The application value of Multi-Latex polygranular technique joint detection of urinary microproteins in noninvasive diagnosis after renal transplantation
-
摘要:
目的 探讨Multi-Latex多聚粒技术联合检测肾损伤相关尿微量蛋白在肾移植术后无创诊断中的应用价值。 方法 回顾性分析72例肾移植受者的临床资料,根据血清肌酐(Scr)水平,分为肾功能正常组(A组,14例);肾功能轻度受损组(B组,37例);肾功能重度受损组(C组,21例);选取20例健康志愿者作为健康对照组(HC组)。采用Multi-Latex多聚粒技术检测上述各组研究对象的尿视黄醇结合蛋白(RBP)、微量白蛋白(mAlb)、IgG、转铁蛋白(TRF)、α1-微球蛋白(MG)和β2-MG含量。分析尿微量蛋白与Scr、血尿素氮(BUN)的相关性,比较各组尿微量蛋白差异,评价单一及联合检测尿微量蛋白的诊断价值。 结果 HC组和A组的6种尿微量蛋白均显著低于B组和C组,B组的6种尿微量蛋白均显著低于C组(均为P < 0.01)。肾移植受者的6种尿微量蛋白均与BUN呈正相关,RBP、mAlb、α1-MG和β2-MG均与Scr呈正相关,相关性均有统计学意义(P < 0.001~0.05)。尿微量蛋白联合检测的诊断价值优于单一指标的检测,其中TRF+mAlb+RBP+α1-MG四联检测诊断价值最高。 结论 6种尿微量蛋白可作为反映移植肾功能的特异性指标,多聚粒技术可同时检测其含量,实现无创诊断。基于TRF+mAlb+RBP+α1-MG四联检测的诊断有望进一步完善肾移植术后的无创诊断体系。 Abstract:Objective To investigate the application value of Multi-Latex polygranular technique joint detection of kidney injury-related urinary microproteins in noninvasive diagnosis after renal transplantation. Methods Clinical data of 72 recipients undergoing renal transplantation were retrospectively analyzed. According to the level of serum creatinine (Scr), the recipients were divided into normal renal function group (group A, n=14), mild kidney injury (group B, n=37), and severe kidney injury group (group C, n=21). 20 healthy volunteers were selected as the healthy control group (HC group). The contents of urinary retinol binding protein (RBP), microalbumin (mAlb), IgG, transferrin (TRF), α1-microglobulin (MG), and β2-MG of subjects in each group were detected using the Multi-Latex polygranular technique. The correlation between urinary microproteins and Scr, blood urea nitrogen (BUN) was analyzed. The differences of urinary microproteins in each group were compared. And the diagnostic value of single and joint detection of urinary microproteins was evaluated. Results Six kinds of urinary microproteins in HC group and group A were significantly lower than those in group B and group C, and six kinds of urinary microproteins in group B were significantly lower than those in group C (all P < 0.01). Six kinds of urinary microproteins in renal transplant recipients were positively correlated with BUN. RBP, mAlb, α1-MG, and β2-MG were positively correlated with Scr. The correlations were statistically significant (P < 0.001-0.05). The diagnostic value of joint detection of urinary microproteins is better than the detection of single index, among which TRF+mAlb+RBP+α1-MG quadruple detection had the highest diagnostic value. Conclusions Six kinds of urinary microproteins can be used as specific indicators to reflect graft renal function. The polygranular technique can simultaneously detect its contents and achieve noninvasive diagnosis. The diagnosis based on TRF+mAlb+RBP+α1-MG quadruple detection is expected to further improve the noninvasive diagnosis system after renal transplantation. -
表 1 各项指标对移植肾功能状态的诊断价值比较
Table 1. Comparison of the diagnostic value of various indicators on the functional status of transplant kidney
参数 AUC 95%可信区间 最佳诊断值(mg/L) 灵敏度 特异度 单一检测 TRF 0.932 0.875~0.989 0.795 0.828 1.000 mAlb 0.913 0.846~0.981 8.850 0.879 0.857 IgG 0.890 0.817~0.964 5.290 0.810 1.000 RBP 0.903 0.834~0.973 0.233 0.776 1.000 α1-MG 0.985 0.961~1.000 11.370 1.000 0.862 β2-MG 0.862 0.777~0.946 0.145 0.845 0.929 联合检测 TRF+mAlb 0.932 0.875~0.990 1.000 0.929 RBP+α1-MG 0.985 0.961~1.000 1.000 0.929 RBP+α1-MG+β2-MG 0.984 0.959~1.000 1.000 0.857 TRF+mAlb+IgG 0.935 0.879~0.990 1.000 0.929 TRF+mAlb+RBP+α1-MG 0.989 0.970~1.000 1.000 0.929 -
[1] DAUBER EM, KOLLMANN D, KOZAKOWSKI N, et al. Quantitative PCR of INDELs to measure donor-derived cell-free DNA-a potential method to detect acute rejection in kidney transplantation: a pilot study[J]. Transpl Int, 2020, 33(3):298-309. DOI: 10.1111/tri.13554. [2] ALBERT C, HAASE M, ALBERT A, et al. Urinary biomarkers may complement the Cleveland score for prediction of adverse kidney events after cardiac surgery: a pilot study[J]. Ann Lab Med, 2020, 40(2):131-141. DOI: 10.3343/alm.2020.40.2.131. [3] 彭景, 唐怡.尿液L-FABP及KIM-1水平用于HBV相关ACLF患者并发AKI的诊断价值[J].肝脏, 2018, 23 (11):959-963. DOI: 10.3969/j.issn.1008-1704.2018.11.007.PENG J, TANG Y. Research of diagnostic value of urinary L-FABP and KIM-1 levels in HBV-related ACLF patients with AKI[J]. Chin Hepatol, 2018, 23(11):959-963. DOI: 10.3969/j.issn.1008-1704.2018.11.007. [4] JUNG HY, LEE CH, CHOI JY, et al. Potential urinary extracellular vesicle protein biomarkers of chronic active antibody-mediated rejection in kidney transplant recipients[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2020, 1138:121958. DOI: 10.1016/j.jchromb. 2019.121958. [5] LAMB KE, LODHI S, MEIER-KRIESCHE HU. Long-term renal allograft survival in the United States: a critical reappraisal[J]. Am J Transplant, 2011, 11(3):450-462. DOI: 10.1111/j.1600-6143.2010.03283.x. [6] JACQUEMONT L, SOULILLOU JP, DEGAUQUE N. Blood biomarkers of kidney transplant rejection, an endless search?[J]. Expert Rev Mol Diagn, 2017, 17(7):687-697. DOI: 10.1080/14737159.2017.1337512. [7] SOLEZ K, COLVIN RB, RACUSEN LC, et al. Banff 07 classification of renal allograft pathology: updates and future directions[J]. Am J Transplant, 2008, 8(4):753-760. DOI: 10.1111/j.1600-6143.2008.02159.x. [8] COLVIN RB, COHEN AH, SAIONTZ C, et al. Evaluation of pathologic criteria for acute renal allograft rejection: reproducibility, sensitivity, and clinical correlation[J]. J Am Soc Nephrol, 1997, 8(12):1930-1941. http://europepmc.org/abstract/MED/9402096 [9] JOELSONS G, DOMENICO T, GONÇALVES LF, et al. Non-invasive messenger RNA transcriptional evaluation in human kidney allograft dysfunction[J]. Braz J Med Biol Res, 2018, 51(7):e6904. DOI: 10.1590/1414-431x20186904. [10] RUAN Y, GUO W, LIANG S, et al. Diagnostic performance of cytomegalovirus (CMV) immune monitoring with ELISPOT and QuantiFERON-CMV assay in kidney transplantation: a PRISMA-compliant article[J]. Medicine (Baltimore), 2019, 98(16):e15228. DOI: 10.1097/MD.0000000000015228. [11] PANAGOPOULOU MS, WARK AW, BIRCH DJS, et al. Phenotypic analysis of extracellular vesicles: a review on the applications of fluorescence[J]. J Extracell Vesicles, 2020, 9(1):1710020. DOI: 10.1080/20013078.2019.1710020. [12] WOUTERS S, DE VOS J, DORES-SOUSA JL, et al. Prototyping of thermoplastic microfluidic chips and their application in high-performance liquid chromatography separations of small molecules[J]. J Chromatogr A, 2017, 1523:224-233. DOI: 10.1016/j.chroma.2017.05.063. [13] VAN DE VRIE M, DEEGENS JK, EIKMANS M, et al. Urinary microRNA as biomarker in renal transplantation[J]. Am J Transplant, 2017, 17(5):1160-1166. DOI: 10.1111/ajt.14082. [14] DING R, LI B, MUTHUKUMAR T, et al. CD103 mRNA levels in urinary cells predict acute rejection of renal allografts[J]. Transplantation, 2003, 75(8):1307-1312. doi: 10.1097/01.TP.0000064210.92444.B5 [15] RENESTO PG, PONCIANO VC, CENEDEZE MA, et al. High expression of Tim-3 mRNA in urinary cells from kidney transplant recipients with acute rejection[J]. Am J Transplant, 2007, 7(6):1661-1665. http://cn.bing.com/academic/profile?id=863dfe5b6879cd0e4bc4e4319a97e4d9&encoded=0&v=paper_preview&mkt=zh-cn [16] MATZ M, BEYER J, WUNSCH D, et al. Early post-transplant urinary IP-10 expression after kidney transplantation is predictive of short- and long-term graft function[J]. Kidney Int, 2006, 69(9):1683-1690. doi: 10.1038/sj.ki.5000343 [17] VAN DEN AKKER EK, DOR FJ, IJZERMANS JN, et al. MicroRNAs in kidney transplantation: living up to their expectations?[J]. J Transplant, 2015:354826. DOI: 10.1155/2015/354826. [18] AL-NEDAWI K, HAAS-NEILL S, GANGJI A, et al. Circulating microvesicle protein is associated with renal transplant outcome[J]. Transpl Immunol, 2019, 55:101210. DOI: 10.1016/j.trim.2019.06.002. [19] AKBARI A, WHITE CA, SHAHBAZI N, et al. Spot urine protein measurements: are these accurate in kidney transplant recipients?[J]. Transplantation, 2012, 94(4):389-395. doi: 10.1097/TP.0b013e31825b413e [20] 罗百文, 邓新强, 范向平, 等.四项尿微量蛋白定量检测在糖尿病肾病早期诊断中的应用价值[J].中国现代医药杂志, 2019, 21(11):87-89.DOI: 10.3969/j.issn.1672-9463.2019.11.025.LUO BW, DENG XQ, FAN XP, et al. Application value of four quantitative urine microprotein detections in early diagnosis of diabetic nephropathy[J]. Mod Med J Chin, 2019, 21(11):87-89. DOI: 10.3969/j.issn.1672-9463.2019.11.025. [21] 林志强, 刘继来, 林青, 等.尿微量白蛋白/尿肌酐、尿转铁蛋白/尿肌酐、尿α1M/尿肌酐、尿免疫球蛋白/尿肌酐参考区间建立[J].临床合理用药杂志, 2017, 10 (31):167-169. DOI: 10.15887/j.cnki.13-1389/r.2017.31.097.LIN ZQ, LIU JL, LIN Q, et al. Establishment of urine microalbumin / urinary creatinine, urine transferrin / urinary creatinine, urine α1M / urinary creatinine, urine immunoglobulin / urinary creatinine reference intervals[J]. Chin J Clin Ration Drug Use, 2017, 10(31):167-169. DOI: 10.15887/j.cnki.13-1389/r.2017.31.097. [22] 刘芳, 薛林霞.血清CysC、尿β2-MG、L-FABP联合检测对心脏手术后急性肾损伤的早期诊断价值[J].中国医师杂志, 2019, 21 (12): 1817-1820, 1824. DOI: 10.3760/cma.j.issn.1008-1372.2019.12.015.LIU F, XUE LX. Early diagnosis value of joint detection of serum CysC, urine β2-MG, and L-FABP for acute kidney injury after cardiac surgery[J]. J Chin Physician, 2019, 21 (12): 1817-1820, 1824. DOI: 10.3760/cma.j.issn.1008-1372.2019.12.015. [23] ABBASI F, MOOSAIE F, KHALOO P, et al. Neutrophil gelatinase-associated lipocalin and retinol-binding protein-4 as biomarkers for diabetic kidney disease[J]. Kidney Blood Press Res, 2020, 45(2):222-232. DOI: 10.1159/000505155. [24] PALLET N, LEGENDRE C. Deciphering calcineurin inhibitor nephrotoxicity: a pharmacological approach[J]. Pharmacogenomics, 2010, 11(10):1491-1501. DOI: 10.2217/pgs.10.137.