Tubular Basement Membrane Immune Deposits in Association with BK Polyomavirus Nephropathy

Bracamonte, Erika; Leca, Nicolae; Smith, Kelly D.; Nicosia, Roberto F.; Nickeleit, Volker; Kendrick, Elizabeth; Furmanczyk, Paul S.; Davis, Connie L.; Alpers, C. E.; Kowalewska, Jolanta

doi:10.1111/j.1600-6143.2007.01794.x

Cited by 55 publications

(37 citation statements)

References 13 publications

(16 reference statements)

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“…In the University of Washington experience, in perhaps as many as 40% of cases of PVN, evaluation of the renal biopsy by immunofluorescence or immunohistochemical techniques that detect deposition of immunoglobulins (IgG, IgM) and/or components of the complement system (C3, C4d) will demonstrate granular staining of tubular basement membranes, indicative of immune complex deposition. This feature of an immune complex deposition process can be confirmed by electron microscopic identification of corresponding electron-dense deposits ( Figure 2) (17). Some of these biopsies also demonstrate striking coating of the surface of enlarged and presumably infected tubular epithelial cells by the same Ig and complement components that are detected in the tubular basement membrane deposits (Figure 2).…”

Section: Polyoma Virus Nephropathymentioning

confidence: 64%

Emerging Paradigms in the Renal Pathology of Viral Diseases

Alpers¹,

Kowalewska²

2007

Clinical Journal of the American Society of Nephrology

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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...

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Section: Polyoma Virus Nephropathymentioning

confidence: 64%

Emerging Paradigms in the Renal Pathology of Viral Diseases

Alpers¹,

Kowalewska²

2007

Clinical Journal of the American Society of Nephrology

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“…In our biopsy material, tubular staining for C4d on frozen specimens did not correlate with the Banff score for tubular atrophy. Another pertinent study with respect to tubular basement membrane staining for C4d is that of Bracamonte et al, 20 who described granular tubular basement membrane immune deposits in 16/30 (53%) of patients showing BK virus nephropathy. In our material, tubular basement membrane staining for C4d could not be related to BK virus infection in frozen sections.…”

Section: Discussionmentioning

confidence: 99%

“…Sijpkens et al 19 described an association between glomerular basement membrane staining and chronic transplant glomerulopathy. Bracamonte et al 20 and Hever et al 21 demonstrated tubular basement membrane deposits in association with BK virus nephropathy. We present our own experience with C4d immunohistochemistry in both fresh frozen and formalin-fixed paraffin-embedded tissues.…”

mentioning

confidence: 97%

Clinical significance of the distribution of C4d deposits in different anatomic compartments of the allograft kidney

et al. 2008

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“…Sin embargo, las decoy cells urinarias también han sido descritas en cuadros de adenovirus, citomegalovirus (CMV) y células malignas (24) . Definitivamente, la aplicación de técnicas moleculares, reacción en cadena de la polimerasa (PCR), virus BK sérico/orina constituyen el instrumento fundamental de diagnóstico etiológico (3,20) .…”

Section: Discussionunclassified

“…Aún no disponemos del uso regular de estas valiosas técnicas moleculares que permitan manejo anticipado de la infección de virus BK (26,35) . Cuando tuvimos el primer caso de sospecha de NPBK, recurrimos a la microscopia electrónica (ME) para identificar el virus al no disponer de reactivos para estudio inmunohistoquimico en la histología renal (2,24) ni téc-nicas moleculares. El estudio de la ME nos permitió corroborar la presencia de genomas de virus BK (partículas típicas electrodensas de aspecto paracristalino tamaño de 40 a 50 nm) (figura 3).…”

Section: Discussionunclassified

Nefropatía asociada a poliomavirus BK en trasplante renal

et al. 2016

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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.

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Tubular Basement Membrane Immune Deposits in Association with BK Polyomavirus Nephropathy

Abstract: Tubular basement membrane immune deposits (TB-MID

Cited by 55 publications

References 13 publications

Emerging Paradigms in the Renal Pathology of Viral Diseases

Emerging Paradigms in the Renal Pathology of Viral Diseases

Clinical significance of the distribution of C4d deposits in different anatomic compartments of the allograft kidney

Nefropatía asociada a poliomavirus BK en trasplante renal

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