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肾移植中的多瘤病毒感染:免疫抑制治疗的作用

Polyoma viral infection in renal transplantation: the role of immunosuppressive therapy.

作者信息

Barri Y M, Ahmad I, Ketel B L, Barone G W, Walker P D, Bonsib S M, Abul-Ezz S R

机构信息

Division of Nephrology, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare Services, Little Rock, AR 72205, USA.

出版信息

Clin Transplant. 2001 Aug;15(4):240-6. doi: 10.1034/j.1399-0012.2001.150404.x.

Abstract

BACKGROUND

Polyoma virus infection in renal transplant recipients has been observed with increasing frequency in recent years. Renal allograft involvement in this condition may occur as a result of primary infection or secondary to reactivation of the latent virus. Interstitial nephritis, ureteric stenosis, rise in serum creatinine and allograft function loss have been attributed to this viral infection.

METHODS

In this study we reviewed our experience with 8 patients who developed polyoma viral infection confirmed by allograft biopsy. All patients were receiving mycophenolate mofetil as part of the immunosuppression and 7 of the 8 patients were on tacrolimus. All patients have biopsy proven polyoma viral infection. The following therapeutic maneuvers were carried out following the diagnosis of polyoma viral infection: 1) stopping mycophenolate and 2) switching tacrolimus to cyclosporine or reducing the tacrolimus dose to adjust it at a lower therapeutic trough level. The clinical course and outcome of our patients were reviewed in relation to manipulation of immunosuppressive medications.

RESULTS

The incidence of this infection in our transplant program in the last 3 yr was 5.3%. Seventy-five percent of the patients had at least one rejection episode and 63% had more than one rejection episode. The main risk factor for the development of polyoma viral infection was related to the intensity of immunosuppression. The use of antirejection therapy after histological diagnosis of polyoma virus infection was not associated with improvement of renal function despite the histological appearance of acute rejection. Thus, the interstitial nephritis associated with polyoma viral infection appears to be an inflammatory response to the virus rather than acute rejection. Six out of the 8 patients stabilized renal function with reduction in immunosuppression.

CONCLUSIONS

Reduction in immunosuppression was associated with the stabilization of renal function when instituted early. However, these patients were left with a degree of allograft dysfunction and their outcome may be significantly compromised. The lack of effective antiviral therapy for polyoma virus may limit the use of newer and more potent immunosuppressive medications.

摘要

背景

近年来,肾移植受者中多瘤病毒感染的发生率日益增加。在这种情况下,肾移植受者受累可能是原发性感染的结果,也可能继发于潜伏病毒的重新激活。间质性肾炎、输尿管狭窄、血清肌酐升高和移植肾功能丧失都归因于这种病毒感染。

方法

在本研究中,我们回顾了8例经移植肾活检确诊为多瘤病毒感染患者的情况。所有患者均接受霉酚酸酯作为免疫抑制治疗的一部分,8例患者中有7例使用他克莫司。所有患者均经活检证实为多瘤病毒感染。在诊断多瘤病毒感染后采取了以下治疗措施:1)停用霉酚酸酯;2)将他克莫司换成环孢素,或将他克莫司剂量减至较低的治疗谷浓度水平。我们根据免疫抑制药物的调整情况,回顾了患者的临床病程和结局。

结果

在过去3年中,我们移植项目中这种感染的发生率为5.3%。75%的患者至少发生过一次排斥反应,63%的患者发生过不止一次排斥反应。发生多瘤病毒感染的主要危险因素与免疫抑制的强度有关。尽管组织学表现为急性排斥反应,但在多瘤病毒感染组织学诊断后使用抗排斥治疗与肾功能改善无关。因此,与多瘤病毒感染相关的间质性肾炎似乎是对病毒的炎症反应,而非急性排斥反应。8例患者中有6例通过降低免疫抑制程度使肾功能稳定。

结论

早期降低免疫抑制程度与肾功能稳定有关。然而,这些患者仍存在一定程度的移植肾功能不全,其结局可能会受到显著影响。缺乏针对多瘤病毒的有效抗病毒治疗可能会限制新型强效免疫抑制药物的使用。

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