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尿L-FABP检测在造血干细胞移植后急性肾损伤检测中的应用

Urinary L-FABP Assay in the Detection of Acute Kidney Injury following Haematopoietic Stem Cell Transplantation.

作者信息

Mitra Roshni, Tholouli Eleni, Rajai Azita, Saha Ananya, Mitra Sandip, Mitsides Nicos

机构信息

Department of Haemato-Oncology, St Bartholomew's Hospital, Barts Health NHS Trust, London EC1A 7BE, UK.

Department of Haematology, Manchester University Hospitals, Oxford Road, Manchester M13 9WL, UK.

出版信息

J Pers Med. 2024 Oct 9;14(10):1046. doi: 10.3390/jpm14101046.

Abstract

: Acute Kidney Injury (AKI) is a condition that affects a significant proportion of acutely unwell patients and is associated with a high mortality rate. Patients undergoing haemopoietic stem cell transplantation (HSCT) are in an extremely high group for AKI. Identifying a biomarker or panel of markers that can reliably identify at-risk individuals undergoing HSCT can potentially impact management and outcomes. Early identification of AKI can reduce its severity and improve prognosis. We evaluated the urinary Liver type fatty acid binding protein (L-FABP), a tubular stress and injury biomarker both as an ELISA and a point of care (POC) assay for AKI detection in HSCT. : 85 patients that had undergone autologous and allogenic HSCT (35 and 50, respectively) had urinary L-FABP (uL-FABP) measured by means of a quantitative ELISA and a semi-quantitative POC at baseline, day 0 and 7 post-transplantation. Serum creatinine (SCr) was also measured at the same time. Patients were followed up for 30 days for the occurrence of AKI and up to 18 months for mortality. The sensitivity and specificity of uL-FABP as an AKI biomarker were evaluated and compared to the performance of sCr using ROC curve analysis and logistic regression. : 39% of participants developed AKI within 1 month of their transplantation. The incidence of AKI was higher in the allogenic group than in the autologous HTSC group (57% vs. 26%, = 0.008) with the median time to AKI being 25 [range 9-30] days. This group was younger (median age 59 vs. 63, < 0.001) with a lower percentage of multiple myeloma as the primary diagnosis (6% vs. 88%, < 0.001). The median time to AKI diagnosis was 25 [range 9-30] days. uL-FABP (mcg/gCr) at baseline, day of transplant and on the 7th day post-transplant were 1.61, 5.39 and 10.27, respectively, for the allogenic group and 0.58, 4.36 and 5.14 for the autologous group. Both SCr and uL-FABP levels rose from baseline to day 7 post-transplantation, while the AUC for predicting AKI for baseline, day 0 and day 7 post-transplant was 0.54, 0.59 and 0.62 for SCr and for 0.49, 0.43 and 0.49 uL-FABP, respectively. Univariate logistic regression showed the risk of AKI to be increased in patients with allogenic HSCT ( = 0.004, 95%CI [0.1; 0.65]) and in those with impaired renal function at baseline ( = 0.01, 95%CI [0.02, 0.54]). The risk of AKI was also significantly associated with SCr levels on day 7 post-transplant ( = 0.03, 95%CI [1; 1.03]). Multivariate logistic regression showed the type of HSCT to be the strongest predictor of AKI at all time points, while SCr levels at days 0 and 7 also correlated with increased risk in the model that included uL-FABP levels at the corresponding time points. The POC device for uL-FABP measurement correlated with ELISA ( < 0.001, Spearman 'correlation' = 0.54) : The urinary biomarker uL-FABP did not demonstrate an independent predictive value in the detection of AKI at all stages. The most powerful risk predictor of AKI in this setting appears to be allograft recipients and baseline renal impairment, highlighting the importance of clinical risk stratification. Urinary L-FAPB as a POC biomarker was comparable to ELISA, which provides an opportunity for simple and rapid testing. However, the utility of LFABP in AKI is unclear and needs further exploration. Whether screening through rapid testing of uL-FABP can prevent or reduce AKI severity is unknown and merits further studies.

摘要

急性肾损伤(AKI)是一种影响相当比例急性病患者的病症,且与高死亡率相关。接受造血干细胞移植(HSCT)的患者属于发生AKI风险极高的群体。识别一种或一组能够可靠识别接受HSCT的高危个体的生物标志物,可能会对治疗管理和治疗结果产生影响。早期识别AKI可降低其严重程度并改善预后。我们评估了尿肝型脂肪酸结合蛋白(L-FABP),一种肾小管应激和损伤生物标志物,采用酶联免疫吸附测定(ELISA)和即时检测(POC)方法来检测HSCT中的AKI。85例接受自体和异体HSCT的患者(分别为35例和50例)在基线、移植后第0天和第7天通过定量ELISA和半定量POC测定尿L-FABP(uL-FABP)。同时也测定血清肌酐(SCr)。对患者进行30天的随访以观察AKI的发生情况,并进行长达18个月的死亡率随访。使用ROC曲线分析和逻辑回归评估uL-FABP作为AKI生物标志物的敏感性和特异性,并与SCr的性能进行比较。39%的参与者在移植后1个月内发生AKI。异体组的AKI发生率高于自体HSCT组(57%对26%,P = 0.008),发生AKI的中位时间为25天[范围9 - 30天]。该组患者更年轻(中位年龄59岁对63岁,P < 0.001),以多发性骨髓瘤作为主要诊断的比例更低(6%对88%,P < 0.001)。AKI诊断的中位时间为25天[范围9 - 30天]。异体组在基线、移植日和移植后第7天的uL-FABP(μg/gCr)分别为1.61、5.39和10.27,自体组分别为0.58、4.36和5.14。SCr和uL-FABP水平从基线到移植后第7天均升高,而移植后基线、第0天和第7天预测AKI的AUC,SCr分别为0.54、0.59和0.62,uL-FABP分别为0.49、0.43和0.49。单因素逻辑回归显示,异体HSCT患者(P = 0.004,95%CI[0.1;0.65])和基线肾功能受损患者(P = 0.01,95%CI[0.02,0.54])发生AKI的风险增加。移植后第7天的AKI风险也与SCr水平显著相关(P = 0.03,95%CI[1;1.03])。多因素逻辑回归显示,HSCT类型在所有时间点都是AKI的最强预测因素,而在包含相应时间点uL-FABP水平的模型中,第0天和第7天的SCr水平也与风险增加相关。用于测量uL-FABP的POC设备与ELISA相关(P < 0.001,Spearman相关性 = 0.54)。尿生物标志物uL-FABP在各阶段AKI检测中均未显示出独立的预测价值。在这种情况下,AKI最有力的风险预测因素似乎是同种异体移植受者和基线肾功能损害,突出了临床风险分层评估的重要性。尿L-FAPB作为POC生物标志物与ELISA相当,这为简单快速检测提供了机会。然而,LFABP在AKI中的效用尚不清楚,需要进一步探索。通过快速检测uL-FABP进行筛查是否能预防或降低AKI严重程度尚不清楚,值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da98/11508925/e37a7f8452db/jpm-14-01046-g001.jpg

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