#740 Very early BK polyomavirus viremia is associated with graft dysfunction in kidney transplant recipients
Authors: Fontana Francesco , Amurri Alessio , Alfano Gaetano , Donati Gabriele 
Published: May 2024

Abstract

Background and Aims
BK polyomavirus-associated nephropathy (BKN) is a leading cause of graft dysfunction and loss, mostly related to the lack of effective treatments. Increasing BK polyomavirus viremia (BKV) precedes BKN, and its monitoring is therefore the focus of preventive strategies; whether BKV itself and its timing of occurrence post-transplant are associated with graft dysfunction is not clearly understood.

Method
We designed a single-center retrospective study enrolling all patients who received a kidney transplant at our center from January 1st 2018 to June 30th 2022. The study received approval from local Ethical Committee (252/2023/OSS*/AOUMO SIRER ID 651-BKNEPHMO). We collected clinical and demographical data at baseline; donor and transplant characteristics, significant clinical parameter during follow-up. Patients were regularly screened for BK viremia (roughly, once every two weeks in the first 3 months, then monthly until 1 year, then at least every 3 months or on clinical indication). We defined sustained viremia as the presence of BK viremia confirmed in 3 different measurements; probable BKN as the presence of BKV with a viral load &gt;3log10 copies/ml; presumptive BKN as BKV with a viral load &gt;4log10 copies/ml.

Results
After exclusion of patients with less than 6 months of follow-up, we considered 138 subjects. We stratified patients in 3 groups: no viremia (group A), any BKV (after more than one month from transplant, group B) and very early BKV (within one month from transplant, group C). Clinical, demographic, transplant characteristics are reported in Fig. 1. Of note, group C had a significantly higher proportion of patients with diabetes mellitus (DM) and positive anti-HBc serology, and a lower proportion of Caucasians; there were no differences in transplant characteristics. During follow-up, patients in group C had a significantly stronger reduction in immunosuppressive treatment (especially with regards to MMF), had higher chance of receiving a graft biopsy and were more likely to develop donor-specific antibodies. While patients in group C had a higher probability of sustained BKV compared to those in group B, there were no differences in the proportion of probable, presumptive and histological BKN. With univariate logistic regression, pre-transplant DM and positive anti-HBc were significantly associated with development of very early BKV, while Caucasian ethnicity was a protective factor; only DM maintained statistical significance at multivariate analysis after adjustment for age and sex (OR 7959 with 95% CI 1593-39 771, p = 0.012). Time to eGFR &lt;50% from baseline and time to graft failure were significantly shorter in group C (see Fig. 2). With univariate logistic regression, higher cold-ischemia time and positive BKV within one month from transplant were significantly associated with eGFR loss &gt;50% at 12 months in our cohort; only BKV within one month maintained statistical significance at multivariate analysis after adjustment for age, sex and baseline eGFR (OR 22.17 with 95% CI 1.81-271.47, p = 0.015).

Conclusion
Patients who develop BKV very early after kidney transplantation are at increased risk of premature severe graft dysfunction (irrespective of the development of BKN); these patients should be offered close and intense surveillance with strategies aiming at identifying treatable causes of progressive kidney damage, and careful management of immunosuppressive treatment. Considering study design and low number of enrolled patients, further data are needed to confirm our findings, to elucidate risk factors for very early BKV and precise causes of rapid deterioration of graft function in these patients.