HLA Mismatching Increases the Risk of BK Virus Nephropathy in Renal Transplant Recipients

Abstract

BK virus (BKV)nephropathy is a serious complication in kidney transplant recipients that may lead to irreversible graft failure. We have analyzed the degree of donor/recipient HLA compatibility and HLA antigen association in 40 kidney transplant patients with BKV nephropathy in comparison with a control group of 404 unaffected transplant recipients who were on tacrolimus-based immunosuppression with no induction. HLA compatibility was assessed by determining the number of HLA-A, -B, -DR-mismatched antigens. BK virus nephropathy was diagnosed histologically and confirmed by immunochemistry. Univariate and multiple logistic regression statistical analyses have shown a significant association between BKV nephropathy and HLA mismatching. This analysis showed also that BKV nephritis is associated with a greater number of rejection episodes and a higher incidence of steroid-resistant rejection requiring antilymphocyte treatment. There was no association between BKV nephropathy and any specific HLA allele. We propose that HLA mismatching promotes the development of BKV nephropathy through rejection-related inflammatory processes and heavy immunosuppression which cause virus reactivation and injury of the tubular epithelium.

Acute Rejection

“…Some authors reported that the injury of the renal allograft may have an important role in the pathogenesis of BKVAN (Drachenberg et al, 2005). The association found between human lymphocyte antigen mismatching and BKVAN supports the hypothesis (Awadalla et al, 2004).…”

BK Virus Nephropathy in Pediatric Renal Transplant Recipients

“…Polyclonal induction therapy was recently associated with an increased risk for infectious complications in pediatric renal transplant patients (17). Other studies have reported that use of antilymphocyte agents for the treatment of steroid-resistant rejection is associated with BKV replication in patients who are on tacrolimus or MMF maintenance therapy (7,18,19). However, other studies that examined BKV specifically did not find an association between use of antilymphocyte preparations and risk for BK viruria, viremia, or BKVN (7,16,18,20).…”

“…However, other studies that examined BKV specifically did not find an association between use of antilymphocyte preparations and risk for BK viruria, viremia, or BKVN (7,16,18,20). HLA mismatching has been identified as a risk factor for BKVN in both retrospective and prospective studies among adult renal transplant patients (7,19). The increased rejection risk with HLA mismatching (21,22) through its treatment with escalation of immunosuppression and/or via direct rejectionrelated inflammatory responses has been proposed as a potential mechanism for this association.…”

BK Virus Nephritis after Renal Transplantation

“…Awadalla et al (29) showed that the occurrence of BKVN correlates with a higher degree of HLA mismatches, which postulates the role of alloimmune activation. Investigators from Emory University (30) showed using a mouse polyoma transplant model that polyoma viral nephritis occurs only in the presence of alloimmune activation.…”