at Day 1, Day 5 and twelve months after kidney transplantation in 217 patients from the CONTEXT study. Free thiol levels were compared to the kidney graft function measured as the estimated time to a 50% reduction in plasma creatinine (tCr50), the risk of DGF and measured GFR (mGFR) at Day 5 and twelve months after transplantation.
Higher levels of free thiols at Day 1 and Day 5 are associated with higher mGFR at Day 5 (p<0.001, r2adj. = 0.16; p<0.001, r2adj. = 0.25), as well as with mGFR at twelve months (p<0.001, r2adj. = 0.20; p<0.001, r2adj. = 0.16). However, plasma levels of free thiols at 30 minutes and 90 minutes, but not Day 1, were significantly higher among patients experiencing DGF.
Higher levels of plasma free thiols at Day 1 and Day 5, which are reflective of lower levels of oxidative stress, are associated with better early and late graft function in recipients of a kidney graft from deceased donors.
ClinicalTrials.gov Identifier: NCT01395719.
血浆中还原型巯基减少表明存在氧化应激，这是导致肾移植中缺血再灌注损伤（IRI）的重要因素，进而导致肾损伤和可能的延迟移植物功能（DGF）。在随机对照 CONTEXT 试验的事后探索性分析中，我们研究了作为氧化应激降低的生物标志物的较高（即氧化程度较低）血浆游离巯基水平是否与更好的初始移植物功能或更高的肾小球滤过率（GFR）相关。
在 217 例 CONTEXT 研究患者中，在肾再灌注后 30 分钟和 90 分钟以及肾移植后第 1 天、第 5 天和 12 个月测量血浆中游离巯基水平。将游离巯基水平与作为血浆肌酐（tCr50）降低 50%所需时间（tCr50）、DGF 风险和移植后第 5 天和 12 个月时测量的 GFR（mGFR）来比较。
第 1 天和第 5 天较高的游离巯基水平与第 5 天较高的 mGFR 相关（p<0.001，r2adj. = 0.16；p<0.001，r2adj. = 0.25），也与第 12 个月时的 mGFR 相关（p<0.001，r2adj. = 0.20；p<0.001，r2adj. = 0.16）。然而，在发生 DGF 的患者中，再灌注后 30 分钟和 90 分钟时，而不是第 1 天，血浆游离巯基水平显著升高。
在死亡供体肾移植受者中，第 1 天和第 5 天较高的血浆游离巯基水平反映了较低的氧化应激水平，与早期和晚期移植物功能较好相关。
ClinicalTrials.gov 标识符：NCT01395719。
