Analysis of risk factors influencing the BK polyomavirus replication in patients with ESRD waiting for kidney transplantation
Introduction
Until the development of a recombinant VLP vaccine and specific antiviral drugs, BK virus would be remained as an insoluble problem in clinic [1,2]. BK virus has now been introduced as a major etiologic agent in developing early and late-onset nephropathy in renal and simultaneous kidney-pancreas (SPK) transplant recipients, respectively [3,4]. Interestingly, in the absence of effective antiviral drugs, it seems BK virus is at least as damaging to kidneys as rejection [5]. On the other hand, the International Agency for Research on Cancer (IARC) reported that BK virus is “possibly carcinogenic to humans”; as BK virus positivity has been reported in rare cases of urothelial carcinomas, mainly in transplant recipients [6,7]. Over the past decades, BK virus has been accompanied strongly by acute graft failure after renal transplantation. Determination of the predictive factors for BK virus replication may give rise to an early prediction algorithm for ensuing BK virus associated nephropathy [8]. Since the pre-transplant condition can influence the post-transplant surveillance, the BK virus incidence and probable risk factors leading to virus replication in ESRD patients may be assumed as a selection criteria and contributing factors in the proper management of renal-transplantation [9]. 60 to 90% of cases of infection with BKV occur before the age of 5–10 years, and then the virus remains hidden in the renal tubular epithelial cells and genitourinary tract [[10], [11], [12]]. The reactivation of latent BK virus could be more likely to occur due to the use of immunosuppressant, post-renal transplantation; Moreover, malignancy and infection with Human Immunodeficiency Virus (HIV) have been introduced as another risk factors for reactivation of BK virus [13]. In addition, a prolonged pre-transplant dialysis protocol among end stage renal disease could boost significantly the chance of BK virus reactivation after renal transplantation [8].
A person with Stage 5 chronic kidney disease (CKD) has end-stage renal disease (ESRD) and defined as irreversible decline in person's own kidney function with a GFR of 15 ml/min or less, and eventually dialysis or a renal transplant is needed to live. The most common causes of CKD and ESRD in developed countries are Diabetes mellitus type 2 and Hypertension [14]. In patients with end-stage renal disease, if dialysis is not provided, Uremia will cause inflammation and immune dysfunction as evidenced by an increased risk of viral-associated cancers, increased susceptibility to infections and decreased vaccination responses [15,16]. On the other hand, dialysis could lead to immune dysfunction in these patients [17,18]. Various factors such as Chronic Kidney Disease (CKD) and End-stage renal disease (ESRD) affect more than 1500 people per million populations in countries with a high prevalence, such as Japan, Taiwan, and the US [19]. Solid organ transplantation is a therapeutic method for many human diseases and becomes an effective therapeutic option for end-stage renal diseases [20]. Approximately, one quarter of people with ESRD receive a kidney transplant. In transplanted patients, BKV infection could lead to severe diseases such as polyomavirus-associated nephropathy and hemorrhagic cystitis. On the other hand, the development of tubulointerstitial nephropathy leads to the lack of performance and rejection of allograft transplantation in 1–10% of kidney transplanted recipients [8,13]. Mitterhofer AP, and colleagues suggested that pre-transplant viral status should be considered as an additional risk factor for post-transplant BKV replication [9]. Therefore, Determination of probable predictive factors leading to BK virus viremia in end-stage renal disease patients may allow us to propound algorithms for early prediction of reactivation and proposing proper surveillance guidelines during pre and post-transplantation. Since the pre-transplant status can affect the success of renal transplantation and ultimately the survival rate, identifying the underlying causes of reactivation of the BK virus in pre-transplantation can help with the proper management of patients. The goal of the present study was to determine the frequency and potential risk factors that may play a role in BK polyomavirus replication in end-stage renal disease patients.
Section snippets
Study subjects, sampling and DNA purification
A descriptive cross-sectional study was performed on all patients who underwent hemodialysis, for at least 3 months, during the year 2017, in Razi and Caspian dialysis centers of Rasht, Iran. The study was approved by ethics committee of Guilan university of medical sciences. Variables such as gender, age, BMI, etiology of ESRD (including chronic glomerulonephritis, polycystic kidney disease, other congenital diseases, kidney stones), underlying diseases (diabetes, hypertension), co-infection
Results
Patients included in this study, 123 (64.1%) male and 69 (35.9%) female, were 29–94 years old and the mean age of them was 60.39 ± 13.70 years. The prevalence of BK viremia was 7.3% (14 subjects) (95%CI 4.2–11.6). Table 1 shows the comparison of demographic and clinical characteristics in patients with and without BK viremia. We found a significant difference between males with and without BK viremia in terms of the mean age (OR: 3.42, P = 0.02 95%CI 0.86–13.61); however, this difference was
Discussion
Swedan SF has confirmed that chronic hemodialysis could raise the chance of BK virus replication in ESRD patients as compared to control group [22]. Nevertheless, we previously demonstrated that prolonged pre-transplant dialysis could be a potential risk factor for shedding of BK virus into urine in renal transplant recipients during post-transplantation [8]. Therefore, it can be concluded that chronic hemodialysis is a risk factor for reactivation of BK virus pre and post-transplantation. In
Author statements
Aydin Pourkazemi: study design. Mohammad Shenagari: study design, and preparation of manuscript. Ali Monfared: study design. Amir Hassankhani: Performing the experiments, and preparation of manuscript. Foroogh Nazari Chamaki: Data analysis, reviewing and editing the article. Masoud Khosravi: Conceived and designed the experiments. Mohammadkazem Lebadi: Preparation the specimens. Babak Ashrafkhani: reviewing and editing the article.
Financial support
This work was financially supported by Guilan University of Medical Sciences through the Grant No. 95120341.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgments
The authors thank all the colleagues at the Guilan University of Medical Sciences, Rasht, Iran who were coordinate in this research. We would like to thank Dr. Babak Ashrafkhani for his valuable comments to improve the manuscript.
References (24)
- et al.
European perspective on human polyomavirus infection, replication and disease in solid organ transplantation
Clin. Microbiol. Infect.
(2014 Sep) - et al.
BK virus replication in renal transplant recipients: analysis of potential risk factors may contribute in reactivation
J. Clin. Virol.
(2017 Nov 1) - et al.
Incidence of BK with tacrolimus versus cyclosporine and impact of preemptive immunosuppression reduction
Am. J. Transplant.
(2005 Mar) - et al.
BK virus in solid organ transplant recipients
Am. J. Transplant.
(2009 Dec) - et al.
KDOQI US commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD
Am. J. Kidney Dis.
(2014 May 1) - et al.
Effect of uremia on structure and function of immune system
J. Ren. Nutr.
(2012 Jan 1) - et al.
Transplantation immunology: solid organ and bone marrow
J. Allergy Clin. Immunol.
(2010 Feb 1) - et al.
Polyomavirus BK replication in de novo kidney transplant patients receiving tacrolimus or cyclosporine: a prospective, randomized, multicenter study
Am. J. Transplant.
(2013 Jan) - et al.
Strategies to prevent BK virus infection in kidney transplant recipients
Curr. Opin. Infect. Dis.
(2016 Aug) - et al.
Risk factors for BK virus viremia and nephropathy after kidney transplantation: a systematic review
J. Clin. Virol.
(2018 Oct 12)