Prospective Evaluation of BK Virus DNAemia in Renal Transplant Patients and Their Transplant Outcome

Basse, Grégoire; Mengelle, Catherine; Kamar, Nassim; Guitard, Joëlle; Ribes, David; Esposito, Laure; Rostaing, Lionel

doi:10.1016/j.transproceed.2006.11.001

Cited by 38 publications

(45 citation statements)

References 17 publications

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“…33 Besides, it is possible to treat BKAN successfully at its early stages. 34 We believe that the introduced noninvasive diagnostic scheme for periodic assessment of urine cytology and urine and plasma PCR can serve not only for monitoring BKAN 35,36 but also for diagnostic and prognostic purposes.…”

Section: Discussionmentioning

confidence: 99%

Human Polyomavirus BK (BKV) Reactivation Among Bulgarian Renal-Allograft Patients

Slavov

Kalvatchev

Simeonov

et al. 2008

Laboratory Medicine

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Section: Discussionmentioning

confidence: 99%

Human Polyomavirus BK (BKV) Reactivation Among Bulgarian Renal-Allograft Patients

Slavov

Kalvatchev

Simeonov

et al. 2008

Laboratory Medicine

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“…A strategy for preemptive decrease in immunosuppression is backed by data suggesting that the presence of viruria predates viremia, which in turn predates the detection of clinical renal disease and histologic evidence of BKVN (14,34,38,65,66). Preemptive reduction in immunosuppressive therapy for those with significant viremia has substantially lowered the prevalence of BKVN at our center (62).…”

Section: Preventionmentioning

confidence: 99%

BK Virus Nephritis after Renal Transplantation

Dall

Hariharan²

2008

Clinical Journal of the American Society of Nephrology

124

108

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BK virus nephritis is an increasing problem and is posing a threat to improving renal transplant graft survival. The pathogenesis of this condition remains to be investigated. Higher prevalence of BK virus infection in recent years has been correlated with declining acute rejection rates and the use of potent immunosuppressive agents. Patients with this infection usually have asymptomatic viremia and/or nephritis with or without worsening of renal function. The diagnosis of this disease is based on detecting the virus or its effects in urine, blood, and renal tissue. In the past, approximately 30 to 60% of patients with BK virus nephritis developed graft failure. In recent years, the combination of early detection, prompt diagnosis, and therapies including preventive measures have resulted in better outcomes.Clin J Am Soc Nephrol 3: S68 -S75, 2008. doi: 10.2215/CJN.02770707 T he term "BK" originated from a patient's initials, in whom it was first detected in 1971 (1). The next observed case was published by investigators from the University of Pittsburgh in 1995 (2). Since then, there have been numerous reports on BK virus (BKV) infection and BKV nephritis (BKVN) in renal transplant recipients (3-8). The factors that lead to its higher incidence in recent years and its pathogenesis remain poorly understood. Increased awareness, the ability of clinicians to recognize this infection, and the availability of better diagnostic tools may be contributing to higher prevalence of this disease in recent years (9). The use of potent immunosuppressive combination therapy with mycophenolate mofetil (MMF) and tacrolimus has been thought to play a role in the occurrence of this infection (10 -12); however, this infection is also seen with cyclosporine and sirolimus therapy (13). Prevalence of BK viremia within 1 yr after transplantation is approximately 20% (6,14) and is higher than the prevalence of acute rejection of 13% reported for the year 2003 (15). This review discusses the pathogenesis, clinical features, therapy, and the short-and long-term renal graft survival with reference to BKV infection. Pathogenesis of BKV InfectionPotential factors that contribute to the pathogenesis of BKVN may be a combination of (1) ineffective immune surveillance by the host T lymphocytes, (2) the absence of previous humoral immunity to BKV, (3) molecular sequence variability of the virus, and (4) alloimmune activation. These details have been reviewed elsewhere (9) and are also discussed next.Cellular immunity in the development and clearance of BKV infection has remained an important area of research in the past several years. Comoli et al. (16) showed a reduction in BKVspecific IFN-␥-secreting lymphocytes in patients with BKVN compared with healthy control subjects. The authors noted an increase in patient IFN-␥-secreting lymphocyte levels with reduction in immunosuppressive therapy similar to that of their healthy counterparts (16). Prosser et al. (17) used an IFN-␥ enzyme-linked immunosorbent spot (ELISPOT) assay to measure cellula...

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“…Suggested target concentrations are based on in vitro IC 50 concentrations, and limited previous studies (7,13,17). The proposed therapeutic goal of A77 1726 serum concentrations is .40 mg/ml (7,(18)(19)(20). Potentially serious adverse effects associated with leflunomide therapy include hepatotoxicity, thrombocytopenia, leukopenia, and hemolytic anemia (18).…”

Section: Introductionmentioning

confidence: 99%

Leflunomide Efficacy and Pharmacodynamics for the Treatment of BK Viral Infection

Krisl¹,

Taber²,

Pilch³

et al. 2012

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives BK virus is an infection in kidney transplantation patients jeopardizing graft survival. Unfortunately, there is no consensus on treatment of BK viremia and nephropathy. Leflunomide has been studied for the treatment of BK viremia and nephropathy, but there are limited data on the utility of leflunomide therapeutic drug monitoring. This study aimed to determine if a pharmacodynamic relationship exists between BK viral load reduction and leflunomide metabolite, A77 1726, serum concentrations.Design, setting, participants, & measurements This study was a retrospective, single-center, longitudinal analysis of patients identified with BK viremia with or without nephropathy. Patients were grouped according to whether they received leflunomide. All BK viral PCR and A77 1726 concentrations were analyzed to determine pharmacodynamics, and were correlated with clinical outcomes.Results Of 76 patients identified, 52 received leflunomide therapy and 24 did not. Patients who received leflunomide were further analyzed according to A77 1726 concentrations and BK clearance; there was no difference in BK clearance. There was a lack of correlation between A77 1726 concentrations and log change in BK viral PCR concentration. Multivariate analysis demonstrated that mycophenolate mofetil discontinuation, BK viremia without nephropathy, and mean BK viral load were significantly associated with BK viral clearance; leflunomide use lacked this association.Conclusions Pharmacodynamic analysis revealed no association between A77 1726 concentrations and BK viral PCR reductions. Multivariate analysis demonstrated that leflunomide therapy was not associated with BK viral clearance. Randomized studies are needed to determine the utility of leflunomide for BK viremia and nephropathy.

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Prospective Evaluation of BK Virus DNAemia in Renal Transplant Patients and Their Transplant Outcome

Cited by 38 publications

References 17 publications

Human Polyomavirus BK (BKV) Reactivation Among Bulgarian Renal-Allograft Patients

Human Polyomavirus BK (BKV) Reactivation Among Bulgarian Renal-Allograft Patients

BK Virus Nephritis after Renal Transplantation

Leflunomide Efficacy and Pharmacodynamics for the Treatment of BK Viral Infection

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