Management of BK Polyomavirus Infection in Kidney and Kidney-Pancreas Transplant Recipients: A Review Article.

BK virus (BKV) can cause graft dysfunction or failure in kidney transplant recipients and hemorrhagic cystitis in allogeneic hematopoietic stem cell transplant patients. BKV-associated nephropathy (BKVAN) emerged as a common complication in the late 1990s, probably due to the introduction of potent immunosuppressive agents. BKVAN occurred in up to 5% of kidney transplant recipients, with graft failure in up to 70%. Since universal implementation of effective screening and treatment strategies, BKV is no longer a common cause of graft failure; reported graft loss is only 0% to 5%. This article briefly describes BK virology, epidemiology, diagnosis, and management.

Transient versus persistent BK viremia and long-term outcomes after kidney and kidney-pancreas transplantation.

BACKGROUND AND OBJECTIVES: The objective was to study the long-term impact of transient versus persistent BK viremia on kidney transplant outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In total, 609 recipients who underwent kidney transplant from 2007 to 2011 were screened at months 1-12 for the occurrence of polyomavirus BK viremia; 130 patients (21.7%) developed BK viremia during the first year post-transplant. BK viremia patients were classified according to duration of infection (more or less than 3 months), and BK viral loads (more or less than 10,000 copies/ml) were classified as transient low viremia (n=42), transient high viremia (n=18), persistent low viremia (n=23), and persistent high viremia (n=47). All patients were followed a median of 36 (3-66) months. The rates of BK polyomavirus-associated nephropathy, acute rejection, and 1-year graft function were compared with the polyomavirus BK-negative control group. RESULTS: Patient and graft survival were not significantly different among the groups. Graft function (creatinine; milligrams per deciliter) at 1 year was significantly worse in the persistent high viremia (1.75±0.6) and transient high viremia (1.85±0.7) groups compared with aviremic controls (1.47±0.4; P=0.01 and P=0.01, respectively). The incidence of BK polyomavirus-associated nephropathy was limited to the persistent high viremia group (1.3%, P<0.001). The transient high viremia (50%) and persistent high viremia (34%) groups showed significantly (P=0.01) increased incidence of acute rejection versus aviremic controls (21.5%), transient low viremia (19%), or persistent low viremia (17.3%) groups. CONCLUSION: Low viral load BK viremia, either transient or persistent, was not associated with long-term transplant outcomes. Persistent high viremia was associated with a greater risk for BK polyomavirus-associated nephropathy and subsequent graft dysfunction. Although transient high viremia was not associated with BK polyomavirus-associated nephropathy, it was associated with worse graft function. These data support the role of surveillance for BK viremia after transplant.

CMV Viremia is associated with a decreased incidence of BKV reactivation after kidney and kidney-pancreas transplantation.

BACKGROUND: Cytomegalovirus (CMV) and BK virus (BKV) infections can cause significant morbidity after kidney and kidney-pancreas transplant. There are limited data on the epidemiology and interactions between these two viral pathogens. METHODS: We prospectively screened 609 kidney or kidney-pancreas transplant recipients from January 2007 to June 2011 for BKV and/or CMV viremia. This included 7453 quantitative BKV polymerase chain reaction and 15,496 quantitative CMV polymerase chain reaction tests. We evaluated risk factors and timing of these infections and the impact of treatment of one infection on the other. RESULTS: Among 609 recipients, 108 (17.7%) developed CMV viremia, of which 95 (88%) were asymptomatic, 5 (5%) had CMV syndrome, and 8 (7%) developed CMV tissue invasive disease at a median of 5.6 months after transplantation. Risk factors for CMV infection using multivariable analysis were D+R- serogroup (P≤0.0001), donor age >50 years (P=0.013), and higher mean tacrolimus (P=0.0009) and mycophenolate mofetil (P=0.01) blood levels. The incidence of BKV infection in the total population was 163 of 609 (26.7%), of which 150 (92%) occurred in patents without antecedent CMV viremia. Such patients demonstrated a higher rate of subsequent BKV viremia than patients with antecedent CMV viremia (P=0.003; hazard ratio, 2.05; 95% confidence interval, 1.2-3.4). Moreover, we found that only symptomatic CMV viremia had a significant negative impact on graft survival when compared with asymptomatic CMV viremia and those without CMV viremia (relative risk, 3.5; 95% confidence interval, 1.06-8.9; P=0.04). CONCLUSION: CMV viremia may indirectly protect against subsequent BK viremia possibly due to a reduction of intensity of immunosuppression after diagnosis of CMV viremia.

The impact of surveillance and rapid reduction in immunosuppression to control BK virus-related graft injury in kidney transplantation.

We prospectively screened 609 consecutive kidney (538) and kidney-pancreas (71) transplant recipients for BK viremia over a 4-year interval using polymerase chain reaction viral load detection and protocol kidney biopsies. We found that BK viremia is common at our center: total cases 26.7%, cases during first year 21.3% (mean 4 months), and recipients with ≥ 10 000 copies/ml 12.3%. We found few predictive clinical or demographic risk factors for any BK viremia or viral loads ≥ 10,000 copies/ml, other than prior treatment of biopsy confirmed acute rejection and/or higher immunosuppressive blood levels of tacrolimus (P = 0.001) or mycophenolate mofetil (P = 0.007). Viral loads at diagnosis (<10 000 copies/ml) demonstrated little impact on graft function or survival. However, rising copy numbers demand early reductions in immunosuppressive drug doses of at least 30-50%. Viral loads >185 000 copies/ml at diagnosis were predictive of BK virus-associated nephropathy (BKVAN; OR: 113.25, 95% CI: 17.22-744.6, P < 0.001). Surveillance for BK viremia and rapid reduction of immunosuppression limited the incidence of BKVAN to 1.3%. The addition of leflunomide or ciprofloxacin to immunosuppressive dose reduction did not result in greater rates of viral clearance. These data support the role of early surveillance for BK viremia to limit the impact on transplant outcome, although the most effective schedule for screening awaits further investigation.