Laham G, Sleiman S, Soler Pujol G, Diaz C, Dávalos M, Vilches A
CEMIC-IUC University Institute CEMIC, Buenos Aires, Argentina.
Transplant Proc. 2010 Jan-Feb;42(1):309-13. doi: 10.1016/j.transproceed.2009.12.043.
The major causes of graft failure are chronic allograft nephropathy (CAN) and patient mortality. Sirolimus (SRL) is a powerful immunosuppressant with a less nephrotoxic profile as well as a lower incidence of cancer. The aim of this study was to evaluate the impact of conversion to SRL from calcineurin inhibitor (CNI)-based therapy in kidney (KT) and kidney-pancreas (SPK) allograft recipients. We analyzed renal function, allograft and patient survival, and SRL-associated adverse effects in 93 adult patients (86 KT and 7 SPK), who were converted to SRL between January 2001 and November 2008. The main reason for conversion was CAN (76; 9%) and 52 (7%) were receiving tacrolimus. Conversion occurred at a median 26.2 months. There was a significant improvement in creatinine clearance (CCr) at 6 months after conversion (CCr(baseline) 51.4 vs CCr(6m) 60.4 mL/min; P < .0001), without changes at 12 and 24 months. However, proteinuria increased significantly at 6 months compared with the baseline: 150 mg/24 hours (0-453) versus 0 mg/24 hours (range, 0-309), respectively (P < .0001), but did not progress at 12 or 24 months. At the same time we observed more extensive use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers: 60/5%; 65/3% and 70/2% at 6, 12, and 24 months. There were no changes in blood pressure control. Cholesterol significantly increased at 6 months (218.2 +/- 37 vs. 186.6 +/- 44 mg/dL; P < .0001). Graft and patient survivals at 4 years were 88% and 95%, respectively. Our experience suggested that conversion to SRL constituted a safe alternative with excellent results in patient and graft survival.
移植失败的主要原因是慢性移植肾肾病(CAN)和患者死亡。西罗莫司(SRL)是一种强效免疫抑制剂,具有较低的肾毒性以及较低的癌症发生率。本研究的目的是评估肾移植(KT)和肾胰联合移植(SPK)受者从基于钙调神经磷酸酶抑制剂(CNI)的治疗转换为SRL的影响。我们分析了93例成年患者(86例KT和7例SPK)的肾功能、移植肾和患者生存率以及SRL相关的不良反应,这些患者于2001年1月至2008年11月期间转换为SRL。转换的主要原因是CAN(76例;9%),52例(7%)正在接受他克莫司治疗。转换发生的中位时间为26.2个月。转换后6个月时肌酐清除率(CCr)有显著改善(CCr(基线)51.4 vs CCr(6个月)60.4 mL/分钟;P <.0001),在12个月和24个月时无变化。然而,与基线相比,6个月时蛋白尿显著增加:分别为150 mg/24小时(0 - 453)和0 mg/24小时(范围,0 - 309)(P <.0001),但在12个月或24个月时未进展。同时,我们观察到血管紧张素转换酶抑制剂/血管紧张素受体阻滞剂的使用更为广泛:在6个月、12个月和24个月时分别为60/5%;65/3%和70/2%。血压控制无变化。6个月时胆固醇显著升高(218.2±37 vs. 186.6±44 mg/dL;P <.0001)。4年时移植肾和患者生存率分别为88%和95%。我们的经验表明,转换为SRL是一种安全的替代方法,在患者和移植肾生存方面有出色的结果。