SUN-127 LONGITUDINAL STUDY OF BKV OUTCOMES, RISK FACTORS, AND KINETICS IN RENAL TRANSPLANTATION PATIENTS

Abstract

In immunocompromised conditions following renal transplantation, BK virus can reactivate and cause BK virus associated nephropathy (BKVN), potentially leading to renal dysfunction and allograft loss. Increased BK viral loads and extended duration of infection have been linked to the risk of BKVN development. The current major treatment option against BK virus is reduction of immunosuppression. The aim of this study was to observe the incidence of BKV infection and BKVN, their risk factors, and the kinetics of infection and disease in renal transplantation recipients. The effectiveness of intravenous immunoglobin (IVIG) on treatment of viremia was also assessed. This is a longitudinal cohort observational study of 139 renal transplantation patients treated at a single clinic from 2014 to 2018. Serum samples were collected from patients within one month after transplantation and at 1–2 month intervals following, for at least 6 and up to 40 months post-transplantation. Quantitative PCR assay was conducted to assess longitudinal BK viral loads. High BK viremia was defined as serum BKV DNA ≥ 4 log10 copies/ml for two or more consecutive readings. BKVN was confirmed by biopsy and defined as an allograft biopsy revealing typical viral cytopathic changes and positive staining for SV40 large T antigen. Distance correlation analysis of patient clinical characteristics was performed to determine risk factors for BKV infection and associated disease. A total of 1785 patient serum samples were assessed, with a mean patient follow-up duration of 19.4 ± 7.3 months. Within our cohort of 139 patients, 110 (79.1%) did not develop high BK viremia. Of the 29 (20.9%) patients who developed high BK viremia, 9 (6.5%) were transient cases (≥ 4 log10 copies/ml for 4 or less months), 13 (9.4%) were persistent cases (≥ 4 log10 copies/ml for more than 4 months), and 7 (5.0%) developed biopsy-confirmed BKVN. Peak viral levels of the BKVN group were significantly higher compared to both the BK viremia transient (6.96 vs. 4.63 log10 copies/ml, p < 0.001) and BK viremia persistent groups (6.96 vs. 5.42 log10 copies/ml, p < 0.001). Time to reach peak viral load was delayed in BKVN (13.55 vs. 3.19 months, p < 0.001) and BK persistent patients (7.43 vs. 3.19 months, p = 0.026) compared to patients with transient BK infection. Clinical parameters associated with diabetes (FBS, HbA1c) and hyperlipidemia (TG, TC, LDL-C) were found to be correlated with development of high BK viremia or BKVN. Significant differences in BK viral loads and kidney function (eGFR) developed between BK viremic patients and BKVN patients by 6–9 months post-transplantation. In 3 of 4 patients receiving IVIG treatment, BK viral loads were reduced by at least 1 log within 3 months of administration. BK viremia and BKVN incidence was in line with previously published figures. Diabetes and hyperlipidemia were identified as potential risk factors for development of high BK viremia and/or BKVN. IVIG treatment was seen to be effective in reducing viral titers. The period 0–9 months post-transplantation was identified as important for the development of BKVN from high BK viremia. Clinicians should pay close attention to patient BKV levels during this time period and respond with the appropriate reduction in immunosuppression and/or treatment with IVIG.