Retransplantation in patients with graft loss caused by polyoma virus nephropathy

Ramos, Emilio; Vincenti, Flavio; Lü, Wei; Shapiro, Ron; Trofe, Jennifer; Stratta, Robert J.; Jonsson, Johann; Randhawa, Parmjeet; Drachenberg, Cinthia B.; Papadimitriou, John C.; Weir, Matthew R.; Wali, Ravinder K.

doi:10.1097/01.tp.0000095898.40458.68

Cited by 81 publications

(49 citation statements)

References 12 publications

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“…Ramos et al (69) reported successful repeat transplantation in nine of 10 patients without recurrent BKVN. Womer et al (68) recently reported successful repeat transplantation in two patients despite active viremia.…”

Section: Short-and Long-term Graft Survivalmentioning

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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Section: Short-and Long-term Graft Survivalmentioning

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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“…Tubulointerstitial damage from direct and indirect effects of the virus and rejection after immunosuppression reduction lead to early graft loss or chronic dysfunction (46,48,51,53,80,86,94,95,124). In recipients who have advanced kidney disease or who have returned to dialysis from BKV nephropathy, retransplantation has been successful (125)(126)(127)(128)(129)(130). In most cases, transplant nephrectomy and/or studies to confirm no active viral replication have been performed.…”

Section: Retransplantationmentioning

confidence: 99%

BK Virus Nephropathy and Kidney Transplantation

Bohl

Brennan

2007

Clinical Journal of the American Society of Nephrology

222

175

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Nephropathy from BK virus (BKV) infection is an evolving challenge in kidney transplant recipients. It is the consequence of modern potent immunosuppression aimed at reducing acute rejection and improving allograft survival. Untreated BKV infections lead to kidney allograft dysfunction or loss. Decreased immunosuppression is the principle treatment but predisposes to acute and chronic rejection. Screening protocols for early detection and prevention of symptomatic BKV nephropathy have improved outcomes. Although no approved antiviral drug is available, leflunomide, cidofovir, quinolones, and intravenous Ig have been used. Retransplantation after BKV nephropathy has been successful.Clin J Am Soc Nephrol 2: S36 -S46, 2007. doi: 10.2215/CJN.00920207 P olyomavirus infection in kidney transplant recipients is of increasing interest and research. Although the two human polyomaviruses, BK virus (BKV) and JC virus (JCV), were reported in 1971 (1,2), their influence and importance were limited. The emergence of polyomavirus nephropathy has coincided with the use of new potent immunosuppressive medications (3,4). It is usually associated with BKV, affects up to 8% of recipients, and frequently results in allograft loss or permanent dysfunction (5). It presents as an asymptomatic gradual rise in creatinine with a tubulointerstitial nephritis that mimics rejection, producing a treatment dilemma. The decrease in immunosuppression that is needed to treat infection is opposite to the increases that are needed to treat rejection.Two studies in kidney transplant recipients who were treated with prednisone and azathioprine in the early 1980s have provided the foundation for much of our current understanding of polyomaviruses in transplant recipients. Hogan et al. (6) and Gardner et al. (7) found that the pretransplantation seroprevalence was 80 to 88% for BKV and 54 to 55% for JCV. The posttransplantation rates of polyomavirus infection were 18 to 44% for BKV and 30 to 35% for JCV. Most polyomavirus infections were asymptomatic and occurred within the first 3 mo after transplantation. BKV infection was associated with a rising creatinine. More than 20 yr ago, Gardner et al. (7) warned, "The detection of polyomavirus infection is important as increased immunosuppression needs to be avoided to prevent possible complications."

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“…Low-dose cidofovir has been used to treat BK nephropathy (143)(144)(145)(146). Renal toxicity may result, especially with calcineurin inhibitors, although it is unclear how much BK infection also contributes to the renal dysfunction.…”

Section: Bk Polyomavirusmentioning

confidence: 99%

“…Clinical studies are needed to further evaluate the efficacy of cidofovir in the treatment of BK nephropathy. Successful retransplantation has been achieved in patients with failed allografts, usually at least 6 to 12 mo after cessation of immune suppression (144,147). Leflunomide and derivatives and fluoroquinolone antimicrobials are under investigation for BK nephropathy.…”

Section: Bk Polyomavirusmentioning

confidence: 99%

Viral Infection in the Renal Transplant Recipient

Kotton

Fishman²

2005

Journal of the American Society of Nephrology

200

181

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Viruses are among the most common causes of opportunistic infection after transplantation and the most important. The risk for viral infection is a function of the specific virus encountered, the intensity of immune suppression used to prevent graft rejection, and other host factors governing susceptibility. Viral infection, both symptomatic and asymptomatic, causes the "direct effects" of invasive disease and "indirect effects," including immune suppression predisposing to other opportunistic infections and oncogenesis. Rapid and sensitive microbiologic assays for many of the common viruses after transplantation have replaced, for the most part, serologic testing and in vitro cultures for the diagnosis of infection. Furthermore, quantitative molecular tests allow the individualization of antiviral therapies for prevention and treatment of infection. This advance is most prominent in the management of cytomegalovirus, Epstein-Barr, hepatitis B, and hepatitis C viruses. Diagnostic advances have not been accompanied by the development of specific and nontoxic anti-viral agents or effective antiviral vaccines. Vaccines, where available, should be given to patients as early as possible and well in advance of transplantation to optimize the immune response. Studies of viral latency, reactivation, and the cellular effects of viral infection will provide clues for future strategies in prevention and treatment of viral infections.

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Retransplantation in patients with graft loss caused by polyoma virus nephropathy

Cited by 81 publications

References 12 publications

BK Virus Nephritis after Renal Transplantation

BK Virus Nephritis after Renal Transplantation

BK Virus Nephropathy and Kidney Transplantation

Viral Infection in the Renal Transplant Recipient

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