Elsevier

Microbial Pathogenesis

Volume 149, December 2020, 104558
Microbial Pathogenesis

Analysis of risk factors influencing the BK polyomavirus replication in patients with ESRD waiting for kidney transplantation

https://doi.org/10.1016/j.micpath.2020.104558Get rights and content

Highlights

  • Pre-transplant viral status could be considered as a risk factor for post-transplant BK virus replication that could lead to acute graft failure.

  • Determination of probable predictive factors leading to BK virus viremia in end-stage renal disease patients can be included in designing proper surveillance guidelines during pre and post-transplantation.

  • The prevalence of BK viremia among 192 patients with ESRD on hemodialysis was 7.3%.

  • Higher mean age among men could be considered as a significant risk factor for BK viremia in ESRD patients.

  • Parameters including: a high body mass index (BMI), older age and male gender can increase the rate of BK virus viremia in ESRD patients.

Abstract

Background

Since the pre-transplant status affects the renal transplantation success and ultimately the survival rate, identifying the probable risk factors that increase the chance of BK virus replication in end-stage renal disease patients can be included in proposing proper surveillance guidelines during pre and post-transplantation.

Methods

A descriptive cross-sectional study was performed by collecting plasma samples from 192 ESRD patients undergoing hemodialysis for at least 3 months. Quantitative Real-time PCR assay was used to detect and measure the BK viral load. Demographic and clinical characteristics of the patients who had BK viremia were documented.

Results

14 (7.3%) out of our 192 participants had BK virus viremia (95%CI 4.2%–11.6%). Demographic characteristics including etiology of ESRD and underlying diseases, mean duration and frequency of dialysis, co-infection with HBV and HCV did not affect the virus replication, since the difference between patients with BK virus viremia and BK virus negative individuals was not statistically significant. However, the statistical significance of the mean age of men with BKV and without BK virus viremia was found (OR: 3.42, P = 0.02 95%CI 0.86–13.61). Also, multiple regression analyses of some other parameters revealed that old age, high body mass index and male gender can be predictive factors of BK virus viremia in ESRD patients.

Conclusion

Based on our findings, elderly male had higher chance of being exposed to BK virus viremia. Some other demographic characteristics such as a high BMI, old age and gender (male) can increase the risk of BK viremia in patients with ESRD prior to 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.

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