[1]王兰君,靳　隽,李梦琪,等.他克莫司血药浓度对肾病综合征患者肝肾功能和血糖的影响[J].新乡医学院学报,2022,39(3):243-247.[doi:10.7683/xxyxyxb.2022.03.009]
　WANG Lanjun,JIN Juan,LI Mengqi,et al.Effect of blood concentration of tacrolimus on liver function,kidney function and blood glucose of patients with nephrotic syndrome[J].Journal of Xinxiang Medical University,2022,39(3):243-247.[doi:10.7683/xxyxyxb.2022.03.009]
点击复制

他克莫司血药浓度对肾病综合征患者肝肾功能和血糖的影响
分享到：

《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
39
期数:
2022年3
页码:
243-247
栏目:
临床研究
出版日期:
2022-03-05

文章信息/Info

Title:
Effect of blood concentration of tacrolimus on liver function,kidney function and blood glucose of patients with nephrotic syndrome
作者:
王兰君1; 靳　隽2; 李梦琪3; 张　敏1
（1.新乡医学院第一附属医院检验科，河南　卫辉　453100；2.新乡医学院人文学院，河南　新乡　453003；3.新乡医学院第一附属医院病案室，河南　卫辉　453100）
Author(s):
WANG Lanjun1; JIN Juan2; LI Mengqi3; ZHANG Min1
(1.Department of Clinical Laboratory,the First Affiliated Hospital of Xinxiang Medical University,Weihui 453100,Henan Province,China;2.College of Humanities,Xinxiang Medical University,Xinxiang 453003,Henan Province,China;3.Department of Medical Record,the First Affiliated Hospital of Xinxiang Medical University,Weihui 453100,Henan Province,China）
关键词:
肾病综合征; 他克莫司; 血药浓度; 肝肾功能; 血糖
Keywords:
nephrotic syndrome; tacrolimus; blood concentration; liver and kidney function; blood glucose
分类号:
R692
DOI:
10.7683/xxyxyxb.2022.03.009
文献标志码:
A
摘要:
目的　探讨肾病综合征患者他克莫司血药浓度变化及其对肝肾功能和血糖等指标的影响，为临床合理用药提供依据。方法　选择2020年1月至2020年12月新乡医学院第一附属医院收治的153例肾病综合征患者为研究对象，所有患者予以他克莫司治疗，开始剂量为0.05 mg·kg-1·d-1,分2次口服；同时给予醋酸泼尼松口服，初始剂量0.5 mg·kg-1·d-1,治疗8周后每周减量10%，减至20 mg·d-1后再持续治疗8周，然后每周减量10%，直至剂量维持在10.0 mg·d-1。于连续服用他克莫司5 d后，抽取患者早晨服药前静脉血2 mL，应用美国雅培全自动免疫化学发光分析仪检测患者的他克莫司血药浓度，根据血药浓度分为高浓度（他克莫司血药浓度>10.0 μg·L-1）组和低浓度（他可莫司血药浓度≤10.0 μg·L-1）组；抽取患者静脉血3 mL，应用贝克曼5800全自动生化分析仪检测血糖（FBG）、丙氨酸转氨酶（ALT）、天门冬氨酸氨基转移酶（AST）、总胆红素（TBIL）、肌酐（Scr）、尿素氮（BUN）水平。观察2组患者不良反应发生情况。结果　9例（5.9%）患者的他克莫司血药浓度<5 μg·L-1，68例（44.4%）患者的他克莫司血药浓度分布在5～10 μg·L-1，59例（38.6%）患者的他克莫司血药浓度分布在>10～15 μg·L-1，17例（11.1%）患者的他克莫司血药浓度>15 μg·L-1。高浓度组76例，男45例（59.2%），女31例（40.8%）；年龄16～75（47.59±16.25）岁。低浓度组77例，男38例（49.4%），女39例（50.6%）；年龄17～78（43.31±17.80）岁。2组患者年龄、性别分布比较差异无统计学意义（P>0.05）。高浓度组患者的血ALT、Scr、BUN、FBG水平显著高于低浓度组(P<0.05)；2组患者的血AST和TBIL水平比较差异无统计学意义(P>0.05)。Pearson相关分析显示，他克莫司血药浓度与Scr、BUN、FBG呈中等程度正相关（r=0.489、0.434、0.468，P<0.05），与ALT呈弱正相关（r=0.187，P<0.05），与AST和TBIL无相关性(r=-0.019、-0.014，P>0.05) 。低浓度组患者发生肾功能损伤2例，高血糖1例，不良反应发生率为3.89%（3/77）；高浓度组患者发生肾功能损伤6例，高血糖5例，不良反应发生率为14.47%（11/76）。高浓度组患者不良反应发生率显著高于低浓度组（χ2=4.570，P<0.05）。结论　肾病综合征患者他克莫司血药浓度个体差异大，他克莫司血药浓度对肾病综合征患者肝功能的影响较小，当他克莫司血药浓度较高时易引起肾病综合征患者肾功能损伤和高血糖。
Abstract:
Objective　To investigate the change of blood concentration of tacrolimus in patients with nephrotic syndrome and its effect on the liver function，kidney function and blood glucose,so as to provide an evidence for clinical rational drug use.Methods　A total of 153 patients with nephrotic syndrome admitted to the First Affiliated Hospital of Xinxiang Medical University from January 2020 to December 2020 were selected as the research subjects,and tacrolimus was given orally,with the initial dose of 0.05 mg·kg-1·d-1,oral administration in two doses.At the same time,prednisone acetate was given orally,with the initial dose of 0.5 mg·kg-1·d-1,and the dose was reduced by 10% per week to 20 mg·d-1 after 8 weeks of treatment,and then decreased by 10% per week after 8 weeks of treatment,until the dose was maintained at 10.0 mg·d-1.Five days after treatment of tacrolimus continuously,2 milliliter of venous blood of patients before taking the medicine in the morning was extracted,and the blood concentration of tacrolimus of patients was detected by Abbott automatic immunity immunochemiluminescence analyzer,the patients were divided into high concentration (the blood concentration of tacrolimus>10 μg·L-1) group and low concentration (the blood concentration of tacrolimus≤10 μg·L-1) group accroding to the blood concentration.Three milliliter of venous blood was extracted,and the levels of fasting blood glucose(FBG),alanine transaminase(ALT),aspartate transaminase(AST),total bilirubin(TBIL),serum creatinine(Scr) and blood urea nitrogen(BUN) were detected by BECKMAN 5800 automatic biochemical analyzer.The adverse reactions of patients in the two groups were observed.Results　The blood concentration of tacrolimus in 9 cases(5.9%) was lower than 5 μg·L-1,the blood concentration of tacrolimus in 68 cases(44.4%) was distributed from 5 to 10 μg·L-1,the blood concentration of tacrolimus in 59 cases(38.6%) was distributed from 10 to 15 μg·L-1,and the blood concentration of tacrolimus in 17 cases(11.0%) was higher than 15 μg·L-1.There were 76 patients in the high concentration group,including 45 males (59.2%) and 31 females (40.8%);they were aged from 16 to 75 (47.59±16.25) years old.There were 77 patients in the low concentration group,including 38 males (49.4%) and 39 females (50.6%);they were aged from 17 to 78 (43.31±17.80) years old.There was no significant difference in age and gender between the two groups (P>0.05).The levels of ALT,Scr,BUN and FBG of patients in the high concentration group were significantly higher than those in the low concentration group(P<0.05).There was no significant difference in the levels of AST and TBIL of patients between the two groups(P>0.05).Pearson correlation analysis showed that blood concentration of tacrolimus had significantly positive correlation with Scr,BUN,FBG(r=0.489,0.434,0.468;P<0.05);the blood concentration of tacrolimus had a weak positive correlation with ALT(r=0.187,P<0.05),and had no correlation with AST and TBIL(r=-0.019,-0.014;P>0.05).In the low concentration group,there were 2 cases of renal dysfunction and 1 case of hyperglycemia,and the incidence of adverse reactions was 3.89%(3/77);in the high concentration group,there were 6 cases of renal dysfunction and 5 cases of hyperglycemia,and the incidence of adverse reactions was 14.47%（11/76).The incidence of adverse reactions in the high concentration group was significantly higher than that in the low concentration group（χ2=4.570，P<0.05).Conclusion　Patients with nephrotic syndrome have large individual differences in the blood concentration of tacrolimus,tacrolimus has little effect on liver function.When the blood concentration of tacrolimus is high,it is easy to cause renal function injury and hyperglycemia.

参考文献/References:

［1］　CHEN X,WANG D D,XU H,et al.Optimization of initial dosing scheme of tacrolimus in pediatric refractory nephrotic syndrome patients based on CYP3A5 genotype and coadministration with wuzhi-capsule［J］.Xenobiotiea,2020,50(5):606-613.
［2］　CORTAZAR F B,LEAF D E,OWENS C T,et al.Combination therapy with rituximab,low-dose eyelophamide,and prednisone for idiopathie membranous nephropathy:a ease series［J］.BMC Nephrol,2017,18(1):44-48.
［3］　谢易,王晶晶,傅海东,等.促皮质素在肾病综合征中的作用机制［J］.中华实用儿科临床杂志,2022,37(1):74-76.
XIE Y,WANG J J,FU H D,et al.Mechanism of adrenocorticotropic hormone in the treatment of nephritic syndrome［J］.Chin J Appl Clin Pediatr,2022,37(1):74-76.
［4］　刘艳玲,赵巍,王晶,等.他可莫司治疗肾病综合征临床疗效及其对T淋巴细胞亚群影响研究［J］.中国现代应用药学,2021,38(9):1084-1088.
LIU Y L,ZHAO W,WANG J,et al.Clinical efficacy of tacrolimus in the treatment of nephrotic syndrome and its influence on T lymphocyte subsets［J］.Chin J Mod Drug Appl,2021,38(9):1084-1088.
［5］　CHOUDHARY N S,SARAF N,SAIGAL S,et al.Revisiting chronic rejection following living donor liver transplantation in the tacrolimusera:a single centre experience［J］.Clin Transplant,2018,32(2):e13161.
［6］　王琳,王琳娜,庞欣欣，等.雷公藤总甙联合他克莫司和糖皮质激素治疗难治性肾病综合征疗效观察［J］.新乡医学院学报,2020,37(6):588-591.
WANG L,WANG L N,PANG X X,et al.Effect of tripterygium glycosides combined with tacrolimus and glucocorticoid in the treatment of refractory nephritic syndrome［J］.J Xinxiang Med Univ,2020,37(6):588-591.
［7］　刘勇,林中军,苏勇.他克莫司联合糖皮质激素治疗难治性肾病综合征的临床疗效［J］.临床合理用药杂志,2020,13(6):16-17.
LIU Y,LIN Z J,SU Y.Clinical effect of tacrolimus combined with glucocorticoid in the treatment of refractory nephritic syndrome［J］.Chin J Clin Rational Drug Use,2020,13(6):16-17.
［8］　李佳,陈文.小剂量泼尼松联合他克莫司治疗难治性肾病综合征的疗效评价［J］.药物评价研究,2020,43(2):283-286.
LI J,CHEN W.Efficacy of low dose prednisone combined with tacrolimus in treatment of refractory nephritic syndrome［J］.Drug Eval Res,2020,43(2):283-286.
［9］　吴凡,李特.他克莫司血药浓度的影响因素研究进展［J］.中国合理用药探索,2021,18(8):5-9.
WU F,LI T.Research progress on influencing factors of plasma concentration of tacrolimus［J］.Chin J Rational Drug Use,2021,18(8):5-9.
［10］　葛均波,徐永健,梅长林,等.内科学［M］.8版.北京:人民卫生出版社,2014:477.
GE J B,XU Y J,MEI C L,et al.Internal medicine［M］.8th ed.Beijing:People′s Medical Publishing House,2014:477.
［11］　DOWNIE M L,GALLIBOIS C,PAREKH R S,et al.Nephrotic syndrome in infants and management［J］.Paediatr Int Child Health,2017,37(4):248-258.
［12］　DASILVA L,HUERTA A,QUINTANA L,et al.Rituximab for steroid-dependent or frequently relapsing idiopathic nephrotic syndrome in adults:a retrospective,multicenter study in spain［J］.Bio Drugs,2017,31(3):239-249.
［13］　李彩玲,关则想,赵起仙,等.双嘧达莫+泼尼松治疗小儿肾病综合征的临床疗效及对肾功能指标水平的影响研究［J］.中国现代药物应用,2021,15(15):161-163.
LI C L,GUAN Z X,ZHAO Q X,et al.Effect of dipyridamole combined with prednisone on nephritic syndrome in children and its influence on renal function indicators［J］.Chin J Mod Drug Appl,2021,15(15):161-163.
［14］　谭红金.他可莫司联合糖皮质激素治疗难治性肾病综合征的临床疗效及安全性［J］.临床合理用药杂志,2021,14(23):95-96.
TAN H J.Clinical efficacy and safety of tacrolimus combined with glucocorticoid in the treatment of refractory nephritic syndrome［J］.Chin J Clin Rational Drug Use,2021,14(23):95-96.
［15］　TAKAHASHI T,OKAMOTO T,SATO Y,et al.Periodically repeated rituximab administrations in children with refractory nephritic syndrome:2-year multicenter observational study［J］. Peliatr Nephrol,2019,34(1):87-96.
［16］　张春燕,黄琳,任晓蕾,等.肾病综合征患者他可莫司血药浓度影响因素研究［J］.中国新药杂志,2021,30(11):1053-1056.
ZHANG C Y,HUANG L,REN X L,et al.Infuence factors on blood concentration of tacrolimus in patients with nephritic syndrome［J］.Chin J New Drugs,2021,30(11):1053-1056.
［17］　胡艳,陈忠辉,束长东,等.他可莫司联合泼尼松治疗肾病综合征的临床疗效研究［J］.新疆医科大学学报,2021,44(6):722-725.
HU Y,CHEN Z H,SHU C D,et al.Clinical efficacy of tacrolimus combined with prednisone in treatment of nephritic syndrome［J］.J Xinjiang Med Univ,2021,44(6):722-725.
［18］　GUO X H,XIN H,DONG F Z,et al.Population pharmacokinetics of tacrolimus in children with nephrotic syndrome［J］.Br J Clin Pharmacol,2018,84(8):1748-1756.
［19］　王熙瑶,刘宁,文凤,等.不同肝病基础乙肝相关原发性肝细胞癌AST/ALT和AFP的表达水平差异及临床应用评价［J］.胃肠病学和肝病学杂志,2021,30(11):1234-1239.
WANG X Y,LIU N,WEN F,et al.Expression levels and application value of AST/ALT and AFP in clinical evaluation of hepatitis B related primary hepatocelluar carcinoma based on different liver disease［J］.Chin J Castroenterol Hepatol,2021,30(11):1234-1239.
［20］　华琳,杨雅芸,孙维罗,等.乙型肝炎患者ALT水平与HBV血清标志物联合检测的应用价值［J］.中华医院感染学杂志,2019,29(18):2746-2753.
HUA L,YANG Y Y,SUN W L,et al.Value of combined detection of ALT and serological markers of HBV in patients with hepatitis B［J］.Chin J Nosocomiol,2019,29(18):2746-2753.
［21］　邓德银,许林,刘凯.他克莫司胶囊联合糖皮质激素对难治性肾病综合征患者肝肾功能与糖脂代谢的影响［J］.临床合理用药杂志,2021,14(32):112-114.
DENG D Y,XU L,LIU K.Effects of tacrolimus capsule combined with glucocorticoid on liver and kidney function and glucolipid metabolism in patients with refractory nephrotic syndrome［J］.Chin J Clin Rational Drug Use,2021,14(32):112-114.
［22］　JOUVE T,NOBLE J,ROSTAING L,et al.An update on the safety of tacrolimus in kidney transplant recipients,with a focus on tacrolimus minimization［J］.Expert Opin Drug Saf,2019,18(4):285-294.
［23］　缪洁,郭慧蕾.糖皮质激素及他克莫司联用致肾病综合征患儿血糖升高1例分析［J］.中国药师,2019,22(11):2065-2067.
MIAO J,GUO H L.A case of hyperglycemia caused by tacrolimus and glucocorticoids in A pediatric patient with nephroticsyndrome［J］.China Pharmacist,2019,22(11):2065-2067.
［24］　CHAKKERA H A,KUDVA Y,KAPLAN B.Calcineurin inhibitors:pharmacologic mechanisms impacting both insulin resistance and insulin secretion leading to glucose dysregulation and diabetes mellitus［J］.Clin Pharmacol Ther,2017,101(1):114-120.

相似文献/References:

[1]王存礼,郭宝瑞,高云馨,等.中西医结合治疗肾病综合征的探讨[J].新乡医学院学报,1986,3(04):016.
[2]杨献云,陈新德,杨达胜,等.激素不同疗法治疗小儿原发性肾病综合征[J].新乡医学院学报,1993,10(03):195.
[3]吴标,刘彩丽,张素红,等.中西医结合综合治疗肾病综合征顽固性蛋白尿16例[J].新乡医学院学报,1993,10(03):237.
[4]窦敬芳.以胸腹水为主要体征的肾病综合征1例[J].新乡医学院学报,1993,10(04):346.
[5]李金兰,仝淑君,姚红波,等.肾病综合征患者的血液流变学变化[J].新乡医学院学报,1996,13(02):164.
[6]郭明好,任忠,魏舒拉,等.肾病综合征患者血浆催乳素的临床研究[J].新乡医学院学报,1996,13(01):042.
[7]石建华,魏崇一,杨福燕,等.应用尿γ—谷氨酰转肽酶预测原发性肾病综合征的疗效[J].新乡医学院学报,2000,17(06):446.
[8]郭明好,刘竹梅,魏素兰,等.抗心磷脂抗体与几种肾脏疾病的关系[J].新乡医学院学报,2000,17(05):323.
[9]薛松梅.肾病综合征复发患儿的健康指导[J].新乡医学院学报,2003,20(02):147.
[10]薛松梅.肾病综合征复发患儿的健康指导[J].新乡医学院学报,2003,20(02):147.

更新日期/Last Update: 2022-03-05