N末端B型利钠肽原和高敏C反应蛋白在心脏移植术后排斥反应中的意义

Association between serum NT-proBNP/hs-CRP and acute rejection after heart transplantation

目的分析原位心脏移植术后心内膜心肌活检（EMB）结果与血N末端B型利钠肽原（NT-proBNP）和高敏C反应蛋白（hs-CRP）水平的关系，评价NT-proBNP和hs-CRP在诊断心脏移植术后排斥反应中的作用。方法回顾分析阜外心血管病医院自2004年6月至2007年1月61例原位心脏移植患者术后3周、3-4个月、5-6个月、12个月的EMB及每次EMB前的血NT-proBNP和hs-CRP检查结果，分析NT-proBNP和hs-CRP与排斥反应之间的相关性。结果NT-proBNP浓度于术后随时间推移呈下降趋势（r=-0.520，P=0.000），术后半年内NT-proBNP水平明显高于半年以后（P=0.002）。排斥反应阳性组（病理分级／〉2级）的NT-proBNP浓度高于阴性组（P=0.073）；在排除时间影响之后，两组NT-proBNP浓度差异有统计学意义（P=0.025）。NT-proBNP测定值的受试者工作特征（ROC）曲线显示，曲线下面积（AUC）为0.566（P=0.344）。界值（cutoff值）为6.00×10^-16mol／L时，其敏感性、特异性分别为57.1％、44.8％；cutoff值为8.00×10^-16mol／L时，其敏感性、特异性分别为38.1％、61.0％。术后半年内hs.CRP水平高于半年以后（P=0.069）。排斥反应阳性组的hs-CRP浓度高于阴性组（P=0.138）；在排除时间影响之后，两组hs-CRP浓度差异仍无统计学意义（P=0.073）。分别以NT-proBNP4.00×10^-16mol／L和hs-CRP 3mg／L为分界点，NT-proBNP和hs-CRP同时高于分界点的有20例次（病理分级I〉2级有5例次），而NT-proBNP和hs-CRP同时低于分界点的有26例次（病理分级≥2级有3例次），两者差异无统计学意义（P=0.232）。结论NT-proBNP浓度于心脏移植术后呈下降趋势，术后NT-proBNP浓度升高与排斥反应有相关性，但其诊断排斥反应的价值较低。心脏移植术后hs-CRP浓度升高与排斥反应无明显相关性，其与NT-proBNP一起不能提高诊断排斥反应的准确性。

Objective The aim of the present work was to investigate the potential relationship between acute rejection and serum concentrations of N-terminal pro-brain natriuretic peptide （NT-proBNP）/ high sensitivity C reactive protein （hs-CRP） in post-transplant patients. Methods Sixty-one consecutive orthotopic heart transplantation recipients were prospectively recruited from the cardiac transplantation programme at Fuwai Hospital. Endomyocardial biopsies （EMB） were performed routinely at 3 weeks, 3, 6 and 12 months after transplantation. EMB were also performed when patients had new symptoms of heart failure or at 2 weeks after steroid pulse therapy. Serum NT-proBNP and hs-CRP were simultaneously measured before EMB procedure. Results A total of 126 biopsy samples were obtained from the 61 patients. Serum NT-proBNP concentrations progressively decreased after transplantation （spearman correlation coefficient -0.520, P =0.000）. NT-proBNP levels within 6 months after transplantation were significantly higher than those beyond 6 months post transplantation [（11.86±11.16）×10^-16moL/L vs. （5.83 ±6.58）×10^-16mol/L,P =0.002]. NT-proBNP concentrations in patients with rejection tended to be higher than patients without rejection （13.68×10^-16mol/L vs. 9.26×10^-16mol/L, P=0.073）. After time adjustment, the difference of NT-proBNP concentrations between patients with or without rejection becomes statistically significant （14.45×10^-16mol/L vs. 9.1×10^-16 mol/L, P = 0. 025 ）. Receiver operating characteristics analysis for NT-proBNP versus rejection grade revealed an area under the curve of 0. 566, indicating a low predictive value for NT-proBNP. A cutoff of 6.00×10^-16mol/L yielded poor specificity （44.8%） and sensitivity （57.1%）, the sensitivity and specificity were 38.1% and 61.0%, respectively with a cutoff of 8.00×10^-16 mol/L, hs-CRP levels within 6 months after transplantation tended to be higher than those beyond 6 months[（2.39±3.90） mg/L vs. （1.34±2.73） mg/L, P =0.069].hs-CRP concentrations in patients with rejection were similar as patients without rejection （2.995 mg/L vs. 1.833 mg/L, P=0.138）. The incidence of rejection was similar in patients with two higher biomarkers （5/20, 25% ） compared to patients with two low biomarkers （3/26, 11.5%, P = 0. 232）. Conclusions NT- proBNP level decreased after transplantation. Although increased NT-proBNP concentrations were related to rejection, the diagnostic capacity was low. Elevated hs-CRP concentrations were not related to rejection after heart transplantation.