BK viremia and nephropathy in pediatric renal transplant recipients

Abstract

The renal survival rate of pediatric renal transplant recipients (pRTR) has improved with the use of modern immunosuppressive agents; however, the incidence of post‐transplantation viral infection has increased. This study investigated the incidence of BK viremia and BK viral–associated nephropathy (BKVAN) in pRTR. One‐hundred‐and‐thirty‐four pRTR were divided into two groups: group 1 (n = 20, 14.9%) comprised those who were prospectively followed with longitudinal analyses after renal transplantation in the time period from May 2007 to June 2008, while group 2 (n = 114, 85.1%) cross‐sectional study of those who were transplanted from January 1994 to April 2007. The mean ages at transplantation in groups 1 and 2 were 10.6 ± 4.7 years and 7.8 ± 4.5 years, respectively. BK viremia was detected in four (20.0%) patients in group 1, and seven (6.1%) in group 2 (P = 0.04), with increased incidence associated with induction therapy. The median time to detection of BK viremia after transplantation was 44 days in group 1 and 142 days in group 2. BKVAN was diagnosed in three patients (two in group 1 and one in group 2). All three patients diagnosed with BKVAN were receiving tacrolimus, mycophenolate mofetil, and corticosteroids as maintenance immunosuppression. Reducing immunosuppression resulted in reduced BK viremia. Monitoring for BK viremia and BKVAN is important in pRTR being treated with the current immunosuppressive regimen. The first line of treatment for BK viremia remains careful reduction of immunosuppression and close monitoring of renal allograft function.

Treatment of BK virus with a stepwise immunosuppression reduction and intravenous immunoglobulin in pediatric kidney transplant

“…The prevalence of BKV for our cohort was 35.7%, of which 85% occurred within the first 12 months post‐transplant. Our results are comparable to reports of 20–37% BKV in children 7–10 ; however, adult studies have lower reports of 10–20% 11,12 . A 7% prevalence of BKVN (presumed and confirmed) in our cohort is similar to other pediatric studies, 7,9,33,34 but lower as compared to 20.3% in CERTAIN Registry research network 8 .…”

“…Infection with BK in pediatric kidney transplants is associated with cystitis (hemorrhagic or non‐hemorrhagic), BKVN (asymptomatic or with slowly increasing creatinine), and rarely ureteral stricture 5,6 . The incidence of BKV in the pediatric population ranges from 20 to 37%, while BKVN rates are 1–16% 7–10 . These pediatric rates have shown an increase in the last decade compared with reported incidence of 10–20% and 2–8%, for BKV and BKVN, respectively, in adult transplant population 11–13 …”

“…Treatment strategies including the use of cidofovir, leflunomide, and fluoroquinolones have been used in controlling BKV and preventing renal injury, but have been shown to be not as beneficial 20–23 . In the absence of effective antiviral therapy, adult and pediatric studies support IR as the most effective first‐line treatment 6,7 . In adult literature, mTOR inhibitor‐based immunosuppression has been suggested to reduce the risk of BKV because of their in vitro antiviral properties, but this has not been addressed in children 24 .…”

“…[20][21][22][23] In the absence of effective antiviral therapy, adult and pediatric studies support IR as the most effective first-line treatment. 6,7 In adult literature, mTOR inhibitor-based immunosuppression has been suggested to reduce the risk of BKV because of their in vitro antiviral properties, but this has not been addressed in children. 24 The role of IVIG as a mediator of humoral immunity and specifically a BK neutralizing effect has been reported in adult studies; however, there are limited data on use of IVIG for treatment of children with BKV and BKVN.…”

Impact of once‐daily ER‐Tac on trough concentration variability in a stable AYA renal transplant recipient cohort

“…Pharmacokinetic studies demonstrate similar area under the plasma concentration‐time curve and maximum serum concentration between IR‐Tac and ER‐Tac, but not necessarily with bioequivalent dosing 24,27 . A 1:1 dosing conversion is recommended by the manufacturer; however pharmacokinetic comparison studies demonstrate that higher doses of ER‐Tac may be required to achieve similar trough concentrations to IR‐Tac 10,28 .…”