【Drugs——编译】 移植后高血糖的处理：新的免疫抑制剂可以吗?
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原题
Management of Hyperglycaemia After Pancreas Transplantation: Are New Immunosuppressants the Answer?[Article]
来源
Drugs. 65(2):153-166, 2005.
Accession Number
00003495-200565020-00001.
Author
Egidi, Francesca M
Institution
Division of Nephrology, University of Tennessee Health Science Center, Memphis, Tennessee, USA
摘要原文
Pancreas transplantation is considered the optimal therapy for patients with diabetes mellitus who reach end-stage renal disease. Despite achievement of euglycaemia after this procedure, the progression to impaired pancreatic function and metabolic exhaustion still represents one of the major concerns that increase the risk of graft loss. This paper reviews the possible mechanisms that can induce post-transplant hyperglycaemia, including those related to immunosuppression and those non-related, and the new strategies available for minimising or preventing this complication.
Different aetiologies can induce pancreatic dysfunction. Technical complications, acute pancreatitis and delayed graft function, mostly related to impaired insulin secretion, are considered the early causes for abnormal glucose control. In general, acute rejection does not affect the endocrine portion of the pancreas graft because islet destruction occurs later than the inflammation of the exocrine components. Hyperinsulinaemia and insulin resistance represent the main concern for the progression of blood glucose intolerance. The anastomotic techniques of the exocrine portion of the pancreas and the immunosuppressive regimens are of critical importance for the development of impaired glucose metabolism. Hyperinsulinaemia, as a result of the fact that systemic-enteric or systemic-bladder drainages reducing the hepatic clearance of insulin, has led to the introduction of more physiological techniques using portal drainage of the endocrine secretions. Experimental and clinical data have shown that many of the current immunosuppressants account, to a large degree, for the increased risk of the development of post-transplant hyperglycaemia. The most common maintenance regimen in pancreatic transplantation still consists of triple therapy with a combination of corticosteroids, calcineurin inhibitors (either ciclosporin [cyclosporine] or tacrolimus), and mycophenolate mofetil (MMF).
The diabetogenic effects of corticosteroids and calcineurin inhibitors have resulted in the need for protocols able to minimise their use. Recent studies have shown the safety and efficacy of steroid-sparing or -free regimens. Sirolimus has shown powerful immunosuppressive potency in absence of nephrotoxicity and diabetogenicity. Multicentre and single-centre reports have demonstrated that both calcineurin inhibitor withdrawal and avoidance were possible when sirolimus was used in a concentration-controlled fashion, with low-dose corticosteroids and MMF. Although the experience with sirolimus in pancreatic transplantation is still limited, the results are promising. Patients affected by diabetic gastroparesis seem to better tolerate a regimen with sirolimus and low-dose tacrolimus than one with tacrolimus in combination with MMF.
For successful, long-term results of pancreatic transplantation, it is crucial to combine donor selection, technical aspects, modified anastomotic techniques and new therapeutic approaches designed to minimise the metabolic and non-metabolic adverse effects of the immunosuppressive regimens.
中文翻译
对于糖尿病末期肾病病人来说，胰移植被认为是最佳的治疗。尽管移植后可以使血糖恢复正常，胰功能的损害和代谢耗竭仍然是增加移植失败的主要涉及因素。这份论文评论了诱导移植后高血糖的可能机制，包括这些相关的免疫抑制剂和非相关的减少或阻止这个并发症的新的可行办法。
不同的病源都可诱导胰功能障碍。技术性并发症、急性胰腺炎及延迟的抑制反应（大部分与胰岛素分泌损害有关）被认为是早期血糖控制异常的原因。一般来说，急性排斥并不影响胰移植后内分泌的分配，因为胰岛破坏比外分泌部件炎症发生的晚。高胰岛素血症和胰岛素抵抗代表了血糖不耐受的主要涉及情况。胰内分泌吻合技术和免疫抑制疗法对治疗糖代谢损害是非常重要的。高胰岛素血症——系统性肠道或膀胱排液诱导肝脏胰岛素清除的一个结果——导致了利用内分泌液经肝门静脉排泄的更多生理技术的引进。实验和临床数据表明很多目前的免疫抑制方法是针对治疗移植后高血糖危险因素增加的治疗。
胰移植中最常用的维持疗法是三联疗法——即糖皮质激素类固醇，神经钙蛋白抑制剂（环孢素或他克莫司）及霉酚酸莫非替克（MMF）的联合。
糖皮质激素类固醇和神经钙蛋白抑制剂的致糖尿病作用限制了其在临床的应用。最近的研究说明了节制激素疗法的安全性和有效性。西罗莫司具有很强的免疫抑制效力，但有肾毒性和糖尿病倾向。多中心和单中心报告说明了神经钙蛋白抑制剂的撤销和不应用是可行的，但这是在西罗莫司应用在浓度控制的方法下，并且应用低剂量糖皮质激素类固醇和MMF。尽管胰移植中应用西罗莫司仍受到限制，这个结果还是很有前途的。被糖尿病胃轻瘫影响的病人对应用西罗莫司和低剂量他克莫司疗法的耐受性要好于应用他克莫司与MMF联合的疗法。
对于成功的，长期的胰移植病人来说，以下几个方面非常重要：选择合适的捐赠者；改进的吻合技术；设计新的治疗方案以使代谢的和非代谢的免疫抑制剂给药法的不利作用最小化。
Management of Hyperglycaemia After Pancreas Transplantation: Are New Immunosuppressants the Answer?[Article]
来源
Drugs. 65(2):153-166, 2005.
Accession Number
00003495-200565020-00001.
Author
Egidi, Francesca M
Institution
Division of Nephrology, University of Tennessee Health Science Center, Memphis, Tennessee, USA
摘要原文
Pancreas transplantation is considered the optimal therapy for patients with diabetes mellitus who reach end-stage renal disease. Despite achievement of euglycaemia after this procedure, the progression to impaired pancreatic function and metabolic exhaustion still represents one of the major concerns that increase the risk of graft loss. This paper reviews the possible mechanisms that can induce post-transplant hyperglycaemia, including those related to immunosuppression and those non-related, and the new strategies available for minimising or preventing this complication.
Different aetiologies can induce pancreatic dysfunction. Technical complications, acute pancreatitis and delayed graft function, mostly related to impaired insulin secretion, are considered the early causes for abnormal glucose control. In general, acute rejection does not affect the endocrine portion of the pancreas graft because islet destruction occurs later than the inflammation of the exocrine components. Hyperinsulinaemia and insulin resistance represent the main concern for the progression of blood glucose intolerance. The anastomotic techniques of the exocrine portion of the pancreas and the immunosuppressive regimens are of critical importance for the development of impaired glucose metabolism. Hyperinsulinaemia, as a result of the fact that systemic-enteric or systemic-bladder drainages reducing the hepatic clearance of insulin, has led to the introduction of more physiological techniques using portal drainage of the endocrine secretions. Experimental and clinical data have shown that many of the current immunosuppressants account, to a large degree, for the increased risk of the development of post-transplant hyperglycaemia. The most common maintenance regimen in pancreatic transplantation still consists of triple therapy with a combination of corticosteroids, calcineurin inhibitors (either ciclosporin [cyclosporine] or tacrolimus), and mycophenolate mofetil (MMF).
The diabetogenic effects of corticosteroids and calcineurin inhibitors have resulted in the need for protocols able to minimise their use. Recent studies have shown the safety and efficacy of steroid-sparing or -free regimens. Sirolimus has shown powerful immunosuppressive potency in absence of nephrotoxicity and diabetogenicity. Multicentre and single-centre reports have demonstrated that both calcineurin inhibitor withdrawal and avoidance were possible when sirolimus was used in a concentration-controlled fashion, with low-dose corticosteroids and MMF. Although the experience with sirolimus in pancreatic transplantation is still limited, the results are promising. Patients affected by diabetic gastroparesis seem to better tolerate a regimen with sirolimus and low-dose tacrolimus than one with tacrolimus in combination with MMF.
For successful, long-term results of pancreatic transplantation, it is crucial to combine donor selection, technical aspects, modified anastomotic techniques and new therapeutic approaches designed to minimise the metabolic and non-metabolic adverse effects of the immunosuppressive regimens.
中文翻译
对于糖尿病末期肾病病人来说，胰移植被认为是最佳的治疗。尽管移植后可以使血糖恢复正常，胰功能的损害和代谢耗竭仍然是增加移植失败的主要涉及因素。这份论文评论了诱导移植后高血糖的可能机制，包括这些相关的免疫抑制剂和非相关的减少或阻止这个并发症的新的可行办法。
不同的病源都可诱导胰功能障碍。技术性并发症、急性胰腺炎及延迟的抑制反应（大部分与胰岛素分泌损害有关）被认为是早期血糖控制异常的原因。一般来说，急性排斥并不影响胰移植后内分泌的分配，因为胰岛破坏比外分泌部件炎症发生的晚。高胰岛素血症和胰岛素抵抗代表了血糖不耐受的主要涉及情况。胰内分泌吻合技术和免疫抑制疗法对治疗糖代谢损害是非常重要的。高胰岛素血症——系统性肠道或膀胱排液诱导肝脏胰岛素清除的一个结果——导致了利用内分泌液经肝门静脉排泄的更多生理技术的引进。实验和临床数据表明很多目前的免疫抑制方法是针对治疗移植后高血糖危险因素增加的治疗。
胰移植中最常用的维持疗法是三联疗法——即糖皮质激素类固醇，神经钙蛋白抑制剂（环孢素或他克莫司）及霉酚酸莫非替克（MMF）的联合。
糖皮质激素类固醇和神经钙蛋白抑制剂的致糖尿病作用限制了其在临床的应用。最近的研究说明了节制激素疗法的安全性和有效性。西罗莫司具有很强的免疫抑制效力，但有肾毒性和糖尿病倾向。多中心和单中心报告说明了神经钙蛋白抑制剂的撤销和不应用是可行的，但这是在西罗莫司应用在浓度控制的方法下，并且应用低剂量糖皮质激素类固醇和MMF。尽管胰移植中应用西罗莫司仍受到限制，这个结果还是很有前途的。被糖尿病胃轻瘫影响的病人对应用西罗莫司和低剂量他克莫司疗法的耐受性要好于应用他克莫司与MMF联合的疗法。
对于成功的，长期的胰移植病人来说，以下几个方面非常重要：选择合适的捐赠者；改进的吻合技术；设计新的治疗方案以使代谢的和非代谢的免疫抑制剂给药法的不利作用最小化。
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