Ebrahimi M, Mohebbi A, Mostakhdem Hashemi M, Ashrafi Shahmirzadi M. Prevalence of BK Virus among Iranian Renal Transplant Recipients: A Systematic Review and Meta-Analysis. jcbr 2020; 4 (4) :50-61
URL:
http://jcbr.goums.ac.ir/article-1-295-en.html
1- Children's Research Center, Golestan University of Medical Sciences, Gorgan, Iran
2- 1.Department of Microbiology, Faculty of Advanced Sciences, Islamic Azad University, Tehran, Iran 2. Student Research Committee, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran 3. Stem Cell Research Center, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran , Mohebbi-a@goums.ac.ir
3- Metabolic Disorder Research Centre, Golestan University of Medical Sciences, Gorgan, Iran
4- Student Research Committee, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
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ABSTRACT
Background and objectives: BK virus (BKV) reactivation is a major challenge for renal transplant recipients. The purpose of this study was to summarize current knowledge on the status of BKV in Iranian renal transplant recipients.
Methods: Specific terms, including “BKV” and “Renal Transplantation” were used to search the online databases. I2 and Cochran’s Q-value were tested for heterogeneity. The incidence rate was determined at 95% confidence interval. Publication bias was also investigated using funnel plot, the Egger’s and Begg’s statics.
Results: Twelve studies were included in the study. The random model's overall evidence rate was 0.347 (CI 95%, 0.225-0.493, p-value=0.04).
Conclusions: In Iran, the estimated prevalence of BKV among renal transplant recipients is 34.7% (~10-60%), which is higher than the rate reported from other parts of the world. Therefore, it is recommended to screen organ donors for BKV in Iran.
Keywords: Bk Virus; Systematic Review; Meta-Analysis; Renal Transplantation
INTRODUCTION
Kidney transplantation is the last-line treatment for end-stage renal disease (ESRD). In this regard, there are major concerns regarding graft rejection due to immunity and a variety of viral infections. BK virus (BKV), a member of the Polyomaviridae family, is involved in the rejection of renal transplants. It is known that > 60% of healthy adults are seropositive to Polyomaviridae that may become active under immunosuppression (1). Reactivation of polyomaviruses in renal and bone marrow transplant recipients is related to the use of immunosuppressive drugs and immunodeficiency (2,3). Therefore, it is important to examine the prevalence of these viruses in transplant recipients in order to assess the impact of the virus on graft rejection (4).
BKV is a human polyomavirus that was first isolated from the urine of an immunocompromised renal transplant patient in 1971 (5). Primary respiratory tract infection contributes to asymptomatic latent BKV infection, which results in a high rate of seropositivity in humans (6). The use of immunosuppressive drugs in transplant recipients increases the risk of BKV infection (7–10). BKV may be reactivated following renal transplantation, leading to nephropathy accompanied with renal graft rejection. BKV may be transmitted via respiratory and oral routes, and has 82% seroprevalence in adults (6). In a previous research in Iran, BKV was detected in 13.1% of biopsy samples from renal transplant patients (11). Samarbasf-Zadeh et al. demonstrated a 3-fold increase in BKV reactivation within four months of renal transplantation (12). BKV strains have also been reported to be associated with BK viruria in liver transplant recipients (13).
BKV is classified into four serotypes (I-IV). Within the world's population, serotype I is the most common (80%), followed by serotype IV (15%) (6). In a small population sample, Motazakker et al. have
shown that BKV serotype I is prevalent in Iranian-Turkish renal transplant recipients (14). In a relatively larger study in Iran, BKV serotype I (94.11%) was found to be predominant serotype compared to serotype IV (5.89%) (15).
Given the clinical significance of BKV examination of renal transplant recipients, particularly immunocompromised patients, this systematic review and meta-analysis was performed to summarize the latest knowledge on BKV incidence in Iranian renal transplant recipients.
MATERIALS AND METHODS
Search strategy
We performed this systematic review and meta-analysis according to the Meta-Analysis of Observational Studies in Epidemiology consensus statement and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). PubMed, Google Scholar and Iranian medical repositories have been screened for reports on BKV prevalence in Iran. For PubMed, the following keywords were used: "BK virus" OR "BKV" in title AND "renal transplantation" OR "kidney transplantation" in title/abstract, AND "Iran" in affiliation. The findings were filtered into "Epidemiology". Last adjustment was rendered by the transfer of data on the human subject/species. For Google Scholar, the exact phrase "BK virus" And "BKV" plus "Iran" plus "renal transplantation" OR "kidney transplantation" were searched. All data published until the end of 2018 were included in the study.
Inclusion and exclusion criteria
Abstract/full manuscripts in English or Persian were included. Accordingly, researches describing BKV experiments in countries other than Iran were excluded. In addition, review papers were not included in the analysis. Studies on BKV incidence in immunocompromised patients, rather than renal transplant recipients, were also excluded. Grey studies or unpublished
papers were included. There was only one report from our department that has not yet been published.
Study screening and data extraction
After retrieval, the abstracts of each study were screened and checked for eligibility. Then full-texts were read by two researchers. Any disagreement between the two researchers was resolved through discussion with a third researcher. Data regarding names of authors, year of publication, number of patients and control subjects, gender, mean age, sample size and BKV detection method(s) in both case (renal transplant recipients) and/or control (healthy volunteers) groups were collected.
Data analysis
Meta-analysis was conducted using the Comprehensive Meta-Analysis Software V2 (16). Study type was specified as "Estimate of means, proportions of rates in one category at a time-point". Effect size data entry was set as two dichotomous formats, representing non-events and sample sizes in each group. This helped determine the incidence rate of BKV among renal transplant recipients. I2 and Cochran’s Q-value were used for heterogeneity. I2 value of more than 25% indicated heterogeneity. The incidence rate was evaluated at 95% confidence interval (CI). Publication bias was also double-checked by funnel plot and Egger's and Begg's methods. A p-value of less than 0.05 was considered as statistically significant.
RESULTS
Literature review and data extraction
Overall, 12 studies as well as a study performed in our department were eligible for inclusion in the analysis. Data were collected for BKV detection in different types of samples. In this respect, the research was extended to 15 studies (Figure 1). For example, results from two urine and plasma samples were obtained in one study and analyzed separately (12). Similar data were collected from two additional studies performed by Shenagari et al. (urine and plasma) and Pakfetrat et al. (plasma and biopsy) (17,18). More data were collected for the study of subgroups. As a result, four groups of BKV detection were derived from the included experiments, including real-time PCR (7/15), PCR (5/15), double PCR and semi-nested PCR (2/15), and light microscopy (1/15)