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肾移植后供体炎症和凋亡相关基因型与移植肾延迟功能的关联

Association of donor inflammation- and apoptosis-related genotypes and delayed allograft function after kidney transplantation.

作者信息

Israni Ajay K, Li Na, Cizman Bojana B, Snyder Jon, Abrams John, Joffe Marshall, Rebbeck Timothy, Feldman Harold I

机构信息

Department of Medicine, Hennepin County Medical Center, University of Minnesota, Minneapolis, MN, USA.

出版信息

Am J Kidney Dis. 2008 Aug;52(2):331-9. doi: 10.1053/j.ajkd.2008.05.006.

DOI:10.1053/j.ajkd.2008.05.006
PMID:18640487
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2562522/
Abstract

BACKGROUND

Delayed renal allograft survival (delayed graft function [DGF]) after deceased donor kidney transplantation is associated with an increased risk of allograft loss. Inflammatory response and apoptosis are associated with increased risk of DGF.

STUDY DESIGN

Cross-sectional study.

SETTING & PARTICIPANTS: We first recruited 616 recipients of kidneys from 512 deceased kidney donors, and donor DNA was genotyped. These recipients, who were included in a prospective cohort study of 9 transplant centers in the Delaware Valley region, had their DGF outcome obtained through medical record abstraction. We then identified the recipient (n = 349) of the contralateral deceased kidney donor, if not part of the cohort, through the US Renal Data System registry. The final cohort consisted of 965 recipients of deceased donor kidneys from 512 donors.

PREDICTORS

Donor single-nucleotide polymorphisms in genes for tumor necrosis factor alpha (TNF), transforming growth factor beta1 (TGFB1), interleukin 10 (IL10), p53 (TP53), and heme oxygenase 1 (HMOX1).

OUTCOMES

DGF, defined as the need for dialysis therapy in the first week posttransplantation. Secondary outcomes included acute rejection and estimated glomerular filtration rate.

MEASUREMENTS

Information for DGF, acute rejection, and estimated glomerular filtration rate for recipients in the Delaware Valley Cohort was obtained through medical record abstraction. For other recipients, information for DGF was obtained from United Network for Organ Sharing forms and Centers for Medicare & Medicaid Services claims in the US Renal Data System registry.

RESULTS

No association was detected between the TGFB1, IL10, TP53, and HMOX1 genes and DGF. The G allele of the TNF polymorphism rs3093662 was associated with DGF in an adjusted analysis (odds ratio, 1.85 compared with A allele; 95% confidence interval, 1.16 to 2.96; P = 0.01). However, this association did not achieve statistical significance after adjusting for multiple comparisons.

LIMITATIONS

Inadequate sample size for infrequent genotypes and multiple comparisons.

CONCLUSION

Because of the low frequency of donor single-nucleotide polymorphisms of interest, a larger sample size and replication are necessary to confirm these findings on the association of donor genotypes with DGF.

摘要

背景

在 deceased 供体肾移植后,移植肾延迟存活(移植肾功能延迟恢复 [DGF])与移植肾丢失风险增加相关。炎症反应和细胞凋亡与 DGF 风险增加有关。

研究设计

横断面研究。

设置与参与者

我们首先招募了来自 512 名 deceased 肾供体的 616 名肾移植受者,并对供体 DNA 进行基因分型。这些受者被纳入特拉华谷地区 9 个移植中心的前瞻性队列研究,通过病历摘要获得他们的 DGF 结果。然后,我们通过美国肾脏数据系统登记处确定了对侧 deceased 肾供体的受者(n = 349),如果他们不是该队列的一部分。最终队列由来自 512 名供体的 965 名 deceased 供体肾移植受者组成。

预测因素

肿瘤坏死因子α(TNF)、转化生长因子β1(TGFB1)、白细胞介素 10(IL10)、p53(TP53)和血红素加氧酶 1(HMOX1)基因中的供体单核苷酸多态性。

结果

DGF,定义为移植后第一周需要透析治疗。次要结果包括急性排斥反应和估计的肾小球滤过率。

测量

通过病历摘要获得特拉华谷队列中受者的 DGF、急性排斥反应和估计的肾小球滤过率信息。对于其他受者,DGF 信息从器官共享联合网络表格和美国肾脏数据系统登记处的医疗保险和医疗补助服务中心索赔中获得。

结果

未检测到 TGFB1、IL10、TP53 和 HMOX1 基因与 DGF 之间的关联。TNF 多态性 rs3093662 的 G 等位基因在调整分析中与 DGF 相关(优势比,与 A 等位基因相比为 1.85;95%置信区间,1.16 至 2.96;P = 0.01)。然而,在进行多重比较调整后,这种关联未达到统计学显著性。

局限性

罕见基因型的样本量不足和多重比较。

结论

由于感兴趣的供体单核苷酸多态性频率较低,需要更大的样本量和重复研究来证实这些关于供体基因型与 DGF 关联的发现。

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