Hyperuricemia and bone marrow transplantation
Hyperuricemia and bone marrow transplantation
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DOI：
10.1159/000082548
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发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Annaloro, C
中科院分区：
文献类型：
--
作者：
Deliliers, GL;Annaloro, C
骨髓移植（BMT）后血尿酸水平和嘌呤代谢受到多方面的影响。尽管BMT通常在患者残留疾病负担较低时进行，但其中一部分患者仍有发生肿瘤溶解综合征的风险，即使是有限的疾病或非清髓性预处理方案;此外，在血尿酸水平持续正常的患者中也可以观察到尿酸转换的改变。除了这种明显的并发症，移植后发生的多种病理生理事件可能会扰乱尿酸稳态。虽然只有间接证据（来源于产科子痫和实验性痛风关节炎），一种移植相关的细胞因子产生增加（特别是TNF、IL-1和IL-6）可能会激活黄嘌呤氧化酶，而黄嘌呤氧化酶反过来可能会导致进一步的细胞因子发作：紊乱的细胞因子稳态参与了一些主要的急性BMT后并发症的发病机制，如肝静脉闭塞病（VOD）和急性移植物抗宿主病（aGVHD）。高尿酸血症也是环孢素A的一种众所周知的副作用，环孢素A是预防BMT后GVHD的参比药物，可能通过减少肾小球滤过和/或影响肾小管处理来影响尿酸转换;现有证据支持前一种解释。高尿酸血症在长期移植患者中被发现是代谢模式的一部分，使人联想到与胰岛素抵抗相关的所谓"X"或"代谢"综合征：对于这种移植后并发症仍然没有精确的解释，也没有任何关于其真实的发病率和结局的确切数据。高尿酸血症通常被认为是X综合征的边缘发现，但它在病因上与该综合征的其他组成部分有关，并且已被证明是组织和血管损伤的自主原因。最后，骨髓移植是一种可能的治疗策略，一些遗传性高尿酸血症，特别是Lesch-Nyhan病，虽然仍然有一些困惑的可能性，防止神经功能障碍的发展。版权所有（c）2005 S. Karger AG，巴塞尔。
Blood uric acid levels and purine metabolism are affected in many ways after bone marrow transplantation (BMT). Although BMT is usually performed when patients have a low residual disease burden, a proportion of them are still at risk of tumor lysis syndrome, even with limited disease or after nonmyeloablative conditioning regimens; moreover, an alteration in uric acid turnover can also be observed in patients with persistently normal uric acid blood levels. Apart from this obvious complication, multiple physiopathological events occurring after transplantation may derange uric acid homeostasis. Although there is only indirect evidence (derived from obstetric eclampsia and experimental gout arthritis), a transplant-related increase in cytokine production (particularly TNF, IL-1 and IL-6) may activate xanthine oxidase which, in turn, may be responsible for a further cytokine bout: deranged cytokine homeostasis is involved in the pathogenesis of some of the main acute post-BMT complications, such as hepatic veno-occlusive disease (VOD) and acute graft-versus-host disease (aGVHD). Hyperuricemia is also a well-known side effect of cyclosporine A, the reference drug for the prevention of post-BMT GVHD, which may affect uric acid turnover by reducing glomerular filtration and/or affecting tubular handling; the available evidence favors the former explanation. Hyperuricemia is found in long-term transplanted patients as part of a metabolic pattern reminiscent of the so-called 'X' or 'metabolic' syndrome related to insulin resistance: there is still no precise interpretation of this post-transplant complication nor any definite data concerning its real incidence and outcome. Hyperuricemia is frequently regarded as a marginal finding in the context of X syndrome, but it is pathogenetically linked to the other component of the syndrome and has proved to be autonomously responsible for tissue and vessel damage. Finally, BMT is a possible therapeutic strategy for some inherited forms of hyperuricemia, particularly Lesch-Nyhan disease, although there is still some perplexity concerning the possibility of preventing the development of neurological impairment. Copyright (c) 2005 S. Karger AG, Basel.