Polyomavirus (BK) in pediatric renal transplants: Evaluation of viremic patients with and without BK associated nephritis

Abstract

Polyoma BK virus (BKV) is emerging as a significant complication in renal transplantation, which may lead to renal dysfunction and graft loss caused by BK nephritis (BKN). We report the management and outcome of 20 children who developed BK viremia. Serum polymerase chain reaction (PCR) for BKV DNA was measured monthly for the first year in transplant recipients and every six months thereafter, or for unexplained creatinine elevation. With seroconversion to +PCR, patients were managed with reduction of immunosuppression. Renal biopsy was performed if PCR or creatinine did not improve. From June 2003 to January 2006, 20 children seroconverted for BKV at 23 to 1410 days post-transplant (mean 467 days). Sixteen underwent renal biopsy. Eight displayed BKN, three acute rejection and five were normal. Patients with BKN displayed higher PCR and serum creatinine and presented later than children with viremia without BKN. There were no differences between the two groups for age, gender, donor source or immunosuppression. Seven children with BKN received treatment with cidofovir. Thirteen patients (65%) remained PCR+ after reduction of immunosuppression or treatment with cidofovir. Renal function was stable in 16 children (80%) at 13 +/- 6 months after seroconversion. Four patients with BKN demonstrated progressive loss of renal function. BKV infection in children can occur as an early complication or may develop years after transplantation. Patients with BKN presented later and displayed higher viral loads and serum creatinine than viremic patients without BKN. Children with BKN remained PCR+ despite reduction of immunosuppression or treatment with cidofovir and were at greater risk for loss of renal function.

Late-Onset BK Viral Nephropathy in a Kidney Transplant Recipient

“…However, some studies show that the rate of decline of GFR can be slowed by 40% with a reduction in immunosuppression alone [22]. On average, the burden of graft loss varies and may range from 15% in adults to 50% in the pediatric population [23].…”

BK Virus in Solid Organ Transplant Recipients

“…A comparison of cidofovir-treated with nontreated patients has been described but not in a randomized controlled trial (88,89 (85,91,92), but not in others (87,93). (94 or VP1 mRNA (14,42,43,51,52,64,99 (39,41,51), or plasma BKV loads of >4 log 10 geq/mL is more than 50% (51,52,103) (52,105,106 (26,30,36). Single-center studies report that enzyme immunoassays (EIA) using BK virus-like particles (BKVLP) assembled in vitro from recombinant VP1 may be more sensitive but equally specific compared to hemagglutination inhibition and neutralization tests (26,34,112 (26,34,75,(115)(116)(117)(118)(119).…”

BK Virus Nephropathy and Kidney Transplantation

“…Rocha et al (49) reported no allograft loss and clearance of viruria in seven patients after discontinuation of MMF and reduction in calcineurin inhibitor dosage despite a mean creatinine of 3.2 mg/dl at diagnosis compared with persistent viruria and allograft loss in two recipients after only reduction in MMF and modification of calcineurin inhibitor. Dosage reduction of the adjuvant agent and calcineurin inhibitor in pediatric patients failed to clear viremia with 50% graft loss (89). Dosage reduction of the adjuvant agent and calcineurin inhibitor in adults failed to improve tubular BKV burden with a rising mean creatinine (51).…”