Incidence of BK with Tacrolimus Versus Cyclosporine and Impact of Preemptive Immunosuppression Reduction

Abstract

Our purposes were to determine the incidence of BK viruria, viremia or nephropathy with tacrolimus (FK506) versus cyclosporine (CyA) and whether intensive monitoring and discontinuation of mycophenolate (MMF) or azathioprine (AZA), upon detection of BK viremia, could prevent BK nephropathy.We randomized 200 adult renal transplant recipients to FK506 (n = 134) or CyA (n = 66). Urine and blood were collected weekly for 16 weeks and at months 5, 6, 9 and 12 and analyzed for BK by polymerase chain reaction (PCR). By 1 year, 70 patients (35%) developed viruria and 23 (11.5%) viremia; neither were affected independently by FK506, CyA, MMF or AZA. Viruria was highest with FK506-MMF (46%) and lowest with CyA-MMF (13%), p = 0.005. Viruria ≥ 9.5 log 10 copies/mL was associated with a 3-fold increased risk of viremia and a 13-fold increased risk of sustained viremia. After reduction of immunosuppression, viremia resolved in 95%, without increased acute rejection, allograft dysfunction or graft loss. No BK nephropathy was observed.Choice of calcineurin inhibitor or adjuvant immunosuppression, independently, did not affect BK viruria or viremia. Viruria was highest with FK506-MMF and lowest with CyA-MMF. Monitoring and preemptive withdrawal of immunosuppression were associated with resolution of viremia and absence of BK nephropathy without acute rejection or graft loss.

Effects of Rituximab on the Development of Viral and Fungal Infections in Renal Transplant Recipients

“…Previously, Kamar et al noted that BK virus was the most common virus detected in RTX-treated patients [8], and Habicht et al found a nonsignificantly higher rate of BK in ABO-incompatible recipients administered RTX [11]. The rates of BK viremia and nephropathy in our cohort are congruent with rates previously reported in the renal transplant population [18][19][20][21]. However, viremia and nephropathy occurred 2-3x more often in the RTX cohort.…”

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

“…In this study, BK viremia prevalence was 18% [20]. This is consistent with the described incidence of BK viremia in renal transplant recipients (10-20%; [8,23]) Importantly, we choose to intervene at plasma BKV loads of log 3 or greater. This value was chosen as the lower limit of detection for a "positive" result using our assay.…”

“…The mainstay of treatment for BK viremia/nephropathy has been reduction of immunosuppression [8]. Unfortunately, the development of BK nephropathy carries with it a significant rate of graft dysfunction/ loss [13,14].…”

“…Currently, 10-20% of renal transplant recipients develop BK viremia, and 5-10% proceed to develop BK nephropathy [6][7][8]. 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].…”

Late-Onset BK Viral Nephropathy in a Kidney Transplant Recipient

“…In those and other studies, viremia cleared in 92%e95% of patients, with a mean time to clearance of 54 days [18,19]. In contrast, rejection rates of up to 30% have been reported with reduction in immunosuppression alone, and allograft loss of 35%e50% despite reduction in total immunosuppression [20,21].…”