Optimizing the approach to monitoring allograft inflammation using serial urinary CXCL10/creatinine testing in pediatric kidney transplant recipients.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-05-01 DOI:10.1111/petr.14718

Ella Barrett-Chan, Li Wang, Jeffrey Bone, Amy Thachil, Kevin Vytlingam, Tom Blydt-Hansen

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Abstract

Background: Urinary CXCL10/creatinine (uCXCL10/Cr) is proposed as an effective biomarker of subclinical rejection in pediatric kidney transplant recipients. This study objective was to model implementation in the clinical setting.

Methods: Banked urine samples at a single center were tested for uCXCL10/Cr to validate published thresholds for rejection diagnosis (>80% specificity). The positive predictive value (PPV) for rejection diagnosis for uCXCL10/Cr-indicated biopsy was modeled with first-positive versus two-test-positive approaches, with accounting for changes associated with urinary tract infection (UTI), BK and CMV viremia, and subsequent recovery.

Results: Seventy patients aged 10.5 ± 5.6 years at transplant (60% male) had n = 726 urine samples with n = 236 associated biopsies (no rejection = 167, borderline = 51, and Banff 1A = 18). A threshold of 12 ng/mmol was validated for Banff 1A versus no-rejection diagnosis (AUC = 0.74, 95% CI = 0.57-0.92). The first-positive test approach (n = 69) did not resolve a clinical diagnosis in 38 cases (55%), whereas the two-test approach resolved a clinical diagnosis in the majority as BK (n = 17/60, 28%), CMV (n = 4/60, 7%), UTI (n = 8/60, 13%), clinical rejection (n = 5/60, 8%), and transient elevation (n = 18, 30%). In those without a resolved clinical diagnosis, PPV from biopsy for subclinical rejection is 24% and 71% (p = .017), for first-test versus two-test models, respectively. After rejection treatment, uCXCL10/Cr level changes were all concordant with change in it-score. Sustained uCXCL10/Cr after CMV and BK viremia resolution was associated with later acute rejection.

Conclusions: Urinary CXCL10/Cr reliably identifies kidney allograft inflammation. These data support a two-test approach to reliably exclude other clinically identifiable sources of inflammation, for kidney biopsy indication to rule out subclinical rejection.

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利用连续尿液CXCL10/肌酐检测优化监测小儿肾移植受者异体移植物炎症的方法。

背景：尿液CXCL10/肌酐（uCXCL10/Cr）被认为是小儿肾移植受者亚临床排斥反应的有效生物标志物。本研究的目的是模拟在临床环境中的实施情况：方法：对一个中心的库存尿样进行uCXCL10/Cr检测，以验证已公布的排斥反应诊断阈值（特异性>80%）。结果：70 名年龄在 10.5 岁（含）以下的患者接受了uCXCL10/Cr检测：70名移植时年龄为（10.5 ± 5.6）岁的患者（60%为男性）共采集了n = 726份尿液样本和n = 236份相关活检样本（无排斥反应 = 167份、边缘 = 51份和Banff 1A = 18份）。班夫 1A 与无排斥诊断的阈值为 12 纳克/毫摩尔（AUC = 0.74，95% CI = 0.57-0.92）。首次阳性检测方法（n = 69）中有 38 例（55%）没有得到临床诊断，而两次检测方法中大多数人得到了临床诊断，分别是 BK（n = 17/60，28%）、CMV（n = 4/60，7%）、UTI（n = 8/60，13%）、临床排斥（n = 5/60，8%）和一过性升高（n = 18，30%）。在没有得到明确临床诊断的患者中，通过活检发现亚临床排斥反应的 PPV 在一测模型和二测模型中分别为 24% 和 71% (p = .017)。排斥治疗后，uCXCL10/Cr水平的变化与it评分的变化一致。CMV和BK病毒血症缓解后，持续的uCXCL10/Cr与后期急性排斥反应有关：结论：尿液中的 CXCL10/Cr 能可靠地识别肾脏移植物炎症。这些数据支持采用两种检测方法可靠地排除其他临床上可识别的炎症来源，以肾活检为指征排除亚临床排斥反应。

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

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.