BK-virus nephropathy in renal transplants—tubular necrosis, MHC-class II expression and rejection in a puzzling game

Abstract

We review BK-virus nephropathy (BKN) as a new complication that increasingly affects renal allografts and causes dysfunction. Since starting in 1996, we have seen 11 cases. Currently, the prevalence of BKN is 3% in our graft biopsies. The diagnosis can only be made histologically. The virus affects tubular epithelial cells that show characteristic intranuclear inclusion bodies. The major reason for impaired graft function and a possible way for viral particles to gain access to the blood via peritubular capillaries is necrosis of infected epithelial cells. BK-virus DNA in the plasma, which can be detected by PCR, is closely associated with nephropathy. BK-virus does not stimulate tubular MHC-class II expression as judged by immunofluorescence double labelling. The inflammatory response is inconsistent and the frequency of rejection episodes is not increased during disease. Clinical manifestation of viral nephropathy evolves in several stages. (i) Initial, asymptomatic and reversible activation of the virus, judged by the presence of inclusion bearing cells in the urine. (ii) High dose immunosuppressive drug regimens, often including tacrolimus. (iii) Tubular injury and viraemia as additional promoting conditions. BKN nephropathy was associated with graft loss in 45% of our patients. The remaining patients with persistent viral nephropathy showed renal dysfunction (serum creatinine levels on average 150% above baseline readings). Currently, no established antiviral therapy is available. We discuss attempts to lower immunosuppression as a means to control viral replication. We propose a diagnostic algorithm for screening and monitoring the disease.

Viral Infection in the Renal Transplant Recipient

“…Several risk factors have been implicated, although there is no consensus. Nickeleit et al found treatment of cellular rejection was more common in patients with BK nephropathy than in controls (137). Other studies have implicated high-dose immunosuppression (particularly tacrolimus and MMF), high-dose steroids, severe ischemia-reperfusion injury, exposure to antilymphocyte therapy, increased number of HLA mismatches between donor and recipient, cadaveric renal transplants, and presence and degree of viremia in the pathogenesis of disease.…”

The risk of polyomavirus BK-associated hemorrhagic cystitis after allogeneic hematopoietic SCT is associated with myeloablative conditioning, CMV viremia and severe acute GVHD

“…1,3,[7][8][9][10][11][12] Polyomavirus BK (BKV) is a double-stranded non-enveloped DNA virus first isolated from a urine sample obtained from a renal transplant recipient. [13][14][15] Primary infection occurs in childhood and remains in a latent phase most commonly in the kidney. [16][17][18][19] The reactivation of the latent virus is observed in patients with immunodeficiency.…”

Polyomavirus Allograft Nephropathy: Sequential Assessment of Histologic Viral Load, Tubulitis, and Graft Function Following Changes in Immunosuppression

“…Most clinicians accept it as a part of viral-induced parenchymal injury, and reduce immunosuppression after a diagnosis of PVAN. However, others contend that tubulitis is a manifestation of concurrent acute cellular rejection, and advocate increased immunosuppression (6). In an attempt to clarify this controversy, we performed a study to determine the effect of changes in immunosuppression on: (a) histologic viral load, (b) grade of tubulitis, and (c) serum creatinine as a marker of graft function.…”