Urinary Post-Translationally Modified Fetuin-A Protein Is Associated with Increased Risk of Graft Failure in Kidney Transplant Recipients.

IF 4.3 3区医学 Q1 UROLOGY & NEPHROLOGY

American Journal of Nephrology Pub Date : 2024-01-01 Epub Date: 2023-11-06 DOI:10.1159/000534829

Firas F Alkaff, Daan Kremer, Charlotte A Te Velde-Keyzer, Jacob van den Born, Stefan P Berger, Gozewijn D Laverman, Lee-Ming Chuang, Tzu-Ling Tseng, Stephan J L Bakker

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Abstract

Introduction: Urinary fetuin-A has been identified as a biomarker for acute kidney injury and is proposed as a biomarker for early detection of kidney function decline. We investigated whether fetuin-A could serve as a marker of graft failure in kidney transplant recipients (KTRs).

Methods: Data of KTR with a functioning graft ≥1 year that were enrolled in the TransplantLines Food and Nutrition Biobank and cohort study were used. Graft failure was defined as the need for re-transplantation or (re-)initiation of dialysis. Urinary fetuin-A was measured using an enzyme-linked immunosorbent assay kit that detected post-translationally modified fetuin-A in the urine (uPTM-FetA). In the main analyses, 24h uPTM-FetA excretion was used. In the sensitivity analyses, we excluded the outliers in 24h uPTM-FetA excretion, and we used uPTM-FetA concentration and uPTM-FetA concentration indexed for creatinine instead of 24h uPTM-FetA excretion.

Results: A total of 627 KTRs (age 53 ± 13 years, 42% females) were included at 5.3 (1.9-12.2) years after transplantation. The estimated glomerular filtration rate (eGFR) was 52 ± 20 mL/min/1.73 m2 and uPTM-FetA excretion was 34 (17-74) µg/24 h. During a median follow-up of 5.3 (4.5-6.0) years after baseline measurements, 73 (12%) KTRs developed graft failure. The association of 24h uPTM-FetA excretion with increased risk of graft failure was not constant over time, with increased risk only observed after 3 years from baseline measurements, independent of potential confounders including kidney function and 24 h urinary protein excretion (hazard ratio per doubling of 24h uPTM-FetA excretion = 1.31; 95% confidence interval = 1.06-1.61). This finding was robust in the sensitivity analyses.

Conclusions: Our findings suggest that uPTM-FetA can be used as a marker for early detection of graft failure in KTR. Further studies are needed to confirm our findings.

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尿中翻译后修饰的胎儿A蛋白与肾移植受者移植失败风险增加有关。

引言：尿胎蛋白-A已被确定为急性肾损伤的生物标志物，并被提议作为早期检测肾功能下降的生物标志。我们研究了胎球蛋白-A是否可以作为肾移植受者（KTR）移植物衰竭的标志物。方法：使用TransplantLines Food and Nutrition Biobank和Cohort研究中登记的移植物功能≥1年的KTR数据。移植物衰竭被定义为需要再次移植或（重新）开始透析）。使用检测尿液中翻译后修饰的胎蛋白-A的酶联免疫吸附测定试剂盒（uPTM-FetA）测量尿中胎蛋白-A。在主要分析中，使用24小时uPTM-FetA排泄。在敏感性分析中，我们排除了24小时uPTM-FetA排泄的异常值，并使用uPTM-FetA浓度和uPTM-Fita浓度作为肌酐指数，而不是24小时uPTM-FetA排出。结果：共有627 KTR（年龄53±13岁，42%为女性）在移植后5.3[1.9-12.2]年被纳入。估计肾小球滤过率（eGFR）为52±20 mL/min/1.73 m2，uPTM-FetA排泄量为34[17-74]µg/24h。在基线测量后5.3[4.5-6.0]年的中位随访期间，73（12%）KTR出现移植物衰竭。24小时uPTM-FetA排泄与移植物衰竭风险增加的相关性并非随时间而恒定，仅在基线测量后3年后观察到风险增加，独立于潜在的混杂因素，包括肾功能和24小时尿蛋白排泄量（24小时uPTM-FetA排泄量每增加一倍的风险比=1.31；95%置信区间=1.06-1.61）。这一发现在敏感性分析中是稳健的。结论：我们的研究结果表明uPTM-FetA可以作为KTR移植物衰竭早期检测的标志物。需要进一步的研究来证实我们的发现。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

American Journal of Nephrology 医学-泌尿学与肾脏学

CiteScore

7.50

自引率

2.40%

发文量

审稿时长

4-8 weeks

期刊介绍： The ''American Journal of Nephrology'' is a peer-reviewed journal that focuses on timely topics in both basic science and clinical research. Papers are divided into several sections, including: