Abstract
Background
Uncontrolled BK Polyomavirus (BK) DNAemia in kidney transplant recipients is a significant cause of allograft dysfunction that can lead to BK Polyomavirus-associated nephropathy with permanent damage and graft loss. BK virus DNAemia can occur early (within the first year) or late (after the first year) following a kidney transplant in children. Prospective monitoring for BK viremia with pre-emptive lowering of immunosuppression has been suggested as an effective approach to prevent BK nephropathy. We evaluated the impact of changes in targeted tacrolimus levels on the incidence of BK DNAemia early post-transplant.
Methods
In response to a cluster of early-onset BK virus DNAemia cases in the first quarter of 2015, we pursued a quality improvement study to determine whether changes to tacrolimus trough targets for the first 100 days post-transplant would reduce the incidence and severity of BK DNAemia. Targeted tacrolimus levels were decreased by approximately 25% (see Table) and patients receiving transplant from March 20, 2015, and December 31, 2018, were prospectively monitored. The incidence rates of BK DNAemia detected on monthly surveillance testing in the first-year post-transplant were compared for patients transplanted between January 1, 2013, and March 14, 2015 (pre-intervention) and March 15, 2015, to December 31, 2018 (post-intervention).
Results
Of 148 children who received kidney transplants during the study period, 52 (35%) were transplanted in the pre-intervention era and 96(65%) were transplanted during the post-intervention era. The median age at transplant was 13.9 years [interquartile range (IQR) 8.0–16.7 years]. Age at transplant, gender (overall 55% male), and race (overall 54% White, 35% Black) was not significantly different between the cohorts. The risk of early-onset BK DNAemia within the first 100 days post-transplant was 19 per 100 patients in the pre-intervention cohort and 13 per 100 patients in the post-intervention cohort, corresponding to a 35% reduction after lowering targeted tacrolimus levels. The median time to first detected BK DNAemia increased from 77 days (IQR 45–90 days) in pre-intervention to 104 days (IQR 47–174 days) in the post-intervention cohort.
Conclusions
BK DNAemia heralds a serious complication of kidney transplantation and may represent over immunosuppression and increased risk for other infectious complications. We were able to reduce the rate of early-onset BK DNAemia by reducing tacrolimus target levels in the first 12 weeks post-transplant. Preventing early uncontrolled viremia may decrease the need for immunosuppression reduction which increases the risk for rejection.
BK Polyomavirus Micro-RNAs: Time Course and Clinical Relevance in Kidney Transplant Recipients