肾功能不全对利奈唑胺血药浓度及其所致血小板减少影响分析

Analysis of Serum Concentration and Thrombocytopenia of Linezolid on Renal Insufficiency

目的:分析不同肾功能对利奈唑胺血药谷浓度的影响,并评估日剂量、肾功能、谷浓度与利奈唑胺相关性血小板减少症的关系。方法:回顾性收集2019年7月~2021年9月使用利奈唑胺并进行血药谷浓度监测的患者,分为肾功能不全组与肾功能正常组,比较两组利奈唑胺血药谷浓度和血小板减少发生率。结果:共纳入肾功能不全组71例,肾功能正常组26例。利奈唑胺谷浓度与日剂量呈正相关(r=0.339 5,P=0.000 2);与肌酐清除率有负相关性(r=-0.318 6,P=0.000 4)。肾功能不全组患者的谷浓度显著高于肾功能正常组[12.12(8.49,20.65)mg·L^(-1)vs.5.93(2.55,11.60)mg·L^(-1),P<0.001];其谷浓度超标率也更高(83.10%vs.42.31%,P<0.001)。共有31例患者发生了血小板减少症(31.96%),肾功能不全组患者血小板减少症发生率高于肾功能正常组(38.03%vs.15.38%,P=0.041),且严重血小板减少症发生率也更高(25.35%vs.3.85%,P=0.043)。利奈唑胺谷浓度>10 mg·L^(-1)时,发生血小板减少症(46.15%vs.15.56%,P=0.002)及严重血小板减少症(28.85%vs.8.89%,P=0.019)的风险更大。绘制谷浓度预测血小板减少的ROC曲线显示,利奈唑胺谷浓度>12.1 mg·L^(-1)时诱导发生血小板减少症的风险增加。结论:肾功能不全患者的利奈唑胺谷浓度水平更高,血小板减少症发生率为肾功能正常患者的3.375倍,谷浓度超过12.1 mg·L^(-1)时发生血小板减少的风险增加。

Objective:To analyze the effect of different renal function on serum trough concentration of linezolid, and to evaluate the correlation between dosage, renal function and trough concentration with the linezolid induced-thrombocytopenia(LIT). Methods:Patients who received linezolid treatment and determined trough concentrations were retrospectively collected during July 2019 to September 2021. The enrolled patients were divided into renal insufficiency group and normal renal function group. The trough concentrations, incidence of thrombocytopenia of linezolid were compared between the two groups. Results:A total of 97 patients were included and divided into the renal insufficiency group(71 cases) and the normal renal function group(26 cases). The trough concentration of linezolid was positively correlated with the daily dose(r=0.339 5, P=0.000 2), however, it was negatively correlated with the creatinine clearance(r=-0.318 6, P=0.000 4). The trough concentration of linezolid in the renal insufficiency group was much higher than that in the normal renal function group [12.12(8.49, 20.65) mg·L^(-1) vs.5.93(2.55, 11.60) mg·L^(-1) ,P<0.001], the rate of trough concentration more than 7 mg·L^(-1) was also higher in the renal insufficiency group(83.10% vs.42.31%, P<0.001). Totally 31 cases occurred of thrombocytopenia, the rate of thrombocytopenia in the renal insufficiency group was much higher than that of the normal renal function group(38.03% vs.15.38%, P=0.041), the rate of severe thrombocytopenia were also higher in the renal insufficiency group(25.35% vs.3.85%, P=0.043). The incidence of thrombocytopenia and severe thrombocytopenia was higher when linezolid trough concentration >10 mg·L^(-1) (46.15% vs.15.56%, P=0.002;28.85% vs.8.89%, P=0.019). Conclusion:Patients with renal insufficiency have a higher level of linezolid trough concentration. The incidence of thrombocytopenia in patients with normal renal function was 3.375 times higher than that in patients with normal renal function. The risk of thrombocytopenia was increased when trough concentration of linezolid more than 12.1 mg·L^(-1) .