Incidence of polyomavirus-nephropathy in renal allografts: influence of modern immunosuppressive drugs

Mengel, Michael; Marwedel, Magali; Radermacher, Jörg; Eden, Gabriele; Schwarz, Anke; Haller, Hermann; Kreipe, Hans

doi:10.1093/ndt/gfg072

Cited by 221 publications

(240 citation statements)

References 19 publications

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“…Following an approximately 40% reduction in overall immunosuppression and a 70% reduction in CNI exposure, 9 of 25 subjects experienced graft loss in a median follow-up period of 8 mo, with evidence that CNI reduction correlated with a slower rate of decline of GFR (20). Although suboptimal, these outcomes are still generally better than smaller series reported in the literature (3,23). In our study, the Withdrawal cohort fared better than these series, with a 71.6% probability of graft survival at 2 yr, while the Reduction cohort fared worse, with 37.4% graft survival probability at 2 yr, consistent with the hypothesis that outcomes of BKVAN are correlated with the degree of remaining immunosuppression.…”

Section: Discussionmentioning

confidence: 97%

Aggressive Immunosuppression Minimization Reduces Graft Loss Following Diagnosis of BK Virus-Associated Nephropathy

Weiss¹,

Gralla²,

Chan³

et al. 2008

Clinical Journal of the American Society of Nephrology

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Results: Of 910 kidney transplants, 35 (3.8%) cases of BKVAN were diagnosed at a median of 15 months after transplant (range, 5.5 to 90 months after transplant), 16 (46%) of which progressed to graft failure at a median of 11 months (range, 2 to 36 months) after diagnosis. Depleting antibody induction was a significant risk factor for graft loss on univariate analysis, whereas early drug withdrawal (<1 mo following diagnosis) protected against graft loss. On multivariate analysis, these findings were independent predictors of graft outcomes. Additionally, when patients were comanaged by referring nephrologists and the transplant center before the diagnosis of BKVAN, the risk of graft loss was 11-fold higher (P ‫؍‬ 0.03) than if patients were managed solely by the transplant center.Conclusions: Increased awareness and early diagnosis of BKVAN, with aggressive tapering of immunosuppression once established, is critical to preserve kidney graft function. Early drug withdrawal to low-dose two-drug therapy maintenance may be preferable to a general reduction of agents.

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Section: Discussionmentioning

confidence: 97%

Aggressive Immunosuppression Minimization Reduces Graft Loss Following Diagnosis of BK Virus-Associated Nephropathy

Weiss¹,

Gralla²,

Chan³

et al. 2008

Clinical Journal of the American Society of Nephrology

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“…The re-emergence of polyomavirus allograft nephropathy (PVAN) has been amply documented in many centers (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). The specific factors that influence outcome are not known, but graft loss has been attributed to a late diagnosis of PVAN in kidneys already showing irreversible tissue damage (scarring) (7).…”

Section: Introductionmentioning

confidence: 99%

Histological Patterns of Polyomavirus Nephropathy: Correlation with Graft Outcome and Viral Load

Drachenberg¹,

Papadimitriou²,

Hirsch

et al. 2004

American Journal of Transplantation

372

390

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“…Epidemiological studies suggest that the most significant cofactor leading to PVN is the degree of immunosuppression. The rise in PVN diagnoses is directly correlated to the increased use of the more potent anti-rejection drugs, tacromilus and mycophenolate mofetil (9,10). Currently, a reduction of immunosuppressive therapy is effectively used to decrease viral replication in PVN patients suggesting that a functional immune system is critical in controlling BKV replication and pathology (11).…”

mentioning

confidence: 99%

Human α-Defensins Inhibit BK Virus Infection by Aggregating Virions and Blocking Binding to Host Cells

Dugan

Maginnis

Jordan

et al. 2008

Journal of Biological Chemistry

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BK virus (BKV) is a polyomavirus that establishes a lifelong persistence in most humans and is a major impediment to success of kidney grafts. The function of the innate immune system in BKV infection and pathology has not been investigated. Here we examine the role of antimicrobial defensins in BKV infection of Vero cells. Our data show that ␣-defensin human neutrophil protein 1 (HNP1) and human ␣-defensin 5 (HD5) inhibit BKV infection by targeting an early event in the viral lifecycle. HD5 treatment of BKV reduced viral attachment to cells, whereas cellular treatment with HD5 did not. Colocalization studies indicated that HD5 interacts directly with BKV. Ultrastructural analysis revealed HD5-induced aggregation of virions. HD5 also inhibited infection of cells by other related polyomaviruses. This is the first study to demonstrate polyomavirus sensitivity to defensins. We also show a novel mechanism whereby HD5 binds to BKV leading to aggregation of virion particles preventing normal virus binding to the cell surface and uptake into cells.BK virus is a member of the polyomaviridae family. Polyomaviruses are small (40 -50 nm in diameter), non-enveloped, double-stranded DNA viruses that cause tumors in some species outside of their natural host range (1). BKV infects ϳ80 -90% of the human population and establishes a lifelong persistence within epithelial cells of the urinary tract (2, 3). Although BKV infection remains asymptomatic throughout the lifetime of most humans, immunocompromised individuals are susceptible to BKV-induced disease. Reactivation of BKV has been linked to hemorrhagic cystitis in bone marrow transplant recipients and is the etiological agent of polyomavirus-induced nephropathy (PVN), 2 a complication found in 5% of kidney transplant recipients (4, 5). In PVN, BKV induces interstitial nephritis resulting in graft destruction and leads to transplant failure in ϳ50% of diagnosed cases (6, 7). BKV reactivation causes a serious viral infection after renal transplantation and is a significant obstacle to the success of kidney grafts.The factors that contribute to BKV-induced disease are largely unknown. As only a subset of kidney transplant recipients develop PVN, this raises the question of what unique factors are present in these situations for pathogenesis to ensue? The factors that contribute to PVN likely comprise multiple conditions that involve the virus, the host, and the graft. Some risk factors for the development of PVN include male gender, older age, and higher number of HLA mismatches (7, 8). Epidemiological studies suggest that the most significant cofactor leading to PVN is the degree of immunosuppression. The rise in PVN diagnoses is directly correlated to the increased use of the more potent anti-rejection drugs, tacromilus and mycophenolate mofetil (9, 10). Currently, a reduction of immunosuppressive therapy is effectively used to decrease viral replication in PVN patients suggesting that a functional immune system is critical in controlling BKV replication and pathology (11). ...

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Incidence of polyomavirus-nephropathy in renal allografts: influence of modern immunosuppressive drugs

Abstract: PV-nephropathy is a rare but serious complication after renal transplantation. A small group of patients under intensive immunosuppression comprising tacrolimus in combination with mycophenolate mofetil has a significantly increased risk of acquiring this deleterious complication.

Cited by 221 publications

References 19 publications

Aggressive Immunosuppression Minimization Reduces Graft Loss Following Diagnosis of BK Virus-Associated Nephropathy

Aggressive Immunosuppression Minimization Reduces Graft Loss Following Diagnosis of BK Virus-Associated Nephropathy

Histological Patterns of Polyomavirus Nephropathy: Correlation with Graft Outcome and Viral Load

Human α-Defensins Inhibit BK Virus Infection by Aggregating Virions and Blocking Binding to Host Cells

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