肾移植术后服药前和服药后2小时新山地明血药浓度监测的临床意义比较

Sandimmun neoral C0 and C2 monitoring after renal transplantation: Comparison of clinical significance

目的:新山地明给药后,个体间吸收变异相当明显,血药浓度监测管理对减少急性排斥反应发生及降低肝肾毒性十分重要。比较传统的服药前血药浓度(谷值)、服药后2h血药浓度(峰值)监测的临床意义。方法:选择2005-01/2006-04在中山大学附属第一医院行首次同种异体尸肾移植的受者60例,均知情同意。按随机数字表法分成服药前血药浓度组和服药后2h血药浓度组,各30例。两组患者肾移植后前3个月均接受新山地明5～7mg/(kg·d)、霉酚酸酯1.0～1.5g/d和皮质激素三联治疗。采用荧光偏振法测定患者新山地明服药前和服药后2h血药浓度,比较服药前血药浓度与服药后2h血药浓度监测方法预测肾移植急性排斥反应和不良反应(肝毒性、肾毒性)的有效性。结果:60例患者全部进入结果分析。①60例患者在术后3个月内急性排斥反应发生率为13.3%(8/60);不良反应发生率为28.3%(17/60),肝毒性发生率为20.0%(12/60),肾毒性发生率为8.3%(5/60)。②急性排斥反应发生时与非急性排斥反应时服药前血药浓度差异无显著性意义(P=0.08);急性排斥反应发生时服药后2h血药浓度显著低于非急性排斥反应时服药后2h血药浓度(P<0.01)。③发生肝肾毒性1周内的服药前血药浓度与未发生时服药前血药浓度差异无显著性意义(P=0.15);发生肝肾毒性1周内的服药后2h血药浓度显著高于肝肾毒性未发生时(P<0.01)。结论:在肾移植术后早期,与服药前血药浓度相比,服药后2h血药浓度能更敏感的反映急性排斥反应和不良反应的发生。

AIM： Sandimmun neoral would lead to distinct absorption mutation between individuals. Detection and monitor of serum drug concentration are important to decrease acute rejection and hepatotoxicity and nephrotoxicity. In this study, the clinical significance of sandimmun neoral trough levels （CO） and C2 early monitoring by regularly detecting the concentrations of sandimmun neoral after renal transplantation was compared. METHODS： Sixty patients who underwent allograft cadaveric renal transplantation in the First Affiliated Hospital of Sun Yat-sen University from January 2005 to April 2006 were selected with the informed consent. They were randomly divided into CO group and C2 group with 30 cases in each group. Sandimmun neoral CO and C2 were measured by fluorescence polarization immunoassay （TDX） in 60 cases treated with Sandimmun neoral （5-7 mg/kg daily）, mycophenolate （1.0-1.5 g/d） and cortical hormone at the first 3 months after renal transplantation, The efficacy to monitor the acute rejection and adverse effects such as hepatotoxicity and nephrotoxicity at CO and C2 was compared. RESULTS： All 60 patients were involved in the result analysis. ①Of 60 patients, 8 cases （13,3 %） had the onset of acute rejection within 3 months after transplantation; The incidence of adverse effects was 28.3 % （17/60）, including hepatoxicity （20%, 12/60） and nephrotoxicity （8,3%, 5/60）. ②The difference was not statistically significant in CO levels between rejection and non-rejection （P =0.08）, while the C2 levels at rejection were remarkably lower than that of non-rejection （P 〈 0.01）. ③There was also no statistically significant in CO levels of patients with hepatoxicity and nephrotoxicity within 1 week and those without adverse effect （P =0.15）, but C2 levels in patients with hepatoxicity and nephrotoxicity within 1 week was markedly higher than that in patients without adverse effects （P 〈 0.01 ）. CONCLUSION： C2 monitoring is more accurate and sensitive than CO to reflect the acute rejection and adverse effects in the early period after renal transplantation.