The human polyomavirus BK (BKPyV): virological background and clinical implications

Abstract

Polyomavirus BK (BKPyV) infects most people subclinically during childhood and establishes a lifelong infection in the renourinary tract. In most immunocompetent individuals, the infection is completely asymptomatic, despite frequent episodes of viral reactivation with shedding into the urine. In immunocompromised patients, reactivation followed by high-level viral replication can lead to severe disease: 1-10% of kidney transplant patients develop polyomavirus-associated nephropathy (PyVAN) and 5-15% of allogenic hematopoietic stem cell transplant patients develop polyomavirus-associated haemorrhagic cystitis (PyVHC). Other conditions such as ureteric stenosis, encephalitis, meningoencephalitis, pneumonia and vasculopathy have also been associated with BKPyV infection in immunocompromised individuals. Although BKPyV has been associated with cancer development, especially in the bladder, definitive evidence of a role in human malignancy is lacking. Diagnosis of PyVAN and PyVHC is mainly achieved by quantitative PCR of urine and plasma, but also by cytology, immunohistology and electron microscopy. Despite more than 40 years of research on BKPyV, there is still no effective antiviral therapy. The current treatment strategy for PyVAN is to allow reconstitution of immune function by reducing or changing the immunosuppressive medication. For PyVHC, treatment is purely supportive. Here, we present a summary of the accrued knowledge regarding BKPyV.

Pretransplantation Donor–Recipient Pair Seroreactivity Against BK Polyomavirus Predicts Viremia and Nephropathy After Kidney Transplantation

“…BKPyV-associated disease is a major problem in the care of kidney transplant recipients for whom no antiviral treatment is available (1,2,10,32). Because timely reduction of immunosuppression is the only effective treatment to date (11,12), all recipients are currently screened for BKPyV viremia on a regular basis after transplantation (10)(11)(12)16).…”

“…BK polyomavirus (BKPyV) causes asymptomatic infection early in life (1,2), reaching a seroprevalence of %90% in adults (3,4). After primary infection, BKPyV latently persists in the urothelium and renal tubular cells (5,6), and small amounts of viral progeny can be temporarily detected in urine of 7-55% of healthy persons, depending on the sampling frequency (7)(8)(9).…”

“…In immunocompromised patients, BKPyV infections can cause manifest disease, such as hemorrhagic cystitis in hematopoietic stem cell transplant recipients and BKPyVassociated nephropathy (BKPyVAN) in kidney transplant recipients (1,2,10). Reduction of immunosuppressive therapy is the only effective evidence-based treatment to date (11,12).…”

“…In a subset of viruric recipients (15-30% of the total number of recipients), viral DNA is detected in the circulation (viremia); of these viremic recipients, a small proportion (1-10% of all recipients) develops BKPyVAN, ultimately causing allograft failure (10,(12)(13)(14)(15)(16). Sustained viremia and BKPyV loads >10 4 genome copies per milliliter (c/mL) are associated with BKPyVAN development (1,2,10). To identify this subgroup of recipients at risk who require tapering of immunosuppression (14,17), most kidney transplantation centers regularly evaluate recipients currently for detectable BKPyV DNA in blood (10)(11)(12)16).…”

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

“…19,20 The two most important diseases are BKV-associated nephropathy in renal transplant and BKV-associated HC (BK-HC) in allo-HSCT. 21 Although the pathogenesis of BKV is not fully understood, it seems that it has a different pathogenesis in HSCT recipients where it more often presents as HC, compared with BKV nephropathy in renal transplant recipients. 21,22 Several risk factors for HC associated with BKV after allo-HSCT have been suggested, such as conditioning regimens containing BU, acute GVHD (aGVHD), intensity of conditioning regimen, donor type, CMV seropositivity and post-transplant mycophenolate use.…”