Vidhun Jayakumar R, Sarwal Minnie M
Department of Pediatrics, Stanford University, 300 Pasteur Drive, Palo Alto, CA 94305, USA.
Pediatr Nephrol. 2005 Mar;20(3):418-26. doi: 10.1007/s00467-004-1786-4. Epub 2005 Feb 3.
Corticosteroids have played a central role in the evolution of renal transplant as the modality of choice for renal replacement in end stage kidney disease. Their use is associated with significant, dose related morbidity including osseous, cardiovascular, metabolic complications, body disfigurement and growth retardation in children. The strategies that have been employed to minimize these side effects include reduction in the daily administered dose of steroids, use of alternate day dosing regimens, steroid withdrawal post-transplantation and complete steroid avoidance. Steroid dose minimization has been associated with increased rates of acute rejection, though introduction of newer and more potent immunosuppressives has helped reduce the incidence of this complication. Steroid minimization will benefit patient morbidity due to cataracts, cardiovascular and osseous complications, but may offer little benefit towards improving linear growth. Alternate day steroid therapy may have a greater impact on growth improvement, but may be troubled by regimen non-adherence. Steroid withdrawal post-transplant, the ultimate target, is successful in a cohort of patients, but overall, has been historically associated with unacceptably high rates of clinical acute rejection, and has thus been used sparingly in adults and even less so in children. Complete corticosteroid avoidance, using newer induction and immunosuppressive agents, has been associated with an 8-23% incidence of acute rejection in pediatric renal transplant patients, significant catch-up growth post-transplant, improvements in post-transplant hypertension and hyperlipidemia, and a high safety profile at current follow-up. Newer induction protocols may allow complete steroid-free immunosuppression thus offering significant advantages in preventing the above-mentioned steroid related morbidity, which could also possibly be applicable to other areas of solid organ transplantation in all age groups.
在终末期肾病的肾脏替代治疗方式中，皮质类固醇在肾移植的发展过程中发挥了核心作用。其使用与显著的、与剂量相关的发病率相关，包括骨骼、心血管、代谢并发症、身体外形改变以及儿童生长发育迟缓。为尽量减少这些副作用所采用的策略包括减少每日皮质类固醇给药剂量、采用隔日给药方案、移植后停用皮质类固醇以及完全避免使用皮质类固醇。尽管引入更新、更强效的免疫抑制剂有助于降低这种并发症的发生率，但皮质类固醇剂量的减少与急性排斥反应发生率的增加有关。减少皮质类固醇剂量将有利于因白内障、心血管和骨骼并发症导致的患者发病率，但对改善线性生长可能益处不大。隔日皮质类固醇疗法可能对生长改善有更大影响，但可能会因治疗方案依从性问题而受到困扰。移植后停用皮质类固醇这一最终目标，在一部分患者中取得了成功，但总体而言，从历史上看，其与临床急性排斥反应的高得令人无法接受的发生率相关，因此在成人中使用较少，在儿童中更少使用。使用更新的诱导和免疫抑制药物完全避免使用皮质类固醇，在小儿肾移植患者中与8% - 23%的急性排斥反应发生率相关，移植后有显著的追赶生长，移植后高血压和高脂血症得到改善，并且在目前的随访中安全性良好。更新的诱导方案可能允许完全无皮质类固醇免疫抑制，从而在预防上述与皮质类固醇相关的发病率方面具有显著优势，这也可能适用于所有年龄组实体器官移植的其他领域。
