儘早停用類固醇之後可以有極佳的腎臟移植結果


  January 18, 2007 — 在五天的抗胸腺細胞球蛋白(ATG) (Thymoglobulin, Genzyme Transplant)和prednisone (Solu-Medrol, Pfizer)誘導治療之後,以sirolimus (Rapamune, Wyeth) 和cyclosporine (Neoral, Novartis) 免疫抑制劑維持初次腎臟移植接受者之治療,有絕佳的一年移植器官和病患存活率,與接受類固醇的對照組的結果相似;在這個單一中心的研究中,未使用類固醇組和對照組相比,也可有經證實較低的無急性排斥反應發生率 (4.9% vs 9.4%; P < .01)。
  
  由俄亥俄州立大學的Amer Rajab醫師所領導的該團隊指出,我們結論認為,使用Neoral 和sirolimus而未使用類固醇的免疫抑制維持規範,可以達成這個極佳的移植器官存活率,以及顯著降低無急性排斥反應發生率。
  
  本篇文章發表於2006年12月的Clinical Transplantation期刊。
  
  未參與該研究的克里夫蘭凱斯西儲大學醫院的Don Hricik醫師向Medscape表示,這個經驗證實了其他單一中心研究有關腎贈移植病患及早停用類固醇後低排斥率以及一般結果良好的研究發現。
  
  【減少類固醇使用比較好嗎?】
  研究者解釋,在最近幾年,實質器官移植的免疫抑制處方已經可以更有效的改善移植器官一年存活率,選擇免疫抑制處方的主要考量已經從預防急性排斥變成減少長期死亡率與發病率;他們補充表示,corticosteroids和糖尿病、高脂血症、高血壓、骨骼疾病,以及肥胖等風險有關。
  在最近的調查中,當器官受贈者被問到,如果有風險的話需要停用藥物時,65%選擇停用類固醇。
  
  過去5年,數個中心採用未使用類固醇的免疫抑制維持規範,且有令人鼓舞的結果—急性排斥反應發生率為10% 到25%。
  
  發表的研究中,該團隊檢視在2002年4月到2004年10月之間,所有在他們的醫學中心接受第一次腎臟移植且接受未使用類固醇之免疫抑制維持規範病患的臨床結果;他們將結果和2000年1月到2003年6月之間,所有在他們的醫學中心接受第一次腎臟移植且接受類固醇為主之治療規範病患的臨床結果進行比較。
  
  這兩組的免疫抑制處方為:
  * 未使用類固醇 (n=301) —以Thymoglobulin 和 prednisone 誘導治療5天和4 天,接著以sirolimus 和 Neoral維持治療。
  * 使用類固醇 (n = 502) — 以basiliximab (Simulect, Novartis)誘導治療,接著以prednisone、霉酚酸酯 (MMF, Cellcept, Roche)和 Neoral維持治療。
  
  【極佳的結果 病患相對風險低】
  兩組的一年移植器官和病患存活率均絕佳,且未使用類固醇組的急性排斥率僅4.9%。
  
  腎臟移植後一年的結果

結果

未使用類固醇維持治療 (%)

使用類固醇維持治療 (%)

P

病患存活

93.1

95.2

NS

未致命的移植器官存活

98.1

95.2

NS

切片證實的急性排斥

4.9

9.4

< .01


  Hricik醫師表示,相對於1990年代初期所認為的,及早停用類固醇會有高的急性排斥率,目前所得到的積極性排斥率的結果是「卓越的」,他指出,併用 sirolimus和 Neoral比早期的免疫抑制劑更有效的唯一合理解釋,可見於他擔任共同作者的一篇有關減少類固醇使用的回顧文獻(Clin J Am Soc Nephrol. 2006;1:1080-1089);目前的研究中,用sirolimus和 Neoral治療不會產生嚴重的不良反應。
  
  移植的第一年,未使用類固醇組病患的平均體重增加比對照組少(8.1% vs 13.5%; P < .05),兩組的血脂肪值和控制血壓值相似;Hricik醫師表示,有一點令人失望的是,作者們無法提出未使用類固醇的處方對代謝方面之任何其他具體效果。
  
  他指出,本研究的一個弱點是,在對照組比未使用類固醇組使用較多的大體器官而較少有活體捐贈者,可能因而造成不同的排斥率;同時,也不清楚這些結果是否可以擴展到高風險病患,如非第一次的腎臟移植接受者或非洲裔美國人。
  
  Clin Transplant. 2006;20:537-546.

Excellent Kidney-Transplant Ou

By Marlene Busko
Medscape Medical News

January 18, 2007 ??Primary kidney-transplant recipients maintained on sirolimus (Rapamune, Wyeth) and cyclosporine (Neoral, Novartis) immunosuppression after a 5-day induction with antithymocyte globulin (Thymoglobulin, Genzyme Transplant) and prednisone (Solu-Medrol, Pfizer) had excellent 1-year graft and patient survival, similar to that of a comparator group receiving steroids. In this single-center study, the steroid-free group also had a lower incidence of biopsy-proven acute rejection than the comparator group (4.9% vs 9.4%; P < .01).

"We conclude that excellent graft survival with a significantly lower incidence of acute rejection can be achieved using a steroid-free maintenance immunosuppressive protocol consisting of Neoral and sirolimus," the group, led by Amer Rajab, MD, from Ohio State University in Columbus, write.

The article is published in the December 2006 issue of Clinical Transplantation.

"This experience confirms the findings of a number of other single centers that have reported low rates of rejection and generally excellent outcomes after early steroid withdrawal in kidney-transplant recipients," Don Hricik, MD, from the University Hospitals of Cleveland and Case Western Reserve University, in Ohio, who was not involved in this study, told Medscape.

Are Steroid-Sparing Protocols Superior?

The researchers explain that in recent years, as immunosuppressive regimens in solid-organ transplant have become more effective in improving 1-year graft survival, the primary concern in selecting an immunosuppressive protocol has shifted from preventing acute rejection to minimizing long-term morbidity and mortality. They add that corticosteroids are associated with risk for diabetes, hyperlipidemia, hypertension, bone disease, and obesity. When transplant recipients were asked, in a recent survey, which drug they would choose to discontinue if there were no associated risk, 65% chose to discontinue steroids.

In the past 5 years, several centers have adopted steroid-free maintenance immunosuppressive protocols and have reported encouraging results ??acute rejection rates ranging from 10% to 25%.
In the present study, the team examined the clinical outcomes of all patients who received first kidney transplants at their center from April 2002 to October 2004 under a new steroid-free maintenance immunosuppressive protocol. They compared this with outcomes of all patients at their center who received first kidney transplants from January 2000 to June 2003 under a steroid-based protocol.

The immunosuppressive regimens of the 2 groups were:

  • Steroid-free-maintenance group (n=301) ??Induction therapy with Thymoglobulin and prednisone over 5 and 4 days, respectively, followed by maintenance therapy with sirolimus and Neoral.
  • Steroid-based-maintenance group (n = 502) ??Induction therapy with basiliximab (Simulect, Novartis), followed by maintenance therapy with prednisone, mycophenolate mofetil (MMF, Cellcept, Roche), and Neoral.

Excellent Outcomes, Relatively Low-Risk Patients

The 1-year patient and graft survival were excellent in both groups, and the acute rejection was only 4.9% in the steroid-free group.

1-Year Post?Kidney-Transplant Outcomes
Outcome
Steroid-Free Maintenance (%)
Steroid-Based Maintenance (%)
P
Patient survival
93.1
95.2
NS
Death-censored graft survival
98.1
95.2
NS
Biopsy-proven acute rejection
4.9
9.4
< .01

The low rate of acute rejection is a "remarkable" contrast with studies from the early 1990s that suggested that early steroid withdrawal was associated with high rates of acute rejection, said Dr. Hricik. He added that the only logical explanation is that the combination of sirolimus and Neoral is more potent than earlier immunosuppressants, which is discussed in a recent review article about steroid sparing that he coauthored (Clin J Am Soc Nephrol. 2006;1:1080-1089). In the current study, therapy with sirolimus and Neoral produced no significant adverse effects.

In the first year posttransplant, the mean weight gain in patients in the steroid-free group was lower than in the comparator group (8.1% vs 13.5%; P < .05), but both groups had similar blood lipid levels and blood pressure control. It is "somewhat disappointing" that the authors were not able to demonstrate any other discernible metabolic benefits of the steroid-free regimen, said Dr. Hricik.

He noted that 1 weakness of this study is that there were more cadaveric donors and fewer living donors in the comparator group than in the steroid-free group, possibly accounting for the different rejection rates. Also, it is also not clear whether the results can be extrapolated to high-risk patients such as non-primary-kidney-transplant recipients or African Americans.

Clin Transplant. 2006;20:537-546.

    
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