肾移植前后检测β2－MG与THP及ALB的临床意义

采用放射免疫方法测定４４例尿毒症患者肾移植前后血清β２－微球蛋白（β２－ＭＧ）Ｔａｍｍ－Ｈｏｒｓｆａｌ蛋白（ＴＨＰ）及尿β２－ＭＧ、ＴＨＰ和白蛋白（ＡＬＢ）水平。结果表明，尿毒症患者血清、尿β２－ＭＧ及尿ＡＬＢ明显高于正常（Ｐ＜０．０１），血清、尿ＴＨＰ明显低于正常值（Ｐ＜０．０１）。术后肾功能正常组血清、尿β２－ＭＧ、尿ＡＬＢ均显著降低，血清、ＴＨＰ均显著升高（Ｐ＜０．０１），但仍未达正常。术后排斥组血清、尿β２－ＭＧ及尿ＡＬＢ显著升高，尿ＴＨＰ显著降低（Ｐ＜０．０５）。而环孢素（ＣｓＡ）急性肾中毒组仅尿β２－ＭＧ显著升高。提示动态观察血清、尿β２－ＭＧ、ＴＨＰ及尿ＡＬＢ变化，对于监测肾移植术后肾小球和肾小管的功能变化，早期诊断急性排斥反应、ＣｓＡ急性肾中毒有一定的临床价值     

肾移植后监测环孢素A血药浓度与β2－微球蛋白的临床意义

本文监测４６例肾移植术后患者６９份环孢素Ａ（ＣｓＡ）血药浓度及血、尿β２－微球蛋白（β２－ＭＧ）水平，并做相关性分析。结果表明在ＣｓＡ、Ｃｒ正常组和ＣｓＡ肾中毒组中ＣｓＡ血药浓度均与尿β２－ＭＧ呈显著正相关，ＣｓＡ肾中毒组尿β２－ＭＧ显著升高，而急、慢性排异组其血、尿β２－ＭＧ均显著升高。结果提示测定β２－ＭＧ有助于鉴别ＣｓＡ肾中毒和移植排异反应，对及时调整ＣｓＡ用量具有重要的临床意义。     

肾移植后监测环孢素A血药浓度与β2—微球蛋白的临床意义

本文监测４６例能移植术后６９份环孢素Ａ（ＣｓＡ）血药浓度及血，尿β２－微球蛋白（β２－ＭＧ）水平，并做相关性分析，结果表明在ＣｓＡ正常组和ＣｓＡ肾中毒组中ＣｓＡ血药浓度的均与尿β２－ＭＧ呈显著正相关，ＣｓＡ肾中毒组尿β２－ＭＧ显著升高，而急，慢性排异组其血，尿β２－ＭＧ均显著升高，结果提示测定β２－ＭＧ有助于鉴别ＣｓＡ肾中毒和移植排异反应，对及时调整ＣｓＡ用量具有重要的临床意义。     

放免法联合检测血尿β＿2—MG及尿AlbIgGTHP对肺心病患者肾功能的评价

本文采用放免法测定６０例肺心病患者血、尿ｐ２—ＭＧ、尿Ａｌｂ、尿ＩｇＧ和尿ＴＨＰ水平，同时化验血ＢｕＮ和血Ｃｒ。结果显示，肺心病患者血、尿β２—ＭＧ、尿Ａｌｂ、尿ＩｇＧ浓度显著升高（Ｐ＜０．０１）并随病情加重而上升（Ｐ＜０．０１），他（１１的阳性率明显高于ＢｕＮ和ｃｒ的阳性率（Ｐ＜０．０１）；尿ＴＨＰ在重度患者明显下降（Ｐ＜０．００１）。本文结果表明中、重度肺心病患者肾小球及肾功能均有不同程度损害，尿β２—ＭＧ是判断肾功能敏感而特异的指标，动态观察上述指标可早期发现肾功能损害并判断其损害部位、范围及程度。     

107例糖尿病患者肾功能放射免疫联检的临床研究

本文采用放射免疫分析（ＲＩＡ）的方法对１０７例糖尿病患者、８０例正常人进行了尿微量白蛋白（Ａｌｂ）β２微球蛋白（β２－ＭＧ）、免疫球蛋白（ＩｇＧ）、血糖蛋白（ＴＨＰ）等肾功能ＲＩＡ联检，结果提示糖尿病患者尿Ａ１ｂ、β２ＭＧ、ＩｇＧ及血ＴＨＰ均明显增高，糖尿病肾病的发生和发展与糖尿病病程、病情控制和有无血管并发症等有关，通过系列闻位有助于对糖尿病患者早期判断肾功能损伤的部位、程度并对预后的评价提供有     

肿瘤患者血循环免疫复合物与尿N—乙酰—β—θ—氨基酸葡萄糖苷酶的相关性研

观察恶性肿瘤患者血中循环免疫复合物（ＣＩＣ）及尿中肾小管标志蛋白水平变化，探讨两者间相关关系及其意义。采用ＰＥＧ沉淀比浊法血检测血ＣＩＣ水平；采用化学显色终点法定量检测尿ＮＡＧ活力，共检测治疗前后恶性肿瘤患者４９例，结果：肿瘤患者血ＣＩＣ及尿ＮＡＧ均较正常对照明显增高，且治疗前较治疗后增高显著，血ＣＩＣ与尿ＮＡＧ水平变化是相关。结果表明恶性肿瘤水ＮＡＧ活力显著增高怀肿瘤相关抗原所致ＣＩＣ水平有关     

紧移植患者血浆可溶性白介素—2受体水平的监测及临床意义

以荧光偏振免疫法和ＥＬＩＳＡ分别测定肾移植患者全血环孢素（ＣｓＡ）浓度和血浆可溶性白介素－２受体（ｓＩＬ－２Ｒ）水平。稳定移植组、排斥反应组和ＣｓＡ毒性组的ＳＩＬ－２Ｒ均与正常对照组者有明显差异（Ｐ＜０．０１）；稳定移植组与排斥反应相差异显著（Ｐ＜０．０１），而与ＣｓＡ毒性组无明显差异（Ｐ＞０．０５）。全血ＣｓＡ浓度与ｓＩＬ－２Ｒ，水平无明显相关关系。提示ＳＩＬ－２Ｒ是鉴别肾移植患者排斥反应或Ｃｓ     

肾移植患者血浆可溶性白介素－2受体水平的监测及临床意义

以荧光偏振免疫法和ＥＬＩＳＡ分别测定肾移植患者全血环孢素（Ｃ＿ｓＡ）浓度和血浆可溶性白介素－２受体（＿ｓＩＬ－２Ｒ）水平。稳定移植组、排斥反应组和Ｃ＿ｓＡ毒性组的＿ｓＩＬ－２Ｒ均与正常对照组者有明显差异（Ｐ＜０．０１）；稳定移植组与排斥反应组差异显著（Ｐ＜０．０１），而与Ｃ＿ｓＡ毒性组无明显差异（Ｐ＞０．０５）。全血Ｃ＿ｓＡ浓度与＿ｓＩＬ－２Ｒ，水平无明显相关关系。提示＿ｓＩＬ－２Ｒ是鉴别肾移植患者排斥反应或Ｃ＿ｓＡ毒性的重要指标，对Ｃ＿ｓＡ合理用药有重要意义。     

影响环孢素A血药浓度的因素分析

应用荧光偏振免疫法（ＦＰＩＡ）测定２５例尸肾移植后患者全血环孢素Ａ（ＣｓＡ）浓度。结合合用酮康唑，西咪替丁后ＣｓＡ血浓度增高２．２１和１．６８倍，肝功能异常患者ＣｓＡ血浓度比正常组高１．６６倍，另外血中有凝血块也是影响原因之一。     

影响环孢素A血药浓度的因素分析

应用荧光偏振免疫法（ＦＰＩＡ）测定２５例尸肾移植后患者全血环孢素Ａ（ＣｓＡ）浓度。结果合用酮康唑．西咪替丁后ＣｓＡ血浓度增高２．２１和１．６８倍，肝功能异常患者ＣｓＡ血浓度比正常组高１．６６倍。另外血中有凝血块也是影响原因之一。     

长期存活肾移植患者环孢素血药浓度监测的临床研究

目的　分析长期存活肾移植患者环孢素 A( Cs A)血浓度监测的临床意义。 方法 　采用荧光偏振免疫法 ( FPIA)测定 674例肾移植患者5 3 93例次 Cs A血药浓度 ,根据术后时间分为正常组、中毒组、排异组 ,分析其疗效 ;并对其术后时间、年龄、药物相互作用、存活情况等进行统计分析。 结果 　中毒组、排异组与正常组相比 ,Cs A全血药浓度有显著性差异 ( P<0 .0 1) ;在同一时间段内 Cs A血药浓度随着年龄的增长呈下降趋势 ,术后时间 1年以上 ,3组患者的 Cs A血药浓度范围重叠较大。 结论 　根据 Cs A血药浓度监测结果及时调整给药方案 ,实行个体化给药方案 ,合理用药 ,建立长期随访制度 ,及时发现和处理并发症 ,是提高长期存活率的根本保证之一     

Relationship between development of nephrotoxicity and blood concentration of cyclosporine A in bone-marrow transplanted recipients who received the continuous intravenous infusion

This study was undertaken to investigate the relationship between blood concentration of cyclosporine A (CsA), administered intravenously by a 24-h continuous infusion, and drug-induced nephrotoxicity or hepatotoxicity. It was investigated retrospectively in 8 patients who had received an allogeneic bone marrow transplant (BMT). The correlation between daily doses and blood concentration of CsA was not significant. Then, the data of blood concentration of CsA and renal or liver function test result were divided into 5-d periods from the date of transplantation, and the mean value for each period was calculated. The maximum values of blood urea nitrogen (BUN) and serum creatinine (SCr) were consistently observed only after the period when the 5-d mean CsA concentration reached the peak level: the maximum BUN and SCr values were witnessed at Periods 2 to 10 and at Periods 1 to 9, respectively. On the other hand, no consistent correlation was found between the 5-d mean CsA concentrations and liver function test result. We also investigated the relationship between renal function and the cumulative dose or AUC of CsA. The parameters of renal function tests reached peak levels at the cumulative dose of 4000 to 10000 mg and at the cumulative AUC of 280000 to 660000 ng/ml.h. These results suggest that: 1) a deterioration of renal function occurs usually after the peak blood concentration of CsA is attained, and 2) the monitoring of the blood concentration of CsA is useful in predicting renal dysfunction in post-BMT patients.     

环孢霉素 A 在服药患者尿液中的含量测定简

目的 了解环孢霉素A在服药患者尿液中的含量.方法检测20例肾移植患者CsA 全血谷值浓度和尿液中CsA浓度.结果 20例肾移植患者CsA 全血谷值浓度为（73.46±15.54）μg·L-1,尿液CsA浓度为（174.83±101.52）μg·L-1.结论 CsA可以通过尿液途径部分排出体外.     

肾移植患者环孢素A血药浓度与胱抑素C的相关性分析

目的:研究肾移植患者术后不同时期的环孢素A(CsA)血药浓度与血清胱抑素C(CysC)和血清肌酐(Scr)的相关性。方法:118例肾移植患者术后肾功能稳定(肌酐清除率>40 ml/min),其中男性60例,女性58例,共监测307例次。术后同时监测CsA血药浓度、CysC值和Scr。结果:随着术后时间的延长,CsA血药浓度呈逐渐下降趋势,CysC的均值高于正常参考范围,而Scr值均在正常参考范围内。术后不同时间段组、不同药物浓度组的CsA血药浓度与CysC和Scr均无显著相关性。结论:肾移植术后CsA血药浓度的高低,不影响CysC、Scr对移植肾功能的评价。     

Tacrolimus in combination with FTY720--an analysis of renal and blood parameters

Calcineurin inhibitors (CNIs) are routinely used in immunosuppressive therapy and both Cyclosporine (CsA) and Tacrolimus (FK506) show similar efficacies to prevent rejection and death within the first year after organ transplantation. However, their use is limited by side effects such as kidney damage, hypertension, onset of diabetes and hyperlipidemia. It is a consensus that compared with CsA, FK506 causes less changes in blood pressures, serum lipids and renal function. Nevertheless, FK506 use is associated with a higher incidence of post-transplant diabetes mellitus (PTDM). FTY720 is a new compound that has shown a protective effect in animal models with respect to rejection in transplantation, ischemia-reperfusion injury, autoimmune diseases and tumor development. FTY720 acts by altering lymphocytes homing from blood to peripheral lymphoid organs. In mice, FTY720 administered in combination with CsA during 21 days has prolonged skin allograft survival without causing significant renal changes. In a model of CsA-induced chronic nephropathy in rats, FTY720 administration prevented renal injury suggesting benefit from using a combination of these drugs. In a canine kidney allograft model, FTY720 in combination with low doses of CsA or FK506 showed an addictive anti-rejection effect without causing critical adverse effects. We therefore, investigated whether 21 days of FTY720 administration in association with FK506 could prevent renal damage and development of diabetes in mice. Mice receiving FK506 alone or FTY720 + FK506 during 21 days showed changes in kidney function and structure besides an increase in blood glucose and lymphopenia. The FTY720 + FK506 combination requires further investigation with an aim toward understanding the mechanisms involved with respect to side effects.     

肾移植术后服用环孢素A2h血药浓度峰值监测及治疗窗浓度探讨

目的探讨肾移植术后国内患者服用环孢素A(CsA)2h血药浓度峰值在不同时期的监测范围。方法用荧光偏振免疫法(FPIA)同时测定92例肾移植受者CsA谷浓度(C0)和服药2h后峰浓度(C2),并观察排斥反应的发生及肝、肾毒性反应。结果肾移植术后CsA C2在不同时期监测范围建议0mo~1mo为1000~1300μg/L,2mo~3mo为950~1250μg/L,4mo~6mo为900~1100μg/L,7mo~12mo为750~1000μg/L,12mo以上为600~800μg/L。结论在上述治疗窗浓度范围,CsA既能达到满意的免疫抑制效果,又能减少排斥反应和肝、肾毒性的发生。     

肾移植病人应用霉酚酸酯与硫唑嘌呤的临床疗效比较

目的：比较霉酚酸酯（MMF）、硫唑嘌呤（Aza）在肾移植病人中的临床效果。方法：肾移植术后服用霉酚酸酯、硫唑嘌呤患者各28例，均采用同服环孢菌素和泼尼松三联用药方案，每月常规监测环孢菌素A（CsA）全血浓度、血常规、肾功能、肝功能、尿常规。结果：MMF组的CsA用量及其血药浓度显著低于Aza组（P〈0．05），MMF组患者血肌酐（Cr）值也显著低于Aza组（P〈0．05），同时MMF组对急慢性排斥反应效果较Aza组好，药物性肝损害发生率低于Aza组。结论：MMF较Aza不良反应小，减少或避免肝、肾功肾功能损害的发生机会，使肾移植的成功率明显提高。     

Tacrolimus in combination with FTY720 — an analysis of renal and blood parameters

Calcineurin inhibitors (CNIs) are routinely used in immunosuppressive therapy and both Cyclosporine (CsA) and Tacrolimus (FK506) show similar efficacies to prevent rejection and death within the first year after organ transplantation. However, their use is limited by side effects such as kidney damage, hypertension, onset of diabetes and hyperlipidemia. It is a consensus that compared with CsA, FK506 causes less changes in blood pressures, serum lipids and renal function. Nevertheless, FK506 use is associated with a higher incidence of post-transplant diabetes mellitus (PTDM). FTY720 is a new compound that has shown a protective effect in animal models with respect to rejection in transplantation, ischemia–reperfusion injury, autoimmune diseases and tumor development. FTY720 acts by altering lymphocytes homing from blood to peripheral lymphoid organs. In mice, FTY720 administered in combination with CsA during 21 days has prolonged skin allograft survival without causing significant renal changes. In a model of CsA-induced chronic nephropathy in rats, FTY720 administration prevented renal injury suggesting benefit from using a combination of these drugs. In a canine kidney allograft model, FTY720 in combination with low doses of CsA or FK506 showed an addictive anti-rejection effect without causing critical adverse effects. We therefore, investigated whether 21 days of FTY720 administration in association with FK506 could prevent renal damage and development of diabetes in mice. Mice receiving FK506 alone or FTY720 + FK506 during 21 days showed changes in kidney function and structure besides an increase in blood glucose and lymphopenia. The FTY720 + FK506 combination requires further investigation with an aim toward understanding the mechanisms involved with respect to side effects.     

Effect of molsidomine and L-arginine in cyclosporine nephrotoxicity: role of nitric oxide

Cyclosporine A (CsA) is a potent and effective immunosuppressive agent, but its action is frequently accompanied by severe renal toxicity. To determine if the renal alterations are mediated directly by cyclosporine or by secondary homodynamic alterations induced by cyclosporine, we evaluated if L-arginine and a nitric oxide donor, molsidomine could prevent these alterations. Eight groups of rats were employed in this study, group 1 served as control, group 2 rats were treated with CsA (20 mg/kg, s.c. for 21 days), group 3 received CsA along with L-arginine (125 mg/kg in drinking water concurrently with CsA), groups 4 and 5 received CsA along with molsidomine (5 and 10 mg/kg, p.o. 24 h before and 21 days concurrently with CsA), group 6 received CsA along with L-arginine (125 mg/l in drinking water concurrently with CsA) and L-NAME (10 mg/kg), groups 7 and 8 received L-NAME (10 mg/kg) along with CsA and molsidomine (5 and 10 mg/kg), respectively. Renal function was assessed by measuring serum creatinine, blood urea nitrogen, creatinine and urea clearance. Tissue and urine nitrite and nitrate levels were measured to estimate the total nitric oxide levels. The renal oxidative stress was measured by renal malondialdehyde levels, reduced glutathione levels and by enzymatic activity of catalase and superoxide dismutase. Renal morphological alterations were assessed by histopathological examination. CsA administration for 21 days resulted in a marked renal oxidative stress, significantly deranged the renal functions as well as renal morphology. Treatment with L-arginine as well as with molsidomine significantly improved the renal dysfunction; tissue and urine total nitric oxide levels, renal oxidative stress and prevented the alterations in renal morphology. This protection against CsA nephrotoxicity was attenuated by treatment with L-NAME, clearly indicating that NO plays a pivotal role in renoprotective effect of L-arginine and molsidomine against cyclosporine nephrotoxicity.     

精氨酸、尼莫地平、细胞生长肽对环孢素毒性及其血药浓度的影响

目的：探讨精氨酸、尼莫地平、细胞生长肽(bFGF)对环孢素的肝、肾、睾丸毒性的防护作用和对体内药物浓度的影响。方法：雄性大鼠给予环孢素后，再分别给予精氨酸、尼莫地平和bFGF，测定大鼠环孢素浓度、细胞凋亡指数、血清谷丙转氨酶(ALT)、肌肝(Cr)、生精功能等。结果：精氨酸明显升高大鼠血中环孢素浓度，尼莫地平和bFGF则降低环孢素浓度。精氨酸、尼莫地平和bFGF具有明显降低肝、肾、睾丸细胞凋亡指数、血清ALT和Cr，以及减轻精子发生障碍的作用。结论：精氨酸、尼莫地平、bFGF可影响血中环孢素浓度，并减轻环孢素引起肝、肾、睾丸的毒性，而以精氨酸的作用较明显。