Thrombotic Micro‐Angiopathy with Sirolimus‐Based Immunosuppression: Potentiation of Calcineurin‐Inhibitor‐Induced Endothelial Damage?

Thrombotic microangiopathy is a rare but important finding in the context of organ transplantation. Acute renal insufficiency in the setting of hemolysis and thrombocytopenia, a triad that constitutes 'hemolytic uremic syndrome', can be associated with, or triggered by, conditions such as verocytotoxin-producing Escherichia coli, viral infections, malignant hypertension, scleroderma, allograft rejection, lupus erythematosus, pregnancy, and medications including mitomycin C, calcineurin inhibitors, and oral contraceptives. After renal transplantation, it can occur, as either a de novo episode, or recurrent disease. Calcineurin inhibitors have long been associated with post-transplantation thrombotic microangiopathy. Sirolimus has been used as a primary immunosuppressant in patients transplanted with a history of earlier hemolytic-uremic syndrome, and also as rescue therapy in patients with calcineurin-inhibitor-associated thrombotic microangiopathy. We describe four cases where there was significant thrombotic microangiopathy in the context of contemporaneous or contiguous calcineurin inhibitor and sirolimus usage. As the intrarenal cyclosporin concentration is thought to be significantly elevated when cyclosporin and sirolimus are used together, this may explain these findings, and mandates caution in their co-administration.     

Liver Transplantation Across Rh Blood Group Barriers Increases the Risk of Biliary Complications

Background Cold ischemia time and the presence of postoperative hepatic arterial thrombosis have been associated with biliary complications (BC) after liver transplantation. An ABO-incompatible blood group has also been suggested as a factor for predisposal towards BC. However, the influence of Rh nonidentity has not been studied previously. Materials Three hundred fifty six liver transplants were performed from 1995 to 2000 at our hospital. BC incidence and risk factors were studied in 345 patients. Results Seventy patients (20%) presented BC after liver transplantation. Bile leakage (24/45%) and stenotic anastomosis (21/30%) were the most frequent complications. Presence of BC in Rh-nonidentical graft–host cases (23/76, 30%) was higher than in Rh-identical grafts (47/269, 17%) (P = 0.01). BC was also more frequent in grafts with arterial thrombosis (9/25, 36% vs 60/319, 19%; P = 0.03) and grafts with cold ischemia time longer than 430 min (26/174, 15% vs 44/171, 26%; P = 0.01). Multivariate logistic regression confirmed that Rh graft–host nonidentical blood groups [RR = 2(1.1–3.6); P = 0.02], arterial thrombosis [RR = 2.6(1.1–6.4); P = 0.02] and cold ischemia time longer than 430 min [RR = 1.8(1–3.2); P = 0.02] were risk factors for presenting BC. Conclusion Liver transplantation using Rh graft–host nonidentical blood groups leads to a greater incidence of BC.     

肝移植术后并发胆道狭窄和胆泥淤积影像诊断及介入治疗

目的:评价肝移植术后胆道狭窄和胆泥淤积影像诊断及介入治疗的价值。方法:对39例肝移植术后并发胆道狭窄和胆泥淤积的影像诊断及介入治疗进行回顾性分析。结果:超声、T型管胆道造影、CT和MRI检查诊断胆道狭窄伴胆泥形成39例,38例介入治疗后胆道梗阻症状明显缓解;1例介入治疗后胆道梗阻症状未明显改善,后行外科胆管修补术。结论:T型管胆道造影或直接经皮胆道造影对肝移植术后胆道狭窄和胆泥淤积诊断特异性及敏感性最高,放射介入和内镜介入技术对其均发挥重要的治疗作用。     

用心肌灌注显像靶心图定量分析评价AMI患者骨髓干细胞移植术疗效

目的 探讨靶心图上心肌灌注缺损区定量分析方法的可靠性、重复性及应用价值。方法 16例急性心肌梗死（AMI）行自体骨髓单个核细胞移植治疗的住院患者，于治疗前、治疗后45和90d行^99Tc^m-MIBI静息心肌灌注显像。在靶心图上勾画缺损区（在左心室靶心图中放射性计数低于40％的区域），并进行定量分析。结果 （1）不同操作者所得ROI结果之间的差异无统计学意义（t=0．52，P〉0．05）。（2）治疗后45d心肌灌注缺损区面积较治疗前缩小34．32％，差异有统计学意义（t=2．83，P〈0．05）；治疗后90d心肌灌注缺损区面积较治疗后45d缩小14．77％，差异有统计学意义（t=2．51，P〈0．05）。示自体骨髓单个核细胞移植对缺血心肌的恢复有一定疗效，能够缩小梗死面积，且自体骨髓单个核细胞冠状动脉内移植治疗AMI的疗效在移植后早期（45d内）即有体现。（3）面积百分比是观察心肌灌注变化的重要定量指标。结论 该方法对心肌病变范围及严重程度能准确定量；对评价AMI骨髓于细胞移植术疗效有一定的价值。     

再次肝移植治疗移植肝失功能22例报告

目的 总结再次肝移植治疗移植肝失功能的临床经验。方法 回顾分析2004年1月至2006年6月期间中山大学附属第三医院施行22例再次肝移植受者的临床资料，结合文献加以讨论。再次肝移植的原因分别为移植术后胆道并发症（12例）、移植术后肝癌复发（4例）、肝动脉栓塞（2例）、肝动脉狭窄（2例）以及乙肝复发（2例）。再次移植率为3．62％，供肝植入均采用改良背驮式肝移植技术。结果 全组无手术死亡，8例随访至今分别存活21、14、8、3个月各1例，12、1个月各2例；14例存活2周到28个月不等。首次肝移植术后8～30d行再次肝移植病人围手术期病死率最高，为66．7％；1年内死亡10例，主要死亡原因为感染（60％）。结论 再次肝移植是移植肝失功能的惟一有效的治疗方法，正确掌握手术时机及适应证，钻研手术技巧，合理的个体化免疫抑制方案以及围手术期有效的抗感染治疗是提高再次肝移植病人存活率的关键。     

肝移植术后缺血型胆道病变的介入治疗进展

肝移植是终末期肝病最有希望的治疗方法之一。移植肝缺血型胆道病变逐渐成为肝移植术后胆道并发症的主要类型，其病因及发病机制复杂，临床处理棘手，日益成为影响肝移植患者长期成活及导致移植物丢失的主要原因之一。国内外尝试用多种方法来预防和治疗缺血型胆道病变，介入治疗被认为是首选治疗方法，疗效显著。     

Tacrolimus Exposure and Evolution of Renal Allograft Histology in the First Year After Transplantation

Tacrolimus has a narrow therapeutic window and is characterized by a large inter-individual variability in bioavailability. The impact of tacrolimus exposure on subclinical evolution of graft histology has not been studied in renal recipients. This analysis included 239 protocol biopsies (obtained at implantation, 3 and 12 months) of 120 consecutive kidney recipients treated with tacrolimus, mycophenolate mofetil (MMF) and corticosteroids. Biopsies were scored according to the Banff 2001 criteria and a chronicity score was calculated. Prospective pharmacokinetic data were included in the analysis (5544 tacrolimus predose blood concentrations and tacrolimus AUC(0-12) at 3 and 12 months). Higher donor age and higher number of human leukocyte antigen-DR (HLA-DR) mismatches were independent predictors of subclinical acute rejection at 3 months, present in 8.7% of patients. The number of HLA-DR mismatches was independently associated with biopsy-proven clinical acute rejection. Biopsy-proven acute rejection episodes and low mean tacrolimus exposure were independently associated with higher increase in chronicity scores between 3 and 12 months after transplantation. This observational study suggests that rejection phenomena and immune-mediated mechanisms remain important in the early progression of chronic allograft pathology. Tacrolimus doses or systemic exposure were not associated with lesions of calcineurin inhibitor nephrotoxicity, suggesting that other factors determine susceptibility to tacrolimus nephrotoxicity.     

Urinary Albumin Excretion and the Risk of Graft Loss and Death in Proteinuric and Non-proteinuric Renal Transplant Recipients

BACKGROUND: Microalbuminuria and macroalbuminuria constitute risk factors for ESRD and death in non-transplanted populations. Whether microalbuminuria (especially in non-proteinuric patients) and macroalbuminuria constitute risk factors for graft loss and death is presently unknown in renal transplantation. METHODS: We retrospectively assessed the association between urinary albumin excretion (UAE) and ESRD and death in renal transplantation. RESULTS: UAE was measured in 616 (397 proteinuric; 219 non-proteinuric patients) renal transplant recipients. They were grafted for 62 months (range: 6-192). During the 40 months (3.7-99) thereafter, 31 patients underwent dialysis and 32 died. Microalbuminuria (vs. normoalbuminuria) and macroalbuminuria (vs. microalbuminuria) were powerful risk factors for graft loss [OR: 14.25 (2.88-52.3) and 16.41 (7.46-36.0), respectively, both p < 0.0001], even after adjustments on renal function and diabetes. Among the 219 non-proteinuric patients, microalbuminuria (vs. normoalbuminuria) was a significant risk factor for graft loss [OR: 23.09 (1.93-276.4), p = 0.0132]. Both microalbuminuria (vs. normoalbuminuria) [OR: 5.55 (2.43-12.66), p < 0.0001] and macroalbuminuria (vs. microalbuminuria) [OR: 4.12 (1.65-10.29), p = 0.0024] were predictive of death. CONCLUSIONS: Microalbuminuria and macroalbuminuria are powerful independent predictors of ESRD and death. Microalbuminuria is a risk factor for graft loss even in non-proteinuric patients. UAE provides additional information on renal and patient prognosis as compared to proteinuria and renal function.     

Switching from Tacrolimus to Sirolimus Halts the Appearance of New Sebaceous Neoplasms in Muir-Torre Syndrome

Little is known about the effects of immunosuppression on patients with hereditary nonpolyposis colorectal cancer (HNPCC). We describe a kidney transplant recipient with unrecognized Muir-Torre syndrome in whom the administration of a tacrolimus-based regimen led to the eruption of multiple sebaceous tumors. The patient was later found to harbor an MSH2 mutation. Switching to a sirolimus-based regimen resulted in arrest of the disease. When the patient was switched back to tacrolimus, new facial lesions rapidly appeared. Switching again to sirolimus resulted again in halting the appearance of new lesions. This finding is in line with the known antiangiogenic activity of sirolimus and reports on the regression of cutaneous Kaposi's sarcoma in kidney transplant recipients switched from another immunosuppressive regimen to sirolimus. Further studies on the potential use of sirolimus for the treatment of de novo tumors in immunosuppressed kidney transplant recipients with HNPCC are warranted.