Meaning of Early Polyomavirus-BK Replication Post Kidney Transplant

doi:10.1016/j.transproceed.2010.03.130

Transplantation Proceedings

Volume 42, Issue 4, May 2010, Pages 1142-1145

https://doi.org/10.1016/j.transproceed.2010.03.130 Get rights and content

Abstract

Polyomavirus BK (BKV) infection is ubiquitous in the human population. Under immunosuppression, BKV can undergo reactivation resulting in viral replication. What really happens in the early hours posttransplantation is not clearly defined; the meaning of early viremia and viruria is not clear. BKV viremia is considered a marker of infection. The aim of our study was to investigate the prevalence of early BKV infection in kidney transplant patients, to evaluate the relationship to infections at 3 and 6 months and the association with recipient, donor, and graft features. We enrolled 36 kidney transplanted patients from May 2006 to April 2007. BKV load was measured on plasma and urine samples by Q-PCR at 12 hours (T₀/early) as well as 3 (T₃) and 6 (T₆) months thereafter. A high percentage of BKV infections were detectable in the first hours after transplantation (33.3%), which remained unchanged to month 6 post transplantation. Moreover, patients who were positive at T₀ had a high probability of remaining positive thereafter. The number of copies in plasma samples tended to increase at 3 months and to decrease thereafter, whereas the urine viral load tended to steadily increase. Among BKV-positive patients, we identified 2 groups according to viremic state at T₀: 9 patients (group A); who were already positive and remained so to T₆ 5 and 3 patients who turned positive at 3 or at 6 months, respectively (group B). Group A included 75% of positive patients at T₀ and 90% of positive patients at either T₃ or T₆ (P = .007). The most important contribution of our study was to highlight the presence of BKV infection in renal transplant recipients from the first hours posttransplantation. This condition seemed to be the most important risk factor for persistent infection in the first 6 months.

Section snippets

Materials and Methods

From May 2006 to April 2007, we enrolled 36 patients (21 men/15 women) listed for and undergoing cadaveric kidney transplantations. BKV load was measured by quantitative real-time polymerase chain reactions (Q-PCR) on plasma and urine samples at 12 hours (T₀/early), 3 (T₃), and 6 (T₆) months thereafter. At the same times we monitored urea, creatinine, blood count, serum sodium, and potassium. The study was approved by the Ethics Committee of the Faculty of Medicine.

We recorded clinical data:

Results

Recipient, donor, and graft characteristics are shown in Table 1. We studied 36 patients for 6 months posttransplant. Three patients were lost at T₃ and 2 subjects at T₆. BKV viremia occurred in 12/36 patients (33.3%; 95% CI, 20.2–49.7) at 12 hours posttransplantation (T₀); in 14/33 (42.4%; 95% CI, 27.2–59.2) at month 3 (T₃) and 16/32 (50%; 95% CI, 33.6–66.4) at month 6 (T₆); (P = .37). Viruria was present in 21/out of 36 patients (58.3%; 95% CI, 42.2–72.9) at T₀; in 18/33 patients (54.5%; 95%

Discussion

BKV infection is ubiquitous in the human population occurring during early childhood. In seropositive individuals with altered immunity, such as the transplant population, viral replication can reactivate, progress, and cause serious organ damage. Disruption of the balance between host immune control and virus replication is generally viewed as a key element in viral pathogenesis. In renal transplant patients, immunosuppression is considered to be the primary risk factor for the onset of BKV

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Early events during BK virus entry and disassembly
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There are more references available in the full text version of this article.

Cited by (12)

Optimisation and analysis of polymerase chain reaction based DNA sequencing for genotyping polyoma virus in renal transplant patients: A report from South India
2015, Indian Journal of Medical Microbiology
Purpose: To optimise a polymerase chain reaction (PCR) based DNA sequencing technique for genotyping polyoma virus in clinical specimens obtained from renal transplant patients. Materials and Methods: A hundred and thirty (106 peripheral blood and 24 urine) clinical specimens collected from renal transplant patients were included in the study for detecting the presence of DNA of BK virus (BKV), JC virus (JCV) by PCR targeting the viral protein 1 (VP1) gene. PCR based DNA sequencing was performed to determine the genotypes of polyoma virus and subjected to bioinformatics analysis to determine the amino acid sequences and screen for mutations in the VP1 gene. Results: Polyoma virus was detected in 23 (17.69%) specimens of which 19 (82.60%) were positive for BK virus, 3 (13.04%) for JC virus and 1 for both BK and JC virus. PCR based DNA sequencing detected BK virus genotype I in 12 (50%), genotype IV in 8 (33.3%) and JC virus in 4 (16.6%) clinical specimens. BKV genotype I was the predominant genotype (64.2% in peripheral blood and 33.33% in urine) prevalent in south India. Six novel mutations were found – at position 29, 30 to 47 of BKV genotype I; at position 11 and 15 of BKV genotype IV and at position 2 and 30 of JCV. Conclusion: BKV genotype I is the prominent genotype in India and novel mutations detected in the VP1 gene of BKV and JCV are being reported for the first time in literature.
BK polyomavirus infection in the renal transplant recipient
2013, Infectious Disease Clinics of North America
Citation Excerpt :
Thakur and colleagues8 published a prospective study monitoring BKV reactivation in 33 renal transplant patients, with a 3-year follow-up observation period, and demonstrated that the highest incidence of BK viruria and BK viremia occurred at 1 month post–renal transplant. Mitterhofer and colleagues,9 however, studied 36 renal transplant recipients prospectively, with the highest levels of viruria and viremia occurring 3 months post-transplant. Most studies have shown that reactivation occurs in the early post-transplant period.
Evaluation of different urine protocols and DNA extraction methods for quantitative detection of BK viruria in kidney transplant patients
2013, Journal of Virological Methods
Most transplant centers screen kidney transplant recipients for BK virus (BKV) infection using molecular techniques for the virus load determination. However, there is no consensus about the pre-analytical methods involved in the viral detection. In this study BK viral load was compared by the means of two urine treatment protocols (pelleted vs. whole urine) and two commercial DNA extraction kits for a quantitative PCR (qPCR) experiment. Ten patients who presented decoy cells in their urine sediment were selected for the study. Viral load was considerable higher (>1.5 log) for pelleted urine, in comparison to whole urine but no significant difference was observed between the extraction kits. PCR inhibition did not occur by using pelleted urine. In order to increase test sensitivity to detect BK viruria, pelleted urine should be the preferred urine compartment for qPCR experiments.
Dual positivity of donor and recipient plasma for BK virus confers a high risk for development of BK nephropathy in renal allograft
2012, Transplantation Proceedings
Citation Excerpt :
Hayat et al from our center described roughly one-third of recipients to be secretors of decoy cells before transplantation, supporting a recipient origin for the development of BKN.13 Similarly, Mitterhofer et al highlighted the presence of BKV infection in the first hours after renal transplantation, hypothesizing that a BKV infection already present before transplantation may have a role in early BKV replication.11 Bohl et al reasoned that if BKV infection in the recipient originates from the donor kidney, recipient pairs would be concordant for BKV infection more often than would be expected by chance.
BK nephropathy (BKN) is an important complication of renal transplantation, with a reported incidence between 1% and 10% in different parts of the world. Known risk factors for the development of BKN are the recently introduced immunosuppressants and steroids. However, the preexisting viral load may add to the risk for development of BKN. Therefore, the present study was designed to monitor the baseline BK virus (BKV) DNA in renal transplant donors and recipients in India for correlation with the development of BKN.
This study used real-time polymerase chain reaction (PCR) for quantification of BKV DNA in the plasma of kidney transplant donors (n = 38) and recipients (n = 87) at the time of surgery. The control BKV DNA was manufactured from a known positive human sample, by cloning a 133-bp PCR product of bases 4,329 to 4,462 of the large T-antigen (TAg) of BKV in a plasmid vector.
Twenty-five of 87 recipient (28.7%) and 17/38 donor (44.7%) plasma samples were positive for BKV DNA at the time of transplantation with a median viral load of 910 (range 49–4770) and 312 (range 79–1508) copies per mL plasma, respectively. Six of 38 donor-recipient pairs showed viremia in both the recipient and donor: 1 developed histologically proven BKN at 18 months, 1 showed positive immunohistochemistry for SV40 TAg, and 2 others had high levels of viremia (14,545 copies at 6 and 2,617,524 copies at 3 months). None of the other 81 recipients showed evidence of BKN in the follow-up period.
This study showed that 28% of recipients and 44% of donors displayed baseline positivity for BKV DNA in plasma, which is higher than the reported incidence in the West. The baseline levels of BKV DNA in recipients with end-stage renal disease were higher than in donors. Dual positivity for BKV DNA in the plasma of donor-recipient pairs conferred a high risk of development of BK nephropathy in the allografted kidney.
Polyomavirus BK replication in adult polycystic kidney disease post-renal transplant patients and possible role of cellular permissivity
2011, Transplantation Proceedings
Citation Excerpt :
Donor characteristics included age, gender, weight, body mass index, cause of death, histological score, and cold ischemia time of the grafts (Table 1). A real-time PCR method quantitated BKV load in plasma and urine samples as previously described.13 Briefly, DNA extraction was performed by the DNeasy Tissue Kit (QIAGEN S.p.A., Milan, Italy) according to the manufacturer's instructions.
Cell division and differentiation but not proliferation seem to be necessary for BK virus (BKV) replication and reactivation of persistent infection. Only terminal differentiating cells are permissive to BKV replication. Renal tubular epithelial cells in human adult polycystic kidney disease (ADPKD) are characterized by increased proliferative activity leading to cyst growth with less cellular differentiation. The aim of this study was to evaluate the possibility of different BKV replication patterns in patients with polycystic kidney disease versus non-ADPKD patients. From May 2006 to April 2008, we performed renal transplantations in 47. Eleven patients were affected by ADPKD (Pc group) and 36 patients, non ADPKD (n-Pc group). BKV replication was evaluated by quantitative real-time polymerase chain reactions (PCR) on plasma and urine samples at 12 hours (T0/early) as well as 3 (T3) and 6 (T6) months after transplantation. BKV viremia occurred in 9%, 12.5%, and 20% among the Pc group versus 33.3%, 42.4%, and 50% among the n-Pc group at 12 hours as well as 3 and 6 months posttransplantation, respectively. A higher discordance (BKV-PCR blood −/urine +) was observed in plasma and urine BKV replication among Pc versus n-Pc groups. We hypothesized that the lower number of patients with active BKV plasma replication in the Pc group may be related to a lower cellular permissivity of the renal tubular epithelial cells in ADPKD.
Polyomavirus BK replication in liver transplant candidates with normal renal function
2011, Transplantation Proceedings
Citation Excerpt :
We excluded patients with transjugular intrahepatic portosystemic shunts, hepatocellular carcinoma, acute infections, and evidence of chronic renal failure. Real-time PCR to detect BKV replication in samples of plasma and urine has been previously described.10 Using a 1-mm urine specimen incubated in lysis buffer and proteinase K (200 mg/mL), we performed DNA extraction using the DNeasy Tissue Kit (QIAGEN S.p.A., Milan, Italy) according to the manufacturer's instructions.
Polyomavirus-associated nephropathy (PVAN) has a predilection for kidney rather than for other solid organ transplants such as the liver. Immunosuppression is widely recognized to be a major risk factor for PVAN development. Since end-stage liver disease (ESLD) patients are immunocompromised and immunosuppression is a major cause of BK virus reactivation, we sought to evaluate BK virus replication in patients listed for liver transplantation. From April to October 2010, we enrolled 20 patients listed for liver transplantation. BK virus load was measured by quantitative real-time polymerase chain reaction on plasma and urine samples. Viremia occurred in only 1 among 20 patients. We hypothesized that in ESLD patients, the low prevalence of BK virus infection may be related to the prevalent impairment of antibacterial immunity rather than to the viral-specific one. In BK virus reactivation, not only the immunodepressive state itself, but also the specific immunologic mechanisms involved may have a role.

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Kidney transplantationComplication: InfectionMeaning of Early Polyomavirus-BK Replication Post Kidney Transplant

Abstract

Section snippets

Materials and Methods

Results

Discussion

Kidney Int

Kidney Int

Am J Transplant

Am J Transplant

Transplant Proceed

Early events during BK virus entry and disassembly

J Virol

Kidney transplantation
Complication: Infection
Meaning of Early Polyomavirus-BK Replication Post Kidney Transplant