BK Virus Allograft Nephropathy: Enhanced Risk for ABO-Compared to HLA-Incompatible Kidney Transplantation

Abstract

Introduction: It has been observed in some studies that ABO-incompatible kidney transplant recipients have a higher incidence of BK virus allograft nephropathy (BKVAN) compared to ABO-compatible recipients. This could be related to desensitisation and induction protocols or a greater risk for rejection treatment. It is unclear whether HLA-incompatible kidney recipients, who share similar treatment protocols, share this risk or whether this phenomenon is unique to ABO-incompatible patients. Methods: We analysed adult incompatible kidney transplant recipients from a prospectively kept database. 68 ABO-incompatible and 221 HLA-incompatible, transplanted between 1998 and 2010, formed the patient cohort. Patients transplanted against both immunological barriers were excluded from analysis. Protocol biopsies were performed for all incompatible patients on months 1, 3, 6 and 12 post-transplantation and indication biopsies in the context of transplant dysfunction (creatinine rise greater than 20% from baseline and/or new-onset proteinuria). All incompatible patients diagnosed with BKVAN on biopsy (protocol or for cause) were identified. Multivariable logistic regression analysis was used to identify independent risk factors for development of BKVAN. Results: Risk of BKVAN was greater amongst ABO-incompatible compared to HLA-incompatible patients (17.7% versus 5.9%, p=0.008). This compared to the BKVAN rate of 3.0% observed amongst all kidney transplant recipients, compatible or not, at this transplant centre. 42% of BKVAN cases were subclinical and diagnosed on protocol biopsy. ABO-incompatibility, male sex and age were independent predictors for development of BKVAN on multivariable logistic regression. C4d deposition without histologic features of rejection (the typical ABO-incompatible graft ‘accommodation’ phenotype) on 1-year protocol biopsies of ABO-incompatible patients, with and without BKVAN, was 40% versus 75.8% respectively (p=0.040), a putative pathophysiological mechanism. At median follow up of 1399 days post-transplantation, ABO-incompatible patients with BKVAN had death-censored graft survival of 91% and serum creatinine of 1.8 mg/dl amongst surviving kidneys. For HLA-incompatible patients, at median of 1017 days post-transplant death-censored graft survival was also 91% and serum creatinine 1.8 mg/dl amongst surviving kidneys. In contrast compatible kidney recipients, at a median of 1117 days post-transplantation, death-censored graft survival were 69% and serum creatinine 2.6 mg/dl amongst surviving kidneys. Conclusion: This study suggests that ABO-incompatible patients have an elevated risk of developing BKVAN unrelated to desensitisation, intensity of immunosuppression or risk of antibody-mediated rejection. However risk of BKVAN related graft loss is negligible, contrary to compatible kidney transplant recipients, which we hypothesise is due to early sub-clinical detection using protocol biopsy surveillance. Thus ABO-incompatible patients may have unique risk profiles and mechanisms for development and progression of BKVAN but this speculation requires further investigation.