Association of Kidney Graft Long-term Outcome With Recipient Cystathionine Gamma-lyase Polymorphisms and Hydrogen Sulfide Levels: A Cohort Study.

IF 1.9 Q3 TRANSPLANTATION
Transplantation Direct Pub Date : 2025-04-17 eCollection Date: 2025-05-01 DOI:10.1097/TXD.0000000000001779
Matthieu Halfon, Raffaella Emsley, Thomas Agius, Arnaud Lyon, Sébastien Déglise, Manuel Pascual, Korkut Uygun, Heidi Yeh, Leonardo V Riella, James F Markmann, Pierre-Yves Bochud, Dela Golshayan, Alban Longchamp
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引用次数: 0

Abstract

Background: Hydrogen sulfide (H2S) produced endogenously by the CTH gene-encoded cystathionine gamma-lyase protects from renal ischemia-reperfusion injury in preclinical models. Here, we hypothesized that CTH gene polymorphisms (single nucleotide polymorphism [SNP]) and recipient H2S serum levels influence kidney graft outcomes after transplantation.

Methods: We included all consecutive recipients of a first kidney transplant in the Swiss Transplant Cohort Study and with available genotyping. In addition, 192 deceased-donor kidney transplant recipients were randomly selected to measure baseline serum H2S levels. The primary endpoint was graft loss during follow-up.

Results: CTH SNPs were identified in up to 50% of the patients. During median follow-up (6.4 y, interquartile range: 3.9-9.8), graft loss was observed in 247 (9.8%) of 2518 patients. The incidence of graft loss was associated with the presence or absence of CTH SNPs. Specifically, rs672203 and rs10458561, increased the risk of graft loss (hazard ratio [HR]: 1.36, 95% confidence interval [CI]: 1.04-1.78, P = 0.02; and HR: 1.29, 95% CI: 1.0-1.66, P = 0.05; respectively), whereas rs113285275 was protective (HR: 0.78, 95% CI: 0.6-1.01, P = 0.05). Interestingly, rs672203 was associated with an increased risk of acute rejection (P = 0.05), whereas rs113285275 was associated with a lower risk of acute rejection (P = 0.01). Finally, in patients with delayed graft function, serum H2S levels correlated with lower graft dysfunction (defined as estimated glomerular filtration rate <30 mL/min/1.73 m2) (P = 0.05).

Conclusions: Graft outcome after kidney transplantation was associated with CTH genotype and, to some extent, H2S serum levels. Further research is needed to define the underlying protective mechanisms.

肾移植长期预后与受体半胱硫氨酸γ -裂解酶多态性和硫化氢水平的关联:一项队列研究。
背景:在临床前模型中,由CTH基因编码的半胱甘氨酸γ -裂解酶内源性产生的硫化氢(H2S)可保护肾脏缺血-再灌注损伤。在这里,我们假设CTH基因多态性(单核苷酸多态性[SNP])和受体H2S血清水平影响肾移植后的移植结果。方法:我们纳入了瑞士移植队列研究中所有首次肾移植的连续接受者,并具有可用的基因分型。此外,随机选择192例死亡供体肾移植受者测量基线血清H2S水平。主要终点是随访期间移植物丢失。结果:高达50%的患者发现了CTH snp。在中位随访期间(6.4年,四分位数间距:3.9-9.8),2518例患者中有247例(9.8%)出现移植物丢失。移植物丢失的发生率与CTH snp的存在与否有关。其中,rs672203和rs10458561增加了移植物丢失的风险(风险比[HR]: 1.36, 95%可信区间[CI]: 1.04-1.78, P = 0.02;HR: 1.29, 95% CI: 1.0 ~ 1.66, P = 0.05;rs113285275具有保护作用(HR: 0.78, 95% CI: 0.6 ~ 1.01, P = 0.05)。有趣的是,rs672203与急性排斥反应风险增加相关(P = 0.05),而rs113285275与急性排斥反应风险降低相关(P = 0.01)。最后,在移植物功能延迟的患者中,血清H2S水平与较低的移植物功能障碍(定义为肾小球滤过率2)相关(P = 0.05)。结论:肾移植术后移植预后与CTH基因型有关,并在一定程度上与血清H2S水平有关。需要进一步的研究来确定潜在的保护机制。
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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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