BK Polyomavirus in Pediatric Kidney Transplant Recipients: Incidence, Risk Factors, dnDSA Development, and the Role...

Polyomavirus-associated nephropathy (BKVAN) is a significant cause of graft dysfunction in pediatric kidney transplant recipients (PKTR). However, there is currently insufficient data regarding the appropriate frequency of screening and management in children. In this study, we present our experience in managing children with BK polyomavirus (BKV) DNAemia and BKVAN following kidney transplantation. We also assessed the incidence of rejection and the development of de novo donor-specific antibodies (dnDSA) and investigated the effectiveness of intravenous immunoglobulin (IVIG) as an adjunctive therapy for managing presumptive or confirmed BKVAN.

From March 2015 to December 2021, all PKTR underwent BKV plasma monitoring using quantitative polymerase chain reaction (qPCR) every 2 weeks for the first 3 months, monthly for the remainder of the first year, and then every 3 months thereafter. If the BKV DNAemia level was between 1000 and 5000 IU/mL, a 50% decrease in mycophenolate mofetil (MMF) was implemented. If BKV DNAemia remained above 5000 IU/mL but below 10 000 IU/mL in the second test, MMF was discontinued. In cases where BKV DNAemia was $\ge$ 10 000 IU/mL, IVIG was administered.

Among the 93 patients included in this study, 32% developed BKV DNAemia at a median of 90 days (Inter Quartile Range [IQR] = 30, 300 days) posttransplantation. The median peak of BKV DNAemia was 10 446 copies at a median of 14 days after the first positive PCR. The incidence of dnDSA was common in our cohort but was not significantly different between patients with and without BKV DNAemia (26.7% vs. 24%, p = 0.8). The median time to BKV DNAemia clearance was similar between the IVIG and non-IVIG groups (86 vs. 70 days, p = 0.1014). No graft loss was reported at the median follow-up of 43 (IQR = 22, 62) months in either group.

The findings of our study suggest a potential benefit of stringent BKV screening and considering timely and intensive treatments before graft dysfunction becomes apparent. Our research also indicates that IVIG might be effective in managing both confirmed and presumptive BKVAN cases, as evidenced by the similar graft outcome observed after a 3-year follow-up period post BKV DNAmia. Notably, despite more frequent adjustments to immunosuppressants and a higher rate of human leukocyte antigen (HLA) mismatch in the BKV DNAemia group, the incidence of dnDSA formation appeared to be comparable between the two groups. These observations warrant controlled trials to confirm their broad applicability.