FK506、肾功能指标及单个核细胞计数判断肾移植患者尿BKV DNA阳性的价值

doi:10.3969/j.issn.1673-8640.2021.08.012

摘要/Abstract

摘要：

目的探讨血FK506、尿素、肌酐（Cr）及单个核细胞计数判断肾移植患者尿BK病毒（BKV）DNA阳性的价值。方法检测197例肾移植患者尿BKV DNA及血FK506、尿素、Cr、淋巴细胞百分比（LYMPH%）、淋巴细胞绝对值（LYMPH#）、单核细胞百分比（MO%）、单核细胞绝对值（MO#）。以尿BKV DNA≥2.0×10³拷贝/mL为BKV阳性组,<2.0×10³拷贝/mL为BKV阴性组。另选取21例术后3~6个月内多次检测尿BKV DNA,并首次出现阴性转阳性的患者进行配对比较。采用受试者工作特征（ROC）曲线评价各项指标判断尿BKV DNA阳性的效能。采用Pearson相关分析或Spearman相关分析评估各项指标与尿BKV DNA载量的相关性。对比21例患者首次出现尿BKV DNA由阴性转阳性时各项指标的变化。结果 BKV阳性组FK506、尿素、Cr水平高于BKV阴性组（P<0.05）,2个组之间LYMPH%、LYMPH#、MO%、MO#差异均无统计学意义（P>0.05）。相关性分析结果显示,尿BKV DNA载量与血FK506水平呈正相关（r=0.466,P<0.001）,与尿素、Cr无相关性（r值分别为0.157、0.156,P>0.05）。ROC曲线分析显示,FK506、尿素和Cr判断尿BKV DNA阳性的曲线下面积（AUC）分别为0.685、0.581、0.606,最佳临界值分别为7.05 ng/mL、7.20 mmol/L、100.5 μmol/L,敏感性分别为58.3%、71.4%、83.3%,特异性分别为74.3%、46.0%、38.1%。与尿BKV DNA阴性时比较,同一患者首次出现尿BKV DNA阳性时的FK506水平明显升高（P<0.001）,尿素及Cr水平差异无统计学意义（P>0.05）。结论血FK506对判断肾移植术后患者尿BKV DNA阳性有一定价值。

关键词: FK506, 肾功能指标, 单个核细胞计数, BK病毒, 肾移植

Abstract:

Objective To investigate the roles of FK506,urea,creatinine（Cr） and mononuclear cell count in the judgment of renal transplant recipients with positive urinary BK virus（BKV） DNA. Methods Urinary BKV DNA were determined in 197 renal transplant recipients,which the cases ≥2.0×10³ copies/mL were enrolled in positive group,and which the cases <2.0×10³ copies/mL were enrolled in negative group. The differences of FK506,urea,Cr,the percentage of lymphocyte（LYMPH%） and the absolute value of lymphocyte（LYMPH#）,the percentage of monocyte（MO%） and the absolute value of monocyte（MO#） between the 2 groups were evaluated. A total of 21 patients with negative to positive urinary BKV DNA within 3 to 6 months after transplantation were enrolled for matching comparison. The efficiency of determining positive urinary BKV DNA by each indicator was evaluated by receiver operating characteristic（ROC） curve,and the correlation between each indicator and urinary BKV DNA load was evaluated by Pearson or Spearman analysis. The indicators with significant difference were compared in 21 recipients with the first change of urinary BKV DNA from negative to positive. Results The levels of FK506,urea and Cr in BKV positive group were higher than those in BKV negative group（P<0.05）. LYMPH%,LYMPH#,MO% and MO# showed no statistical significance between the 2 groups（P>0.05）. Urinary BKV DNA load was positively correlated with FK506（r=0.466,P<0.001）,and there was no correlation with urea（r=0.157） and Cr（r=0.156）（P>0.05）. ROC curve analysis showed that the areas under curves（AUC）of FK506,urea and Cr for the positive determination of urinary BKV DNA were 0.685,0.581 and 0.606,respectively. The optimal cut-off values were 7.05 ng/mL,7.20 mmol/L and 100.5 μmol/L,respectively. The sensitivities were 58.3%,71.4% and 83.3%,and the specificities were 74.3%,46.0% and 38.1%,respectively. FK506 was increased in the 21 recipients when they firstly experienced urinary BKV DNA conversion from negative to positive（P<0.001）,and urea and Cr had no statistical significance（P>0.05）. Conclusions FK506 is valuable in the judgment of renal transplant recipients with positive urinary BKV DNA.

Key words: FK506, Renal function index, Mononuclear cell count, BK virus, Renal transplantation

中图分类号:

R446.69

黄思聪, 石永杰, 嘉红云. FK506、肾功能指标及单个核细胞计数判断肾移植患者尿BKV DNA阳性的价值[J]. 检验医学, 2021, 36(8): 837-842.

HUANG Sicong, SHI Yongjie, JIA Hongyun. Roles of FK506,renal function indexes and mononuclear cell count in the judgment of renal transplant recipients with positive urinary BKV DNA[J]. Laboratory Medicine, 2021, 36(8): 837-842.

图/表 5

表1 BKV阳性组与BKV阴性组各项指标的比较

组别	例数	年龄/岁	性别		FK506/ （ng/mL）	尿素/（mmol/L）
组别	例数	年龄/岁	男/例	女/例	FK506/ （ng/mL）	尿素/（mmol/L）
BKV阳性组	84	41.49±0.97	58	26	7.33±0.22	8.43（4.39~19.10）
BKV阴性组	113	41.44±1.08	74	39	6.24±0.14	7.61（2.80~15.70）
统计值		1.971	0.267		4.423	5 558.000
P值		0.669	0.599		<0.001	0.040
组别	Cr/（μmol/L）		LYMPH%/%	LYMPH#/（×10⁹/L）	MO%/%	MO#/（×10⁹/L）
BKV阳性组	126.9（63.5~262.2）		23.54±0.76	1.48（0.51~5.83）	8.57±0.41	0.63（0.01~1.43）
BKV阴性组	114.1（49.9~241.1）		22.17±0.89	1.50（0.43~5.02）	8.85±0.37	0.60（0.01~1.81）
统计值	5 755.000		1.177	4 803.000	0.633	4 546.000
P值	0.011		0.241	0.885	0.607	0.613

图1 血FK506、尿素、Cr与尿BKV DNA的相关性注：（a）血FK506与尿BKV DNA载量的相关性[Y=0.426X+4.374（r=0.466,P<0.01）];（b）血尿素与尿BKV DNA载量的相关性[Y=0.178X+7.643（r=0.157,P>0.05）];（c）血Cr与尿BKV DNA载量的相关性[Y=2.339X+119.1（r=1.156,P>0.05）]。

图2 血FK506、尿素、Cr判断尿BKV DNA阳性的ROC曲线注： FK506; 尿素; Cr; 参考线。

图3 肾移植患者术后首次出现尿BKV DNA阴性转阳性的时间分布

图4 同一肾移植患者尿BKV DNA首次阴性转阳性时FK506、尿素、Cr的变化注：（a）FK506;（b）尿素;（c）Cr。

参考文献 18

[1]	张志刚, 曹璐, 王鑫, 等. BK病毒感染诊断与治疗的研究现状[J]. 检验医学, 2017, 32(5):440-445.
[2]	BOAN P, HEWISON C, SWAMINATHAN R, et al. Optimal use of plasma and urine BK viral loads for screening and predicting BK nephropathy[J]. BMC Infect Dis, 2016, 16:342. DOI URL
[3]	DEMEY B, TINEZ C, FRANÇOIS C, et al. Risk factors for BK virus viremia and nephropathy after kidney transplantation:a systematic review[J]. J Clin Virol, 2018, 109:6-12. DOI URL
[4]	LI P, CHENG D, WEN J, et al. Risk factors for BK virus infection in living-donor renal transplant recipients:a single-center study from China[J]. Ren Fail, 2018, 40(1):442-446. DOI URL
[5]	SHENAGARI M, MONFARED A, EGHTEDARI H, et al. BK virus replication in renal transplant recipients:analysis of potential risk factors may contribute in reactivation[J]. J Clin Virol, 2017, 96:7-11. DOI URL
[6]	吴蓓颖, 蔡刚, 林佳菲, 等. 移植患者BK病毒监测的临床意义[J]. 检验医学, 2014, 29(5):493-497.
[7]	马锡慧, 高钰, 韩永, 等. 流式细胞术在肾移植术后感染中的诊断价值[J]. 器官移植, 2018, 9(2):137-141.
[8]	PANG X L, MARTIN K, PREIKSAITIS J K. The use of unprocessed urine samples for detecting and monitoring BK viruses in renal transplant recipients by a quantitative real-time PCR assay[J]. J Virol Methods, 2008, 149(1):118-122. DOI URL
[9]	SANTEUSANIO A D, LUKENS B E, EUN J. Antiviral treatment of BK virus viremia after kidney transplantation[J]. Am J Health Syst Pharm, 2017, 74(24):2037-2045. DOI URL
[10]	CHEN X T, LI J, DENG R H, et al. The therapeutic effect of switching from tacrolimus to low-dose cyclosporine A in renal transplant recipients with BK virus nephropathy[J]. Biosci Rep, 2019, 39(2):BSR20182058.
[11]	周易, 姚雷雨, 于哲, 等. BK多瘤病毒在肾移植受者中的感染特征[J]. 南方医科大学学报, 2019, 39(1):120-124.
[12]	AHLENSTIEL-GRUNOW T, SESTER M, SESTER U, et al. BK polyomavirus-specific T cells as a diagnostic and prognostic marker for BK polyomavirus infections after pediatric kidney transplantation[J]. Transplantation, 2020, 104(11):2393-2402. DOI URL
[13]	AMBALATHINGAL G R, FRANCIS R S, CORVINO D, et al. Proteome-wide analysis of T-cell response to BK polyomavirus in healthy virus carriers and kidney transplant recipients reveals a unique transcriptional and functional profile[J]. Clin Transl Immunol, 2020, 9(1):e01102.
[14]	范宇, 石炳毅, 钱叶勇, 等. 肾移植术后BK病毒感染对移植肾功能影响的临床研究[J]. 器官移植, 2018, 9(1):51-57.
[15]	HIRSCH H H, YAKHONTOVA K, LU M, et al. BK polyomavirus replication in renal tubular epithelial cells is inhibited by sirolimus,but activated by tacrolimus through a pathway involving FKBP-12[J]. Am J Transplant, 2016, 16(3):821-832. DOI URL
[16]	HIRSCH H H, VINCENTI F, FRIMAN S, et al. Polyomavirus BK replication in de novo kidney transplant patients receiving tacrolimus or cyclosporine:a prospective,randomized,multicenter study[J]. Am J Transplant, 2013, 13(1):136-145. DOI URL
[17]	李平, 程东瑞, 季曙明, 等. 肾移植术后BK病毒感染及危险因素分析[J]. 医学研究生学报, 2017, 30(5):525-529.
[18]	THÖLKING G, SCHMIDT C, KOCH R, et al. Influence of tacrolimus metabolism rate on BKV infection after kidney transplantation[J]. Sci Rep, 2016, 6:32273. DOI URL