他克莫司致老年患者肾损害的回顾性分析

Retrospective analysis of kidney injury induced by tacrolimus in elderly patients

目的 探讨他克莫司致老年患者肾损害的发生情况和相关因素. 方法 以2010年11月1日至2013年10月31日在中南大学湘雅医院住院期间使用他克莫司、年龄＞60岁并有完整病历资料的所有患者为研究对象,收集其病历资料进行回顾性分析.主要分析指标为用药后血清肌酐水平变化、他克莫司全血谷浓度和联合用药情况.以他克莫司全血谷浓度＞ 15.0 μg/L为阳性,对肾损害组和无肾损害组患者应用他克莫司后全血谷浓度阳性率进行比较. 结果 共收集到127例患者,肾损害组11例（肾损害发生率为8.7％）,无肾损害组116例.肾损害组男性6例,年龄60 ～ 85（71±6）岁;女性5例,年龄61 ～80（69±11）岁;无肾损害组男性64例,年龄60～89（74±9）岁;女性52例,年龄60～85（70±6）岁,2组性别分布和年龄差异无统计学意义（P＞0.05）.应用他克莫司前,肾损害组患者血清肌酐浓度为57 ～ 363（179±90） μmol/L,无肾损害组为42 ～350（150±65） μmol/L,组间差异无统计学意义（P＞0.05）.肾损害组患者应用他克莫司5～20（11±6）d后血清肌酐升高为176 ～ 639（358±183）μmol/L,与用药前比较差异有统计学意义（P＜0.05）.肾损害组11例患者他克莫司全血谷浓度为5.9～15.1 μg/L,其中9例＞15.0 μg/L,阳性率为81.8％;无肾损害组116例患者为4.7～16.9 μg/L,其中42例＞15.0 μg/L,阳性率为36.2％.2组他克莫司全血谷浓度阳性率差异有统计学意义（P=0.00）.11例肾损害患者均联用细胞色素P450 3A酶诱导剂或抑制剂及糖皮质激素,3例同时联用肾毒性药物.11例患者中9例出现肾损害后立即改用其他免疫抑制剂,2例调整给药剂量,均未发生不可逆肾损害. 结论 他克莫司可导致老年患者发生肾损害,该药全血谷浓度及与联用药物的相互作用可能与肾损害的发生相关.

Objective To explore the occurrence and related factors of kidney injury induced by tacrolimus in elderly patients.Methods The clinical data of patients who were hospitalized in Xiangya Hospital during December 2011 to October 2013 and had complete medical records,aged ≥ 60 years,and received tacrolimus treatments were collected and analyzed retrospectively.The main analytic indicators included the change of serum creatinine before and after tacrolimus treatment,the blood trough concentration of tacrolimus,and the drug combinations.The tacrolimus trough concentration 〉 15.0 μg/L was considered as a positive result and the positive rates after tacrolimus treatment in patients in the renal damage and the no renal damage groups were compared.Results A total of 127 patients were enrolled in this study.There were 11 （8.7%）patients in the renal damage group and 116 patients in the no renal damage group.It comprised 6 men with age of 61 to 80 （69 ± 11） years,and 5 women with age of 60 to 85 （69 ± 11） years in the renal damage group; while it comprised 64 men with age of 60 to 89 （74 ± 9） years,and 52 women with age of 60 to 85 （70 ± 6） years in the no renal damage group.There were no statistical significance in gender and age distribution in patients between the 2 groups （P 〉 0.05）.The serum creatinine levels before tacrolimus treatment were 57-363 （179 ± 90） μmol/L in patients in the renal damage group and 42-350 （150 ± 65） μmol/L in patients in the no renal damage group.The difference was no statistical significance between the 2 groups （P 〉0.05）.The serum creatinine levels increased to 176-639 （358 ± 183） μmol/L after 5 to 20 （11 ± 6） days receiving tacrolimus treatments in patients in the renal damage group.The difference before and after treatment was statistically significant （P 〈 0.05）.The blood trough concentration of tacrolimus was 5.9-15.1 μg/L in 11 patients in the renal damage group and 〉 15.0 μg/L （81.8%） in 9 of them; the tacrolimus trough concentration was 4.7-16.9 μg/L in 116 patients in the no renal damage group and 〉 15.0 μg/L （36.2%） in 42 of them.The difference between the 2 groups was statistically significant （P =0.00）.Eleven patients with renal damage were treated with cytochrome P450 3A inducers/ inhibitors combined with glucocorticoid; 3 of them combined with nephrotoxic drug at the same time.When the kidney injury appeared in the 11 patients,tacrolimus was stopped immediately and changed to other immunosuppressants in 9 patients and the drug dosages were adjusted in 2 patients.No irreversible kidney injury occurred in any of the patients.Conclusion Tacrolimus may induce renal damage in elderly patients,which may be related to the blood trough concentration of tacrolimus as well as potential interactions among combined drugs.