Risk factors for BK viremia in kidney transplant recipients

Background. In the past 20 years, BK virus has emerged as a cause of early graft dysfunction after kidney transplantation. In the setting of chronic immunosuppression (IS), the latent virus can reactivate, leading to BK viremia (10-20%) and in 1-10% of kidney transplant recipients to BK virus nephropathy (BKVN). The early detection of BK viremia by serum DNA PCR screening allows prompt but controlled reduction of IS, which, despite numerous attempts to find specific antiviral agents, remains the mainstay therapy. So far, besides potent IS, no risk factor has been consistently associated with BK viremia/BKVN. The use of a ureteral stent at the time of transplantation to protect the ureterovesical anastomosis has been described as a potential trigger. In this study, we aimed at defining the incidence and kinetics of BK viremia in our local cohort of kidney transplant recipients, and analysed potential predictors of BK viremia/BKVN, including ureteral stents. Methods. We performed a single-centre retrospective study on consecutive patients who received a kidney transplant at the CHUV between 01.11.03 and 31.12.12, with at least 12 months follow-up. First, descriptive statistics were done to define the general characteristics of the population. From a total 308 patients, a subpopulation of 195, transplanted between 01.01.08 and 31.12.12, had enough data for relevant analysis of BK viremia status during the first year as well as the use of a ureteral stent. Statistical analyses were performed using R-software. Results. BK viremia (>1000 copies/ml at least twice) was detected in 37/195 (19%) patients within the first year post-transplantation, with an early onset in the first 4 months for 65%, whereas only 6 patients were newly diagnosed after 12 months. 28/195 (14.4%) had a peak BK viremia >10’000 copies/ml, which represents a high positive predictive value for BKVN. Patients with BK viremia had a significantly lower kidney function at one year as compared to BK viremia negative recipients (eGFR=58 vs. 67 ml/min; p=0.019), and eGFR decreased as viremia levels increased, in particular >10’000 copies/ml. We found no significant association with the type of graft (living vs. cadaveric donor), or IS protocols (Basiliximab vs. Thymoglobulin induction, tacrolimus vs. cyclosporine). Interestingly, combining recipient’s age and gender, we observed a higher risk to reactivate BK virus in older men (p=0.05). Ureteral stents were placed in 76/195 patients (39%), but their use did not significantly influence BK viremia. Conclusion. Considering the incidence of BK viremia in our population (22%), the fact that BKVN represents a poor prognosis factor for graft function and that viremia detection by PCR allows early diagnosis and management, our data reinforce the importance of regular screening early after kidney transplantation and in the case of unexplained rise in serum creatinine. Based on current knowledge and on our data, a prospective randomized multicentre study with controlled variables (IS, ureteral stents) and standardized follow-up charts (including urological complications/manipulations) would help better understand the determinants of BK viremia/BKVN