Nephrology Service, Walter Reed Army Medical Center, Washington, DC, USA.
Nephrol Dial Transplant. 2009 Dec;24(12):3861-6. doi: 10.1093/ndt/gfp416. Epub 2009 Sep 3.
There are several case reports of rhabdomyolysis (RM) in renal transplant recipients, but the actual incidence of this complication is not known. Most of the reported cases have been attributed to drug-drug interactions with calcineurin inhibitors, with the majority of interactions reported between cyclosporine and 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins). Pharmacokinetic studies have demonstrated that cyclosporine increases statin drug levels, presumably via competitive inhibition of cytochrome P450 3A4.
In a retrospective cohort of 20 366 adult Medicare primary renal transplant recipients in the USRDS database transplanted from 1 January 2003 to 31 July 2005 and followed through 31 December 2005, we assessed Medicare claims for RM and dyslipidaemia (HPL), which was used as a surrogate for statin use.
The incidence rate of RM post-transplant for the study period was 1.4 (95% CI 1.1-1.8) per 1000 person-years. By Cox regression analysis, cyclosporine (versus tacrolimus) use [AHR 2.36 (95% CI 1.23-4.35); P = 0.006] and black race [AHR 2.33 (95% CI 1.30-4.17); P = 0.005] were associated with RM. By Cox non-proportional hazards regression, RM was associated with graft loss (including death) [AHR 2.84 (95% CI 1.70-4.72); P < 0.001].
RM is a rare complication after renal transplantation and is significantly associated with allograft loss (including death). RM is significantly more likely to occur with cyclosporine (versus tacrolimus)-based immunosuppression and possibly in persons of black race. Increased surveillance for RM is warranted in these at-risk patients.
肾移植受者横纹肌溶解症(RM)的病例报告已有数例,但这种并发症的实际发生率尚不清楚。大多数报告的病例归因于与钙调神经磷酸酶抑制剂的药物-药物相互作用,大多数相互作用报告发生在环孢素与 3-羟基-3-甲基戊二酰辅酶 A 还原酶抑制剂(他汀类药物)之间。药代动力学研究表明,环孢素增加了他汀类药物的药物水平,推测可能是通过细胞色素 P450 3A4 的竞争性抑制作用。
我们在美国肾脏数据系统(USRDS)数据库中回顾性分析了 20366 名成年医疗保险初级肾移植受者的队列,这些受者于 2003 年 1 月 1 日至 2005 年 7 月 31 日接受移植,并随访至 2005 年 12 月 31 日,我们评估了医疗保险索赔中 RM 和血脂异常(HPL)的情况,HPL 作为他汀类药物使用的替代指标。
研究期间移植后 RM 的发生率为每 1000 人年 1.4(95%CI 1.1-1.8)。通过 Cox 回归分析,环孢素(与他克莫司相比)的使用[调整危险比(AHR)2.36(95%CI 1.23-4.35);P=0.006]和黑种人种族[AHR 2.33(95%CI 1.30-4.17);P=0.005]与 RM 相关。通过 Cox 非比例风险回归分析,RM 与移植物丢失(包括死亡)相关[AHR 2.84(95%CI 1.70-4.72);P<0.001]。
RM 是肾移植后的一种罕见并发症,与移植物丢失(包括死亡)显著相关。与基于他克莫司的免疫抑制相比,RM 更可能发生在环孢素治疗的患者中,而且可能发生在黑种人种族中。在这些高危患者中,需要加强对 RM 的监测。