Maintenance immunosuppression use and the associated risk of avascular necrosis after kidney transplantation in the United States
Maintenance immunosuppression use and the associated risk of avascular necrosis after kidney transplantation in the United States
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DOI：
10.1097/01.tp.0000149894.95435.7f
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发表时间：
2005-02-15
期刊：
影响因子：
6.2
通讯作者：
Schnitzler, MA
中科院分区：
文献类型：
--
作者：
Abbott, KC;Koff, J;Schnitzler, MA
背景肾移植术后的缺血性坏死（AVN）在很大程度上归因于皮质类固醇的使用。然而，其他危险因素，如微血管血栓形成和高脂血症已被充分描述，并可能在早期类固醇停止和避免的时代增加的重要性。我们假设已知与这些AVN危险因素相关的维持免疫抑制药物也与较高的AVN风险相关。通过使用美国肾脏数据系统数据库，我们研究了27，772名在1996年1月1日至2000年7月31日期间接受单肾移植的医疗保险初级患者。考克斯比例风险回归模型用于计算AVN医疗保险索赔的患者和移植相关因素（包括同种异体移植排斥反应）的校正风险比（AHR）。皮质类固醇使用的强度和持续时间无法评估。在出院时接受西罗莫司处方的患者中，接受西罗莫司-环孢素A（CsA）联合治疗的患者中有3.5%出现AVN，而接受西罗莫司-他克莫司联合治疗的患者中有1.4%出现AVN（χ 2检验，P = 0.06）。在考克斯回归分析中，CsA使用（与他克莫司相比）（AHR 1.36，95%置信区间，1.09 - 1.71）与AVN风险增加独立相关。西罗莫司的使用显示出显著性趋势（AHR 1.59，95%置信区间，0.99 - 2.56），与CsA无显著相互作用。与其他维持性免疫抑制剂相比，在肾移植出院时使用CsA处方后，AVN明显更常见。尚不能确定这种AVN风险增加是否直接归因于高脂血症、微血管血栓形成或皮质类固醇剂量的差异。
Background. Avascular necrosis (AVN) after renal transplantation has been largely attributed to the use of corticosteroids. However, other risk factors such as microvascular thrombosis and hyperlipidemia have been well described and may be of increased importance in the era of early steroid cessation and avoidance. We hypothesized that maintenance immunosuppressive medications known to be associated with these risk factors for AVN would also be associated with a higher risk of AVN.Methods. By using the U.S. Renal Data System database, we studied 27,772 primary patients on Medicare who received a solitary kidney transplant between January 1, 1996, and July 31, 2000. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (AHRs) for patient- and transplant-related factors (including allograft rejection) with Medicare claims for AVN. The intensity and duration of corticosteroid use could not be assessed.Results. Among patients who were prescribed sirolimus at discharge, 3.5% of patients who received the combination of sirolimus-cyclosporine A (CsA) demonstrated AVN, compared with 1.4% of patients who received the combination of siroli-mus-tacrolimus (P=0.06 by chi(2)). In Cox regression, CsA use (vs. tacrolimus) (AHR 1.36, 95% confidence interval, 1.09-1.71) was independently associated with an increased risk of AVN. Sirolimus use showed a trend toward significance (AHR 1.59, 95% confidence interval, 0.99-2.56), with no significant interaction with CsA.Conclusions. Compared with other maintenance immunosuppression, AVN was significantly more common after use of CsA prescribed at the time of discharge for renal transplantation. Whether this increased risk of AVN was directly attributable to hyperlipidemia, microvascular thrombosis, or differences in corticosteroid dosing could not be determined.