Persistent BK Viremia Does Not Increase Intermediate-Term Graft Loss but Is Associated with De Novo Donor-Specific Antibodies

Abstract

There are limited data regarding intermediate-term outcomes in patients with persistent BK viremia. Other viral infections have been implicated in the development of allosensitization through heterologous immunity, but the relationship between BK viremia and donor-specific antibodies (DSAs) is unexplored. In 2008, we initiated routine post-transplant BK viremia and DSA screening at our center; 785 kidney or kidney-pancreas transplant recipients were included in our study. Of these recipients, 132 (17%) recipients developed BK viremia during the study period. The median duration of BK viremia was 140 days (interquartile range=40-393 days), and persistent BK viremia was defined as lasting $140 days. Kaplan-Meier curves were generated to assess differences in patient and allograft survival on the basis of BK viremia status; survival was modeled using Cox proportional hazard regression. After a median follow-up of 3 years, there was no significant difference in terms of patient (hazard ratio [HR], 0.83; 95% confidence interval [95% CI], 0.28 to 2.49) or allograft survival (HR, 0.80; 95% CI, 0.37 to 1.73) between patients with and without BK viremia, which was confirmed in a time-varying analysis. In our logistic regression model, persistent BK viremia was strongly associated with the development of class II (HR, 2.55; 95% CI, 1.30 to 4.98) but not class I (HR, 1.13; 95% CI, 0.46 to 2.77) DSAs. These data suggest that persistent BK viremia does not negatively affect intermediate-term patient or allograft survival but is associated with increased risk for de novo DSA, although the exact mechanism is unclear.

Risk factors for the development of donor‐specific antibodies after pediatric heart transplantation

“…Urschel et al demonstrated that DSA occur more frequently in patients who are older at the time of HTx, a finding that is supported by our current analysis. Adult studies in solid organ transplant recipients also indicate that rejection episodes, HLA mismatch, pretransplant PRA > 10%, viral infections, and non‐compliance are associated with the development of DSA . Similar to these studies, our analysis suggests that elevated PRA pre‐HTx is associated with the development of DSA.…”

Clinical characteristics and outcomes of late‐onset BK virus nephropathy in kidney and kidney‐pancreas transplant recipients

“…The incidence of graft loss overall was low, likely reflecting overall greater experience in managing BKPyVAN, as reported previously . The development of HLA antibodies has been reported after BKPyV infection in prior studies, but was not routinely performed in this cohort. Future studies should assess the relationship between early and late BKPyVAN and development of anti‐HLA antibodies.…”

BK polyomavirus genotypes in renal transplant recipients in the United States: A meta‐analysis

“…Development of Donor specific antibodies leading to sequela of acute rejection seems to be a major consequence from reduction of immunosuppression for among patients with BKV infection with no available effective treatment options at this time . Thus, findings from our study on epidemiology of BKV genotypes may serve as a resource for development of vaccines against BKV in United States .…”