Pre‐transplant shedding of BK virus in urine is unrelated to post‐transplant viruria and viremia in kidney transplant recipients

BK virus‐(BKV) associated nephropathy (BKVN) is a major cause of allograft injury in kidney transplant recipients. In such patients, subclinical reactivation of latent BKV infection can occur in the pre‐transplant period. The purpose of this study was to determine whether urinary BKV shedding in the immediate pre‐transplant period is associated with a higher incidence of viruria and viremia during the first year after kidney transplantation. We examined urine samples from 34 kidney transplant recipients, using real‐time quantitative polymerase chain reaction to detect BKV. Urine samples were obtained in the immediate pre‐transplant period and during the first year after transplant on a monthly basis. If BKV viruria was detected, blood samples were collected and screened for BKV viremia. In the immediate pre‐transplant period, we detected BKV viruria in 11 (32.3%) of the 34 recipients. During the first year after transplantation, we detected BKV viruria in all 34 patients and viremia in eight (23.5%). We found no correlation between pre‐transplant viruria and post‐transplant viruria or viremia (p = 0.2). Although reactivation of latent BKV infection in the pre‐transplant period is fairly common among kidney transplant recipients, it is not a risk factor for post‐transplant BKV viruria or viremia.     

Does reduction in immunosuppression in viremic patients prevent BK virus nephropathy in de novo renal transplant recipients? A prospective study

BACKGROUND: BK virus nephropathy (BKVN) is a severe complication of renal transplantation, resulting in graft loss in >50% of cases. Because patients with BKV viremia are at high risk for developing BKVN, the aim of our study was to analyze whether early reduction of immunosuppression (IS) could prevent BKVN in viremic patients. METHODS: BKV viruria was prospectively screened every 3 months by real-time polymerase chain reaction during the first year after transplantation in 123 consecutive renal transplant recipients. Plasma viral load was measured by polymerase chain reaction whenever viruria was positive; in viremic patients a graft biopsy was systematically performed and IS was reduced. RESULTS: Viruria, viremia, and BKVN occurred in 48.8%, 10.5%, and 2.4% of patients, respectively. In the 13 patients with positive viremia, initial graft biopsy showed BKVN in two. After reduction of IS in patients without BKVN, viremia disappeared in 8 of 11, decreased in 2 of 11, and increased in one patient who eventually developed BKVN. In contrast, viremia remained positive in one patient with BKVN and disappeared in the second but renal function deteriorated in both of them. Initial viral load was higher in patients who developed BKVN. CONCLUSION: Reduction of IS is probably an effective therapeutic option to clear viremia and prevent BKVN in viremic renal transplant patients.     

BK virus nephropathy in renal transplant recipients in Kuwait: a preliminary report

INTRODUCTION: BK virus nephropathy (BKVN) is a significant cause of graft loss among renal transplant recipients. The treatment outcomes of BKVN have been variably reported in the literature. PATIENTS AND METHODS: We prospectively investigated BKV infection and BKVN among a population of renal transplant recipients with suspected BKV infection. The 42 subjects who all had acute allograft dysfunction, were categorized in three groups: those with clinical, laboratory, and histological findings that did not suggest acute rejection, drug toxicity, or obstruction (group 1, n = 24); those with findings that suggested probable acute cellular rejection but did not respond to antirejection treatment (group 2, n = 10); and those whose renal histology suggested BKVN (group 3, n = 8). Polymerase chain reaction analysis was done to detect BKV DNA in urine and blood samples from each subject. BKV DNA was detected in 19 (45%) urine samples with 11 of these subjects (26.1% of total) having BK viremia as well. RESULTS: No evidence of BKVN was detected histologically in seven subjects with isolated BK viruria, while the others proved to be JC virus infections. Among the 11 subjects with BK viremia, eight had BKVN based on renal histology at the time of diagnosis with BKV infection, while the other three subsequently developed histological features of BKVN. BKVN developed after 5.3 +/- 2.5 (2 to 44) months after transplantation. The serum creatinine at time of BKVN diagnosis was 158.9 +/- 58 (87 to 285) micromol/L. All subjects were initially treated with a 50% reduction in immunosuppressive drug doses. Further decreases in immunosuppression were performed in all patients with close monitoring of renal function. All subjects were followed up for a of 18.2 +/- 5 (12 to 26) months. Two grafts were lost not due to BKVN, and one patient was lost to follow-up during this period. The latest serum creatinine in eight recipients is 113 + 20 (81 to 138) micromol/L, which is better than the renal function at diagnosis. CONCLUSION: The prevalence of BKVN in suspected BKV infection was 26%. Although the study period was short (30 months), BK viremia strongly correlated with BKVN, which seemed to be successfully treated with reduction in immunosuppression.     

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.     

Reactivation of BK Virus in the Early Period After Kidney Transplantation

Background

Typically, polyoma BK virus (BKV) remains latent in the urogenital tract after primary infection. Reactivation of BKV in recipients of kidney allografts can cause progressive graft dysfunction known as BK virus nephropathy (BKVN). The cornerstone of treatment for BKVN is prevention; therefore, it is important to detect BKV reactivation early and reduce immunosuppression. We sought to identify the BKV reactivation rate and associated factors in a prospective study.

Materials and Methods

We studied 37 consecutive unselected adult recipients who underwent deceased donor kidney transplantation in 2007 and completed at least 3 months of observation. Qualitative nested polymerase chain reaction (PCR) testing was performed to detect BKV DNA in urine and plasma specimens.

Results

In all cases, BK viremia or viruria was not detected on the postoperative day or 2 weeks thereafter. At 3 months, BKV reactivation developed in 6 (16%) of 37 recipients. Simultaneous viremia and viruria were present on 5 patients and viremia only in 1 patient. Significant risk factors for BK viremia were body mass index >30 kg/m² (P = .02), retransplantation (P =.04), and use of tacrolimus (P = .02). Serum creatinine values at 3 months after transplantation were significantly higher among patients with active BKV infection (P = .008).

Conclusions

Early BKV reactivation is associated with worse graft function as early as 3 months after transplantation. Obesity, retransplantation, and use of tacrolimus were factors promoting early development of BKV viremia.     

BK virus nephritis after renal transplantation

BK viremia and nephritis are increasing problems in renal transplant recipients. The exact cause of the increasing prevalence of this condition remains poorly understood. Increasing prevalence has been correlated with newer immunosuppressive agents and the decline in acute rejection rates in recent years. The clinical manifestation varies from the asymptomatic state of viremia and nephritis to clinical renal dysfunction. The diagnosis of this infection is based on the combination of the presence of urinary decoy cells, virus in the urine/blood, and typical renal histological findings of interstitial nephritis. Routine post-transplant screening for BK viremia and viruria prior to the occurrence of nephritis and the reduction in immunosuppressive therapy for subjects with viremia appear to be attractive approaches. The treatment of BKV nephritis (BKVN) consists of reduction in immunosuppressive therapy and antiviral therapy with cidofovir or leflunomide or a combination of both. Approximately 30-60% of subjects with BKVN experienced irreversible graft failure. However, in recent years, the combinations of early detection, prompt diagnosis, and appropriate reduction in immunosuppressive therapy have been associated with better outcome. The pathogenesis of BK virus infection in renal transplant recipients needs to be explored. The source of BKV infection (donor as opposed to recipient), the role of host humoral, and cellular immunity to BKV, and the role of alloimmune activation in renal graft to the occurrence of nephritis are discussed in this review.     

Prevalence and risk factors of polyomavirus BK replication in simultaneous pancreas/kidney transplant recipients from a single transplant center

Mindlova M, Boucek P, Saudek F, Skibova J, Jedinakova T, Lipar K, Adamec M, Hirsch HH. Prevalence and risk factors of polyomavirus BK replication in simultaneous pancreas/kidney transplant recipients from a single transplant center.
Clin Transplant 2011 DOI: 10.1111/j.1399‐0012.2011.01488.x.
© 2011 John Wiley & Sons A/S. Abstract: Background: BK virus (BKV) replication is considered as a marker of risk for polyomavirus BK‐associated nephropathy (PVAN). We evaluated the occurrence and risk factors for BKV DNA positivity following simultaneous pancreas/kidney transplantation (SPK). Methods: Point prevalence of BK viruria and viremia was assessed in 183 SPK recipients. Real‐time polymerase chain reaction was used with a detection threshold of 10³ copies/mL. High‐level BKV positivity was defined as viruria and/or viremia >10⁷ and >10⁴ copies/mL, respectively. BKV‐positive patients were retested after 4–13 months and underwent an additional six‐month clinical follow‐up. Results: Urine and serum BKV positivity was detected in 28 (17.3% of available samples) and 7 (3.8%) patients, with high‐level viruria and viremia occurring in 6 (3.7%) and 3 (1.6%) patients, respectively. PVAN was biopsy‐confirmed in 1 and suspected as a cause of progressive renal failure in another SPK recipient. Patients with single low‐level viruria did not progress to high‐level positivity or PVAN at follow‐up. In multivariate analysis, pre‐transplant diabetes duration and delayed graft function were independently associated with BKV positivity. Conclusions: Point prevalence of high‐level BKV positivity and PVAN was low in SPK recipients from a single center. Diabetes duration and delayed graft function were independent risk factors for BKV replication.     

Inhibitory interactions between BK and JC virus among kidney transplant recipients

BK and JC polyomaviruses can reactivate after transplantation, causing renal dysfunction and graft loss. The incidence of JC reactivation after renal transplant is not well understood. Here, we characterized JC reactivation using samples collected during the first year after transplantation from 200 kidney recipients. We detected BK and JC viruses in the urine of 35 and 16% of transplant recipients, respectively. The median viral load in the urine was 400 times higher for BK virus than JC virus. The presence of BK viruria made concurrent JC viruria less likely: JC viruria was detected in 22% of non-BK viruric recipients compared with 4% of BK viruric recipients (P=0.001). The co-detection rate was 1.5%, which is less than the expected 5.6% if reactivation of each virus was independent (P=0.001). We did not observe JC viremia, JC nephropathy, or progressive multifocal leukoencephalopathy. The onset of JC viruria was associated with donor, but not recipient, JC-specific antibody in a titer-dependent fashion and inversely associated with donor and recipient BK-specific antibody. Donor and recipient JC seropositivity did not predict BK viruria or viremia. In conclusion, among renal transplant recipients, infection with one polyomavirus inversely associates with infection with the other.     

BK virus nephropathy: Clinical experience in a university hospital in Japan

Objectives: To review the medical records of patients with BK virus nephropathy (BKVN) following kidney transplantation in our institution. Methods: We screened patients for decoy cells using urine cytology, assessed serum creatinine levels, and conducted a graft biopsy, as well as assessed the presence of plasma BK virus DNA by quantitative real‐time polymerase chain reaction. The treatment of BKVN was based on the decreased use of immunosuppressants. Results: Overall, six male patients were studied (mean age 40.8 years, range 18–58; mean donor age 45.2 years, range 15–67). A positive urine cytology screen led to the subsequent detection of plasma BK virus DNA in the five patients with urine cytology results positive for decoy cells. In the four patients in whom plasma BK virus DNA was detected, a maximum value of DNA of ≥10 000 copies/mL was observed. Time elapsed from transplantation to BKVN diagnosis ranged from 3 to 62 months. Although the two cadaver grafts were lost, the loss was not due to any effects directly associated with BKVN. The other four grafts are still functioning with a mean creatinine level of 1.8 mg/dL. Most of the patients with BKVN were regarded as being in a state of heightened immunosuppression. BK virus transition to blood was prevented in one patient. Conclusions: Early diagnosis of BKV infection with reduction of immunosuppression may potentially counter BK viremia and retard progression of BKV nephropathy. Decoy cell screening by urine cytology as well as plasma BK virus DNA screening should be considered in addition to the required graft biopsy in kidney transplant recipients, particularly in those with impaired graft function.     

Identification of BK Virus Genotypes in Recipients of Renal Transplant in Vietnam

ObjectivesThis study aims to investigate the prevalence and distribution of BK polyomavirus (BKV) genotypes in recipients of renal transplant in Vietnam.MethodsOne hundred six patients who underwent renal transplantation were included in this study. These patients were from the Department of Nephrology, Military Hospital 103, Vietnam Military Medical University. Quantification and genotyping of the BK virus was performed using in-house molecular methods from urine and plasma samples.ResultsBKV infection was detected in 82 patients (77.4%), including 58 patients who had the presence of both BK viremia and BK viruria, and 24 patients (22.60%) with BKV positive findings in the urine alone. Particularly, 16 patients (15.09%) had high BK viremia >10⁴ copies/mL and 20 patients (18.9%) had BK viruria >10⁷ copies/mL. BK virus nephropathy (BKVN) was confirmed in 6 patients (5.66%) by immunohistochemistry examination. Genotyping of BKV was performed successfully in 50 out of the 82 patients, with 36 out of 50 (72%) belonging to the BKV-I subtype and 14 out of 50 (28%) belonging to the BKV-IV subtype; no cases of genotypes II or III were observed. Using phylogenetic analysis of the subgroups, the BKV-I/b-1 subtype was found the predominant subgroup (100%), whereas BKV-IV included 21.43% of IV/a-1, 6.67% of IV/a-2, and 50% of IV/c-1, respectively. There remain 3 cases of BKV-IV (21.43%) that could not be categorized into any subgroups. In the 6 patients diagnosed BKVN, 5 of them were infected with subgroup I/b-1 (83.3%) and 1 patient was infected with subgroup IV/c-1 (16.7%). No significant difference between BKV genotypes was observed in relation to age, sex, HLA mismatch, viral load, BKVN, and immunosuppressive therapy.ConclusionsThis research indicated a high prevalence of BKV infection and BKV-I was predominant, followed by BKV-IV among recipients of renal transplant in Vietnam.     

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.     

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.     

Risk Factors for BK Virus Infection and BK Virus–Associated Nephropathy Under the Impact of Intensive Monitoring and Pre-emptive Immunosuppression Reduction

BackgroundBK virus (BKV) nephropathy (BKVN) is an increasingly recognized cause of kidney allograft loss and is thought to be related to the newer, more potent immunosuppressive agents. However, the risk factors for different types of BKV infection under the impact of intensive monitoring and reduction of maintenance immunosuppression are not well understood.MethodsQuantitative BKV DNA surveillance in plasma/urine and cytological testing in urine were performed regularly within the first year post-transplantation in 229 kidney recipients. Patients with BK viremia and BKVAN treated with immunosuppression reduction were monitored for BKV every 3–6 months. All the patients were followed up for a minimum of 5 years to exclude later development of BKVAN. Potential variables were compared and analyzed using logistic regression model multivariate analysis to assess and rank the BKV infection-related factors.ResultsSeventy-eight (34.1%) patients had decoy cells, 99 (43.2%) BK viruria, 38 (16.6%) BK viremia, and 7 (3.1%) BKVAN. Risk for decoy cells, BK viruria, and viremia, and BKVAN in univariate analyses were higher with tacrolimus (Tac) and deceased kidney donation. Multivariate analysis showed that Tac ([HR, 2.7; P = .008], [HR, 2.3; P = .016], [HR, 2.9; P = .032]) and deceased kidney donation ([HR, 2.5; P = .004], [HR, 2.6; P = .002], [HR, 2.1; P = .071]) were risk factors for BK decoy cells, BK viruria, and viremia, respectively. BKVAN was inclined to the patients with the combination of Tac and mycophenolate mofetil and longer BKV clearance time.ConclusionsTac and deceased kidney donation are independent risk factors for BKV infection under the impact of therapeutic drug monitoring.     

Prevalence,Risk Factors,Treatment, and Overall Impact of BK Viremia on Kidney Transplantation

BK viremia (BKV) is a recognized and potentially serious problem in renal transplantation. The risk factors and the impact of BKV on renal allograft and patient survival are controversial. This study reports an 8-year, single-center experience on the prevalence, risk factors, and outcomes of BKV in kidney transplant recipients. This is a retrospective analysis of all patients who received a kidney transplant at the University of Kentucky and had BK viral titers available from 2009 to 2017. BKV was defined by a polymerase chain reaction viral load of ≥ 10,000 copies per mL. Demographic, clinical, and laboratory data generated during routine outpatient follow up and inpatients records were collected. Independent risk factors for BKV were determined using uni- and multivariate analysis. Graft and patient survival was compared using Kaplan-Meier analysis, and the severity of polyomavirus nephropathy on biopsy was scored using the Banff 2017 classification. We identified 122 BK positive (19%) and 527 BK negative (81%) patients. BKV developed after a median of 115 days (range, 80–249 days) following kidney transplantation. The 1-, 5-, and 10-year graft survival was 97%, 75%, and 33% in the BKV group and 96%, 85%, and 71% in the BK negative group, respectively. Likewise, the 1-, 5-, and 10-year patient survival was 98%, 84%, and 52% in the BKV group and 98%, 92%, and 84% in the BK negative group. Male sex, age at transplantation, maintenance steroids, and alemtuzumab induction were associated with developing BKV in the multivariate analysis. We concluded that BKV is not uncommon after renal transplantation. The determinants for BKV are male sex, older transplant recipients, and maintenance steroids. BKV adversely affected graft and patient survival. A unified approach for BKV and polyomavirus nephropathy treatment is needed.     

Prospective Monitoring of Polyomavirus BK Replication and Impact of Pre-Emptive Intervention in Pediatric Kidney Recipients

Polyoma BK virus (BKV)-associated nephropathy (PVAN) is a relevant cause of poor renal allograft survival. In a prospective analysis, we monitored BKV DNA in blood and urine samples from 62 consecutive pediatric kidney recipients. In patients with BKV replication, we analyzed the impact of reduction of maintenance immunosuppression on viral load kinetics and PVAN in patients with BKV replication. BKV-specific immunity was concomitantly evaluated on blood samples of viremic patients, by measuring the frequency of BKV-specific interferon-gamma-producing and cytotoxic T cells, and BKV IgG antibody levels. At a median follow-up of 24 months, BK viruria was observed in 39 of 62 patients, while BK viremia developed in 13 patients (21%). In all viremic patients, immunosuppression reduction resulted in the clearance of viremia, and prevented development of PVAN, without increasing the rate of acute rejection or causing graft dysfunction. As a consequence of immunosuppression adjustment, an expansion of BKV-specific cellular immunity was observed that coincided with viral clearance. We conclude that treating pediatric kidney transplant patients pre-emptively with immunosuppression reduction guided by BKV DNA in blood is safe and effective to prevent onset of PVAN. BKV-specific cellular immunity may be useful to guide this intervention.     

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。     

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.     

The status of BK polyomavirus replication in adult renal transplant recipients in northeastern Poland

Purpose

BK polyomavirus (BKV) infection and BKV-associated nephropathy (BKVAN) are among the most important problems in renal transplantation. We aimed to determine the incidence of BK viruria, viremia, and BKVAN in renal transplant recipients in the northeastern part of Poland.

Methods

Urine and blood samples from 126 cadaveric renal transplant recipients were analyzed for BK viruria and viremia using quantitative real-time polymerase chain reaction and the patients were followed prospectively. The diagnosis of BKVAN was established on the allograft biopsy.

Results

Based on the BKV DNA analysis, the patients were divided into three groups: group 1 (n = 89; 70.6%) without viruria or viremia, group 2 (n = 24; 19.1%) with isolated viruria, and group 3 (n = 13; 10.3%) with both viruria and viremia. The presence of BK viremia negatively correlated with time after the transplantation. BK viruria was associated with mycophenolate mofetil daily dose. In group 3 there were four patients (3.2%) with high viremia (>10⁴ genome equivalents [gEq]/mL) and viruria (>10⁷ gEq/mL) loads. Only one patient from this group developed clinical symptoms and had BKVAN in allograft biopsy. In all four cases, the maintenance immunosuppression therapy was based on tacrolimus and steroids.

Conclusion

Prevalence of BKV infection in renal transplant recipients in the northeastern part of Poland is similar to that reported by studies from other countries. We confirm that BK viremia could be predicted by the presence of intense viruria. Time after transplantation and the type of immunosuppression strategy are the most important predictors of BK viremia and viruria in patients after renal transplantation.     

Does JC polyomavirus cause nephropathy in renal transplant patients?

Introduction

BK polyomavirus (BKV) reactivation characterized by active viruria occurs in 23%-57% of renal allograft recipients and BKV-associated nephropathy in as many as 8% of renal allograft recipients. Only a few cases of nephritis have been attributed to JC polyomavirus (JCV) with limited information about JCV replication and its impact on graft function and survival of kidney transplant patients. We sought to determine the prevalence of BKV and JCV replication, the risk factors associated with viral reactivation, and their implications for the development of polyomavirus nephropathy (PVN) among renal transplant patients.

Materials and Methods

The study included 186 kidney transplant recipients who were transplanted between 2005 and 2009 with a 1-year follow-up. If the urine polymerase chain reaction (PCR) was positive, we performed a PCR on blood. If this was positive or renal dysfunction was present, we performed a renal biopsy.

Results

Viruria was positive in 72 cases (39%) and viremia in 12 (6.5%); including, 3 patients (1.6%) who developed PVN. In the patients with viruria, BKV was detected in 47% and JCV in 46%; both were detected in 7%, although the combination of viremia and nephropathy were caused by BKV in all cases.

Conclusion

In renal transplant patients, the incidence of BKV and JCV viruria was similar, although in our series the JCV serotype did not cause viremia or PVN. Our experience suggested that JCV did not have the ability to cause PVN.     

Polyoma virus BK and renal dysfunction in a transplanted population

INTRODUCTION: Reactivation of polyoma virus BK (BKV) is increasingly recognized as a cause of severe renal-allograft dysfunction. The aim of the present study was to evaluate prevalence of BKV infection and activity in a population of kidney (KT) and liver (LT) transplant patients and search for a possible correlation with renal dysfunction. METHODS: We studied 118 patients for BKV viruria and, when present, for BKV viremia. We also assessed HCV status. RESULTS: Among 16 patients with BKV viruria (5 LT and 11 KT), eight showed BKV viremia (one LT and seven KT). Among BKV viruria-positive patients, three LT recipients were HCV-positive. All LT BKV viruria-positive patients showed normal renal function with a mean serum creatinine (sCr) blood level of 0.9 mg% and a mean blood urea nitrogen (BUN) value of about 36 mg%. The mean transplant age was 2.5 years. In contrast, KT BKV viruria-positive patients showed impaired renal function which was slightly worse in patients who also displayed BKV viremia, namely, a mean sCr blood level 1.7 mg% and a mean BUN value about 80 mg%. The mean transplant age was 7 years. CONCLUSION: Based on these findings, it seems that BKV viruria in renal allograft recipients may be associated with viremia and related to nephropathy that may lead to allograft rejection. The study will be completed with a 2-year follow-up of positive patients to assess the possible relationship between BKV active infection and eventual decrease of renal function and loss of transplanted organ.