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Abstract BK virus nephropathy in kidney transplantation is widely recognized as an important cause of graft dysfunction and loss. In the case of transplants of organs other than kidney, BK virus nephropathy in native kidneys has been recognized as a cause of chronic kidney disease, which is related with immunosuppression; however, the diagnosis is usually late because the renal dysfunction is attributed to other causes, such as toxicity by anticalcineurinic drugs, interstitial nephritis due to medications, hemodynamic changes, diabetes, hypertension, etc. We report a case of BK virus nephropathy in a patient who underwent heart transplantation due to peripartum cardiomyopathy. The kidney biopsy reported active chronic tubulointerstitial nephritis associated with late stage polyomavirus nephritis and the blood viral load for BK virus was positive (logarithm 4.5). The immunosuppressive treatment was reduced, and after two years of follow-up, the patient had stable renal function with a serum creatinine of 2.5 mg/dL (GFR of 23.4 mL/min/1.73m2). We recommend that the BK virus be considered as a cause of renal dysfunction in heart transplant recipients, with the aim of detecting its replication in time to reduce immunosuppressive therapy before irreversible compromise of renal function may manifest.
Resumo A nefropatia pelo vírus BK no transplante renal é amplamente reconhecida como uma importante causa de disfunção e perda do enxerto. No caso de transplantes de órgãos que não sejam rins, a nefropatia pelo vírus BK em rins nativos tem sido reconhecida como uma causa de doença renal crônica, que está relacionada com imunossupressão; entretanto, o diagnóstico é geralmente tardio porque a disfunção renal é atribuída a outras causas, tais como toxicidade por drogas anticalcineurínicas, nefrite intersticial devido a medicamentos, alterações hemodinâmicas, diabetes, hipertensão, etc. Relatamos um caso de nefropatia pelo vírus BK em um paciente que foi submetido a transplante cardíaco devido à cardiomiopatia periparto. A biópsia renal relatou nefrite túbulo-intersticial crônica ativa associada à nefrite por poliomavírus em estágio avançado e a carga viral sanguínea para o vírus BK foi positiva (logaritmo 4,5). O tratamento imunossupressor foi reduzido, e após dois anos de acompanhamento, o paciente apresentava função renal estável com creatinina sérica de 2,5 mg/dL (TFG de 23,4 mL/min/1,73m2). Recomendamos que o vírus BK seja considerado como uma causa de disfunção renal em receptores de transplante cardíaco, com o objetivo de detectar sua replicação a tempo de reduzir a terapia imunossupressora antes que um comprometimento irreversível da função renal possa se manifestar.
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Objective To investigate the relationship between the metabolic rate of tacrolimus (FK506) and BK virus infection early after renal transplantation. Methods Eighty recipients undergoing allogenic renal transplantation in Institute of Organ Transplantation of the 309thHospital of Chinese People's Liberation Army were recruited in this study. The polymorphism of cytochrome P450 (CYP) 3A5 gene was detected in 80 recipients. All patients were divided into fast metabolism group ( CYP3A5*1/*3 and CYP3A5*1/*1 genotypes, n=38) and slow metabolism group ( CYP3A5*3/*3 genotype, n=42) based on the gene detection results. The distribution of CYP3A5 genotypes in 80 recipients was analyzed. The metabolic rate [concentration/dose ratio (C/D value)] of FK506 was statistically compared between two groups. The incidence of BK virus infection events [BK viruria, BK viremia and BK virus nephropathy(BKVN)] within postoperative 6 months were compared between two groups. Results Among 80 recipients, 5 cases (6%) were detected with CYP3A5*1/*1 genotype, 33 (41%) with CYP3A5*1/*3 genotype, and 42 (53%) with CYP3A5*3/*3 genotype. Among the 160 alleles in 80 recipients, 117 CYP3A5*3 allele were identified, suggesting that the mutation rate of CYP3A5*3 allele was 73.1%. In the fast metabolism group, the C/D values at postoperative 1, 3, and 6 months were significantly lower than those in the slow metabolism group (all P<0.01). The incidence rates of BK viruria in the fast and slow metabolism groups were 37% and 29%, 18% and 2% for BK viremia, and 3% and 0 for BKVN, respectively. In the fast metabolism group, the incidence of BK virenia was significantly higher than that in the slow metabolism group (P=0.02). The incidence of BK viruria and BKVN did not significantly differ between two groups (both P>0.05). Conclusions According to the CYP3A5 genotyping outcomes, the recipients with a high metabolic rate of FK506 have a high risk of BK viremia early after renal transplantation.
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Objective To analyze the impairment of renal allograft function in renal transplant recipients caused by BK virus infection after renal transplantation. Methods Clinical data of 210 recipients who underwent allogenic renal transplantation and received BK virus monitoring regularly were analyzed retrospectively. The incidence of BK viruria, viremia and BK virus nephropathy (BKVN) after renal transplantation was summarized. The effect of BK virus infection on renal allograft function and prognosis of renal allograft function after the removement of BK virus were analyzed. Results Among the 210 recipients, there were 46 cases with pure viruria, 46 cases with viremia complicated with viruria and 7 cases with BKVN confirmed by pathological biopsy. The level of serum creatinine (Scr) in the recipients with viremia after renal transplantation was linearly related to BK viral load in urine and blood (r=0.594, 0.672, both P<0.01). The level of Scr increased significantly when BK viral load in blood of the recipients with viremia was found positive for the first time, and increased continuously after viremia sustained. And the level of Scr decreased slightly when blood viral load turned to negative after treatment, but still significantly higher than before virus infection. All the above differences were statistically significant (all P<0.05). Compared with the basic level, there was no significant difference in the level of Scr of recipients with pure viruria during positive viruria (all P>0.05). Conclusions It will impair the renal allograft function when BK viremia occurs after renal transplantation, and it is necessary to monitor viral infection regularly. Once the blood BK virus is found positive, it shall be implemented immediately to reduce the intensity of immunosuppression as the preferred clinical intervention.
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Objective To compare the effects of cyclosporine A (CsA) and tacrolimus (FK506) on BK virus infection after renal transplantation by retrospective clinical study.Methods The data of calcineurin inhibitor (CNI)-based immunosuppression and virus infection were collected in allograft renal transplantation recipients (n =135) from Jan.2014 to Dec.2015.According to the severity of the virus infection the recipients were divided into three groups:viruria,viremia and virus nephropathy.The difference in BK virus infection between FK506 and CsA was compared.Results A total of 135 cases of transplant recipients,postoperative were enrolled.The number of viruria recipients given FK506 and CsA was 41 cases (69.5％) and 18 cases (30.5％),and that of viremia recipients was 26 cases (86.7 ％) and 4 cases (13.3 ％).Statistical analysis showed that CNI immunosuppressive agents had a significant correlation with viremia only (P＜0.05).There was a positive correlation between FK506 and viremia (r =0.423,P =0.018),and CsA showed a negative correlation yet (r =-0.336,P =0.022).Conclusion Tacrolimus is independent risk factors for early BK viremia after kidney transplantation,and CsA may inhibit the progression of BK viremia.
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Objective To investigate the characteristics and manifestations of the different stages of BK virus infection in the recipients after renal transplantation.Methods A retrospective survey from January 2015 to December 2016 was done in our hospital.A total 135 recipients were included and accepted BK virus detection in 1,3,6,9,12,15 months respectively after renal transplantation.The prevalence of decoy cell,BK virus DNA load in urine and BK virus DNA load in blood was 56 cases (41.5％),9 cases (43.7％) and 30 cases (22.2％),5 cases of BK vims nephropathy confirmed by pathological biopsy (3.7％).At the same time,51 cases (37.8％) were combined with decoy cells and virus DNA load in urine.Positive decoy cells and negative BK virus DNA load in urine was 5 cases,and Positive BK virus DNA load in urine and negative decoy cells was 8 cases.The recipients were divided into positive group of urine decoy cell,positive group of urinary BK virus DNA load,and positive group of blood BK virus DNA load.Statistical correlation analysis was conducted on the laboratory test results of the 3 groups.Results The positive group of blood BK virus DNA load were detected the high level urine decoy cell count [median of 23/10HPF(2-48/10HPF)] and high level of urinary BK virus DNA load [4.52 × 106 copies/ml (6.51 × 103-7.89 × 109 copies/ml)],significantly higher than the positive group of decoy cells [8/10HPF(2-40/10HPF)] and the positive group of urine BK virus DNA load [4.56 × 105 copies/ml(5.62 × 103-7.89 ×109 copies/ml)] (P ＜ 0.05).The decoy cell count and urine DNA load has a significant linear correlation in viruria recipients,and the urinary BK DNA load and blood BK virus DNA load has the same significant 0.939 and 0.702 in 3 months,0.969 and 0.910 in 6 months,0.782 and 0.766 in 9 months,0.898 and 0.615 in 12 months after renal transplantation.Conclusions There is a linear correlation between decoy cell in urine,viruria and viremia,suggesting that the infection of BK virus in kidney transplant recipients is a continuous process.linear correlation in viremia recipients(P ＜ 0.05).The correlation coefficients at different time points were
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Objective To explore the clinical application experience of leflunomide in rescuing therapy of BK virus nephropathy (BKVN ) after renal transplantation in the case of ineffective treatment with reduction of immunosuppressant.Methods Four recipients with BKVN after renal transplantation were diagnosed at 1 35 th-737 th day after operation,with the pathological staging as following:2 cases in stage A1 ,1 case in stage B1 and 1 case in stage B2.For all recipients, leflunomide was used for rescuing therapy due to ineffective treatment with reduction of immunosuppressant for 0.5-3.0 months.Initially,50 mg/d of leflunomide was given continuously for 3 days,so as to reach therapeutic serum concentration,and then 20 mg/d of leflunomide was given for maintaining.The efficacy and safety were observed.Results After a follow-up for an average of 6 months (5-7 months),3 recipients with development of BKVN were controlled effectively,1 recipient (stage B2)with ineffective treatment.No obvious adverse reactions occurred during medication.Conclusions It is possible to slow down the development of BKVN and reduce the incidence of renal allograft loss by using leflunomide to conduct rescuing therapy of BKVN after renal transplantation in the case of ineffective treatment with reduction of immunosuppressant.Better effect can be achieved if early detection and diagnosis of BKVN are conducted as well as effective measures are taken timely in the early pathological stage.
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BACKGROUND: Although early monitoring of BK virus infection in renal transplant patients has led to improved outcomes over the past decade, it remains unclear whether monitoring for viremia is the best screening tool for BK virus nephropathy (BKVN). METHODS: We conducted a retrospective review of the medical records of 368 renal transplant recipients who had a minimum of 18 months of posttransplantation follow-up. The relationship between the presence of BK viruria and a composite end point of BK viremia/BKVN was established, and the predictive value of high-grade BK viruria for development of viremia/BKVN was determined. RESULTS: High grade of BK viruria was present in 110 (30.1%) of the renal transplant recipients. BK viremia/BKVN was present in 64 (17.4%) patients and was 50 times more likely to be present in patients with high-grade BK viruria. The risk of developing BK viremia/BKVN was 3 times higher in high-grade viruria patients, and viruria preceded viremia by nearly 7 weeks. CONCLUSION: The presence of high-grade viruria is an early marker for developing BK viremia/BKVN. Detection of high-grade viruria should prompt early allograft biopsy and/or preemptive reduction in immunosuppression.
Subject(s)
Humans , Allografts , Biopsy , BK Virus , Follow-Up Studies , Immunosuppression Therapy , Mass Screening , Medical Records , Retrospective Studies , Transplant Recipients , ViremiaABSTRACT
Methods: The BKV DNA load in urine and blood samples of 43 renal transplant recipients, who had received renal transplantation in 309 Hospital from Feb. 2012 to Feb. 2013, was determined at preoperative period and 0.5, 1, 3, 6, 9, 12 and 15 months after transplantation. Meanwhile, the biopsy of grafted kidney was performed in those patients with continuously elevated serum creatinine and those with higher BKV DNA load. Patients were divided into 3 groups as follows according to the test results: BK viruria group, BK viremia group and pathologically diagnosed BKVN group. Data of each group were then recorded, including gender, age, postoperative diabetes (PTDM), acute rejection (AR), delayed recovery of graft function (DGF), postoperative pulmonary infection, preoperative immune induction therapy, postoperative immunosuppressive regimen, and other information. The risk factors for postoperative BKV infection and BKVN were analyzed.
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Background: Polyomavirus nephropathy, also termed BK virus nephropathy, is an infectious complication after kidney transplantation, causing allograft failure. The state of immunosuppression of the patient is the principal risk for the infection. Most cases of BK virus nephropathy were associated with the use of potent immunosuppressive regimens like tacrolimus and mycophenolate mofetil. To the best of our knowledge, no patient with BK virus nephropathy has been reported in Southeast Asia.Objective: We report two cases of BK virus nephropathy in patients who received the immunosuppressive regimen of sirolimus with cyclosporine. We also review the literature regarding the pathogenesis, clinical manifestations, and treatment strategies.