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载脂蛋白 L1(APOL1)编码变异与心脏手术后肌酐升高相关。

Apolipoprotein L1 (APOL1) Coding Variants Are Associated With Creatinine Rise After Cardiac Surgery.

机构信息

Department of Anesthesiology, Duke University Medical Center, Durham, NC.

Department of Anesthesiology, Duke University Medical Center, Durham, NC; Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC; Duke Molecular Physiology Institute, Duke University, Durham, NC.

出版信息

J Cardiothorac Vasc Anesth. 2020 Dec;34(12):3314-3320. doi: 10.1053/j.jvca.2020.04.017. Epub 2020 May 11.

Abstract

OBJECTIVE

Acute kidney injury (AKI) is a complication of cardiac surgery that is considerably more common in African Americans (1.5-fold). Although homozygous status for apolipoprotein L1 (APOL1) risk alleles is associated with chronic kidney disease in individuals of African ancestry, whether these coding variants confer AKI risk is unknown. The present study examined whether APOL1 homozygous risk allele status was associated with AKI in African Americans after cardiac surgery.

DESIGN

Retrospective analysis of a cohort.

SETTING

Single-center university hospital.

PARTICIPANTS

African American patients from the CATHeterization GENetics study cohort who underwent cardiac surgery with cardiopulmonary bypass.

INTERVENTIONS

Genotyping of APOL1 alleles.

MEASUREMENTS AND MAIN RESULTS

Data from 125 African American patients included 12 APOL1 risk (ie, homozygous for risk alleles) patients and 113 APOL1 control (ie, wildtype or heterozygous for risk alleles) patients. The primary outcome to reflect AKI was peak serum creatinine rise after surgery relative to the preoperative creatinine (%ΔCr). The secondary outcome was Kidney Disease: Improving Global Outcomes (KDIGO) AKI criteria. In the primary analysis, peak creatinine rise was higher in risk compared with control patients in both univariate (%ΔCr 69.1 v 29.6%; p = 0.005) and multivariate regression (%ΔCr 88.5 v 43.7%; p = 0.006) analyses. For the secondary outcome, a trend toward KDIGO AKI development was noted in APOL1 risk patients, but this was not statistically significant.

CONCLUSIONS

African American cardiac surgery patients homozygous for APOL1 chronic kidney disease risk variants averaged a more than 2-fold higher postoperative creatinine rise even after adjustment for other risk factors, suggesting these alleles also are independent risk factors for AKI.

摘要

目的

急性肾损伤(AKI)是心脏手术的一种并发症,在非裔美国人中更为常见(1.5 倍)。虽然载脂蛋白 L1(APOL1)风险等位基因的纯合状态与非裔个体的慢性肾脏病有关,但这些编码变异是否会导致 AKI 风险尚不清楚。本研究旨在探讨 APOL1 纯合风险等位基因状态是否与心脏手术后非裔美国人的 AKI 相关。

设计

队列的回顾性分析。

地点

单中心大学医院。

参与者

接受体外循环心脏手术的 CATHeterization GENetics 研究队列中的非裔美国患者。

干预措施

APOL1 等位基因的基因分型。

测量和主要结果

纳入 125 名非裔美国患者的数据,包括 12 名 APOL1 风险(即,纯合风险等位基因)患者和 113 名 APOL1 对照(即,野生型或杂合风险等位基因)患者。反映 AKI 的主要结果是手术后相对于术前肌酐的血清肌酐峰值升高(%ΔCr)。次要结果是肾脏病:改善全球结局(KDIGO)AKI 标准。在单因素分析中,风险组患者的肌酐峰值升高高于对照组(%ΔCr 69.1 比 29.6%;p=0.005),多因素回归分析中也如此(%ΔCr 88.5 比 43.7%;p=0.006)。对于次要结果,APOL1 风险患者 KDIGO AKI 发展呈趋势,但无统计学意义。

结论

即使在调整其他危险因素后,携带 APOL1 慢性肾脏病风险变异的非裔美国心脏手术患者的术后肌酐升高平均高出 2 倍以上,提示这些等位基因也是 AKI 的独立危险因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a714/7655610/b507ede8a194/nihms-1594419-f0001.jpg

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本文引用的文献

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Genetic variants and acute kidney injury: A review of the literature.遗传变异与急性肾损伤:文献综述。
J Crit Care. 2018 Apr;44:203-211. doi: 10.1016/j.jcrc.2017.11.019. Epub 2017 Nov 13.
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