Role of symmetric dimethylarginine in predicting future renal impairment in liver transplant recipients.
Role of symmetric dimethylarginine in predicting future renal impairment in liver transplant recipients.
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对称二甲基精氨酸在预测肝移植受者未来肾损伤中的作用。
DOI：
10.1111/tri.13771
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Watt,KymberlyD
中科院分区：
文献类型：
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作者：
Izzy,Manhal;Angirekula,Mounika;Bentall,Andrew;Plevak,Matthew;Dierkhising,Ross;Lerman,LilachO;Tang,Hui;Hickson,LaTonya;Watt,KymberlyD
慢性肾脏病（CKD）在肝移植受者（LTR）中很常见，与移植物和患者生存率较差有关。多种因素与LTR中肾功能不全的发生相关，包括钙调磷酸酶抑制剂的使用、糖尿病（DM）和高血压[1]。CKD发展的基础病理生理学涉及肾内皮的变化[2]。对称二甲基精氨酸（SDMA）被认为与内皮功能障碍有关[3]，主要通过肾脏消除[4]。SDMA显示可预测肾移植受者的肾功能恶化[5]。然而，不知道SDMA是否在LTR中表现出相同的优势。我们研究了移植后早期SDMA水平相对于肾功能后期下降的关系。本研究是对2012年2月至2015年2月期间在马约诊所-罗切斯特接受肝移植并储存了既往研究血清标本的LTR记录的初步回顾性分析。最初的队列包括18至70岁的患者，他们在肝移植评估期间参加了前瞻性长期随访研究。移植后3周收集标本。排除了同时接受肝肾移植的患者。SDMA测试是使用ALPCO公司提供的酶联免疫吸附测定试剂盒进行的。收集人口统计学、临床和生化数据。主要终点是肾功能不良，定义为eGFR下降至< 30 ml/min/1.73 m2。使用SAS 9.4版（SAS Institute Inc.，卡里，北卡罗来纳州，美国）。本研究中有49名LTR，平均年龄为55.4（± 11.8）岁，其中18名为女性。移植前eGFR中位数为78.3（IQR 58.5，123.1）ml/min/1.73 m2。移植后3周的中位eGFR为73.6（IQR 60.9-91.1）ml/min/1.73 m2。17例患者患有DM。整个队列的中位随访时间为4.2年，其中25例患者达到终点。3周时中位SDMA水平为1.1（IQR 0.7，1.6）μmol/l。在单变量分析中，移植后3周时SDMA水平每增加1.0 μmol/l，未来肾脏不良结局的风险增加（HR 1.99，95% CI 1.03-3.84，P= 0.04）。在基于SDMA四分位数分析队列时，较高的四分位数与肾脏不良结局的较高风险相关（图1）。在控制DM后，在双变量分析中，移植后3周SDMA显示出与未来不良肾脏结局相关的显著性趋势（HR 1.92，CI 95% 0.97-3.82，P= 0.06）。校正基线eGFR后，SDMA和基线eGFR均未显示与最终肾脏结局不良的统计学显著相关性。这项初步研究揭示了SDMA在LTR中的潜在效用，并表明移植后早期SDMA水平较高，反映了内皮功能障碍增加和肾清除率降低，可能与未来的肾脏不良结局有关。虽然肾脏结局不良的发生率较高表明选择偏倚，因为样本来自既往研究储存库，但这不会影响关于预测肾脏结局的研究概念。这些初步观察结果确定了未来研究这种新型生物标志物的潜力，以帮助早期预测肝移植后肾脏不良结局。
Dear Editors Chronic kidney disease (CKD) is common among liver transplant recipients (LTR) and is associated with worse graft and patient survival. Multiple factors are associated with development of renal dysfunction in LTRs including use of calcineurin inhibitors, diabetes mellitus (DM), and hypertension [1]. The underlying pathophysiology for the development of CKD involves changes in renal endothelium [2]. Symmetric dimethylarginine (SDMA) is believed to be related to endothelial dysfunction [3], and it is eliminated mainly by the kidney [4]. SDMA was shown to predict worsening renal function in kidney transplant recipients [5]. However, it is unknown if SDMA demonstrates the same advantage in LTR. We studied SDMA levels in the early post-transplant period relative to later decline in kidney function. The study was a pilot retrospective analysis of records of LTRs who underwent liver transplant between 2/2012 and 2/2015 at Mayo Clinic-Rochester and had stored serum specimens from prior a research study. The original cohort included patients between 18 and 70 years old who, during liver transplant evaluation, were enrolled in a prospective long-term follow-up study. The specimens had been collected 3 weeks post-transplant. Recipients of simultaneous kidney–liver transplant were excluded. The SDMA testing was performed using enzyme-linked immunosorbent assay kits provided by ALPCO â. Demographic, clinical, and biochemical data were collected. The primary endpoint was poor renal outcomes defined by decline of eGFR to< 30 ml/min per 1.73 m2. Statistical analysis was performed using SAS â version 9.4 (SAS Institute Inc., Cary, NC, USA).There were forty-nine LTRs in this study with mean age 55.4 (+ 11.8) years of whom 18 were females. Median pretransplant eGFR was 78.3 (IQR 58.5, 123.1) ml/min/1.73 m2. Median eGFR at 3 weeks post-transplant was 73.6 (IQR 60.9–91.1) ml/min/1.73 m2. 17 patients had DM. The median follow-up time of the whole cohort was 4.2 years during which twenty-five patients reached the endpoint. Median SDMA level was 1.1 (IQR 0.7, 1.6) μmol/l at 3 weeks. On univariate analysis, for every 1.0 μmol/l increase in SDMA level at 3 weeks post-transplant there was increased risk of future poor renal outcomes (HR 1.99, 95% CI 1.03–3.84, P= 0.04). Upon analyzing the cohort based on SDMA quartiles, higher quartiles associated with higher risk of poor renal outcomes (Fig. 1). After controlling for DM, on bivariate analysis, 3 weeks post-transplant SDMA showed a trend toward significance (HR 1.92, CI 95% 0.97–3.82, P= 0.06) in relation to future poor renal outcomes. Upon adjusting for baseline eGFR, neither SDMA nor baseline eGFR showed statistically significant association with eventual poor renal outcomes. This pilot study sheds light on the potential utility of SDMA in LTRs and suggests that higher levels of SDMA in the early post-transplant setting, reflective of increased endothelial dysfunction and decreased renal clearance, may relate to future poor renal outcomes. While the high rate of poor renal outcomes suggests selection bias as specimens were obtained from prior study repository, this would not affect the study concept regarding predicting renal outcomes. These preliminary observations identify a potential for future investigation of this novel biomarker to aid in early prediction of poor renal outcomes after liver transplant.