全反式维甲酸对糖尿病大鼠足细胞损伤的保护作用

目的探讨全反式维甲酸(ATRA)对糖尿病大鼠足细胞损伤的保护作用。方法24只链脲佐菌素(STZ)诱导的糖尿病大鼠模型,随机分为糖尿病组(DM)和治疗组(T)各12只,另以12只正常大鼠作为对照组(N)。T组给予ATRA 20 mg·kg-1·d-1灌胃。于第4、8周末检测各组大鼠尿蛋白定量(24 h)、Cer、肾重/体重、尿中足细胞以及肾脏病理改变。结果DM组尿蛋白定量(24 h)、Ccr、肾重/体重、尿中足细胞数[8周时,0．84(0．60～1．50)个/ml]均显著高于同期N组[0．03(0-0．15)个/m1],而肾小球足细胞数(8周时,11．27±2．15)显著低于同期N组(14．07±2．07),且足细胞足突增宽、融合。T组尿蛋白定量(24 h)、Cer、肾重/体重、尿中足细胞数较同期DM组显著降低[0．46(0．25～0．70)个/ml],且病理改变减轻。结论ATRA可以减少糖尿病大鼠尿足细胞的排泄、降低尿蛋白,对肾脏足细胞损伤具有保护作用。     

尿毒清颗粒对糖尿病大鼠足细胞损伤的保护作用研究

目的：探讨尿毒清颗粒对糖尿病大鼠足细胞损伤的保护作用。方法：将SD大鼠制备成STZ糖尿病模型,实验分3组：正常对照组、糖尿病未干预组、尿毒清颗粒治疗组（2.6g·kg-1·d-1灌胃）,于实验第4周、8周末检测血糖、血肌酐、尿肌酐及尿白蛋白排泄率,光镜、电镜下观察肾组织病理改变并计数足突宽度,免疫组化观察足细胞相关蛋白分子nepherin、podocin的表达,Real time-PCR检测肾皮质nepherin、podocin mRNA表达。结果：尿毒清颗粒可以改善糖尿病大鼠肌酐清除率,降低尿白蛋白排泄,改善肾脏病理,减轻足突融合,维持足细胞相关蛋白分子的分布与表达。结论：初步证实尿毒清颗粒能通过上调足细胞相关蛋白分子水平减轻足细胞损伤,对糖尿病大鼠足细胞损伤具有保护作用。     

洛沙坦对糖尿病大鼠肾脏炎症反应及足细胞损伤的影响

目的 探讨洛沙坦对糖尿病大鼠模型肾组织炎症反应及足细胞损伤的影响。方法 Wistar大鼠随机分为3组：对照组（NC）、糖尿病组（DM）、洛沙坦治疗组（DL）。链脲菌素（STZ）注射建立糖尿病动物模型，洛沙坦治疗组在大鼠建立糖尿病同时即开始以洛沙坦（20mg·kg·d^-1）灌胃治疗。分别于2周和12周杀鼠，观察体重、肾重、肾重／体重指数、尿蛋白量（24h）、Scr、Ccr以及肾组织病理改变；免疫组化染色观察肾小球细胞间黏附分子（ICAM-1）、白细胞共同抗原（CD45）、nephrin、血管内皮生长因子（VEGF）表达的改变；免疫印迹观察肾组织nephrin、VEGF表达的改变。结果 （1）DL组大鼠肾重／体重指数、尿蛋白量（24h）、Ccr则均低于DM组，差异均有统计学意义（P均〈0．05），其病理改变程度也比DM组轻。（2）免疫组化及免疫印迹显示，DM组和DL组肾小球ICAM-1、CD45、VEGF表达均高于对照组，而DL组ICAM-1、CD45、VEGF表达均低于DM组；DM组和DL组大鼠肾小球nephrin表达低于对照组；DL组肾小球nephrin表达高于DM组，差异均有统计学意义（P均〈0．01）。结论 洛沙坦可能通过抑制肾组织白细胞浸润、炎症反应及减轻足细胞损伤，达到肾脏保护作用。     

糖尿病肾病中足细胞损伤机制的研究进展

糖尿病肾病（ diabetic nephropathy,DN）是糖尿病重要的微血管并发症之一,也是终末期肾衰竭重要的病因。足细胞（ podocyte）在DN进展过程中发挥了重要作用,并且足细胞损伤涉及多条信号通路的共同影响,比如Rho／ROCK信号通路、炎症反应、氧化应激及线粒体损伤等。本文就这些机制进行论述,旨在阐明足细胞损伤在DN发病过程中的重要作用,为进一步研究DN的病理生理机制及防治带来新的理论依据。     

霉酚酸酯及缬沙坦对糖尿病大鼠足细胞的保护机制研究

目的探讨霉酚酸酯、缬沙坦及2者联合应用对糖尿病。肾病（DN）大鼠足细胞损伤的保护作用。方法雄性Wistar大鼠行右肾切除后，腹腔注射链脲佐菌素（STZ，65mg／kg）建立糖尿病模型。将实验动物随机分为右。肾切除对照组（NC）、糖尿病组（DM）、霉酚酸酯治疗组（M）、缬沙坦治疗组（V）、缬沙坦和霉酚酸酯联合治疗组（V＋M）。治疗组分别给予霉酚酸酯15mg·kg^-1·d^-1，缬沙坦40mg·kg^-1·d^-1；联合治疗组为上述两组之和。检测各组8周末的左肾质量／体质量比值、尿蛋白量（24h）、血糖（Glu）、Scr。光镜及电镜观察肾组织形态学变化。免疫组化检测肾组织中nephrin、结蛋白（desmin）及单核细胞趋化因子1（MCP-1）蛋白表达。实时PCR测定肾组织中nephrin及MCP-1mRNA表达。结果与NC组相比，DM组大鼠血糖、尿蛋白量及左肾质量／体质量比值均显著上升（P〈0．01）；肾小球硬化指数（GSI）及肾间质损害加重（P〈0．01）；肾组织内MCP-1、desmin蛋白表达均显著上调（P〈0．01）。与DM组比较，M组、V组及V＋M组上述指标除Glu、Scr外，均明显改善（P〈0．05或P〈0．01）。与NC组（100％）相比，DM组nephrinmRNA表达下调（78％，P〈0.05）；各治疗组nephrinmRNA表达增加，以M组增加最明显（134％，P〈0．01）。与NC组（100％）相比，DM组MCP-1mRNA表达明显上调（251％，P〈0.05）；各治疗组明显降低，以M组最显著（126％，P〈0．01）。nephrinmRNA与MCP-1mRNA表达呈负相关（r=-0，86。P〈0．01）。尿蛋白量（24h）与MCP-1mRNA呈正相关fr=0．82，P〈0．01）；与nephrinmRNA呈负相关（r=-0．78，P〈0．01）。结论霉酚酸酯及缬沙坦均能下调糖尿病大鼠肾组织中desmin及MCP-1基因及蛋白的表达，上调nephrin基因及蛋白表达，降低尿蛋白量，预防肾损伤。联合治疗不优于单一治疗。霉酚酸酯可能通过抗炎性反应减轻足细胞损伤，减少蛋白尿，对早期DN大鼠具有明显的肾保护作用。     

缬沙坦联合苯那普利对糖尿病大鼠足细胞损伤的影响及肾脏保护机制的研究

目的：研究缬沙坦联合苯那普利对糖尿病大鼠足细胞损伤的影响及肾脏保护机制的作用。方法：将SD大鼠随机分为正常对照组（A组），糖尿病对照组（B组），糖尿病苯那普利治疗组（C组），糖尿病缬沙坦治疗组（D组），缬沙坦联合苯那普利（E组）。分别于实验第4、6周末各组随机取8只测定大鼠平均动脉压、血糖、血肌酐、尿肌酐、肾重／体重、尿白蛋白排泄率，对肾脏标本进行光镜、电镜观察，用图像分析仪测量各组大鼠的平均肾小球横截面积、平均肾小球体积，并于6周末用逆转录-PCR（RT-PCR）方法检测各组肾皮质TGF-β1 mRNA表达。采用免疫组织化学染色检查足细胞特异标记物nephrin、desmin，对足细胞进行准确的定位及其密度定量观察，同时结合临床和肾组织病理有关指标进行分析。结果：苯那普利、缬沙坦、缬沙坦联合苯那普利治疗均使Ccr、肾重／体重、尿白蛋白排泄率、TGF-β1mRNA表达降低，而缬沙坦联合苯那普利组对TGF-β1mRNA抑制程度最大，同时肾脏病理变化亦最轻。B组、E组均伴肾小球足细胞数目及密度的减少，其中以B组最为显著，C组、D组次之，E最轻。足细胞数目及其密度与尿蛋白量呈显著负相关（P〈0．01）。nephrin、desmin在A组沿肾小球基底膜呈连续、线形分布。C组、D组、E组nephrin、desmin的表达量降低，与正常组织比较，无统计学意义，B组nephrin、desmin的表达呈点状、短线条状，与正常组织比较，有统计学意义（P〈0．05）。糖尿病大鼠足细胞数目的减少还与肾小球病理改变相关，足细胞融合、微绒毛化改变较多，肾小球硬化数明显增多。结论：糖尿病大鼠表现出肾小球足细胞数目及其密度的减少，肾小球足细胞中nephrin、desmin的表达和分布的减少，足细胞病变不仅导致大量白蛋白尿的发生，而且还与肾小球硬化和肾功?     

糖尿病肾脏疾病足细胞损伤机制及中医药干预研究进展

糖尿病肾脏疾病(diabetic kidney disease,DKD)是慢性肾脏病和终末期肾病的首要病因,发病机制尚不明确.足细胞损伤在DKD发生和发展过程中有关键性作用.本文从的代谢紊乱、氧化应激、炎症反应、自噬失调方面综述DKD足细胞损伤机制,以及中药干预的靶点和途径,为中药防治DKD研究提供新的思路与借鉴.     

N-乙酰半胱氨酸对糖尿病肾病大鼠足细胞的保护作用

目的：探讨N-乙酰半胱氨酸（NAC）对糖尿病肾病（DN）大鼠足细胞的保护作用。方法：制备DN大鼠模型,将动物随机分为正常对照组、DN组和NAC组。8周后观察尿蛋白排泄量,免疫荧光方法和Western blotting检测肾皮质nephrin和podocin蛋白表达,透射电镜检测足细胞超微结构变化。结果：（1）与正常对照组比较,DN组和NAC组尿白蛋白排泄率增多（P〈0.01）,nephrin和podocin蛋白表达减少（P〈0.01或P〈0.05）和肾脏病理病变明显;（2）与DN组比较,NAC组尿蛋白排泄减少（P〈0.01）,nephrin和podocin蛋白表达较高（P〈0.01或P〈0.05）和足细胞的病变较轻。结论：NAC对DN大鼠肾脏保护作用,其部分机制与上调nephrin和podocin蛋白表达及改善足细胞病变有关。     

益肾胶囊对糖尿病肾病大鼠足细胞损伤的影响

目的：观察益肾胶囊对糖尿病肾病大鼠足细胞损伤的影响。方法：32只大鼠随机分为正常对照组、糖尿病肾病模型组（模型组）、益肾胶囊组、苯那普利组,每组各8只。益肾胶囊组每日每只灌胃益肾胶囊（2.5g·kg^-1·d^-1）,苯那普利组每日每只灌胃苯那普利（2.5g·kg^-1·d^-1）,正常对照组及模型组每日给予等量的蒸镏水。测定血压、24h尿蛋白定量、血肌酐（Scr）、尿素氮（BUN）,并计算内生肌酐清除率（Ccr）;光镜检查肾组织病理变化,电镜及免疫荧光法检测肾组织及尿液中足细胞变化等。结果：实验24周后,模型组大鼠血压、24h尿蛋白定量、BUN、Scr较正常对照组明显增高（均P〈0.05）,益肾胶囊组和苯那普利组可降低糖尿病肾病大鼠血压、24h尿蛋白定量、BUN、Scr（均P〈0.05）等;模型组足细胞podocalyxin蛋白表达明显低于正常对照组（P〈0.05）,益肾胶囊组及苯那普利组大鼠足细胞podocalyxin蛋白表达较模型组显著增加（P〈0.05）;两治疗组之间比较无统计学差异。正常对照组尿液偶见podocalyxin阳性足细胞,模型组尿液足细胞排泄较正常对照组明显增多（P〈0.05）,益肾胶囊组及苯那普利组,大鼠尿液足细胞排泄减少（P〈0.05）。结论：益肾胶囊可通过减轻糖尿病肾病大鼠足细胞损伤而具有一定的肾保护作用。     

足细胞在糖尿病肾病中损伤机制研究进展

流行病学研究结果发现,糖尿病肾病是目前导致终末期肾功能衰竭的主要原因之一.微量蛋白尿的产生不仅可以作为临床糖尿病肾病早期诊断指标之一,其持续的存在也是肾脏病进行性发展的独立危险因子.以往肾小球血流动力学的改变被认为是蛋白尿产生的基础,现在足细胞病变在蛋白尿形成中的作用越来越受到重视.探讨足细胞损伤机制不仅有利于阐明糖尿...     

胃旁路术对糖尿病大鼠的降糖作用及其机制

目的观察胃旁路术(GBP)对链脲佐菌素(STZ)诱发的糖尿病大鼠降糖作用。探讨其机制。方法SD大鼠注射STZ建立糖尿病模型后分为手术组(O组)、假手术组(S组)、饮食控制组(F组)、对照组(C组),每组8只,测术前,术后第1、2、3、4、8周空腹和口服葡萄糖后血糖、胰岛素、胰高血糖素样肽-1(GLP-1)和体重、平均进食量。结果O组GBP后3周,空腹和餐后血糖分别由(16.84±3.82)、(31.88±6.22)mmol/L下降到(13.24±3.53)、(17.35±3.47)mmol/L(P值均＜0.05),空腹和餐后胰岛素分别由(28.66±8.17)、(30.73±8.99)mIU/L上升到(46.48±10.41)、(51.14±11.45)mIU/L(P值均＜0.01)。空腹和餐后GLP-1分别由(7.02±2.10)、(42.20±11.16)pmol/L上升到(25.16±7.30)、(97.83±30.23)pmol/L(P值均＜0.01)。GLP-1和血糖成负相关(P＜0.01),GLP-1和胰岛素成正相关(P＜0.01)。S组体重改变与O组相似,血糖无明显下降；F组控制平均进食量约为O组的1/3并致显著体重下降,血糖下降没有O组明显(P＜0.05)。结论GBP能显著降低STZ大鼠血糖,可能通过术后GLP-1分泌增多起作用。GBP的降糖作用与术后大鼠饮食减少和体重下降无关。     

Roux-en-Y胃旁路术对糖尿病大鼠肾脏的保护作用

目的 观察Roux-en-Y胃旁路术对糖尿病Goto-Kakizaki (GK)大鼠肾脏的保护作用.方法 18只GK大鼠随机等分为Roux-en-Y胃旁路手术组(RYGP组)、假RYGP组和对照组;观察手术前、手术后12周各组大鼠血清血栓素(TXB2)、6-酮-前列环素(6-kET-1o-PGF1a)、内皮素-1( ET-1)、尿素氮(sCr)、肌酐(BUN)和24h尿蛋白(24 h uPro)含量;手术后12周苏木素-伊红(HE)染色观察大鼠肾脏病理变化.结果 手术前3组大鼠各检测指标差异无统计学意义(P＞0.05).与手术前比较,手术后12周,假RYGP组大鼠TXB2(66.31±6.13) ng/L比(101.42 ±9.70) ng/L、ET-1 (58.31±5.32) ng/L比(79.01±6.89) ng/L、sCr( 48.78±3.66) μmol/L比(70.33±6.21)μmol/L、BUN(5.41±0.68) mmol/L比(8.35±0.92) mmol/L和24h uPro (0.44±0.10) g/24 h比(0.86 ±0.17) g/24 h均显著升高,6-kET-1o-PGF1a(85.72±6.87) ng/L比(60.41±8.23) ng/L显著降低,差异均有统计学意义(P＜0.05);对照组与假RYGP组一样获得相似的结果;RYGP组大鼠各检测指标变化差异无统计学意义(P＞0.05).手术后12周,RYGP组与假RYGP组比较TXB2(72.31±7.56) ng/L比(101.42±9.70)ng/L、ET-1 (62.11±6.26) ng/L比(79.01 ±6.89)ng/L、sCr (54.36±4.12)μmol/L比(70.33±6.21)μmol/L、BUN( 5.71±0.86) mmol/L比(8.35±0.92) mmoL/L、24 h uPro(0.52 ±0.10) g/24 h比(0.86±0.17)g/24 h和6-kET-1o-PGF1a( 83.22±5.62) ng/L比(60.41±8.23) ng/L差异均有统计学意义(P＜0.05);RYGP组与对照组比较,各检测指标差异均有统计学意义(P＜0.05);假RYGP组、对照组血清TXB2与6-kET-1o-PGF1a呈显著负相关,与ET-1呈显著正相关(P＜0.05).手术后12周,假RYGP组和对照组大鼠肾脏有明显病理性损害;RYGP组大鼠肾脏病理变化不明显.结论 Roux-en-Y胃旁路术对GK大鼠肾脏具有保护作用.     

Glucose metabolism in liver transplant recipients treated with FK 506 or cyclosporin in the European multicentre study

Abstract From September 1990 to January 1992, 545 liver transplant patients were randomised to treatment with either FK 506 and prednisolone or a conventional cyclosporin-based immunosuppressive regimen (CBIR). Eight European centres participated in the study. Adverse events were reported as defined by each centre. Hyperglycaemia was reported as an adverse event in 30.7% of patients receiving FK 506 compared with 20.5% in the CBIR group ( P < 0.01). Diabetes mellitus was reported in 17.2% of patients treated with FK 506 and 9.5% of CBIR-treated patients ( P < 0.05). Treatment with insulin was required in 12.0% of patients in the DK 506 treatment group and in 5% in the CBIR group at 6 months. Initially, higher doses of FK 506 were used. During the study, the protocol was changed to allow a lower dose of FK 506. When the early and late cohorts of patients were compared, the incidence of diabetes mellitus fell from 23.9% to 10.5% in FK 506-treated patients but remained relatively constant in the CBIR group (10.4% to 8.7%). The median cumulative doses of i.v. and p. o. corticosteroids were significantly greater in the CBIR group. Thus, in the overall series, the incidence of diabetes mellitus was significantly greater in the FK 506 group as compared with the CBIR group. However, when a lower FK 506 dose was used during the second half of the study, the difference in the incidence of diabetes mellitus disappeared.     

罗格列酮对糖尿病大鼠肾保护机制的研究

目的探讨罗格列酮对糖尿病肾损害的保护作用机制。方法单次腹腔注射50mg/kg链脲佐菌素制备糖尿病大鼠模型,糖尿病大鼠随机分成糖尿病组、罗格列酮治疗组(5mg·kg-1·d-1),和正常对照组。用免疫组化、RT-PCR及Western印迹的方法检测8周后过氧化物酶体增殖物激活受体(PPAR)γ、TGF-β1表达的改变。结果与正常对照组相比,糖尿病组及治疗组PPARγ及TGF-β1表达增加(P<0.05);而治疗组PPARγ及TGF-β1表达显著低于糖尿病组(P<0.05)。结论罗格列酮可通过活化PPARγ,下调TGF-β1,显著减少糖尿病大鼠尿蛋白,从而延缓肾脏损伤。     

Fever of unknown origin in renal transplant patients with tacrolimus

Abstract:  The immunosuppressive agent tacrolimus is now widely used for the prevention of acute and chronic rejection in renal allograft recipients. We here report on three patients, who developed drug-induced fever due to tacrolimus one to five months after renal transplantation. Extensive search for a focus, autoantibodies and virus infection remained inconclusive. Therefore, drug-induced fever was suggested. After discontinuing tacrolimus and switching to cyclosporine A fever completely resolved within 24 h. This report demonstrates that tacrolimus-induced drug fever should be included in the differential diagnosis of fever of unknown origin in renal transplant recipients.     

FK506对离体肝再灌注后TNF-α mRNA表达的影响

目的探讨 FK506 对肝脏保存再灌注中TNF-α mRNA表达的影响 .方法建立离体大鼠肝脏再灌注模型,应用RT-PCR方法检测TNF-α mRNA的表达,观察FK506对不同时间保存的肝脏TNF-α mRNA表达的影响. 结果 FK506组保存16,24和32h 再灌注,TNF-α mRNA表达分别为0.83±0.07,0.91±0.06和1.32±0.08, 明显低于对照组的0.98±0.05,1.42±0.09和1.86±0.16. 结论 FK506能抑制肝脏保存再灌注中TNF-α mRNA的表达,对离体肝的再灌注损伤可能具有保护作用.     

Co-administration of ketoconazole and tacrolimus therapy: a transplanted rat model

Background/aim The aim of this work is to study the effect of addition of ketoconazole to experimental kidney transplanted rat treated with tacrolimus and precludes the percentage of tacrolimus dose reduction. Material and methods The material of this work included 60 male Sprague Dawely rats subjected to renal allotransplantation. They were equally divided into five groups: Group I: served as control group, Group II: received FK506 3.2 mg/kg/bw, Group III: received FK506 2 mg/kg/bw, Group IV: received FK506 1 mg/kg/bw, Group V: received FK506 1 mg/kg/bw plus ketoconazole 20 mg/kg/day. FK506 trough level and laboratory investigations were determined at 0, 3, 7, 10, 14, and 27 days post-transplantation. Results In all groups loss of body weight was observed at day 27 after treatment compared to that before transplantation. Serum creatinine significantly increased at day 27 compared to the basal level in groups treated with 1.0 mg and 3.2 mg FK506 (1.80 ± 0.50 vs. 0.39 ± 0.06 P = 0.001) and (1.03 ± 0.26 vs. 0.50 ± 0.07 P = 0.001) respectively. While for 2.0 mg or 1.0 mg plus keto groups, no significant differences in serum creatinine levels over time (0.56 ± 0.22 vs. 0.44 ± 0.10 P = 0.106) and (0.55 ± 0.30 vs. 0.42 ± 0.08 P = 0.160) were observed. Conclusion Concomitant administration of ketoconazole and FK506 is safe and results in increase blood trough level concentration of FK506 with 50% dose reduction in transplanted rat model.     

他克莫司和环孢素A对大鼠肾脏转化生长因子及其受体表达影响的比较

目的比较他克莫司（FK506）和环孢素A（CsA）所致慢性肾毒性大鼠模型肾组织转化生长因子目（TGF-1β）及其受体（TβRⅡ）的表达。方法分别以FK506和CsA灌胃复制大鼠FK506和CsA慢性肾毒性模型，观察大鼠的一般情况，计算肌酐清除率，观察大鼠肾组织病理变化，以免疫组织化学法检测肾组织中TGF-1β、TβR Ⅰ、TBRⅡ蛋白表达的变化，原位杂交法检测肾组织中TβR Ⅰ mRNA及TβR Ⅱ mRNA表达的变化。结果CsA组和FK506组的肾小管、小管间质和人球小动脉均有损伤，但CsA组的损伤明显较FK506组重（P〈0．05）。正常对照组大鼠肾组织中仅见少量TGF-[3，、TβR I和T13RⅡ表达，CsA组和FK506组的TGF-β，、TβR I和TβR Ⅱ表达均明显增加，但FK506组稍轻；正常对照组大鼠肾组织中仅见少量TβR I mRNA、TβR Ⅱ mRNA表达，CsA组和FK506组TβR I mRNA、TβR Ⅱ mRNA明显表达，但FK506组较CsA组为轻。结论FK506的慢性肾毒性弱于CsA，它所诱导的大鼠肾组织中TGF-β，及其受体TβR I和TβR Ⅱ的表达均低于CsA。     

Roles of the jejunum and ileum in the first-pass effect as absorptive barriers for orally administered tacrolimus

BACKGROUND: The immunosuppressant tacrolimus shows poor and variable bioavailability following oral administration in clinical use. Recently, the hepatic and intestinal metabolisms, or first-pass effect, of tacrolimus have been suggested to be responsible for its bioavailability. In the present study, we investigated the respective contribution of the jejunum and ileum to the first-pass effect of tacrolimus in rats. METHODS: The metabolism of tacrolimus in everted sacs of the duodenum, jejunum, and ileum was examined. Tacrolimus was administered intravenously or intraintestinally to sham-operated, jejunum-resected, or ileum-resected rats. Blood samples were collected over a 240-min period, and whole-blood tacrolimus concentrations were measured by semiautomated microparticle enzyme immunoassay. The pharmacokinetic parameters of tacrolimus in each group were estimated. RESULTS: The metabolic activity of tacrolimus appeared to be the highest in the everted sacs of the duodenum. The bioavailability of tacrolimus in the jejunum- or ileum-resected rats was higher than that in sham-operated controls. On the other hand, the time to peak concentration in the jejunum-resected rats was about twofold slower than those in ileum-resected and sham-operated rats. CONCLUSIONS: These results suggested that the first-pass effect of tacrolimus in the small intestine shows regional differences and the extraction of tacrolimus in the small intestine consists of the amount of extraction in the jejunum and ileum. In addition, the ileum rather than the jejunum as a graft of segmental small bowel transplantation would be useful to avoid the adverse effects of tacrolimus.     

Improved renal allograft survival in children treated with FK 506 (tacrolimus) rescue therapy

FK 506 has been reported to be effective in reversing acute renal allograft rejection that is resistant to steroids and to OKT3. The contribution of FK 506 “rescue” therapy to long-term graft survival has not been determined. We report 23 children transplanted between January 1993 and December 1994, 10 of whom received FK 506 “rescue” therapy. Acute rejection was reversed in 8 of 10, with 7 of the remaining grafts still functioning after a mean follow-up of 10.9±7.8 (SD) months (range 1 – 26 months). The actuarial 1-year graft survival rate was 86% compared with 66% for historical controls (P <0.05). We conclude that FK 506 may provide long-term benefits to children facing allograft loss due to acute rejection. Received August 15, 1995; received in revised form and accepted April 1, 1996