Bobadilla Norma A, Gamba Gerardo
Molecular Physiology Unit, Universidad Nacional Autónoma de México, 14000 México City, Mexico.
Am J Physiol Renal Physiol. 2007 Jul;293(1):F2-9. doi: 10.1152/ajprenal.00072.2007. Epub 2007 Apr 11.
Cyclosporine A (CsA), a calcineurin inhibitor, has improved allograft survival in solid organ transplantation and has been increasingly applied in the management of autoimmune diseases. While marked progress has been made in patient and allograft survival rates, clinical use of CsA is often limited by its nephrotoxic effect, which can be presented as two distinct and well-characterized forms: acute and chronic nephrotoxicity. The acute form is characterized by renal vasoconstriction, induced by an imbalance of vasoactive substances release, which leads to renal dysfunction. This form is reversible. The chronic toxicity, in contrast, is characterized by the vasoconstriction plus the development of structural damage that includes arteriolopathy and tubulointerstitial fibrosis that are often not reversible. The exact mechanisms of these deleterious effects are not fully understood, but major advances have occurred over the last few years. Here we review the current literature regarding the pathogenesis and strategies that have been used to ameliorate renal injury in chronic CsA nephrotoxicity. Recent observations suggest that aldosterone plays a central role in the pathogenesis of CsA nephrotoxicity and that spironolactone could be a useful agent to prevent it. These studies and the use of mineralocorticoid receptor blockade are discussed.
环孢素A（CsA）是一种钙调神经磷酸酶抑制剂，可提高实体器官移植中同种异体移植物的存活率，并越来越多地应用于自身免疫性疾病的治疗。虽然在患者和同种异体移植物存活率方面取得了显著进展，但CsA的临床应用常常受到其肾毒性作用的限制，肾毒性可表现为两种不同且特征明确的形式：急性和慢性肾毒性。急性形式的特征是肾血管收缩，由血管活性物质释放失衡引起，导致肾功能障碍。这种形式是可逆的。相比之下，慢性毒性的特征是血管收缩加上结构损伤的发展，包括小动脉病变和肾小管间质纤维化，这些通常是不可逆的。这些有害作用的确切机制尚未完全了解，但在过去几年中已经取得了重大进展。在此，我们综述了关于慢性CsA肾毒性发病机制和用于改善肾损伤的策略的当前文献。最近的观察结果表明，醛固酮在CsA肾毒性发病机制中起核心作用，螺内酯可能是预防它的有用药物。本文将讨论这些研究以及盐皮质激素受体阻断剂的应用。
