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西班牙裔肾移植人群中BK病毒肾病的相关因素及结局

Factors and outcome in BK virus nephropathy in a Hispanic kidney transplant population.

作者信息

Pérez-Torres D, Bertrán-Pasarell J, Santiago-Delpín E, González-Ramos M, Medina-Mangual S, Morales-Otero L, González-Caraballo Z

机构信息

Department of Medicine, Division of Infectious Diseases, University of Puerto Rico School of Medicine, San Juan, Puerto Rico.

出版信息

Transpl Infect Dis. 2010 Feb;12(1):16-22. doi: 10.1111/j.1399-3062.2009.00458.x. Epub 2009 Oct 5.

Abstract

UNLABELLED

BK virus nephropathy (BKVN) is an increasingly recognized cause of kidney allograft loss and is thought to be related to the newer, more potent immunosuppressive agents. Conflicting information has been reported on risk factors for BK infection.

PURPOSE

To determine incidence, associated factors, and outcome of BKVN in our kidney transplant population in order to improve identification and management.

METHODS

Kidney transplants from January 2000 to December 2005 were retrospectively reviewed. Data were collected for patients with biopsy-proven BKVN including age, sex, body mass index (BMI), etiology of renal failure, other medical diseases, donor type, surgical complications, rejection and infection, time to diagnosis, induction, immunosuppressive and antiviral therapy, and clinical outcome. A control group of patients matched for sex, age, type of graft, etiology of kidney disease, and BMI, was established for comparison.

STUDY GROUP

During this period, 20 (4%) of 497 transplanted patients were diagnosed with BKVN. Thirteen (65%) were males, 8 (40%) were young adults (ages 21-40), and 18 (90%) received grafts from cadaveric donors (P=0.05). Twelve (60%) had hypertensive renal disease, 2 (10%) also had diabetes, and 16 (80%) had a BMI >25 (P=0.01). Lymphoceles occurred in 5 patients (25%). Mean creatinine level at diagnosis was 2.7 mg/dL and mean time to diagnosis was 23 months. Ten patients (50%) had leukopenia at or within a year before biopsy (P=0.001). Viruses other than BK occurred in 9 patients: varicella zoster virus in 3, cytomegalovirus in 2, herpes simplex virus in 1, molluscum contagiosum in 1, Epstein-Barr virus in 1, and human papillomavirus in 1. Eighteen patients (90%) had related rejection (P= 0.001) and 4 (20%) suffered allograft loss (P= 0.001). Basiliximab (living donors) and anti-thymocyte globulin (cadaver donors) were given for induction. All patients were on triple therapy; 15 on prednisone and sirolimus, with either tacrolimus in 8, cyclosporine in 4, mycophenolate in 1, or mycophenolate and tacrolimus in 2. The other 5 received prednisone with tacrolimus and mycophenolate. Graft loss occurred in 2 patients on tacrolimus and mycophenolate, 1 patient on tacrolimus and sirolimus, and 1 patient on cyclosporine and sirolimus. Immunosuppression was decreased in all patients. Two were given cidofovir for 6 months and had stable creatinine levels at the end of the study. Records were reviewed until April 2007. There were no deaths in this cohort.

CONTROL GROUP

The number of rejections experienced by patients with BKV was much higher (P<0.0001), but the rate of graft loss was similar between the 2 groups (P=0.19). Viral co-infection was more frequent in patients with BKV (P=0.04). No episodes of leukopenia were reported for any of the patients in the control group (P=0.001). Immunosuppression with tacrolimus and sirolimus was more frequent in the BKV group, but this was not statistically significant (P=0.18, 0.28, respectively). The number of lymphoceles was larger in patients with BKV, but the difference was not statistically significant (P=0.35).

CONCLUSION

BKVN is present in our transplant population and results in a high rate of allograft rejection with varying rates of graft loss. Associated factors were deceased donor and immunosuppression with potent agents, particularly tacrolimus and sirolimus. We also found a higher frequency of obesity, viral co-infection, and leukopenia. Routine screening and timely biopsy could prove cost-effective and significantly reduce morbidity.

摘要

未标注

BK病毒肾病(BKVN)是导致肾移植失败的一个日益被认识到的原因,被认为与更新的、更强效的免疫抑制剂有关。关于BK感染的危险因素已有相互矛盾的报道。

目的

确定我们肾移植人群中BKVN的发病率、相关因素及预后,以改善识别和管理。

方法

回顾性分析2000年1月至2005年12月期间的肾移植病例。收集经活检证实为BKVN患者的数据,包括年龄、性别、体重指数(BMI)、肾衰竭病因、其他内科疾病、供体类型、手术并发症、排斥反应和感染情况、诊断时间、诱导治疗、免疫抑制和抗病毒治疗以及临床结局。设立一个在性别、年龄、移植类型、肾病病因和BMI方面相匹配的对照组进行比较。

研究组

在此期间,497例移植患者中有20例(4%)被诊断为BKVN。13例(65%)为男性,8例(40%)为年轻人(21 - 40岁),18例(90%)接受尸体供体移植(P = 0.05)。12例(60%)有高血压肾病,2例(10%)同时患有糖尿病,16例(80%)BMI>25(P = 0.01)。5例患者(25%)发生淋巴囊肿。诊断时平均肌酐水平为2.7mg/dL,平均诊断时间为23个月。10例患者(50%)在活检时或活检前一年内出现白细胞减少(P = 0.001)。9例患者感染了BK病毒以外的其他病毒:3例为水痘 - 带状疱疹病毒,2例为巨细胞病毒,1例为单纯疱疹病毒,1例为传染性软疣病毒,1例为EB病毒,1例为人乳头瘤病毒。18例患者(90%)发生相关排斥反应(P = 0.001),4例(20%)移植失败(P = 0.001)。诱导治疗使用巴利昔单抗(活体供体)和抗胸腺细胞球蛋白(尸体供体)。所有患者均接受三联治疗;15例使用泼尼松和西罗莫司,其中8例联合他克莫司,4例联合环孢素,1例联合霉酚酸酯,2例联合霉酚酸酯和他克莫司。另外5例接受泼尼松联合他克莫司和霉酚酸酯治疗。移植失败发生在2例使用他克莫司和霉酚酸酯的患者、1例使用他克莫司和西罗莫司的患者以及1例使用环孢素和西罗莫司的患者身上。所有患者免疫抑制均减量。2例患者接受西多福韦治疗6个月,研究结束时肌酐水平稳定。记录回顾至2007年4月。该队列中无死亡病例。

对照组

BK病毒感染患者的排斥反应发生率更高(P<0.0001),但两组移植失败率相似(P = 0.19)。BK病毒感染患者病毒合并感染更常见(P = 0.04)。对照组患者均未报告白细胞减少发作(P = 0.001)。BK病毒感染组更频繁使用他克莫司和西罗莫司进行免疫抑制,但差异无统计学意义(分别为P = 0.18、0.28)。BK病毒感染患者淋巴囊肿数量更多,但差异无统计学意义(P = 0.35)。

结论

BKVN存在于我们的移植人群中,导致移植排斥率高,移植失败率各异。相关因素包括尸体供体以及使用强效免疫抑制剂,尤其是他克莫司和西罗莫司。我们还发现肥胖、病毒合并感染和白细胞减少的发生率更高。常规筛查和及时活检可能具有成本效益,并显著降低发病率。

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