P1605the Early Rise of Urinary Exosomal Bk Virus Microrna as a Predictive Marker for Bk Virus Nephropathy in a Prospective Kidney Transplantation Cohort

Abstract

Background and Aims BK virus nephropathy (BKVN) is one of the significant contributors to allograft dysfunction in kidney transplantation. Because of the lack of effective anti-viral medication, early detection of BKV replication and preemptive management is vital to preserving allograft function. Herein, we investigated the predictive value of urinary exosomal BKV-microRNA for BKVN in the kidney transplantation cohort. Method ARTKT (assessment of immunologic risk and tolerance in kidney transplantation) is a prospective observational cohort in which a total of 420 kidney transplant recipients were enrolled from 7 teaching hospitals in South Korea since 2015. Urine samples were collected at 0.5, 3, 6, 12, and 24 months after kidney transplantation in this cohort. All enrolled patients were reviewed to identify the patients diagnosed with BKVN histologically (biopsy-proven BKVN) and those experienced BK viremia defined as plasma BKV DNA load > 4 log10 copies per mL (presumptive BKVN). Urinary exosomal miR was quantified using real-time reverse transcription PCR. Results 10 patients and 14 patients developed biopsy-proven BKVN and presumptive BKVN, respectively. Because of unavailable urine samples, urinary exosomal BKV-microRNA was investigated in 8 patients with biopsy-proven BKVN and 13 patients with presumptive BKVN. 61 patients with no evidence of BKVN were selected as a negative control. Most of BKVN was developed in a median time of 3.4 months after transplantation. In line with this pattern, urinary exosomal BKV-microRNA peaked at 3 months after transplantation and decreased thereafter in biopsy-proven BKVN and presumptive BKVN, keeping higher value in biopsy-proven BKVN compared to presumptive BKVN after 3 months. At 2 weeks after transplantation, half of the patients with biopsy-proven BKVN showed an early rise of urinary exosomal BKV-microRNA, whereas patients with presumptive BKVN and no evidence of BKVN did not. However, plasma BK virus DNA was not detected in all groups at 2 weeks after transplantation. In multivariate cox proportional hazards model, urinary exosomal BKV-microRNA was significantly associated with biopsy-proven BKVN. Conclusion A urinary exosomal BKV-microRNA increase as early as 2 weeks after kidney transplantation predicts future BKVN development, enabling early intervention.