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

Drachenberg, Cinthia B.; Papadimitriou, John C.; Hirsch, Hans H.; Wali, Ravinder K.; Crowder, Clinton D.; Nogueira, Joseph M.; Cangro, Charles B.; Mendley, Susan R.; Mian, Ayesa; Ramos, Emilio

doi:10.1046/j.1600-6143.2004.00603.x

Cited by 358 publications

(437 citation statements)

References 33 publications

(78 reference statements)

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“…High titers in urine and plasma can be considered as predictive markers for BKV-associated nephropathy. The proposed threshold for viruria as a predictive value for BKVAN is >2.5Eþ07 BKV copies/ ml, and the viremic threshold is >1.6Eþ04 BKV copies/ ml [Drachenberg et al, 2004[Drachenberg et al, , 2007Bressollette-Bodin et al, 2005;Funk et al, 2006;Viscount et al, 2007;Costa et al, 2008]. The reasons for the reactivation of BKV are not well understood.…”

Section: Introductionmentioning

confidence: 99%

Mutations in the BC‐loop of the BKV VP1 region do not influence viral load in renal transplant patients

Krautkrämer

Klein

Sommerer

et al. 2008

Journal of Medical Virology

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The reactivation and replication of the BK polyomavirus (BKV) leading to BKV-associated nephropathy (BKVAN) is one of the major complications in renal transplantation patients. BKV isolates were classified into four subtypes (I-IV) based on genotype variations within the VP1-coding region. The type-specific amino acid differences cluster within the BC-loop of the major capsid protein VP1. As demonstrated in vitro, mutations in this region also play a role in the infectivity, attachment and stability of viral particles. Therefore, we analyzed the prevalence of BC-loop mutations in isolates of kidney transplant patients and compared their viral load in the urine. The VP1 subtyping regions of BKV isolates obtained from urine samples of 45 renal transplant patients were sequenced. The phylogenetic analysis of these sequences revealed that subtype I (66.67%) is the most prevalent genotype. The remaining isolates belong to subtype IV (33.33%). A high frequency of changes to specific amino acids within the BC-loop was identified among the BKV isolates from renal transplant patients. Patients with BKVAN exhibited a higher viral replication than patients without nephropathy. Although titers of isolates of subtype I were higher than titers of subtype IV isolates, the difference did not reach statistical significance. In addition, amino acid changes in the BC-loop did not influence the viral load and the incidence of BKVAN. These in vivo results demonstrate that high replication rates which serve as a predictive marker for BKVAN are not caused by altered receptor binding or affinity via mutated BC-loops.

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Section: Introductionmentioning

confidence: 99%

Mutations in the BC‐loop of the BKV VP1 region do not influence viral load in renal transplant patients

Krautkrämer

Klein

Sommerer

et al. 2008

Journal of Medical Virology

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“…Although the biopsy findings at diagnosis are proposed to be a predictive tool for assessing prognosis (18,19), quantitative assessments of viral load at diagnosis have generally not been predictive of outcomes. To date, there has not been an assessment of clinical risk factors for disease progression or a comparison of immunosuppression withdrawal strategies.…”

mentioning

confidence: 99%

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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“…All of these risk factors agree with a lack of specific CD4 þ and CD8 þ T cell-mediated immune control of BKV, leading to uncontrolled viral replication, increased BKV early gene expression and enhanced cytopathic effects in the allograft. In contrast with the deleterious consequences of other viruses for allograft function by immunomodulatory effects, the mechanism of injury produced by BKV is the effect of direct renal epithelial tubular cell invasion and necrosis (109,110). BKV replication appears to induce the production of proinflammatory and profibrotic cytokines (e.g.…”

Section: Type Of Organ Transplantmentioning

confidence: 99%

The Impact of Infection on Chronic Allograft Dysfunction and Allograft Survival After Solid Organ Transplantation

Martín-Gandul

Mueller

Pascual

et al. 2015

American Journal of Transplantation

130

103

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Infectious diseases after solid organ transplantation (SOT) are a significant cause of morbidity and reduced allograft and patient survival; however, the influence of infection on the development of chronic allograft dysfunction has not been completely delineated. Some viral infections appear to affect allograft function by both inducing direct tissue damage and immunologically related injury, including acute rejection. In particular, this has been observed for cytomegalovirus (CMV) infection in all SOT recipients and for BK virus infection in kidney transplant recipients, for community-acquired respiratory viruses in lung transplant recipients, and for hepatitis C virus in liver transplant recipients. The impact of bacterial and fungal infections is less clear, but bacterial urinary tract infections and respiratory tract colonization by Pseudomonas aeruginosa and Aspergillus spp appear to be correlated with higher rates of chronic allograft dysfunction in kidney and lung transplant recipients, respectively. Evidence supports the beneficial effects of the use of antiviral prophylaxis for CMV in improving allograft function and survival in SOT recipients. Nevertheless, there is still a need for prospective interventional trials assessing the potential effects of preventive and therapeutic strategies against bacterial and fungal infection for reducing or delaying the development of chronic allograft dysfunction.

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

Abstract: Polyomavirus-associated nephropathy (PVAN) is

Cited by 358 publications

References 33 publications

Mutations in the BC‐loop of the BKV VP1 region do not influence viral load in renal transplant patients

Mutations in the BC‐loop of the BKV VP1 region do not influence viral load in renal transplant patients

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

The Impact of Infection on Chronic Allograft Dysfunction and Allograft Survival After Solid Organ Transplantation

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