影响肾移植受者BK病毒感染的危险因素分析

目的 探讨影响肾移植受者BK病毒(BKV)感染的危险因素.方法 选取2006年3月至2007年3月间进行肾移植术的90例受者为研究对象,分别于肾移植术后第1、3、6、9、12个月收集血、尿标本,进行尿沉渣Decoy细胞计数与BK病毒DNA含量的检测,对部分肾移植受者进行移植肾活检.根据尿液BKV DNA是否阳性分成BKV感染组与非感染组.比较2组受者在年龄、性别、术前有无糖尿病、是否为活体肾移植、是否使用抗白细胞介素-2受体单克隆抗体进行诱导、围手术期是否使用多克隆抗体及抗CD3单克隆抗体、术后免疫抑制剂方案、术后是否发生急性排斥反应、移植肾功能恢复延迟及肺部感染等临床指标的差异,应用Logistic回归法分析筛选BKV感染的危险因素.结果 90例肾移植受者尿液Decoy细胞、尿BKV DNA及血BKVA DNA的阳性率分别为42.2%(38/90)、45.6%(41/90)和22.2%(20/90).BKV感染组应用他克莫司(FK506)加霉酚酸酯(MMF)方案的比例为68.3%(28/41),明显高于BKV非感染组40.8%(20/49,P＜0.01).FKS06加MMF的免疫抑制方案是影响肾移植受者BKV感染的独立危险因素(X2=6.579,P=0.01,OR=3.123).确诊BKV相关性肾病(BKVAN)5例.结论 FK506加MMF的组合免疫抑制方案易发生BKV活化及BKVAN,术后受者需进行密切观察并进行相关检测.     

肾移植受者BK病毒的感染特点

目的 探讨肾移植受者BK病毒（BKV）的感染特点。 方法 于我院门诊选取肾移植术后48个月内的患者共243例作为试验组,同时选取门诊健康体检者82例作为对照组。采集上述2组的血、尿标本,行BKV尿沉渣细胞学计数与实时荧光定量PCR检测。 结果 试验组受者的尿Decoy细胞、BKV尿症与BKV血症的阳性率分别为35.4 %、36.6%和16.9%;对照组分别为4.9%、20.7%和2.9%。试验组受者的尿Decoy 细胞阳性者Decoy细胞中位数水平为6个/10 HPF,BKV DNA阳性者尿液和外周血BKV中位数水平分别为1.50×104拷贝/ml和6.87×103拷贝/ml;对照组分别为2个/10 HPF,1.10×104拷贝/ ml和2.24×103拷贝/ml。与健康者相比,肾移植术后试验组BKV DNA阳性率及水平明显升高（P < 0.01）。肾移植受者的尿液Decoy 细胞计数与尿液BKV含量呈正相关（r = 0.636,P < 0.01）;尿Decoy大量组（＞10个/10 HPF）的血BKV DNA阳性率及水平显著高于少量组（1～5个/10 HPF）（P < 0.05）。 结论　肾移植受者较健康人群易发生BKV再活化。定量尿沉渣细胞学检测简单、易行、敏感,可以作为BKV活化的指标,预测病毒尿症及病毒血症。此外,也可检测血、尿BKV DNA,以了解病毒活化情况和筛查BKV相关的移植肾肾病。     

BK病毒活化对移植肾功能的影响

目的 探讨肾移植后BK病毒活化情况对移植肾功能的影响.方法 88例肾移植受者分别于术后0.5、1、2、3、6、9和12个月采集尿液和血液,应用实时定量聚合酶链反应方法检测BK病毒DNA载量.结果 88例肾移植受者中,发生BK病毒尿症27例,发生率为30.7％,其中持续性17例,一过性10例;37.0％％(10/27)的BK病毒尿症继续发展为病毒血症,其中持续性和一过性者各5例,移植肾病理活检确诊BK病毒肾病(BKVAN)4例.持续BK病毒血症受者的BK病毒DNA载量较一过性者显著升高,差异有统计学意义(P＜0.05),诊断为BK病毒血症时血清肌酐显著升高,差异有统计学意义(P＜0.05).结论 肾移植术后BK病毒血症进展时移植肾功能受损,定期规律检测BK病毒及临床干预BK病毒血症能有效预防移植肾功能损伤.     

移植肾BK病毒肾病的防治和预后

目的总结分析肾移植后BK病毒性肾病的防治和预后。方法回顾性分析2006年1月-2016年10月中山大学附属第一医院器官移植科行移植肾穿刺活检的101例多瘤病毒性肾病(PVN)患者的临床资料,检测尿沉渣Decoy细胞计数、血和尿BKV DNA载量。结果共纳入101例确诊为PVN的患者,其中98例为BK病毒性肾病(BKVN),感染广泛的病例电镜下可观察到肾小管上皮细胞核内的病毒颗粒,98例中的40例患者进行重复活检显示随着病毒血病的下降SV40T的染色可由片状变为局灶性,BKVN患者可合并出现细胞性或体液性排斥反应。BKV血中的检测预测BKVN阳性预测值有30%~85%,血浆BKV DNA持续阳性及负荷>104copies/ml可以作为治疗干预开始的依据。结论术后规律监测早期发现移植肾BKVN及时减少免疫抑制剂,并规律监测注意并发的排斥反应可提高移植肾BKVN的远期存活。     

肾移植受者BK病毒感染的检测方法及免疫抑制方案对BK病毒活化的影响

目的 探讨肾移植术后受者BK病毒感染的检测方法及免疫抑制方案对BK病毒活化的影响.方法 选择1999年1月至2007年1月问进行肾移植术的200例受者为研究对象,其中100例基础免疫抑制方案为他克莫司(FK506)十霉酚酸酯(MMF)的受者作为密切观察组;另100例基础免疫抑制方案不同、但在年龄和术后是否发生急性排斥反应方面与密切观察组受者相一致(按1:1匹配)的受者作为对照观察组.在肾移植术后平均15.3个月时,分别采集所有受者的血、尿样本,行BK病毒尿沉渣Decoy细胞计数与BK病毒DNA含量的检测.分析和比较尿Decoy细胞计数、尿BK病毒含量及血BK病毒含量之间的关系;比较两组Decoy细胞、BK病毒尿症与BK病毒血症阳性率的差异.结果 200例受者的尿Decoy细胞、BK病毒尿症与病毒血症的阳性率分别为:34.0%、36.0%和16.5%.尿Decoy细胞计数与尿BK病毒含量呈正相关(r=0.714,P＜0.001),但尿液和外周血中BK病毒含量无明显相关性(P＞0.05).密切观察组的尿Decoy细胞、BK病毒尿症与BK病毒血症的阳性率分别为49%、50%和24%,对照观察组上述指标的阳性率分别是19%、22%和9%,两组的差异有统计学意义(P＜0.01).结论 尿沉渣Decoy细胞计数方法简单、易行并敏感,可以做为BK病毒活化的指标;血、尿BK病毒DNA的检测可进一步了解病毒活化情况、筛杳BK病毒相关的移植肾肾病.FK506+MMF的组合免疫抑制方案易发生BK病毒的活化,受者术后需进行密切观察和相关的检测.     

肾移植术后BK病毒相关性肾病合并环孢素中毒1例报告

<正>BK病毒(BK virus,BKV)属多瘤病毒(polyomavirus)家族成员,是导致肾移植术后移植肾肾病的重要危险因素之一[1]。随着全球肾移植手术的广泛开展,由BKV感染导致移植物功能受损,进展为BK病毒性肾病(BK virus-associated nephropathy,BKVN)而导致移植肾丢失的病例报道逐渐增多[2]。国外研究报告显示,在肾移植受者中有1%~5%的人会发生BKVN,其中大约50%的受者继而发生移植肾失功,由此引起了移植     

BK病毒血症对肾移植术后受者和移植肾功能影响临床研究

目的探究肾移植术后BK病毒(BKV)血症对受者及移植肾功能的影响。 方法回顾性分析2014年1月至2018年1月于中国科学技术大学附属第一医院接受肾移植229例受者临床资料。根据移植术后24个月内受者血清BKV最大载量,将其分为无病毒组(血清BKV持续阴性)、低病毒载量组(血清BKV最大载量≤1×10⁴ copies/mL)和高病毒载量组(血清BKV最大载量>1×10⁴ copies/mL)。以估算肾小球滤过率(eGFR)作为评价移植肾功能的指标。观察受者年龄和性别、供肾来源、供肾冷/热缺血时间、免疫抑制方案、术后3个月他克莫司血药浓度谷值、排斥反应和移植肾失功发生率以及术后24个月内eGFR。采用单因素方差分析比较3组受者年龄、供肾冷/热缺血时间、术后3个月他克莫司血药浓度谷值及术后24个月内eGFR,组间两两比较采用LSD法。采用成组t检验比较低病毒载量组与高病毒载量组受者首次检测到BKV的术后时间。采用卡方检验比较3组受者供肾来源、免疫抑制方案以及排斥反应和移植肾失功发生率。P<0.05为差异有统计学意义。 结果229例受者中28%(64/229)的受者肾移植术后血清检测到BKV,其中19%(43/229)为低病毒载量,9%(21/229)为高病毒载量。截至2018年7月,229例受者平均随访时间(44±8)个月。低病毒载量组受者术后首次检测到BKV的时间为移植后(10±8)个月,高病毒载量组为(8±6)个月,差异有统计学意义(t＝2.10,P<0.05)。无病毒组受者排斥反应发生率[24.8%(41/165)]低于低病毒载量组[60.5%(26/43)]和高病毒载量组[61.9%(13/21)](χ²＝19.82和12.42,P均<0.017)。无病毒组受者细胞排斥反应发生率[13.9%(23/165)]低于低病毒载量组[39.5%(17/43)]和高病毒载量组[42.9%(9/21)](χ²＝14.38和10.94,P均<0.017)。无病毒组受者中12例发生移植肾失功,低病毒载量组受者中2例发生移植肾失功,高病毒载量组受者中4例(3例发生BKVAN,1例病因不明确)发生移植肾失功,差异无统计学意义(χ²＝4.727,P>0.05)。高病毒载量组受者术后第3个月他克莫司血药浓度谷值高于无病毒组和低病毒载量组(P均<0.05)。高病毒载量组受者术后第3、6、12、24个月eGFR均低于无病毒组和低病毒载量组(P均<0.05)。 结论肾移植术后高BKV血症会影响肾移植受者预后及移植肾功能;而低BKV血症对移植肾功能无明显不良影响,此类受者无需调整他克莫司剂量。     

肾移植受者BK病毒的感染特点

Objective To investigate the characteristics of BK virus (BKV) infection in renal transplant recipients. Methods A total of 243 renal recipients from our clinic within 48 months after transplantation were enrolled as the trial group and 82 healthy people as the control group. Urine and peripheral blood samples of these two groups were harvested for urinary sediment BKV cytology by Decoy cell counting and BKV DNA by real-time PCR. Results The positive rates of urinary Decoy cell, BKV viruria and viremia were 35.4%, 36.6% and 16.9% in trial group, and 4.9%, 20.7% and 2.9% in control group, respectively. In trial group, the medians of urinary Decoy cell, urinary BKV and peripheral blood BKV were 6/10 HPF, 1.00×104 copy/ml and 6.87×103 copy/ml respectively, while in control group, they were 2/10 HPF, 1.10×104 copy/ml and 2.24×1(3 copy/ml. Compared with the healthy people, the positive rates and the levels of BKV DNA in urine and peripheral blood of recipients were significantly higher. The amount of urinary Decoy cells was positively correlated to urinary BKV load (r=0.636, P＜0.01). Conclusions BKV replication is easier to happen in renal recipients as compared to healthy people. Counting of urinary Decoy cells is convenient, useful and sensitive to evaluate BK viruria and viremia in renaltransplant recipients. BKV DNA detection in urine and peripheral blood can be used to screen the evidence of BK reaction in order to prevent irreversible graft damage by BKV.[ Key words ] Kidney transplantation; BK virus; Kidney diseases; Decoy cells     

肾移植术后多瘤病毒感染的临床诊断和治疗

目的 探讨肾移植术后多瘤病毒（BKV）感染的诊断方法、监测指标及初步治疗方法。方法 采集64例肾移植受者的血、尿样本，行BKV细胞学与聚合酶链反应（PCR）检测。对肾移植术后BKV感染的流行病学以及相关因素进行分析，并对BKV感染的受者进行试验性治疗。结果 64例受者的尿Decoy细胞、多瘤病毒尿症与多瘤病毒血症的阳性率分别为28．7％、17．2％和6．3％。血肌酐（Cr）升高的受者尿Decoy细胞阳性率高于血Cr稳定的受者（P=0．04）。受者的性别、年龄、诱导治疗方案、是否发生急性排斥反应以及术后肾功能恢复情况等临床因素与尿Decoy细胞、多瘤病毒尿症及多瘤病毒血症的出现无明显相关性。应用更昔洛韦试验性治疗4例BKV感染的受者，治疗2～3周后，受者的尿Decoy细胞以及血、尿BKV DNA均转为阴性。结论 血肌酐水平升高的肾移植受者易发生BKV再活化。可通过检测血BKV DNA筛查BKV相关的移植肾肾病。更昔洛韦治疗BKV具有良好的疗效，但需进一步验证。     

肾移植受者BK病毒的感染特点

Objective To investigate the characteristics of BK virus (BKV) infection in renal transplant recipients. Methods A total of 243 renal recipients from our clinic within 48 months after transplantation were enrolled as the trial group and 82 healthy people as the control group. Urine and peripheral blood samples of these two groups were harvested for urinary sediment BKV cytology by Decoy cell counting and BKV DNA by real-time PCR. Results The positive rates of urinary Decoy cell, BKV viruria and viremia were 35.4%, 36.6% and 16.9% in trial group, and 4.9%, 20.7% and 2.9% in control group, respectively. In trial group, the medians of urinary Decoy cell, urinary BKV and peripheral blood BKV were 6/10 HPF, 1.00×104 copy/ml and 6.87×103 copy/ml respectively, while in control group, they were 2/10 HPF, 1.10×104 copy/ml and 2.24×1(3 copy/ml. Compared with the healthy people, the positive rates and the levels of BKV DNA in urine and peripheral blood of recipients were significantly higher. The amount of urinary Decoy cells was positively correlated to urinary BKV load (r=0.636, P＜0.01). Conclusions BKV replication is easier to happen in renal recipients as compared to healthy people. Counting of urinary Decoy cells is convenient, useful and sensitive to evaluate BK viruria and viremia in renaltransplant recipients. BKV DNA detection in urine and peripheral blood can be used to screen the evidence of BK reaction in order to prevent irreversible graft damage by BKV.[ Key words ] Kidney transplantation; BK virus; Kidney diseases; Decoy cells     

Prospective study of polyomavirus BK replication and nephropathy in renal transplant recipients in China: a single‐center analysis of incidence,reduction in immunosuppression and clinical course

Huang G, Chen L‐Z, Qiu J, Wang C‐X, Fei J‐G, Deng S‐X, Li J, Chen G‐D, Zhang L, Fu Q, Zeng W‐T, Zhao D‐Q. Prospective study of polyomavirus BK replication and nephropathy in renal transplant recipients in China: a single‐center analysis of incidence, reduction in immunosuppression and clinical course.
Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01141.x
© 2009 John Wiley & Sons A/S. Abstract: Background: BK virus (BKV)‐associated nephropathy (BKVAN) in renal transplant recipients is an important cause of renal transplant dysfunction. Our aim was to determine the kinetics of BKV load within one yr after kidney transplantation under the impact of intensive monitoring and reduction in maintenance immunosuppression, the incidence of BKVAN, and the outcome of BKVAN treatment. Methods: Urine and peripheral blood (PB) were taken from 90 renal transplant recipients for BKV cytological testing and real‐time PCR for BKV DNA at one, three, six, nine, and 12 months after transplantation and treatment. Graft biopsies and urinary sediments of recipients with BKVAN were taken to monitor viral particles by conventional transmission electron microscopy (TEM). Results: By one post‐transplant year, urinary decoy cells (median, 8/10 HPF), BKV viruria (median, 2.60 × 10⁵ copies/mL), viremia (median, 9.65 × 10³ copies/mL ) , and BKVAN occurred in 42.2%, 45.6%, 22.2%, and 5.6% of patients, respectively. The incidence of BK infection was lower in patients who received cyclosporine A (CsA) (28.9%) compared to tacrolimus (FK506) (57.7%) (p = 0.007). An increased hazard of BK infection was associated with the use of FK506 (HR 2.6, p = 0.009) relative to CsA. After reduction in immunosuppression, viremia resolved in 95%, without increased acute rejection, allograft dysfunction, or graft loss. BKVAN was diagnosed in five patients (5.6%). The treatment of immunosuppression reduction was effective (i.e., decreased the viral load and number of decoy cells, and improved graft function) in our five patients with BKVAN. Quantitative count of decoy cells (e.g., >10 per 10 HPF) as a marker of viremia and BKVAN had increased positive predictive values of 85.7% and 57.1%, respectively. Conclusions: Choice of FK506 as immunosuppressive agent is an independent risk factor affecting BKV infection. Monitoring and pre‐emptive of immunosuppression reduction were associated with resolution of viremia and showed effective in BKVAN recipients at the early stage without acute rejection or graft loss. Quantitative count of urine cytology is a very convenient, useful, and sensitive method for evaluating BKV infection in renal transplant recipients.     

Quantitation of viral DNA in renal allograft tissue from patients with BK virus nephropathy

BACKGROUND: BK virus (BKV) allograft nephropathy (BKVAN) is a complication in renal transplantation recipients. Histopathology is the gold standard for diagnosis. Quantitative polymerase chain reaction (PCR) assay for renal biopsy has not been evaluated as a diagnostic test. Determination of renal BKV load may identify patients at risk for disease before histologic nephropathy. METHODS: Quantitative PCR assay for BKV DNA was performed in 28 biopsies of patients with BKVAN; 50 biopsies were performed before a diagnosis of BKVAN, and 126 control biopsies were from patients without a history of BKVAN. RESULTS: BKV DNA was present in 19 of 50 (38%) biopsies performed 1 to 164 weeks before diagnosis of BKVAN. The viral load (mean 216 copies/cell) was lower than in biopsies of patients with BKVAN (mean 6063 viral copies/cell, <0.05). In 10 of 127 (7.8%) control biopsies, a low level of BKV DNA (mean 3.8 copies/cell) was found in three biopsies from chronic allograft nephropathy patients; two biopsies with acute rejection; four biopsies with borderline change; and one biopsy with cytomegalovirus nephritis. CONCLUSION: BKV load exceeding 59 copies per cell identified all cases of BKVAN. The diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of quantitative PCR were 100%, 92.1%, 73.6%, and 100%, respectively. Lower levels of BKV DNA were identified in biopsies performed before viral nephropathy development. Future research will determine if earlier recognition of at-risk patients allows application of antiviral strategies to improve graft outcome.     

Quantitative viral load monitoring and cidofovir therapy for the management of BK virus-associated nephropathy in children and adults

BACKGROUND: BK virus (BKV)-associated nephropathy (BKVAN) has been increasingly recognized as an important cause of renal transplant dysfunction. We report the role of quantitative viral load monitoring in the management of BKVAN. METHODS: We developed a real-time quantitative polymerase chain reaction (PCR) assay for BKV detection in urine and plasma. Four renal allograft recipients, including two children, with BKVAN were treated with low-dose cidofovir and followed prospectively. RESULTS: The PCR assay showed a detection limit of 10 viral copies with an intra-assay coefficient of variation of 19%. All four patients with BKVAN demonstrated intranuclear inclusions on allograft biopsy and a progressive rise in serum creatinine; three patients underwent multiple biopsies before the diagnosis of BKVAN was made. Three of the patients experienced a "viral syndrome" before the onset of renal dysfunction. One child also demonstrated an echogenic renal mass. All of the patients demonstrated strongly positive urinary PCR values (>100,000 copies/microL). BKV DNA was also detected in the plasma of three patients. All the patients were treated with intravenous low-dose cidofovir (0.25-1 mg/kg per dose, every 2-3 weeks, without probenecid). BK viruria resolved within 4 to 12 weeks (after 1-4 doses) of the cidofovir therapy, and all patients remain with stable renal function 6 to 26 months posttherapy. CONCLUSIONS: Quantitative PCR for BKV is a sensitive and reliable method for following the course of the infection in renal transplant patients. In addition, cidofovir therapy may be useful in the treatment of some of these patients, and its role needs to be investigated further.     

Polyomavirus DNA and RNA detection in renal allograft biopsies: results from a European multicenter study

Polyomavirus mediated nephropathy is an increasingly recognized complication in renal transplant recipients. In all, 362 renal biopsies collected from 15 European transplant centers were analyzed for presence of Polyomavirus nucleic acid (BK virus [BKV] and JC virus [JCV]). We evaluated 302 biopsies of patients with renal allograft dysfunction, including three with known BKV allograft nephropathy (BKVAN), and 60 native kidney biopsies. BKV DNA was detected in 8 of the 302 (2.6 %) biopsies obtained for transplant dysfunction, but in none of the controls. BKV RNA, indicating active viral replication, was found in all BKV DNA positive biopsies available for mRNA expression studies. Retrospective immunohistochemical staining was positive for SV40 large T antigen in all seven evaluated biopsies. BKV DNA and RNA were detected in biopsy tissues from patients with inconspicuous light microscopy for BKVAN. Further studies will evaluate the potential of intrarenal viral BKV RNA as an early predictor for BKVAN.     

Polyomavirus Nephropathy in Pediatric Kidney Transplant Recipients

Given the limited information regarding BK virus-associated nephropathy (BKVN) in pediatric kidney transplant recipients, we assessed the incidence, risk factors, clinical and virologic features of BKVN in pediatric renal transplant recipients at a single transplant center by means of a retrospective cohort study. Histologically confirmed BKVN developed in 6 of 173 (3.5%) kidney transplant recipients at a median of 15 months post-transplant (range: 4-47 months). At a median follow-up of 28 months (range: 5-32), all patients had functioning grafts with mean creatinine and GFR of 1.9 mg/dL and 58 mL/min/1.73 m2, respectively. At the time of diagnosis, all cases had viruria (median 6.1 x 10(6) copies/mL, range: 10(5) to 3.9 x 10(8) copies/mL) and viremia (median 21,000 copies/mL, range: 10,000-40,000 copies/mL). Recipient seronegativity for BKV was significantly associated with the development of BKVN (p = 0.01). BKVN is an important cause of late allograft dysfunction and is strongly associated with recipient seronegativity in pediatric kidney transplant recipients. Further studies to confirm this finding and to define the clinical utility of routine pre-transplant BKV serologic testing are warranted.     

Association of DNA Amplification With Progress of BK Polyomavirus Infection and Nephropathy in Renal Transplant Recipients

Purpose

BK polyomavirus-associated nephropathy (BKVAN) is an important cause of renal allograft loss. Immunosuppression therapy in renal transplant recipients can lead to the reactivation of latent BK polyomavirus (BKV) infection, leading to BK viruria and viremia. This single-center study aimed to clarify the association between quantitative measurement of BKV DNA and the progression of BKV infection, and secondly to identify the risk factors associated with the evolution of viruria to viremia.

Methods

We retrospectively analyzed 266 patients who underwent renal transplantation in our center from October 2006 to February 2013. We examined the viral loads of BKV in urine and plasma by quantitative real-time polymerase chain reaction assay after screening all of the recipients by urinary sediment examination. BKVAN was diagnosed by histological examination with immunohistochemistry of the large T antigen in biopsy specimens.

Results

Overall, 22 recipients showed BK viruria alone, whereas 22 progressed to BK viremia, of which 6 patients were diagnosed with BKVAN. Among BKVAN patients, 2 cases progressed to graft loss at 59 months and 31 months after diagnosis, respectively. In BKVAN group, the plasma viral loads were significantly higher than those in viremia without nephropathy (P < .001). Multivariate analysis revealed that the evolution of viruria to viremia was associated with recipient age over 55 years (odds ratio, 32.08; 95% confidence interval, 2.1–489.5) and tacrolimus exposure (odds ratio, 11.98; 95% confidence interval, 1.34–107.04).

Conclusions

The progression from viremia to BKVAN was strongly associated with increasing plasma viral loads for BKV DNA. The cutoff value of 1 × 10⁴ copies/mL for plasma viral loads could differentiate between BKVAN and viremia alone. Further, recipient age over 55 years and tacrolimus exposure were independently associated with the evolution of viruria to viremia.     

Combined measurement of serum DNA and urine VP1 messenger RNA in monitoring BK virus replication in kidney graft recipients

Evaluation of BK virus replication is a fundamental tool in the monitoring of renal transplant recipients. Herein, we investigated the role of urine VP1 messenger RNA (mRNA) quantification and combined measurement of serum DNA and urine VP1 mRNA in 428 kidney allograft recipients. BK viremia and viruria were detected in 24 (5.6%) and 54 (12.6%) patients, respectively. A diagnosis of BKV-associated nephropathy (BKVAN) was established in 2 patients, both within the first year posttransplantation. Based on urine VP1 mRNA measurement, BKV replication was observed in 10 (2.1%) patients, 2 of whom displayed BKVAN. Urine VP1 mRNA was detected in all cases in association with viremia except 5 and in all cases with viruria. No difference among VP1 mRNA levels was noted between the 2 BKVAN patients and the highest values in patients without BKVAN. The urine VP1 mRNA result by analysis using the operating characteristics was not superior to viremia, despite the improvement obtained with the combined measurement of viremia (cut-off, 16,000 copies/mL) and urine VP1 mRNA (>10,000 copies/10³ cells). In conclusion, VP1 mRNA measurements may complement viremia and viruria to monitor BKV replication, although its use is limited by its technical complexity in comparison with DNA detection.     

Clinical usefulness of BK virus plasma quantitative PCR to prevent BK virus associated nephropathy

The present study investigated the clinical usefulness of plasma real-time polymerase chain reaction (PCR) (plasma-PCR) in the prevention of BK virus-associated nephropathy (BKVAN). First, we investigated the diagnostic value of plasma BK-PCR, urine BK-PCR, and urine cytology for the prediction of BKVAN retrospectively. Then we designed a prospective study of regular plasma-PCR monitoring and pre-emptive immunosuppression (IS) reduction based on the result. In the retrospective cohort, the prevalence of BKVAN was 3.7% (14/379) and the positive rate of decoy cells, urine-PCR (>1 × 10(10) copies/ml), and plasma-PCR (>1 × 10(4) copies/ml) was 18.6%, 11.1%, and 5.5%, respectively. Plasma-PCR was superior to urine-PCR or urine cytology in specificity and positive predictive value for detection of BKVAN. In prospective study, regular monitoring of plasma-PCR detected significant BKV viremia in 8.3% (12/145) and BKVAN in 1 patient (0.6%). After IS reduction, BKV viremia was eliminated in 91.6% (11/12) within 103 days (25-254). In patients with viremia, the frequency of acute rejection did not increase and allograft function did not differ significantly compared with those in patients without viremia during the first year post-transplant (P > 0.05, in both). Plasma-PCR is useful to predict an increased risk for BKVAN, and regular monitoring is effective to prevent the development of BKVAN.