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.     

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 Infection in Thai Kidney Transplant Recipients: A Single-Center Experience

Introduction

BK virus-associated nephropathy (BKVAN) is a significant cause of allograft dysfunction and failure in kidney transplant recipients. Early detection and proper adjustment of immunosuppression is the best method for treatment of this condition and to improve long-term allograft outcome. Here, we reported the prevalence and risk factors of BK virus (BKV) infection in our population.

Conversion From Mycophenolates to Mizoribine Is Associated With Lower BK Virus Load in Kidney Transplant Recipients: A Prospective Study

Background

BK virus allograft nephropathy (BKVAN) is a graft-threatening complication after kidney transplantation. Current consensus regarding the prevention of BKVAN is to screen for BK viremia and to treat sustained BK viremia through reducing immunosuppression. This study assessed the effect of conversion from mycophenolates to mizoribine (MZR) on the prevention of BK viremia in kidney transplant recipients.

BK Virus in Liver Transplant Recipients: A Prospective Study

Background

BK virus (BKV) is a polyomavirus that is associated with nephropathy and graft loss among kidney transplant recipients. The role of BK virus in nonrenal solid organ transplant recipients has not been clearly established; only anecdotal case reports have been published.

Methods

From August 2005 to September 2007, all orthotopic liver transplant (OLT) recipients who gave their consent were enrolled in this prospective longitudinal study. BK viral load was measured using real-time quantitative polymerase chain reaction assays of urine and plasma, using samples collected at week 1 and months 1, 3, 6, 9, 12, 15, 18, 21, and 24 posttransplantation. We also collected demographic and clinical data, including serum creatinine and immunosuppressive therapy.

Results

The mean age of the 62 patients was 51.4 years including 14 (22.5%) women. Hepatitis C infection was present in 24 patients (38.7%). BK viruria was detected in 14.5% of 290 samples, corresponding to 13 patients (21%). BK viremia was detected in 5.1% of 317 samples, corresponding to 11 patients (18%). Almost all cases of BK viremia (91%) occurred in the first 3 months after OLT. BK viremia was more common among patients experiencing a rejection episode (10.6 vs 40%, P = .01). We did not observe a relationship between single episodes of BKV replication and renal function: median plasma creatinine 1.1 mg/dL in patients without versus 1.2 mg/dL with BK viremia. The three patients with persistent viremia displayed renal insufficiency; one of them died due to multiorgan failure of unknown origin.

Conclusions

BKV is frequently detected in OLT recipients (viruria 21% and viremia 18%) early after transplantation. It is more common among patients with rejection episodes. Persistent BK viremia may be related to renal dysfunction in OLT patients.     

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.     

Nucleic Acid Tests for BK Polyomavirus Is Critical in Renal Transplant Recipients

This study evaluates the incidence of BK polyomavirus (BKV) and prognosis of BKV infection in kidney transplant recipients (KTRs) who received transplantation in our hospital before and after regular BKV nucleic acid test (NAT) was implemented.

Dual positivity of donor and recipient plasma for BK virus confers a high risk for development of bk nephropathy in renal allograft

Background

BK nephropathy (BKN) is an important complication of renal transplantation, with a reported incidence between 1% and 10% in different parts of the world. Known risk factors for the development of BKN are the recently introduced immunosuppressants and steroids. However, the preexisting viral load may add to the risk for development of BKN. Therefore, the present study was designed to monitor the baseline BK virus (BKV) DNA in renal transplant donors and recipients in India for correlation with the development of BKN.

Methods

This study used real-time polymerase chain reaction (PCR) for quantification of BKV DNA in the plasma of kidney transplant donors (n = 38) and recipients (n = 87) at the time of surgery. The control BKV DNA was manufactured from a known positive human sample, by cloning a 133-bp PCR product of bases 4,329 to 4,462 of the large T-antigen (TAg) of BKV in a plasmid vector.

Results

Twenty-five of 87 recipient (28.7%) and 17/38 donor (44.7%) plasma samples were positive for BKV DNA at the time of transplantation with a median viral load of 910 (range 49-4770) and 312 (range 79-1508) copies per mL plasma, respectively. Six of 38 donor-recipient pairs showed viremia in both the recipient and donor: 1 developed histologically proven BKN at 18 months, 1 showed positive immunohistochemistry for SV40 TAg, and 2 others had high levels of viremia (14,545 copies at 6 and 2,617,524 copies at 3 months). None of the other 81 recipients showed evidence of BKN in the follow-up period.

Conclusions

This study showed that 28% of recipients and 44% of donors displayed baseline positivity for BKV DNA in plasma, which is higher than the reported incidence in the West. The baseline levels of BKV DNA in recipients with end-stage renal disease were higher than in donors. Dual positivity for BKV DNA in the plasma of donor-recipient pairs conferred a high risk of development of BK nephropathy in the allografted kidney.     

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.     

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.     

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.     

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.     

Clinical Courses of Renal Transplant Recipients with High BK Viremia

Objective

We sought to investigate the clinical courses of renal transplant recipients with plasma BK viral loads >10⁴ copies/mL.

Methods

A single-center retrospective review was performed of 88 kidney transplant patients in whom high BK viremia (defined as plasma BKV load >10⁴ copies/mL) was detected more than once from January 1, 2004, to December 31, 2011.

Results

At the time of transplantation, the mean recipient and donor ages were 44.5 ± 11.1 and 43.9 ± 11.3 years, respectively, and 59 subjects (67.0%) were male. The median times to first BK positivity and high BK viremia after transplantation were 44 and 136 days, respectively. Within 3 months after transplantation, we detected, 56 cases of high BK viremia (63.6%). The mean duration of high BK viremia was 8.2 ± 7.7 months. When plasma BKV load was first >4 logs, the mean log BKV load was 5.50 ± 1.11 log copies/mL, which rose to a maximum of 5.82 ± 1.11. At these times, mean serum creatinine concentrations were 1.67 ± 0.79 and 2.64 ± 2.78 mg/dL, respectively. There were 31 cases (35%) of biopsy-proven BK nephropathy patients among 51 (58%) biopsies. Treatment modalities included discontinuation or dose reduction of mycophenolic acid drugs (n = 68) and switch from tacrolimus to cyclosporine (n = 9), cidofovir (n = 9), and leflunomide (n = 3). Based on the serum creatinine elevation after high BK viremia, patients were divided into group 1 (n = 27; 30.1%), whose maximal creatinine change was <0.5 mg/dL, and group 2, with a greater alteration. On multivariate logistic regression analysis, the maximal plasma BK viral load was significantly associated with a greater serum creatinine elevation (P < .001).

Conclusions

High BK viremia mostly occurred within 3 months after kidney transplantation. About 30% of renal allograft recipients with high BK viremia maintained stable renal function. Maximal plasma BK viral load was the only independent risk factor for high serum creatinine elevation.     

肾移植受者BK病毒相关性肾病的临床诊断

目的 探讨肾移植受者BK病毒相关性肾病(BKVAN)的临床诊断方法 .方法 分别于肾移植术后第1、3、6、9、12个月收集90例肾移植受者血、尿标本,进行尿沉渣Decoy细胞计数与BK病毒(BKV)DNA含量的检测.应用免疫组织化学技术检测移植肾组织中的SV40-T蛋白,移植肾组织及确诊为BKVAN患者的尿沉渣中脱落的肾小管上皮细胞进行普通透射电镜观察.结果 90例肾移植受者1年内尿液Decoy细胞、BKV DNA及血浆BKV DNA阳性率分别为:42.2%(38/90)、45.6%(41/90)和22.2%(20/90);阳性者中位数水平分别为8个/10 HPF、2.60×10~5拷贝/ml和9.65×10~3拷贝/ml.确诊BKVAN 5例.结论 肾移植术后定期规律监测有关BKV活动的指标非常必要.确诊BKVAN需依靠普通病理染色与免疫组织化学染色或普通透射电子显微镜并结合临床表现.     

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.     

Mycophenolate Mofetil Withdrawal With Conversion to Everolimus to Treat BK Virus Infection in Kidney Transplant Recipients

Background

BK virus (BKV) is a significant post-transplant infection. Mammalian target of rapamycin inhibitors (mTORis) reduce BKV large T antigen expression in vitro and are associated with lower rates of BKV infection when used as de novo immunosuppression in clinical studies.

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.     

Prospective evaluation of BK virus DNAemia in renal transplant patients and their transplant outcome

BACKGROUND: After renal transplantation, the prevalence of BK virus (BKV) viruria, viremia, and nephritis (BKVAN) has been estimated at 30%, 13%, and 8%, respectively. PATIENTS AND METHODS: The aim of this prospective study was to assess the occurrence of BKV DNAemia during the first year after renal transplantation and to determine the prevalence of BKVAN, in the absence of immunosuppression alteration, following positive BKV DNA. BKV DNAemia was assessed systematically in 104 renal transplant patients on postoperative days 60, 90, 135, 180, 270, and 360. RESULTS: Of the 104 patients, 7 (6.7%) presented with at least 1 episode of BKV DNAemia. Those with positive BKV DNAemia had a cumulative steroid dose administered from days 0 to 7 which was higher than those without BKV DNAemia (2.13 +/- 0.6 vs 1.6 +/- 0.4; P = .024). The first BKV DNAemia occurred at 170 (30-460) days posttransplantation. Of the 7 patients who experienced at least 1 BKV DNAemia, 3 had 1 occurrence, but the other 4 had repeated occurrences. These 4 patients developed overt BKVAN at 1 (2 cases) to 2 weeks (2 cases) after the first occurrence of BKV DNAemia. These 4 patients were withdrawn from mycophenolate mofetil, which was in all cases replaced by leflunomide. With a follow-up ranging from 14 to 24 months after the first episode of BKV DNAemia, patient and graft survivals were both 100%. Current serum creatinine ranges from 97 to 173 micro mol/L for those who had only 1 episode of BKV DNAemia, and from 144 to 240 micro mol/L for those who had overt BKVAN. CONCLUSION: Although BKV DNAemia is a rare event after renal transplantation, it is often associated with BKVAN, which may be treated successfully by the alleviation of immunosuppression and leflunomide therapies.     

Lack of cytomegalovirus and polyomavirus coexistence in Iranian kidney transplant recipients

Introduction

Maintenance of kidney graft function is essential, averting infection and coinfection. Cytomegalovirus (CMV) and BK polyomavirus (BKV) coinfection have been reported. There are a few studies of CMV and BKV infection in kidney transplant recipients in Iran, but no studies of their coinfection.

Objective

To assess the coexistence of CMV and BKV infection in renal transplant recipients.

Patients and Methods

The presence of CMV and BKV was assessed using real-time polymerase chain reaction in a cross-sectional study in 91 renal transplant recipients at 1 month posttransplantation. Assessment of CMV was performed only in blood samples, whereas BKV was assessed in both serum and urine samples.

Results

The 91 patients included 57 men (62.6%) and 34 women (37.4%), who ranged in age from 19 to 76 years. Simultaneous evaluation of CMV in plasma and BKV in urine demonstrated no significant association. Of 24 patients positive for BKV in urine, 8 (33.3%) were positive for CMV in plasma. Sixty-seven patients tested negative for BKV in urine, whereas 23 (34.4%) tested positive for CMV, which is unremarkable. Comparison of coinfection with plasma CMV and plasma BKV demonstrated no significant correlation. In 3 patients positive for BKV in plasma only, 1 (33.3%) was positive for CMV, whereas in 88 patients negative for BKV in plasma, 30 were positive for CMV.

Conclusion

No significant association was observed between CMV and BKV infections in kidney transplant recipients.     

Intensive polyoma virus nephropathy treatment as a preferable approach for graft surveillance

Background

Polyoma BK virus nephropathy (BKVN) is one of the important causes of graft failure and loss among renal transplant patients. Reduction of immunosuppression is the most important preferred treatment approach; however, there is no agreed protocol for additional treatments.

Objective

Our aim was to investigate the effects on graft survival of intensive treatment protocols for BKVN among renaltransplant patients.

Methods

214 patients were included in the study. All patients underwent investigation for the presence of BKV in plasma samples every 3 months starting from the third month after transplantation. Biopsies were obtained upon detection of graft dysfunction or viremia. If BKVN was positive, viremia was investigated monthly.

Results

Plasma plus biopsy-proven BKVN were detected in 19 patients (8.9%), whose mean age was 45.8 ± 12.0 years; 68.4% (n = 13) were male and 94.7% (n = 18) were recipients of a living-donor kidney. There were 5.2% (n = 1) diabetic subjects, and the mean time prior to dialysis was 39.6 ± 44.8 (3-125) months. BKVN was observed at a mean of 6.8 ± 2.9 (4-14) months after the transplantation. It positively correlated with the baseline serum creatinine level (r = 0.159; P = .02), application and cumulative dose of antithymocyte globulin (r = 0.177; r = 0.165; respectively; P = .01), mean tacrolimus dose (r = 0.303; P < .001), and hepatitis B virus positivity (r = 0.169; P = .01). Immunosuppression was decreased in all patients who developed BKVN. In addition, leflunomide was applied in 68%, intravenous immunoglobulin in 74%, and cidofovir in 32% of patients. Acute rejection rates did not increase significantly after lowering immunosuppression (P > .05).

Conclusion

BKVN is one of the important problems in renal transplant patients. Intensive treatment of BKVN with heterogeneous regimens, including combined treatment with leflunamide + IVIG together with immunosuppressive dose reduction, was an effective approach to prolong graft survival.