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.     

BK virus subtype 1 infection associated with tubulointerstitial nephritis in a renal allograft recipient

The BK polyomavirus (BKV) infects most of the human population, but clinically relevant infections are usually limited to individuals who are in an immunosuppressed state. The significance of BKV infection was investigated in a 50-year-old man who underwent cadaveric kidney transplantation and was treated with tacrolimus, mycophenolate mofetil and prednisolone. By staining renal biopsy specimens with a monoclonal antibody against BK large T antigen, we were able to observe the relationship between the appearance of the BKV antigen and the extent of immunosuppression in this patient. We also determined that BKV belonged to genotype I by analysis of viral DNA from the patient's urine.     

Retransplantation After BK Virus Nephropathy in Prior Kidney Transplant: An OPTN Database Analysis

BK virus (BKV) has emerged as a major complication of kidney transplantation. Since June 30, 2004, the OPTN in the USA collects BKV as a primary or secondary cause of graft loss and also if treatment for BK virus (TBKV) is administered. In this study, we determined characteristics of those recipients of repeat kidney transplants from the OPTN database, where either (a) a graft loss occurred between June 30, 2004 and December 31, 2008 and database recorded prior TBKV in that allograft or (b) a graft loss between June 30, 2004 and December 31, 2008 was attributed primarily or secondarily due to BKV. In the study time period, 823 graft losses have occurred where TBKV or graft failure attributable to BKV was reported in prior transplant; of these, 126 have received a retransplant as of June 5, 2009. Induction and maintenance immunosuppression usage mirrored current trends. As of June 5, 2009, 118/126 grafts are still functioning, one graft failure attributed to BKV. TBKV was reported in 17.5% of the retransplants. In the retransplants performed through December 31, 2007, 1‐year acute rejection rate was 7%, 1‐year and 3‐year Kaplan–Meier graft survival rates and median GFR were 98.5%, 93.6%, 65.5 and 68.4 mL/min, respectively. Retransplantation after BKV appears to be associated with good results.     

Prevalence of human polyoma virus (BK virus and JC virus) infection in patients with chronic renal disease

Background Polyoma virus infection in renal transplant patients is sometimes critical in graft survival. But, to date, polyoma virus infection or reactivation has not been checked before renal transplantation. The prevalence of polyoma viruses (BK virus and JC virus) was investigated in 45 patients with renal disease who were future candidates as renal graft recipients.Methods Because these viruses are excreted in urine, the urine of these 45 patients was analyzed by polymerase chain reaction (PCR). The urine of 37 age-matched normal subjects (control group) was also investigated.Results In the control group, 13.5% of the normal subjects were positive for BK virus and 24.3% were positive for JC virus. In the patients with renal disease, 33.3% were positive for BK virus and 33.3% were positive for JC virus; the prevalence of BK virus infection was significantly higher than that in the normal subjects. Patients with renal disease with corticosteroid therapy revealed an especially high prevalence of BK virus infection (55.6%), indicating the possibility of viral reactivation by corticosteroid therapy.Conclusions More attention should be paid to polyoma virus infection in candidates for renal transplantation with a previous therapeutic history of corticosteroid administration.     

No clinical benefit of rapid versus gradual tapering of immunosuppression to treat sustained BK virus viremia after kidney transplantation: a single‐center experience

Immunosuppressive drug tapering is currently the recommended treatment of BK virus (BKV) viremia after kidney transplantation; however, its exact modalities remain unclear. We retrospectively compared two consecutive strategies in 111 patients with sustained viremia: a gradual monitoring/tapering group (GT, n = 57) before 2012 and a rapid monitoring/tapering group (RT, n = 54) after 2012. At viremia diagnosis, the dose of mycophenolic acid (MPA) and tacrolimus levels (T₀) were similar among patient groups. However, following onset, the dose of MPA at 1 month (P = 0.002) and 3 months (P = 0.005) and Tac T₀ at 1 month (P = 0.030) and 3 months (P = 0.006) were lower in the RT group. This rapid minimization shortened BKV viremia (P < 0.001) and resulted in a better protection of graft function in patients with confirmed BKV‐associated nephropathy (P = 0.033) without impacting 5‐year graft survival. Survival without rejection was similar (P = 0.571), but the RT group had increased the development of de novo donor‐specific antibodies (dnDSAs; P < 0.001). Multivariate Cox analysis identified basiliximab versus Thymoglobulin^® induction [hazard ratio (HR), 3.090; P = 0.001] and the RT strategy (HR, 6.021; P = 0.002) as independently associated with dnDSAs. Compared to a gradual tapering, rapid immunosuppression tapering to treat sustained BKV viremia does not improve medium‐term clinical outcome but increases the risk of developing dnDSAs.     

Rapid kidney allograft failure in patients with polyoma virus nephritis with prior treatment with antilymphocyte agents

Interstitial nephritis owing to polyoma virus infection (PVi) mimics acute allograft rejection. The risk factors for graft failure associated with PVi are unknown. This prompted us to analyse the relationship between the use of antilymphocyte agents (ALA) and graft dysfunction in renal transplant recipients with PVi. Renal transplant recipients who were diagnosed to have PVi nephritis at the Medical College of Wisconsin were included in this study. PVi nephritis was confirmed by urine cytology and characteristic renal histological findings in a total of 14 cases. Other viruses were excluded by immunohistochemistry studies. Patients were divided into two groups: Group A (n = 7) received ALA (OKT3/ATGAM) as treatment for presumptive acute rejection and Group B (n = 7) did not receive ALA therapy. The progression of renal function (GFR) was estimated by a 100/ plasma creatinine and an actuarial kidney survival was estimated by the Kaplan-Meier method. The demographics (age, gender, race, retransplant and kidney versus. kidney/pancreas), prior treatment with steroids for presumptive acute rejection, and renal function at the time of PVi diagnosis were similar betwoen groups. The fall in GFR/month was 6 mL/min/month with prior ALA therapy compared with 1 mL/min/month in those who did not receive ALA, p = 0.002. All seven grafts were lost in the ALA group compared with only two of seven grafts in the other group, p = 0.005. The use of ALA was associated with a rapid fall in GFR and graft failure in patients with PVi nephritis. Careful diagnosis of PVi is warranted in renal allograft recipients prior to initiating ALA therapy.     

Renal transplant patient with polyoma virus bladder infection and subsequent polyoma virus nephropathy

Polyoma virus nephropathy (PVN) is a significant cause of renal allograft dysfunction in transplant patients. A 58-year-old male received a cadaveric renal transplant and 12 weeks later presented with fever, diarrhea, and dysuria. He was diagnosed with a polyoma virus infection of the bladder by a transurethral bladder biopsy. One year post-transplant, he presented with renal allograft dysfunction and was diagnosed by biopsy with PVN of the non-native kidney. The diagnosis of a polyoma virus infection was confirmed by immunoreactivity to the polyoma T-antigen. We suggest that polyoma virus infection of the bladder be included in the differential diagnosis of urinary dysfunction in post-transplant patients, as such infections might be an under-recognized comorbidity in individuals with PVN.     

术前巨细胞病毒感染对移植肾急性排斥的影响

目的 研究肾移植受者术前巨细胞病毒(CMV)感染对术后急性排斥的影响及预防性抗病毒治疗的意义。方法 回顾性分析416例肾移植受者的术前巨细胞病毒感染，预防性抗病毒治疗和急性排斥的发生情况，并用Logistic回归分析各因素对急性排斥的影响。术前感染受者根据有无预防性抗病毒治疗分为治疗组和非治疗组，比较两组间急性排斥发生率。结果术前巨细胞病毒感染组的急性排斥率显著高于非感染组(29．9％比19．5％，P=0．014)，术前感染受者发生急性排斥的风险增高将近1倍。预防性抗病毒治疗能降低术后CMV疾病的发生率但对急性排斥无影响。结论术前巨细胞病毒感染是术后急性排斥独立的危险因子。常规的预防性抗病毒治疗并不能减少由感染介导的免疫损伤而导致的急性排斥的发生。     

A direct association of polyomavirus BK viruria with deterioration of renal allograft function in renal transplant patients

Abstract: Background:  Polyomavirus BK virus (BKV) causes a BKV-associated nephropathy (BKVAN), frequently causing allograft dysfunction in renal transplant recipients. As BK viruria is a surrogate marker for early detection of BKVAN, the aim of this study was to clarify an association between BK viruria and allograft dysfunction in renal transplant recipients.
Methods:  One hundred and six renal transplant recipients with average 5.9-yr transplant duration received screening for quantification of BK viruria detected by real time polymerase chain reaction and were followed up for 12 months.
Results:  Twenty-six patients (25%) had detectable BK viruria. In comparison of the patients without BK viruria, more patients in the BK viruria group were treated with steroids and had a past history of acute rejection. There was no difference in sex, age, transplant duration, allograft type and previous cytomegalovirus infection. During follow-up, the patients with BK viruria had higher serum creatinine levels at the sixth, ninth and 12th month. Multiple logistic regression analysis revealed that BK viruria was the only risk factor for more than 25% or 50% rise of serum creatinine level above baseline at the end of one yr follow-up.
Conclusions:  BK viruria alone is associated with allograft dysfunction and early intervention is indicated.     

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.     

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.     

Association of treatment with 15-deoxyspergualin and BK virus nephropathy in kidney allograft recipients

OBJECTIVE: BK virus nephropathy (BKVN) has been proposed as an important cause of allograft dysfunction and loss in kidney allograft recipient over the last decade. Intense immunosuppression and tubular injury have been shown to promote the replication of polyomavirus. 15-deoxyspergualin (DSG), an effective immunosuppressive agent, is used as a rescue drug for acute rejection in clinical renal transplantation in Japan. To determine whether DSG is a risk factor for BKVN and outline the relationship among BKVN, DSG, and other risk factors, we analyzed 88 patients who received living-related renal transplantation between January 1999 and April 2003. METHODS: A total of 114 biopsy specimens from 88 living-related kidney transplantation recipients (performed between January 1999 to April 2003) were retrospectively analyzed. Patients received immunosuppression therapy based on calcineurin inhibitors and corticosteroid [tacrolimus (TAC) 33 and cyclosporin (CyA) 55]. Additionally, mycophenolate mofeteil (MMF) was used in 21 patients; DSG was used in seven patients; and anti-CD3 monoclonal antibody was used in 16 patients. We analyzed the degree of donor/recipient human leucocyte antigen (HLA) compatibility assessed by the number of HLA-A, -B, and -DR-mismatched antigens in 88 patients. The diagnosis of BKVN was made by the light microscopic examination and a positive immunohistochemical staining of anti-40 antibody in biopsy specimens. Patients were divided into two groups of group A (mild histological change) and group B (moderate or severe histological change) to determine the risk factors in different histological staging. The clinical course of two typical patients in different histological stage is described briefly to outline the risk factors of BKVN. RESULTS: We identified seven cases of BKVN (8.0%) from 88 transplanted patients. Significantly higher incidence of combination regimen consisting of TAC and MMF in BKVN group was noticed compared with non-BKVN group (57.1% vs. 9.9%; p = 0.003). BKVN was associated with a significantly higher incidence of DSG administration compared with non-BKVN group (57.1% vs. 3.7%; p 相似文献   

肾移植术后BK病毒感染的危险因素分析

目的 分析肾移植术后BK病毒(BKV)感染发生的危险因素.方法 应用荧光实时定量PCR技术检测129例肾移植患者血液中BKV并行尿液细胞学检查,记录BKV-DNA阳性及阴性组患者性别、年龄、供肾冷缺血时间,术前血液透析时间、急性排斥反应、是否发生移植肾功能延迟恢复、免疫抑制剂方案、合并其他病毒感染等指标.应用二项多元逻辑回归法分析肾移植术后BKV感染发生的危险因素.结果 129例患者血中BKV-DNA阳性20例(15.5%).阴性109例(84.5%);BKV-DNA阳性患者尿细胞学检测Decoy细胞阳性15例,尿Decoy细胞阳性率与血BKV-DNA阳性率之间有明显的相关性(r=0.428,P<0.01).回归分析结果 显示:供肾冷却血时间(χ~2=9.243,95%CI:1.099～1.545,P<0.05)、患者术前透析时间(χ~2=7.599,95%CI:1.038～1.243,P<0.05)、是否为亲体供肾(χ~2=4.150,95%CI:0.012～0.070,P<0.05)为BKV感染的危险因素.结论 荧光实时定量PCR及尿细胞学检查可以作为肾移植术后BKV感染的筛查指标;供肾冷缺血时间长、术前血液透析时间长、尸体供肾均可增加患者术后BKV感染的风险.     

BK polyomavirus in solid organ transplantation—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

The present AST‐IDCOP guidelines update information on BK polyomavirus (BKPyV) infection, replication, and disease, which impact kidney transplantation (KT), but rarely non‐kidney solid organ transplantation (SOT). As pretransplant risk factors in KT donors and recipients presently do not translate into clinically validated measures regarding organ allocation, antiviral prophylaxis, or screening, all KT recipients should be screened for BKPyV‐DNAemia monthly until month 9, and then every 3 months until 2 years posttransplant. Extended screening after 2 years may be considered in pediatric KT. Stepwise immunosuppression reduction is recommended for KT patients with plasma BKPyV‐DNAemia of >1000 copies/mL sustained for 3 weeks or increasing to >10 000 copies/mL reflecting probable and presumptive BKPyV‐associated nephropathy, respectively. Reducing immunosuppression is also the primary intervention for biopsy‐proven BKPyV‐associated nephropathy. Hence, allograft biopsy is not required for treating BKPyV‐DNAemic patients with baseline renal function. Despite virological rationales, proper randomized clinical trials are lacking to generally recommend treatment by switching from tacrolimus to cyclosporine‐A, from mycophenolate to mTOR inhibitors or leflunomide or by the adjunct use of intravenous immunoglobulins, leflunomide, or cidofovir. Fluoroquinolones are not recommended for prophylaxis or therapy. Retransplantation after allograft loss due to BKPyV nephropathy can be successful if BKPyV‐DNAemia is definitively cleared, independent of failed allograft nephrectomy.     

Treatment for BK virus: incidence, risk factors and outcomes for kidney transplant recipients in the United States

There has been a notable rise of BK virus among kidney transplant recipients. Single-center reports have identified risk factors for development of BK virus. However, there has not been an assessment of risk factors and incidence of this complication at a national level. This study utilized newly collected follow-up information from the national SRTR database to investigate incidence, risk factors and outcomes for solitary kidney transplant recipients associated with treatment for BK virus (TBKV) from 2004 to 2006. Logistic and Cox models were utilized to assess risk factors and evaluate graft survival associated with TBKV. Incidence of TBKV was 1.6% at 6 months and 2.6% at 1 year following transplantation. Patients with and without TBKV at 6 months had 79% and 90% 3-year overall graft survival respectively. Risk factors included advanced donor age, pediatric, African American and male recipients, human leukocyte antigen-mismatching and tacrolimus and thymoglobulin induction as baseline immunosuppression. Acute rejection episodes were more frequent prior to and following TBKV. TBKV is a common and rising incidence, varies based on transplant characteristics and should be included as a safety endpoint in studies investigating immunosuppressive protocols. Careful monitoring and further understanding of disease etiology and treatment strategies are needed.     

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。     

BK virus nephropathy in renal transplant recipients

BK virus nephropathy (BKVN) occurs in up to 10% of renal transplant recipients and can result in graft loss. The reactivation of BK virus in renal transplant recipients is largely asymptomatic, and routine surveillance especially in the first 12–24 months after transplant is necessary for early recognition and intervention. Reduced immunosuppression and anti‐viral treatment in the early stages may be effective in stopping BK virus replication. Urinary decoy cells, although highly specific, lack sensitivity to diagnose BKVN. Transplant biopsy remains the gold standard to diagnose BKVN, good surrogate markers for surveillance using quantitative urinary decoy cells, urinary SV40 T immunochemical staining or polyoma virus‐Haufen bodies are offered by recent studies. Advanced BKVN results in severe tubulo‐interstitial damage and graft failure. Retransplantation after BKVN is associated with good outcomes. Newer treatment modalities are emerging.