应用国产雷帕霉素延长肾脏移植物存活的实验研究

目的探讨国产雷帕霉素(rapamycin, RPM)及其与环孢素A(CsA)联合应用延长大鼠移植肾存活的效能.方法肾移植大鼠分为对照组、RPM组、CsA组、RPM 小剂量CsA组和RPM 大剂量CsA 4个治疗组.观察移植肾存活时间、血肌酐浓度和移植肾病理改变.结果与对照组相比,RPM组、CsA组、RPM CsA组移植肾存活时间均显著延长(P<0.01),其中,RPM 小剂量CsA组移植肾存活时间最长(69.2±10.3)d,术后15、30d组血肌酐浓度最低,未见明显的肾小管空泡变性.结论国产雷帕霉素可有效延长大鼠移植肾存活时间;与小剂量CsA合用可避免严重肾中毒,进一步延长移植肾的存活.     

肾移植患者应用咪唑立宾的临床研究

目的:研究咪唑立宾(MZR)在肾移植患者中应用的临床特点。方法:2005年9月至2006年2月间共16例肾移植患者接受MZR治疗。5例患者为肾移植术后直接应用MZR,11例患者由于经济原因从霉酚酸酯(MMF)切换成MZR。全部患者均采用以钙调神经蛋白抑制剂为基础的三联免疫抑制方案。本组患者随访期间重点监测用药后血常规、移植肾功能、肝功能、尿酸、血糖、血脂等生化指标,同时记录患者出现的所有临床不良反应及治疗,包括:各种细菌、病毒感染,移植肾急性排斥反应等。综合评价该药物作为免疫抑制治疗方案的安全性、有效性。结果:在MZR治疗后3个月~15个月的随访期间,患者全部存活,且移植肾功能良好。急性排斥发生率为12.5%,未出现难治性排斥。消化道副反应发生少。患者主要不良反应是高尿酸血症和骨髓抑制,但通过MZR减量及对症处理后基本都可以控制,预后好。术后感染方面与其他药物相比差异无显著性。结论:MZR是一种安全有效的免疫抑制剂,具有疗效稳定,副反应程度轻的特点。在严密随访的情况下可取得良好的临床效果。     

舒莱预防肾脏移植物急性排斥反应的随机对照试验研究

目的：探讨白细胞介素2受体单克隆抗体——舒莱（Simulect）对移植肾急性排斥反应的预防作用以及用药的安全性与药物的毒副作用。方法：将我器官移植移植中心1999年3月～2002年10月共46例肾移植受者为研究对象，随机分成舒莱组（23例）和对照组（23例），两组肾移植术后均接受以Neoral为基础的三联免疫抑制剂。舒莱组术前2h和术后4d各给予舒莱20mg静脉滴注。观察急性排斥反应、Neoral、皮质激素和硫唑嘌呤用量及药物的毒副作用。实验室检测血CsA浓度和肝肾功能。结果：研究结果表明，舒莱组无1例发生急性排斥反应，对照组术后8周内发生3例4次急性排斥反应。两组均未发生明显的毒副作用。两组间Neoral用量及血CsA浓度无明显差异。对照组因发生急性排斥反应，8周内皮质激素用药量总量大于舒莱组。结论：舒莱对移植肾急性排斥反应具有明显的预防作用，且用药方法简便，疗程短，无明显的毒副作用。     

Ganciclovir treatment of cytomegalovirus disease in transplant recipients and other immunocompromised hosts

Thirty-one immunocompromised patients with severe cytomegalovirus (CMV) disease were treated with intravenous ganciclovir. Twenty-one patients had received transplants--15 bone marrow recipients, five renal allograft recipients, and one liver transplant recipient--while the other ten were immunocompromised due to acquired immunodeficiency syndrome (six), hematologic malignancies (three), and systemic lupus erythematosus (one). They presented with one or more of the following syndromes: CMV pneumonitis (19), CMV of the gastrointestinal tract (six), CMV retinitis (seven), and CMV hepatitis (three). Seventeen (55%) of 31 patients demonstrated clinical improvement during ganciclovir therapy, with the best response seen in the transplant recipients. Viremia ceased in 14 (93.3%) of 15 patients after a mean of 4.7 days of therapy; viruria ceased in eight (53.3%) of 15 patients after a mean of 11 days of therapy. Ganciclovir plasma concentrations at a dosage of 2.5 mg/kg/three times a day were as follows: mean peak, 16.04 mumol/L; mean trough, 2.38 mumol/L. Neutropenia occurred in 11 (35%) of 31 patients and in nine (60%) of 15 bone marrow transplant recipients. We conclude that ganciclovir exerted an antiviral effect against CMV and may play a role in the treatment of CMV disease in patients with depressed immunity, especially bone marrow and organ transplant recipients.     

大剂量ARB对肾移植后蛋白尿治疗作用的临床研究

目的观察大剂量ARB对肾移植后蛋白尿的疗效及安全性。方法83例肾移植后蛋白尿患者,分为治疗组50例(采用2~4倍剂量ARB治疗)和对照组33例(不使用ARB治疗),观察不同治疗时间两组患者24h尿蛋白、血肌酐、血生化、血压、远期人/肾生存率及药物不良反应。结果治疗组24h尿蛋白排出显著低于对照组;治疗组血肌酐倍增时间、进展到移植肾功能衰竭或死亡的时间显著高于对照组〔(34.42±12.56)个月与(17.51±10.26)个月,(38.12±22.51)个月与(24.25±13.56)个月〕;治疗组出现2例血钾升高,4例低血压。结论大剂量ARB可有效控制肾移植后蛋白尿,提高移植患者人/肾远期存活率,使用安全有效。     

Influenza vaccination in renal transplant recipients.

Renal transplant recipients receiving immunosuppressive therapy are prone to major pulmonary infections. Development of influenza virus infection may lead to renal allograft damage or rejection. These patients should therefore be protected against influenza viruses by vaccination. A satisfactory antibody response was found in 12 (60%) of 20 renal transplant recipients vaccinated. Among 15 control subjects, the antibody response was satisfactory in all participants (100%). Factors that might play a role in suppression of antibody response include use of immunosuppressive drugs and renal allograft function. Immunization is safe and does not appear to affect renal allograft function.     

Clinical application of real time-polymerase chain reaction in determining cytomegalovirus viral DNA load in renal transplant recipients

Background Cytomegalovirus (CMV) remains a significant clinical problem among immunosuppressed renal transplant patients.Quantitative PCR assays have become the most common methods in the determination of CMV infections in transplant patients.This study was to determine the relationship between CMV infection and the acute rejection of the transplanted kidney.Methods Plasma samples from 77 renal transplant patients that were pre-transplant negative for CMV infection were tested using real-time quantitative PCR and CMV gene-specific primers.The detected viral loads were retrospectively compared with the acute rejection rate and the chronic or mild rejection rates of the renal transplant.Results CMV-DNA was detected in 29 of 77 recipients,yielding a positive rate of detection of 37.7％ for this procedure.Twelve of the 21 recipients (57.1％) who suffered acute rejection had positive CMV-DNA.Among the 56 recipients suffered from chronic or mild rejection,17 (30.4％) had positive CMV-DNA plasma.Moreover,of the 29 recipients who had detectable CMV-DNA after transplant,12 (41.4％) suffered from acute rejection; of the 48 recipients with undetectable CMV-DNA,only nine (18.8％) developed acute rejection.Post-transplant patients with acute rejection had a higher rate (57.1％ vs.30.4％,P=0.03) of post-transplant CMV infection than those with chronic or mild rejection.Conclusion CMV infection is a risk factor of acute renal transplant rejection and CMV infection should be prevented and treated in renal transplant recipients.Chin Med J 2012; 125(19):3575-3577     

双侧上尿路尿路上皮癌30例临床诊疗分析

目的：探讨双侧上尿路尿路上皮癌的临床治疗策略。方法回顾性分析北京大学第一医院2002年1月至2011年5月诊治的30例原发性双侧上尿路尿路上皮癌患者,根据患者肾功能分组,按 eGFR≥60 mL/ min,15 mL/ min≤eGFR〈60 mL/ min, eGFR〈15 mL/ min 分为 A、B、C 3组,A、B 组患者主要采用一侧保留肾功能和另一侧根治性切除的主要治疗方式,C 组患者主要采用双侧根治性切除的方式治疗,分析各种手术方式对不同肾功能状态的上尿路尿路上皮癌患者的治疗效果。结果30例患者手术治疗均取得成功,其中 A 组患者,术后肿瘤复发率为33.33%,1例患者术后肾衰竭行透析治疗,1例患者术后7年因肿瘤原因死亡。 B 组患者,尿路上皮肿瘤复发率为31.25%,3例患者随访期间因肾衰竭行透析治疗,3例患者死亡。 C 组患者术后均行透析治疗,尿路上皮肿瘤复发率为37.5%,随访期间死亡3例。3组生存率、复发率差异无统计学意义。结论应根据患者肾功能情况和肿瘤特征,选择合适的方式治疗双侧上尿路尿路上皮癌。保留肾功能的治疗方法对于双侧上尿路尿路上皮癌患者而言是一种可选的治疗方法。     

Kidney

Conversion from cyclosporine to tacrolimus for the treatment of chronic allograft nephropathy , Clinical diagnosis and treatment of BK virus infection in renal transplant recipients , Clinical study on avascular necrosis of the femoral head in 24 renal transplantation patients , Clinical and histopathological analysis in living donor kidney transplantation recipients, Evaluation of the early-stage safety of livingrelated kidney transplant donors , Living-related donor kidney transplantation101 cases reports     

Ten-year review of disease pattern from percutaneous renal biopsy: an experience from a paediatric tertiary renal centre in Hong Kong

OBJECTIVE: To study the childhood renal disease pattern based on the renal biopsy histology in a local paediatric tertiary renal centre. DESIGN: Retrospective study. SETTING: Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital, Hong Kong. PATIENTS: All patients who underwent real-time ultrasound-guided closed renal biopsy from 1 April 1997 to 31 March 2007 were included. RESULTS: A total of 209 renal biopsies were performed, 162 on native kidneys and 47 on grafts. In the native group, major indications were renal manifestations secondary to systemic diseases (34%), followed by idiopathic nephrotic syndrome (28%) and haematuria (27%). In 94% the histopathology revealed glomerular diseases. Among the primary glomerular diseases, thin glomerular basement membrane disease, immunoglobulin A nephropathy, minimal change disease, and focal segmental glomerulosclerosis accounted for most. In all, 37% of patients with steroid-resistant nephrotic syndrome had focal segmental glomerulosclerosis and its relative incidence was increased when compared to previous studies. Minimal change disease and minimal change disease with mesangial immunoglobulin M deposits accounted for the majority of steroid dependent and frequent relapsers. Among patients with isolated microscopic haematuria, 73% had thin glomerular basement membrane disease, while patients with concomitant haematuria and proteinuria had a wide variety of pathology. In the kidney graft group, acute graft dysfunction was due to acute rejection in 38% of the patients, followed by calcineurin inhibitor toxicity in 14%. Chronic allograft nephropathy caused chronic allograft dysfunction in the majority of cases. Post-transplant proteinuria was caused by recurrence of the primary renal disease in all of our patients. CONCLUSION: This study provides updated epidemiological information for childhood renal disease and a change in the pattern of disease was observed.     

Conversion from calcineurin inhibitor to sirolimus for renal function deterioration in kidney allograft recipients

BACKGROUND: Calcineurin inhibitors play an important role in chronic allograft dysfunction. Sirolimus is an interesting alternative in renal transplant patients because it is less nephrotoxic than calcineurin inhibitors. METHODS: A chart review of the clinical outcome of kidney transplant patients converted to sirolimus with progressive allograft dysfunction is reported herein. Fifteen patients (average age: 32.3 years, 44 months mean time of conversion) were included. Indication for conversion was a >20% increase in serum creatinine over the last 6 months or progression to the range of 2-4.5 mg/dL. Patients underwent abrupt cessation of cyclosporine and sirolimus addition at 2-5 mg/day. RESULTS: Concomitant immunosuppression remained unchanged during conversion. Targeted sirolimus level was 8-12 ng/mL. Serum creatinine dropped from pre-conversion level of 2.75 +/- 0.83 to 2.14 +/- 0.67 and 1.97 +/- 0.66 mg/dL at 3 and 6 months (p <0.05). There was a significant decrease in blood urea nitrogen, hemoglobin and serum calcium at 3 months post-conversion as well as serum calcium and potassium at 6 months post-conversion (p <0.05). There were no rejection episodes. Patient and graft survival was 100% with three infectious complications. CONCLUSIONS: Monitored sirolimus conversion with sharp withdrawal of calcineurin inhibitor is an alternative for patients with deteriorating renal function and chronic allograft nephropathy.     

肾移植术后恶性肿瘤的临床分析

目的总结分析肾移植术后恶性肿瘤的发病率、临床特点及治疗效果。方法回顾分析1992年1月至2008年1月山西省第二人民医院肾移植透析中心825例肾移植受者术后恶性肿瘤的发生率、临床特点、免疫抑制剂调整及预后情况。结果 825例肾移植受者中有27例发生恶性肿瘤,发病率为3.3%,其中男性12例,女性15例。泌尿系肿瘤11例,占恶性肿瘤的40.7%;消化系统肿瘤6例,占恶性肿瘤的22.2%;乳腺癌2例,占恶性肿瘤的7.4%;皮肤癌3例,占恶性肿瘤的11.1%;肺癌2例,占恶性肿瘤的7.4%;卵巢癌、骨转移癌、颅内肿瘤各1例,分别占恶性肿瘤的3.7%。发现肿瘤时5例有远处转移,诊断肿瘤时26例移植肾功能正常,1例移植肾失功恢复血液透析。27例患者均及时调整免疫抑制剂剂量辅以化疗或放疗,18例行手术治疗,死亡9例,病死率为33.3%。结论肾移植术后恶性肿瘤发病率明显高于普通人群,泌尿系肿瘤的发病率位居第一,该现象与肾移植受者长期应用免疫抑制剂密切相关。     

肾移植患者高尿酸血症与痛风的研究进展

高尿酸血症在肾移植患者中较为常见，在接受环孢素A(CsA)治疗的患者中发病率更高。尿酸升高的原因多与药物治疗时间的长短有关，与剂量、血药浓度、血肌酐水平无明显相关性。肾移植患者痛风的发生率较低，其确切的病因目前尚不清楚。肾移植术后高尿酸血症和痛风的处理，目前尚有争议，作者对肾移植患者高尿酸血症和痛风作一综述。     

雷帕霉素转换在肝移植术后肾功能不全患者中的应用

目的 总结肝移植术后患者出现钙调磷酸酶抑制剂(CNI)相关性性肾功能不全时,进行雷帕霉素(Rap)转换的临床效果.方法 回顾性分析中山大学附属第一医院从2004年1月到2008年6月间肝移植术后因肾功能不全而从CNI转向Rap治疗的病例.观察免疫抑制剂转换前后肾功能的变化,以及相关的副作用.结果 转换后4个月肾功能获得明显改善(P<0.05).转换后3个月血脂水平明显升高(P<0.05),但在控制范围内.结论 当肝移植术后患者出现CNI相关性肾功能不全时,Rap是一种安全有效的替代免疫抑制剂.

Abstract：

Objective To investigate the efficacy of conversion from calcineurin-inhibitor (CNI) to rapamycin in liver recipients with CNI-associated renal insufficiency. Methods This retrospective study examined the liver transplant recipients who had switched from CNI to rapamycin between January 2004 and June 2008 in the first affiliated hospital of Sun Yat-sen University. The data of renal function before and after the conversion were analyzed by Wilcoxon sum rank test, and rapamycin-related adverse effects were also observed. Results Compared with that before conversion, the renal funtion 4 months after the conversion improved significantly (P<0.05). The blood lipid level 3 months after the conversion increased significantly (P<0.05) but were well controlled. Conclusion Rapamycin can be used safely as a good alternative in liver transplant recipients with CNI-related renal insufficiency.     

供体脾灌注对高度致敏肾移植受者嵌合体形成的影响

目的探讨供体脾灌注对高度致敏肾移植受者稳定期嵌合体形成及移植肾功能的影响。方法对16例高度致敏患者进行配对分组，实验组肾移植术中先予供体脾灌注40min，前瞻性观察脾灌注对患者术后6个月内嵌合体形成、移植肾排斥反应发生及移植肾功能的变化。结果脾灌注后受者外周血中供者来源的有核细胞数量显著增加，受者形成稳定嵌合体的时间较早，例数比对照组更多；肾移植术后脾灌注组排斥反应发生时间较对照组延迟，排斥反应严重程度明显较对照组轻微；术后6个月时，脾灌注组患者血肌酐值低于对照组。结论供体脾灌注可以显著提高高敏肾移植受者外周血中供者来源的有核细胞数量，减轻排斥反应强度，从而促进受者嵌合体的形成，有利于改善稳定期移植肾功能。     

肾移植受者他克莫司剂量/浓度个体差异影响因素及其变化规律

目的 探讨肾移植受者他克莫司剂量/浓度个体差异影响因素及其变化规律.方法 观察118例肾移植术后早期(3、7、14、30 d)、103例术后3月、75例术后6月、119例稳定期(≥1年)口服他克莫司+霉酚酸酯+泼尼松三联免疫抑制抗排斥的受者,记录性别、年龄、身高、体质量、他克莫司剂量、激素剂量、腹泻、血脂、肝功、肾功、白蛋白、红细胞比容.测定每个受者CYP3A5和MDR1 3435、2677、1236位点基因多态性及不同时期他克莫司药物浓度.然后以他克莫司浓度/剂量×体表面积为因变量分别进行多元线性回归分析.结果 肾移植术后早期多元线性回归模型拟合度偏低,术后3月明显增高,术后6月进一步增高并逐渐趋于稳定;影响他克莫司剂垦/浓度的因素在术后早期较多且变化剧烈,术后3月以后逐渐趋于稳定.从药物基因组学角度来看,影响他克莫司剂量/浓度的主要因素是MDR1 3435、MDR12677、MDR1 1236且术后早期变化剧烈,CYP3A5作用相对较弱且仅在稳定期入选,稳定期影响他克莫司代谢的主要因素是MDR1 3435.除药物基因组学因素外,年龄、肝功值、白蛋白和红细胞比容与他克莫司浓度/剂量×体表面积呈正相关,是个体差异的重要原因.结论 肾移植术后他克莫司剂量/浓度影响因素的变化规律与肾移植临床特点相吻合.不同时期他克莫司剂量/浓度个体差异的影响因素不同.药物基因组学是影响他克莫司剂量/浓度个体差异的重要因素,临床用药应尽量避免对他克莫司代谢干扰大的药物.年龄、肝功、白蛋白、红细胞比容和激素剂量也是他克莫司剂量/浓度个体差异的重要原因.     

HLA-DRw6 as a risk factor for active cytomegalovirus but not for herpes simplex virus infection after renal allograft transplantation

To study genetically determined susceptibility to cytomegalovirus and herpes simplex virus infections in patients given renal transplants a prospective study was performed of 68 consecutive patients receiving their first cadaveric kidney allograft. The recipients positive for HLA-DRw6 showed a significantly increased incidence of active cytomegalovirus infection as early as the 10th week after transplantation (p less than 0.05). No relation with other human leucocyte antigens was found, nor did a correlation exist between HLA typing and the incidence of herpes simplex virus infections. Furthermore, recipients positive for HLA-DRw6 with secondary cytomegalovirus infections excreted infectious virus more often (p less than 0.01) and showed more clinical symptoms (p less than 0.01) than a comparable group of recipients negative for HLA-DRw6. These observations may have practical implications for the treatment of patients who have had renal transplant operations.     

Primary hepatocellular carcinoma arising in a renal transplant recipient with polycystic disease

Malignant disease arises more commonly in renal transplant recipients than in non-transplanted individuals. Renal polycystic disease is the only cause of renal failure that has a statistically significant association with the acquisition of malignancy in renal transplant recipients. This patient, who had renal failure due to polycystic disease, is the first reported renal transplant recipient to develop a hepatocellular carcinoma in an otherwise completely normal liver. It is suggested that patients with polycystic renal disease may have an unidentified factor that predisposes to the development of malignancy in them after transplantation.     

60岁以上供肾亲属肾移植临床疗效分析

 目的 总结单中心供体年龄超过60岁亲属肾移植的临床经验。方法 回顾性分析复旦大学附属中山医院肾移植中心2004年至2008年供体年龄超过60岁供肾肾移植病例15例,其中母亲作为供体7例,父亲作为供体7例,丈夫作为供体1例。采用回顾性方法及基本统计方法进行分析。结果 供体9例采用手助腹腔镜手术方式取肾（60%）,6例采用小切口开放方式（40%）,左肾作为供肾13例（86.7%）,右肾2例（13.3%）。受体12例肌酐平均3.5 d降至正常水平。供受体均随访1～4年,供体3例肾功能异常,受体死亡1例（移植肾血栓形成）,介入B超穿刺9例,病理结果示细胞排斥6例（40%）;细胞毒性损伤2例（13.3%）;1例细胞排斥证据不足。7例受体肾功能异常（46.7%）,均为男性。结论 60以上老年供体肾移植排斥发生率较高,且供肾肾单位多数不能满足男性受体代谢需要。     

肿瘤坏死因子和组织粘附分子在慢性排斥移植肾中的表达

目的探讨肿瘤坏死因子-α(TNF-α)细胞间粘附分子-1(ICAM-1)和血管细胞粘附分子(VCAM-1)在慢性排斥移植肾组织中的表达及其意义.方法采用免疫组化技术对30例慢性排斥移植肾活检组织中TNF-α、ICAM-1和VCAM-1表达进行检测.12例正常肾脏组织作为对照.结果在发生慢性排斥的移植肾组织中,大多数病例有活动性间质及血管周围淋巴细胞浸润和小管局部炎症,肾小球、肾小管及间质浸润细胞TNF-α、ICAM-1和VCAM-1表达程度和分布普遍增强,但主要见于间质浸润细胞、肾小管损伤部位上皮细胞、炎症区域管周毛细血管和微小动脉内皮细胞,与正常对照有明显差异.结论细胞免疫可能在慢性排斥发病中起作用,细胞因子和粘附分子则是一过程中的重要介质.