Skip to main content
Top
Published in: BMC Infectious Diseases 1/2016

Open Access 01-12-2016 | Research article

Optimal use of plasma and urine BK viral loads for screening and predicting BK nephropathy

Authors: Peter Boan, Christopher Hewison, Ramyasuda Swaminathan, Ashley Irish, Kevin Warr, Rajalingam Sinniah, Todd M. Pryce, James Flexman

Published in: BMC Infectious Diseases | Issue 1/2016

Login to get access

Abstract

Background

BK virus is a polyoma virus causing renal allograft nephropathy. Reduction of immunosuppression with the early recognition of significant BK viral loads in urine and plasma can effectively prevent BKV associated nephropathy (BKVN), however the optimal compartment and frequency of BK viral load measurement post renal transplantation are undetermined. Our purpose was to examine time to detection and viral loads in urine compared to plasma, and establish viral load cut-offs associated with histological BKVN.

Methods

We performed a retrospective analysis of the BKV screening frequency and compartment(s) of 277 adult renal transplant recipients (RTR).

Results

BKVN was histologically diagnosed in 17 (6.1 %) RTR. In cases where both urine and plasma were tested fortnightly for 6 months (n = 53), BKV was detected in the urine 29 days earlier than plasma. Fortnightly (n = 72) versus 3-monthly (n = 78) testing demonstrated that BKV was detected in the urine significantly earlier (median 63 versus 97 days, p = 0.001) and at a lower level (median 3.27 versus 6.71 log10 c/mL, p < 0.001) with more frequent testing, but this difference was not evident in plasma first detection (80 versus 95 days, p = 0.536) or first positive viral load (3.18 versus 3.30 log10 c/mL, p = 0.603). The optimum cut-off BK viral load for histological diagnosis of BKVN was 4.10 log10 c/mL for the first positive urine, 3.79 log10 c/mL for the first positive plasma, 9.24 log10 c/mL for the peak urine, and 4.53 log10 c/mL for the peak plasma.

Conclusions

Frequent urinary BK viral load screening for the prevention of BKVN is suggested due to its high sensitivity and earlier detection.
Literature
1.
go back to reference Bressollette-Bodin C, Coste-Burel M, Hourmant M, Sebille V, Andre-Garnier E, Imbert-Marcille BM. A prospective longitudinal study of BK virus infection in 104 renal transplant recipients. Am J Transplant. 2005;5(8):1926–33.CrossRefPubMed Bressollette-Bodin C, Coste-Burel M, Hourmant M, Sebille V, Andre-Garnier E, Imbert-Marcille BM. A prospective longitudinal study of BK virus infection in 104 renal transplant recipients. Am J Transplant. 2005;5(8):1926–33.CrossRefPubMed
2.
go back to reference Hirsch HH, Randhawa P. BK Polyomavirus in solid organ transplantation. Am J Transplant. 2013;13:179–88.CrossRefPubMed Hirsch HH, Randhawa P. BK Polyomavirus in solid organ transplantation. Am J Transplant. 2013;13:179–88.CrossRefPubMed
3.
go back to reference Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009;9 Suppl 3:S1–S157. Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009;9 Suppl 3:S1–S157.
4.
go back to reference Hirsch HH, Brennan DC, Drachenberg CB, Ginevri F, Gordon J, Limaye AP, et al. Polyomavirus-associated nephropathy in renal transplantation: interdisciplinary analyses and recommendations. Transplantation. 2005;79:1277–86.CrossRefPubMed Hirsch HH, Brennan DC, Drachenberg CB, Ginevri F, Gordon J, Limaye AP, et al. Polyomavirus-associated nephropathy in renal transplantation: interdisciplinary analyses and recommendations. Transplantation. 2005;79:1277–86.CrossRefPubMed
5.
go back to reference Lim L, Kay ID, Palladino S, Flexman J. Variability in patterns of BK viral load after renal transplantation. Diagn Microbiol Infect Dis. 2008;61(3):302–8.CrossRefPubMed Lim L, Kay ID, Palladino S, Flexman J. Variability in patterns of BK viral load after renal transplantation. Diagn Microbiol Infect Dis. 2008;61(3):302–8.CrossRefPubMed
6.
go back to reference DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44:837–45.CrossRefPubMed DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44:837–45.CrossRefPubMed
8.
go back to reference Funk GA, Gosert R, Comoli P, Ginevri F, Hirsch HH. Polyomavirus BK replication dynamics in vivo and in silico to predict cytopathology and viral clearance in kidney transplants. Am J Transplant. 2008;8:2368–77.CrossRefPubMed Funk GA, Gosert R, Comoli P, Ginevri F, Hirsch HH. Polyomavirus BK replication dynamics in vivo and in silico to predict cytopathology and viral clearance in kidney transplants. Am J Transplant. 2008;8:2368–77.CrossRefPubMed
9.
go back to reference Babel N, Fendt J, Karaivanov S, Bold G, Arnold S, Sefrin A, et al. Sustained BK viruria as an early marker for the development of BKV-associated nephropathy: analysis of 4128 urine and serum samples. Transplantation. 2009;88:89–95.CrossRefPubMed Babel N, Fendt J, Karaivanov S, Bold G, Arnold S, Sefrin A, et al. Sustained BK viruria as an early marker for the development of BKV-associated nephropathy: analysis of 4128 urine and serum samples. Transplantation. 2009;88:89–95.CrossRefPubMed
10.
go back to reference Randhawa P, Ho A, Shapiro R, Vats A, Swalsky P, Finkelstein S, et al. Correlates of quantitative measurement of BK Polyomavirus (BKV) DNA with clinical course of BKV Infection in renal transplant patients. J Clin Microbiol. 2004;42(3):1176–80.CrossRefPubMedPubMedCentral Randhawa P, Ho A, Shapiro R, Vats A, Swalsky P, Finkelstein S, et al. Correlates of quantitative measurement of BK Polyomavirus (BKV) DNA with clinical course of BKV Infection in renal transplant patients. J Clin Microbiol. 2004;42(3):1176–80.CrossRefPubMedPubMedCentral
11.
go back to reference Kudose S, Dong J. Clinical validation study of quantitative real-time PCR assay for detection and monitoring of BK virus nephropathy. Ann Clin Lab Sci. 2014;44(4):455–60.PubMed Kudose S, Dong J. Clinical validation study of quantitative real-time PCR assay for detection and monitoring of BK virus nephropathy. Ann Clin Lab Sci. 2014;44(4):455–60.PubMed
12.
go back to reference Pollara CP, Corbellini S, Chiappini S, Sandrini S, De Tomasi D, Bonfanti C, et al. Quantitative viral load measurement for BKV infection in renal transplant recipients as a predictive tool for BKVAN. New Microbiol. 2011;34(2):165–71.PubMed Pollara CP, Corbellini S, Chiappini S, Sandrini S, De Tomasi D, Bonfanti C, et al. Quantitative viral load measurement for BKV infection in renal transplant recipients as a predictive tool for BKVAN. New Microbiol. 2011;34(2):165–71.PubMed
13.
go back to reference Hirsch HH, Knowles W, Dickenmann J, Passweq J, Klimkait T, Mihatsch MJ, et al. Prospective study of polyomavirus type BK replication and nephropathy in renal-transplant recipients. N Engl J Med. 2002;347:488–96.CrossRefPubMed Hirsch HH, Knowles W, Dickenmann J, Passweq J, Klimkait T, Mihatsch MJ, et al. Prospective study of polyomavirus type BK replication and nephropathy in renal-transplant recipients. N Engl J Med. 2002;347:488–96.CrossRefPubMed
14.
go back to reference Hassan S, Mittal C, Amer S, Khalid F, Patel A, Delbusto R, et al. Currently recommended BK virus (BKV) plasma viral load cutoff of ≥4 log10/mL underestimates the diagnosis of BKV-associated nephropathy: a single transplant center experience. Transpl Infect Dis. 2014;16(1):55–60.CrossRefPubMed Hassan S, Mittal C, Amer S, Khalid F, Patel A, Delbusto R, et al. Currently recommended BK virus (BKV) plasma viral load cutoff of ≥4 log10/mL underestimates the diagnosis of BKV-associated nephropathy: a single transplant center experience. Transpl Infect Dis. 2014;16(1):55–60.CrossRefPubMed
15.
go back to reference Costa C, Mantovani S, Piceghello A, Di Nauta A, Sinesi F, Sidoti F, et al. Evaluation of polyomavirus BK cellular immune response by an ELISpot assay and relation to viral replication in kidney transplant recipients. New Microbiol. 2014;37:219–23.PubMed Costa C, Mantovani S, Piceghello A, Di Nauta A, Sinesi F, Sidoti F, et al. Evaluation of polyomavirus BK cellular immune response by an ELISpot assay and relation to viral replication in kidney transplant recipients. New Microbiol. 2014;37:219–23.PubMed
16.
17.
go back to reference Chakera A, Bennett S, Lawrence S, Morteau O, Mason PD, O’Callaghan CA, et al. Antigen-specific T cell responses to BK polyomavirus antigens identify functional anti-viral immunity and may help to guide immunosuppression following renal transplantation. Clin Exp Immunol. 2011;165:401–9.CrossRefPubMedPubMedCentral Chakera A, Bennett S, Lawrence S, Morteau O, Mason PD, O’Callaghan CA, et al. Antigen-specific T cell responses to BK polyomavirus antigens identify functional anti-viral immunity and may help to guide immunosuppression following renal transplantation. Clin Exp Immunol. 2011;165:401–9.CrossRefPubMedPubMedCentral
18.
go back to reference Schachtner T, Muller K, Stein M, Diezemann C, Sefrin A, Babel N, et al. BK virus-specific immunity kinetics: a predictor of recovery from polyoma BK-associated nephropathy. Am J Transplant. 2011;11:2443–52.CrossRefPubMed Schachtner T, Muller K, Stein M, Diezemann C, Sefrin A, Babel N, et al. BK virus-specific immunity kinetics: a predictor of recovery from polyoma BK-associated nephropathy. Am J Transplant. 2011;11:2443–52.CrossRefPubMed
19.
go back to reference Randhawa PS, Khaleel-Ur-Rehman K, Swalsky PA, Vats A, Scantlebury V, Shapiro R, et al. DNA sequencing of viral capsid protein VP-1 region in patients with BK virus interstitial nephritis. Transplantation. 2002;73(7):1090–4.CrossRefPubMed Randhawa PS, Khaleel-Ur-Rehman K, Swalsky PA, Vats A, Scantlebury V, Shapiro R, et al. DNA sequencing of viral capsid protein VP-1 region in patients with BK virus interstitial nephritis. Transplantation. 2002;73(7):1090–4.CrossRefPubMed
20.
go back to reference Boldorini R, Omodeo-Zorini E, Suno A, Benigni E, Nebuloni M, Garino E, et al. Molecular characterization and sequence analysis of polyomavirus strains isolated from needle biopsy specimens of kidney transplant recipients. Am J Clin Path. 2001;116(4):489–94.CrossRefPubMed Boldorini R, Omodeo-Zorini E, Suno A, Benigni E, Nebuloni M, Garino E, et al. Molecular characterization and sequence analysis of polyomavirus strains isolated from needle biopsy specimens of kidney transplant recipients. Am J Clin Path. 2001;116(4):489–94.CrossRefPubMed
Metadata
Title
Optimal use of plasma and urine BK viral loads for screening and predicting BK nephropathy
Authors
Peter Boan
Christopher Hewison
Ramyasuda Swaminathan
Ashley Irish
Kevin Warr
Rajalingam Sinniah
Todd M. Pryce
James Flexman
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2016
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-016-1652-6

Other articles of this Issue 1/2016

BMC Infectious Diseases 1/2016 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.