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。     

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.     

Correlation between CYP3A5 gene polymorphism and BK virus infection in kidney transplant recipients

BackgroundCytochrome P450 3A5 (CYP3A5) includes two active genotypes, namely CYP3A5*1/*1 or *1/*3 with the fast metabolic activity and CYP3A5*3/*3 with slow metabolic. We retrospectively analyzed the correlation between CYP3A5 gene polymorphism and the susceptibility to the BK virus (BKV) infection in renal transplant recipients.MethodsAccording to the inclusion/ exclusion criteria, we selected 134 recipients who received kidney transplantation at the Renmin Hospital of Wuhan University from January 2019 to December 2019. Based on the pre-operative CYP3A5 sequencing results, 134 recipients were divided into two groups: those expressing the fast metabolic CYP3A5*1/*1 or *1/*3 genotype; and, those expressing slow metabolic CYP3A5*3/*3 genotype. These two recipient groups were then analyzed for the BKV infection rate with different metabolic types to establish the potential relationship between CYP3A5 gene polymorphism and BKV infection.ResultsThe overall incidence of BKV viruria was 37.3%, whereas BKV viremia was 4.5% among all 134 recipients. The fast metabolism group had 9.1% incidence of BKV viremia and 49.1% incidence of BKV viruria. In contrast, the slow metabolism group had only 1.3%incidence of BKV viremia (P = 0.031) with only 29.1% BKV viruria (P = 0.011). The incidence of low levels of urinary BKV in the fast metabolism group was higher than that in the slow metabolism group (P = 0.005), while no significant statistical difference in the incidence of high levels of urinary BKV and high and low levels of blood BKV.ConclusionAfter kidney transplantation, CYP3A5 gene polymorphism of recipients present a certain relationship with the occurrence of BKV infection, which may be of value for the prediction and prevention of BKV infection.     

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.     

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.     

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。     

Polyomavirus BK infection in Greek renal transplant recipients

BK polyoma virus associated nephropathy is increasingly recognized as an important cause of allograft dysfunction among renal transplant recipients. Herein we present the cases of two renal transplant recipients who developed progressive functional deterioration suspicious for BK polyoma virus involvement. One patient had been treated with mycophenolate mofetil (MMF), cyclosporine (CsA), and prednisolone (P), and the second patient with tacrolimus (Tac), MMF, and (P). Using quantitative real-time polymerase chain reactions for BK virus DNA, we monitored the content of BK virus in the blood to evaluate disease progression. The high BK virus load initially detected in the blood samples from these patients decreased in the patient who received MMF, CsA, and P after the reduction of immunosuppression, but not in the patient who was treated with Tac, MMF and P. In contrast to previous reports, our patients had not received treatment with anti-lymphocyte globulin (ALG) or monoclonal anti-CD3 antibody (OKT3) after transplantation. It is concluded that even in the absence of vigorous antirejection treatment, immunosuppressive therapy based on Tac and MMF may carry the risk of BK virus-associated nephropathy. Because BK virus specific antiviral therapy is not available, its course may be monitored by measuring the viral load in blood.     

Hepatitis C virus infection among kidney transplant recipients.

The extent of hepatitis C virus (HCV) infection among kidney recipients was investigated in 67 patients by testing for anti-HCV paired serum samples, collected at time of transplantation and during follow-up (average 32 +/- 20 months). Prevalence of anti-HCV at transplant time was 48%, and was related to the time on dialysis and to the amount of blood transfusions. Following transplantation, nine (28%) seropositive patients lost anti-HCV and five (14%), previously seronegative, seroconverted. Anti-HCV was found to be positive in 92% of the patients with chronic liver disease who were on hemodialysis, but in 56% in kidney recipients with chronic hepatitis. Anti-HCV was positive in 50% of patients with resolving hepatitis before transplantation, but only in 21% of those with acute hepatitis following transplantation. This study confirms the high risk of HCV infection among hemodialysis and kidney recipient populations, and also that HCV is closely related with the length of time the patient is on hemodialysis as well as the number of blood units transfused. HCV is the main cause of acute and chronic liver disease in hemodialysis patients and of chronic liver disease in kidney recipients, but does not clearly influence the survival of the allograft nor that of patients.     

Hepatitis E virus infection and rejection in kidney transplant recipients

BackgroundHepatitis E virus (HEV) infection has been associated with immune-mediated kidney diseases in developing countries. However, its relationship with kidney transplant outcomes has never been studied. We investigated the association between HEV infection and kidney graft rejection among kidney transplant recipients (KTRs).MethodsWe conducted a matched cohort and longitudinal study utilizing banked sera following kidney transplantation during 1988–2012. Studies with evidence of post-transplantation HEV infection were identified by positive ELISA tests (anti-HEV IgM or anti-HEV IgG seroconversion) or positive HEV PCR and matched to KTR controls with negative HEV ELISA and PCR tests in a 1:5 ratio by age, sex, crossmatch status, immunosuppression era, and time of HEV testing. Outcome data collected included time to first kidney graft rejection, transaminases, and glomerular filtration rates. Log-ranked test was used to analyze survival.ResultsOf 271 KTRs, 9 (3%) had evidence of post-transplantation HEV infection and were compared to 45 negative, matched controls. Median age at transplantation was 46 years. Kidney graft rejection was reported in 8 (89%) of cases and 21 (47%) of controls. Median time to first episode of kidney graft rejection was 17.4 months in cases and 30.8 months in controls (p = 0.029), with a higher hazard of developing kidney graft rejection in cases (HR = 3.23, 95% CI: 1.19–8.79). Lower mean glomerular filtration rates over time were observed in cases (35 mL/min/1.73m²) versus controls (42.4 mL/min/1.73m²) but did not reach significance (p = 0.24).ConclusionSubjects with evidence of post-transplantation HEV infection demonstrated earlier kidney graft rejection compared to controls.     

The high incidence of BK polyoma virus infection among renal transplant recipients in India

BK polyoma virus causes allograft dysfunction as a result of tubulo-interstitial nephritis in 2% to 5% of renal transplant recipients. The incidence of BK virus infection among renal transplant recipients in India is unknown. We used routine histologic examination, immunohistochemistry, and electron microscopy to retrospectively screen for BK polyoma virus in 414 renal allograft biopsy specimens from 321 transplant recipients presenting with allograft dysfunction. All patients had received a combination of cyclosporine, azathioprine, and prednisolone. A total of 30 biopsy specimens (9.3%) were positive for BK polyoma virus, suggesting a high incidence of this infection in Indian transplant recipients. BK virus infection coexisted with acute rejection in a majority of patients. This is the first report of this infection among Indian renal transplant recipients.     

BK polyoma virus nephropathy among Iranian renal transplant recipients

BACKGROUND: BK virus nephropathy (BKVN) is recognized as a cause of graft loss in renal transplant patients. The disorder may be related to the introduction of new, potent immunosuppressive regimens. We sought to assess the prevalence, outcome, and clinical characteristics of BKVN. MATERIALS AND METHODS: We retrospectively analyzed 160 specimens from episode biopsies. BKVN was diagnosed by light microscopic examination and positive immunohistochemical staining. RESULTS: Among 160 patients, 21 (13.1%) were diagnosed as BKVN. The mean interval between biopsy and transplantation was 13.6 +/- 10.67 months. There were no significant differences between BKVN patients and non-BKVN patients with respect to age, sex, interval between diagnosis and transplantation, cyclosporine blood level, and azathioprine versus mycophenolate mofetil immunosuppression. Graft loss occurred in 57.1% of BKVN versus 12.2% of non-BKVN subjects (P = .005). There was a significant difference between antilymphocyte globulin (ALG)- and non-ALG-treated groups with respect to the incidence of BKVN (6.6% in non-ALG versus 19% in ALG groups; P < .01). BKVN was diagnosed by immunohistochemistry in 61% of specimens with acute rejection according to light microscopic evaluation. CONCLUSIONS: This is the first report of BKVN in Iranian renal allograft recipients. In our hospital, the prevalence of BKVN was higher than that previously reported for non-Iranian recipients. BKVN had a negative impact on graft survival.     

The prevalence of BK polyomavirus infection in outpatient kidney transplant recipients followed in a single center

Abstract: Background: BK polyomavirus (BKV) infection has emerged as an important cause of renal allograft loss. There is no proven therapy, and much basic clinical information is still lacking. Methods: We serially enrolled 95 outpatient renal transplant recipients (43% of whom were African American) in a single center cross‐sectional screening study to determine the prevalence of BKV infection by whole blood polymerase chain reaction, and the prevalence of decoy cells by urinalysis and cytology. We also investigated the demographic and clinical factors associated with BKV infection, and the performance of urinalysis for decoy cells as a screening test for BKV infection. Results: The point prevalence of active BKV viremia was 7.4%. When subjects without active viremia but with a history of viremia and/or nephropathy were included, the overall prevalence was 15.8%. Urinary decoy cells were common, present in 50% of subjects at study entry. Urinalysis for decoy cells as a screen for BKV viremia had a sensitivity of 86%, specificity of 52%, positive predictive value of 13% and negative predictive value of 98%. Conclusions: Decoy cells on urinalysis were the only factor independently associated with an increased risk of BKV infection on multivariate analysis. Although associated with BKV infection on univariate analysis, thymoglobulin, mycophenolate mofetil, and tacrolimus use were not independently associated with BKV infection on multivariate analysis, neither were history of acute rejection, gender, race, nor cause of end‐stage renal disease.     

Polyoma BK virus reactivation in kidney and pancreas-kidney recipients

BK virus infection has become important factor affecting graft function in renal transplant recipients. One of the most important complication of BK infection is nephropathy in patients after renal transplantation. The aim of this study was to evaluate incidence of BK reactivation and nephropathy in our population of renal allograft recipients. One hundred twelve renal or pancreas-kidney allograft recipients were included for the 24 months follow-up. The incidence of BK nephropathy was 7.85% and viremia 27.96%. In the second study group there were 28 patients with graft function deterioration evaluated at the time of biopsy. In this group incidence of BK nephropathy was 7.1% and viral reactivation was diagnosed in 10.7% of patients. In our center, the incidence of BK nephropathy is the same as worldwide. The risk of BK virus replication is highest during first 15 months after the surgical procedure.     

Nocardial infection in immunosuppressed kidney transplant recipients

OBJECTIVE: Nocardiosis is a very rare, opportunistic infection caused by microorganisms of the genus Nocardia, and is associated with significant morbidity and mortality in kidney transplant patients receiving immunosuppressive therapy. MATERIAL AND METHODS: Since 1980, our Renal Transplant Unit has carried out 1239 kidney transplants, and five cases of Nocardia infection have occurred during this time. In this retrospective study, special consideration is given to clinical manifestations, treatment response (efficacy and side-effects) and the evolution of both the patient and the graft. Microbiological factors studied included biochemical profiles and antimicrobial sensitivity. RESULTS: Nocardiosis was observed in five men with a mean age of 49.2 years who had received immunosuppressive therapy (generally cyclosporin/azathioprine and prednisone) for a mean of 47.8 months (range 1-148 months). Four of the patients had good previous renal function. The clinical presentation of nocardiosis was as follows: pleuropulmonary pattern of infection, n = 3; subcutaneous abscess, n = 1; and fulminant multi-organ disseminated nocardiosis, n = 1. In all cases, direct observation using modified Ziehl-Neelsen staining proved positive, and in vitro culture revealed good sensitivity to trimethoprim-sulfamethoxazole and variable sensitivity to the other groups of antibiotics. Nocardia brasiliensis was isolated in two cases, and Nocardia asteroides in three. Two patients died, one due to multiple organ involvement and the other due to acute respiratory failure associated with severe hepatopathy caused by hepatitis C virus. The remaining cases improved. CONCLUSION: A low incidence of nocardiosis following kidney transplantation was observed. Fatal cases occurred in patients with bacteremia and serious comorbid medical conditions, in whom early diagnosis and specific treatment was required.     

Hepatitis G virus infection in chronic dialysis patients and kidney transplant recipients

Background: The cloning of the hepatitis G virus (HGV), a novel RNA virus of the Flaviviridae family, has been very recently developed. HGV is known to be parenterally transmitted and has been detected in several patients with cryptogenic hepatitis. However, little information exists about the epidemiology of HGV infection in renal patients. We studied 178 chronic dialysis patients and 11 renal transplant individuals to evaluate prevalence risk factors and clinical manifestations of HGV infection in this population. Method: Hepatitis G virus infection has been detected by a modified PCR technology which incorporates digoxigenin-labelled nucleotides into the amplicon. Primers from the non-coding region and the NS-5 region of HGV are utilized for a single round amplification. Using a streptavidin surface and a biotin-labelled capture probe the labelled nucleic acid is bound through the capture probe to the surface, and the amplified nucleic acid is detected using antibody to digoxigenin. Results: HGV RNA was detected in 6% of chronic haemodialysis (HD) patients (11/172), 36% of renal transplant recipients (4/11), and 17% (1/6) of patients on peritoneal dialysis treatment (CAPD). There were no significant differences between HGV positive and negative patients on chronic HD treatment with regard to several demographic, biochemical and virological features. However, the frequency of anti-HCV antibody was significantly higher in HGV-positive than HGV-negative patients (9/11 (82%) vs 51/161 (32%), P=0.006). In the whole group of HGV RNA-positive patients, 78% (11/14) had a history of blood transfusion requirements, 14/16 (87%) had co-infection with HCV, and 1 (6%) had co-infection with HBsAg. There was no significant association between HCV genotypes and HGV RNA positivity. Six (27.5%) of 16 HGV RNA-positive patients showed raised aminotransferase values in serum. Conclusion: Patients on maintenance dialysis and kidney transplant recipients are at increased risk of HGV infection; HGV is very frequently associated to hepatitis C co-infection, regardless of HCV genotype. HGV may be transmitted by blood transfusions but transmission routes other than transfusion are possible; 37.5% of HGV RNA-positive patients showed raised serum amoinotransferase levels. Further investigations are necessary to clarify the role of HGV infection in the development of liver disease in this clinical setting.     

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.