Ureteral Stent Placement Increases the Risk for Developing BK Viremia after Kidney Transplantation

Hindawi Publishing Corporation Journal of Transplantation Volume 2014, Article ID 459747, 6 pages http://dx.doi.org/10.1155/2014/459747 Research Article Ureteral Stent Placement Increases the Risk for Developing BK Viremia after Kidney Transplantation Faris Hashim,1 Shehzad Rehman,2 Jon A. Gregg,2 and Vikas R. Dharnidharka1,3 1 Divisions of Pediatric Nephrology, University of Florida College of Medicine, Gainesville, FL, USA Transplant Nephrology, University of Florida College of Medicine, Gainesville, FL, USA 3 St. Louis Children’s Hospital-Division of Pediatric Nephrology, Washington University School of Medicine, St. Louis, MO 63110-1093, USA 2 Correspondence should be addressed to Vikas R. Dharnidharka; Received 21 April 2014; Revised 5 August 2014; Accepted 21 August 2014; Published 11 September 2014 Academic Editor: Parmjeet Randhawa Copyright © 2014 Faris Hashim et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The placement of ureteral stent (UrSt) at kidney transplantation reduces major urological complications but increases the risk for developing nephropathy from the BK virus. It is unclear whether UrSt placement increases nephropathy risk by increasing risk of precursor viral replication or by other mechanisms. We retrospectively investigated whether UrSt placement increased the risk for developing BK Viremia (BKVM) in adult and pediatric kidney transplants performed at the University of Florida between July 1, 2007, and December 31, 2010. In this period all recipients underwent prospective BKV PCR monitoring and were maintained on similar immunosuppression. Stent placement or not was based on surgeon preference. In 621 transplants, UrSt were placed in 295 (47.5%). BKVM was seen in 22% versus 16% without UrSt (𝑃 = 0.05). In multivariate analyses, adjusting for multiple transplant covariates, only UrSt placement remained significantly associated with BKVM (𝑃 = 0.04). UrSt placement significantly increased the risk for BKVM. Routine UrSt placement needs to be revaluated, since benefits may be negated by the need for more BK PCR testing and potential for graft survival-affecting nephritis. 1. Introduction BK virus (BKV) was first isolated in 1971 from the urine of a Sudanese renal transplant recipient who presented with ureteral stenosis [1]. Years later, a new era in the study of BKV began when BK nephropathy (BKN) was diagnosed by a needle biopsy in a renal transplant (RTx) recipient suspected of having acute rejection [2]. In the following years, additional cases were reported from kidney transplant centers worldwide [3–5]. In nonimmunosuppressed hosts, BKV infection remains latent and asymptomatic in uroepithelial cells, though a fraction of asymptomatic seropositive subjects shed virus into the urine [6]. In states of immunosuppression, such as after kidney transplantation, BKV is reactivated and infection can progress from viruria to viremia, followed by nephropathy [7]. Efforts to eradicate this problem have included the identification of risk factors, early detection of BK viruria (BKVU) and BK viremia (BKVM) through serial PCR screening, early diagnostic biopsy for allograft dysfunction, minimization of immunosuppression for biopsy-proven BKN, and the employment of pharmacotherapy [8]. Risk factors for BKV infection include a higher degree of human leukocyte antigen mismatch, pediatric status, aggressive immunosuppressive regimen, and transplant ureteral stent use [9]. The role of stents is controversial. In two prior single center adult studies, the placement of ureteral stent (UrSt) at the time of kidney transplant was associated with 4-fold increase in the risk for developing BKVN [10, 11]. Our previous pediatric study also showed a 4-fold higher risk, but this result did not reach statistical significance due to limited single center sample size [12]. In this era, the precursor viral replication stages BK viremia (BKVM) and BK viruria (BKVU) were not monitored. It was unclear from these studies whether the increased BK virus nephropathy (BKVN) risk with UrSt placement was secondary to increased likelihood of viral replication or due to other factors unrelated 2 to, or after, replication initiation. Two studies reported an increased risk in the precursor viral replication stage BKVM with UrSt placement at kidney transplant. In both studies, BKVU was not assessed [13, 14]. A twelve-month prospective multicenter study that randomized renal transplant patients to cyclosporine or tacrolimus showed that BKV viremia increased in recipients with any of: higher corticosteroids, using tacrolimus compared to cyclosporine, older age and male gender at month 12 post-transplant [15]. Diagnosing a direct effect of UrSt placement is difficult since by the time there is a clinical correlation such as acute renal failure, hydronephrosis, and ureteral stenosis there is so much fibrosis that BK is not evident. Animal studies have confirmed this [16]. After our adult and pediatric kidney transplant programs instituted a universal BKV serum screening protocol, our practice has been to reduce immunosuppression at time of BK viremia. This has led to a change in the natural history of BKV infection, with nephropathy much less frequent but viruria and viremia commonly detected. The purpose of this study was to determine the association between transplant UrSt placement and both BKVM/BKVU in a larger group of recipients at a center that performs a large number of adult and pediatric kidney transplants. We report the largest series to date demonstrating the relationship between transplant ureteral stenting and early stages of BKV infection. 2. Methods After approval from the Shands Hospital at University of Florida Institutional Review Board, we conducted a retrospective secondary data analysis of all eligible adult and pediatric renal transplants conducted at our institution between July 1, 2007, and December 31, 2010. All eligible subjects had to have at least 15 days of graft survival and at least 12 months of follow up; otherwise those cases were censored out. At our center, all ureteroneocystostomies during the study time period were performed by extravesical (Lich-Gregoir) technique. All indwelling stents placed were 6-French 12 cm double-J type. All transplants were performed by four surgeons in which certain surgeons almost always stented, whereas others never stented, and that choice of surgeon was arbitrary. Transplant ureteral stents were removed 6–8 weeks following transplantation. We extracted data on recipient demographics (age, sex, race, and primary diagnosis), donor demographics (age, sex, and race), donor source (living or deceased), transplant characteristics (ureteral stent or not, PRA, HLA mismatch, ischemia times, and DGF or not), and initial posttransplant immunosuppression (...truncated)