Sirolimus use in heart transplantation recipients with chronic renal dysfunction
10.3760/cma.j.issn.0253-3758.2012.02.012
- VernacularTitle:心脏移植术后慢性肾功能不全患者应用西罗莫司的经验
- Author:
Dong YIN
1
;
Jie HUANG
;
Lei FENG
;
Zhong-Kai LIAO
;
Guang-Xun FENG
;
Wei WANG
;
Yun-Hu SONG
;
Sheng-Shou HU
Author Information
1. 中国医学科学院北京协和医学院阜外心血管病医院
- Keywords:
Heart transplantation;
Renal insufficiency;
Sirolimus
- From:
Chinese Journal of Cardiology
2012;40(2):136-140
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the effect of sirolimus-based immunosuppression administered on heart transplant recipients with chronic renal dysfunction.Methods From June 2004 to December 2008,standard calcineurin inhibitors( CNI)-based immunosuppressive regimen was changed to reduced-dose CNI plus sirolimus due to CNI-related chronic renal dysfunction in 20 out of 138 cardiac transplant recipients at Fuwai Hospital. The standard immunosuppressive regimen included steroid, CNI (cyclosporine or tacrolimus),and mycophenolate mofetil or azathioprine. Sirolimus was started at 0.75 - 1.50 mg/d with titration to achieve levels of 5 -15 μg/L,and CNI dose was reduced gradually to 1/2 -2/3 of the baseline level.Patients were followed for changes in renal function,lipid level and clinical side effects related to immunosuppressive therapy.Endomyocardial biopsy (EMB) was performed routinely at 3 weeks,3,6 and 12 months after transplantation.EMB was also performed at 3 months after regimen change within 1 year post-transplantation or when rejections were suspected in patients beyond 1 year post-transplantation.Echocardiography was performed for monitoring purpose.Results The mean follow-up after regimen change was (7.9 ±6.3) months.Final sirolimus dose was (0.89 ± 0.22) mg/d and blood drug level was (7.6 ±3.8 ) μg/L.Cyclosporine dose was reduced from ( 191.7 ± 60.0) mg/d to ( 123.6 ± 34.8 ) mg/d,with blood drug concentation reduced from ( 175.5 ± 58.0) μg/L to ( 111.9 ± 56.0) μg/L in 18 patients ( P ＜ 0.01 ).Tacrolimus average dose was reduced from 4.25 mg/d to 3.00 mg/d,with blood drug concentation reduced from 13.5 μg/L to 10.5 μg/L in 2 patients.Serum creatinine level fell from ( 160.4 ± 25.5 ) μmol/L to ( 134.4 ± 26.8 ) μmol/L ( P ＜ 0.01 ) and urea nitrogen fell from ( 13.8 ± 4.7 ) μmol/L to ( 10.4±3.0 )μmol/L(P ＜0.01 )at one month after regimen change.Twenty two EMBs were performed in 11 patients within 1 year post-transplant,there were 4 episodes of acute rejecte ( ISHLT grade 2).Twenty patients are all alive and cardiac function was normal.The most common side effect was hyperlipidemia,and triglycerides,total cholesterol and low density lipoprotein levels were significantly increased at 1 month post regimen change(P ＜ 0.05 or P ＜ 0.01 ).Leukocyte,hemoglobin and platelet as well as liver function remained unchanged at 1 month post regimen change ( all P ＞ 0.05).Conclusion Our results show that change from CNI-based immunosuppressive regimen to reduced-dose CNI plus sirolimus is an effective and safe approach for the management of patients with CNI-related chronic renal dysfunction,leading to an improvement in renal function without compromise in anti-rejection efficacy and with tolerable side effects.
