BK Virus Infection in Transplant Recipients: An Overview and Update

Randhawa, Parmjeet; Brennan, Daniel C.

doi:10.1111/j.1600-6143.2006.01403.x

Cited by 188 publications

(164 citation statements)

References 35 publications

Supporting

Mentioning

152

Contrasting

Unclassified

Order By: Relevance

“…It has been widely recognized that latent polyoma virus infection is widespread in the general population but that a process of reactivation occurs in a significant proportion of kidneys that are subjected to the stresses of transplantation and exposed to the various immunosuppressive regimens that have been used in the past decade (16). Although the specific mechanisms of viral activation remain unknown, it is thought that infected cells elicit a host inflammatory reaction that is mediated by the cellular immune system and is manifest in tissues by an inflammatory infiltrate of lymphocytes and monocytes/macrophages, centered around tubules in which epithelial cells may demonstrate large intranuclear inclusions with a cytopathic effect that is characteristic of this type of viral infection ( Figure 2).…”

Section: Polyoma Virus Nephropathymentioning

confidence: 99%

Emerging Paradigms in the Renal Pathology of Viral Diseases

Alpers¹,

Kowalewska²

2007

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

This review considers recent information that illuminates pathogenetic mechanisms that involve three of the major viral infections that cause renal injury in the form of HIV-associated nephropathy, polyoma virus nephropathy, and hepatitis C virus-associated glomerulonephritis.Clin J Am Soc Nephrol 2: S6 -S12, 2007. doi: 10.2215/CJN.00280107 HIV-Associated NephropathyA nephropathy that is associated with HIV infection was identified soon after the epidemic of HIV/AIDS first became recognized in the early 1980s. HIV-associated nephropathy (HIVAN) is a combined glomerular and tubular injury that is characterized by a collapsing glomerulopathy (CG) with collapse of glomerular capillary structures and a striking hyperplasia of podocytes, microcystic transformation of renal tubules, and concomitant and likely nonspecific interstitial inflammation and fibrosis consequent to the glomerular and tubular injuries (Figure 1). From a pathology standpoint, three major areas of investigation have led to a deeper understanding of this lesion.The first of these addresses the issue of whether HIVAN is a direct consequence of viral infection of the renal parenchyma or is a secondary consequence of systemic infection. Cohen et al.(1) first reported the presence of HIV RNA in podocytes as revealed by in situ hybridization (ISH) in 1989, a finding that was supported by microdissection studies of Kimmel et al. (2). These studies were difficult to validate because of the failure of others to replicate these findings using conventional techniques of ISH, the inability to demonstrate the presence of viral peptides in renal parenchymal cells by immunohistochemistry, and the inability to demonstrate appropriate receptors for viral entry into cells, namely CD4 and the chemokine receptors CXCR4 or CCR5, on renal parenchymal cells (3). This created a conundrum in that a mechanism for viral entry into renal cells could not be defined. Some but not all of the difficulties were resolved by a more sophisticated form of ISH, which is based on a technique that detects forms of viral DNA that are characteristic of replicating virus (4 -6). With these techniques, it was possible to substantiate the findings of Cohen et al. and convincingly demonstrate HIV infection of podocytes and tubular epithelial cells.A second key development concomitant with the demonstration of HIV infection of human renal epithelial cells was the development of murine models of HIVAN. The best studied of these involves the Tg26 mouse: Mice are made transgenic for a nearly whole-length HIV virus but with a deletion of HIV gag and pol genes to render the virus nonreplicative (7). Studies of these mice, largely by the group of Klotman and their collaborators, have established that expression of HIV genes, presumably modeling the events of renal HIV infection, is sufficient to produce a renal injury in the mouse that is similar to HIVAN in humans. Studies in which kidneys from transgenic mice were transplanted into wild-type controls demonstrated that renal expression of HIV gene...

show abstract

Section: Polyoma Virus Nephropathymentioning

confidence: 99%

Emerging Paradigms in the Renal Pathology of Viral Diseases

Alpers¹,

Kowalewska²

2007

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

show abstract

“…Los regíme-nes actuales de inmunosupresión son más potentes e incrementan el riesgo de infecciones virales oportunistas presentes mayormente dentro del primer año (17) . Ambos pacientes fueron admitidos a hospitalización por aumento inexplicable de la creatinina sérica (18) , sin signos ni síntomas específicos de infección o rechazo. Las biopsias del injerto renal mostraron lesiones típicas de NPBK (19,20) (figura 1).…”

Section: Discussionunclassified

“…La simultánea ocurrencia de NPBK y aparente imagen histológica de rechazo agudo en ambos casos constituyó un serio problema clínico de interpretación en la estrategia del manejo, es decir, las imágenes simultáneas pueden corresponder únicamente al virus (2,15) , optándose entonces por el pronto retiro de las drogas inmunosupresoras a fin de restaurar espontáneamente la inmunidad antiviral, elemento clave del tratamiento (3,14) . El uso de drogas antivirales constituye actualmente un problema controversial en sus resultados, optando nosotros por añadir leflunonamida (18,(25)(26)(27) y ciprofloxacina (18,34) para el caso 1 y administración de inmunoglobulina endovenosa para el caso 2 (28,29) , drogas antivirales todas ellas con capacidad de inhibir la replicación viral BK in vitro (14) . El objetivo primario de la terapia es disminuir la replicación viral BK (VBK) sérico, que tiene que ver con la restauración de la inmunidad y su repercusión en la evolución de la histología renal y preservación de la función.…”

Section: Discussionunclassified

Nefropatía asociada a poliomavirus BK en trasplante renal

et al. 2016

View full text Add to dashboard Cite

ResumenEl objetivo del presente reporte es dar a conocer los dos primeros casos de nefropatía del injerto asociada a poliomavirus BK (NPBK) ocurridos en el Hospital Edgardo Rebagliati Martins, EsSalud, Lima, Perú. El diagnóstico definitivo de la NPBK se corroboró mediante biopsia renal y estudio de microscopia electrónica. En el caso 1, el deterioro funcional renal no se controló a pesar de reducir la inmunosupresión y añadir drogas antivirales (leflunamide y ciprofloxacina), evolucionando a falla renal y su posterior acceso a retrasplante renal. En el caso 2, la alternativa terapéutica se basó en infusión de inmunoglobulina endovenosa asociada a reducción de la inmunosupresión, resultando en moderada mejora histológica y estabilización de la función renal. En ambos injertos renales hubo concomitantemente NPBK y lesiones histológicas compatibles con rechazo agudo celular pendientes de interpretar. En conclusión, la presencia del poliomavirus BK representa serio problema en el riñón trasplantado. La mejor conducta terapéutica se basa en el diagnóstico precoz y subsecuente reducción de la inmunosupresión. Es imprescindible disponer de metodología apropiada que posibilite un diagnóstico preciso. Se utiliza tamizaje de células señuelo o marcadoras (decoy cells) en orina, reacción de cadena polimerasa (PCR), biopsia renal o la microscopia electrónica como método valioso de ayuda en el diagnóstico etiológico viral. Se considera el retrasplante como opción ante la pérdida del injerto por NPBK (caso 1). Palabras clave. Poliomavirus BK; Nefropatía; Trasplante de riñón; Inmunología. Abstract Two documented cases of BK polyomavirus-associated nephropathy (BKVN) seen at Hospital Edgardo Rebagliati Martins, EsSalud, Lima, Peru are reported. Final BKVN diagnosis was confirmed by renal biopsy and electron microscopy study. Case 1: Renal functional deterioration was not controlled despite reduction of immunosuppression and addition of antiviral drugs (leflunomide and ciprofloxacin), evolving to renal failure and subsequent kidney retransplantation. Case 2: The therapeutical management consisted in intravenous immunoglobulin infusion linked to reduction of immunosuppression; this resulted in modest histological improvement and stabilization of renal function. Both renal grafts concomitantly presented BKVN and histological lesions consistent with acute rejection, pending interpretation. In conclusion presence of BK polyomavirus is a serious problem for transplanted kidneys. The best treatment is based on early diagnosis and subsequent reduction of immunosuppression. It is essential to have an appropriate methodology for precise diagnosis. Early electron microscopy is a valuable method for viral etiologic diagnosis. Retransplantation is considered a treatment option when faced with possible BKVN-related graft loss (Case 1). Keywords. BK polyomavirus; Nephropathy; Kidney transplantation; Immunology.

show abstract

“…Before the mid 1990's, BK virus nephropathy was rarely identified as a clinical problem in renal transplantation. However specific pathological hallmarks ascribed to tissue invasive disease not only improved the detection and description of BK nephropathy, but led to alteration in post-transplant immunotherapy to minimize the damage [4]. Today, BK virus nephropathy is an important and emerging cause of renal transplant dysfunction and loss [2,3,5].…”

Section: Introductionmentioning

confidence: 99%

“…Brennan et al prospectively evaluated the differences between viremia, viuria, and BK virus nephropathy with 3 different immunosuppressive regimens showing the direct relationship between immunosuppression and BK infection [4,9]. New immunosuppression and combination therapies are thought to be a contributing factor in the increasing prevalence of BK virus infection.…”

Section: Introductionmentioning

confidence: 99%

Long-Term Results of a Screening and Immunosuppression Protocol for Polyoma BK Viremia after Renal Transplantation

Schuster¹,

Eldor²,

Leutters³

et al. 2017

Glob Surg

View full text Add to dashboard Cite

There is currently no treatment consensus with regards to BK Nephropathy (BKN). Thus, balancing minimization of immunosuppression with the attendant risk of acute rejection remains paramount for long-term allograft survival.Between Jan. 1, 2006 and Dec. 31, 2012, 371 adult renal transplants were performed at our center. Immunosuppression consisted of Thymoglobulin induction followed by maintenance therapy with Tacrolimus, Mycophenolate Mofetil (MMF) and either Sirolimus (88%) or prednisone (12%). Serum PCR screening for BK virus was obtained monthly. BK viremia was detected in 66 (18%) recipients (Group A) while the remaining 305 recipients were never detected to have viremia (Group B). Minimizing immunosuppression for Group A recipients occurred in a stepwise fashion and consisted of an immediate 50% reduction in MMF dosing following by complete discontinuation if viremia did not clear within 3 months. No MMF dosing adjustments were made in Group B patients. All recipients were followed longterm for patient survival and graft function and survival.Group A patient survival at 1, 3, and 5 years was 100%, 98.5%, and 97% compared to 99.3%, 98.4%, and 95.4% in Group B. Graft survival at the same time intervals in Group A was 100%, 98.5%, and 93.9% versus 99%, 97.7%, and 92.5% in Group B recipients. Mean serum creatinine, mg/dl, levels at 1, 3, and 5 years in Group A were 1.6, 1.7 and 1.6 compared to 1.5, 1.5, and 1.6 in Group B. Subsequent to MMF dose reduction/elimination, only on Group A patient progressed to BKN (1.5%) and only 2 patients suffered from an episode of acute rejection (3%).This pre-emptive reduction in immunotherapy at the detection of BK viremia was associated with a low rate of progression to BKN and the development of acute rejection. In addition to comparable long-term function.

show abstract

BK Virus Infection in Transplant Recipients: An Overview and Update

Cited by 188 publications

References 35 publications

Emerging Paradigms in the Renal Pathology of Viral Diseases

Emerging Paradigms in the Renal Pathology of Viral Diseases

Nefropatía asociada a poliomavirus BK en trasplante renal

Long-Term Results of a Screening and Immunosuppression Protocol for Polyoma BK Viremia after Renal Transplantation

Contact Info

Product

Resources

About