An observational cohort study of histological screening for BK polyomavirus nephropathy following viral replication in plasma

Evert Cleenders, Priyanka Koshy, Elisabet Van Loon, Katrien Lagrou, Kurt Beuselinck, Graciela Andrei, Marta Crespo, Katrien De Vusser, Dirk Kuypers, Evelyne Lerut, Kris Mertens, Olga Mineeva-Sangwo, Parmjeet Randhawa, Aleksandar Senev, Robert Snoeck, Ben Sprangers, Claire Tinel, Amaryllis Van Craenenbroeck, Jan van den Brand, Marc Van RanstGeert Verbeke, Maarten Coemans, Maarten Naesens*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Systematic screening for BKPyV-DNAemia has been advocated to aid prevention and treatment of polyomavirus associated nephropathy (PyVAN), an important cause of kidney graft failure. The added value of performing a biopsy at time of BKPyV-DNAemia, to distinguish presumptive PyVAN (negative SV40 immunohistochemistry) and proven PyVAN (positive SV40) has not been established. Therefore, we studied an unselected cohort of 950 transplantations, performed between 2008-2017. BKPyV-DNAemia was detected in 250 (26.3%) transplant recipients, and positive SV40 in 91 cases (9.6%). Among 209 patients with a concurrent biopsy at time of first BKPyV-DNAemia, 60 (28.7%) biopsies were SV40 positive. Plasma viral load showed high diagnostic value for concurrent SV40 positivity (ROC-AUC 0.950, 95% confidence interval 0.916-0.978) and the semiquantitatively scored percentage of tubules with evidence of polyomavirus replication (pvl score) (0.979, 0.968-0.988). SV40 positivity was highly unlikely when plasma viral load is below 4 log10 copies/ml (negative predictive value 0.989, 0.979-0.994). In SV40 positive patients, higher plasma BKPyV-DNA load and higher pvl scores were associated with slower viral clearance from the blood (hazard ratio 0.712, 95% confidence interval 0.604-0.839, and 0.327, 0.161-0.668, respectively), whereas the dichotomy positivity/negativity of SV40 immunohistochemistry did not predict viral clearance. Although the pvl score offers some prognostic value for viral clearance on top of plasma viral load, the latter provided good guidance for when a biopsy was unnecessary to exclude PyVAN. Thus, the distinction between presumptive and proven PyVAN, based on SV40 immunohistochemistry, has limited clinical value. Hence, management of BKPyV-DNAemia and immunosuppression reduction should be weighed against the risk of occurrence of rejection, or exacerbation of rejection observed concomitantly.

Original languageEnglish (US)
Pages (from-to)1018-1034
Number of pages17
JournalKidney international
Volume104
Issue number5
DOIs
StatePublished - Nov 2023

Funding

This work was supported by the Research Foundation – Flanders (FWO; grant number: T004417N). MN and BS are supported by the Research Foundation – Flanders (FWO) as senior clinical investigator (grant agreement numbers: 1844019N and 1842919N, respectively). MC is partially supported by INT21/00003 (Spanish Ministry of Health ISCIII FIS-FEDER). EC and MN designed the study. EC performed data analysis and prepared the figures and tables. EVL, AVC, PK, and MN were involved in data and sample collection. The manuscript was written by EC and MN and was revised by all co-authors. This work was supported by the Research Foundation – Flanders (FWO; grant number: T004417N ). MN and BS are supported by the Research Foundation – Flanders (FWO) as senior clinical investigator (grant agreement numbers: 1844019N and 1842919N, respectively). MC is partially supported by INT21/00003 (Spanish Ministry of Health ISCIII FIS-FEDER).

Keywords

  • biopsy
  • kidney transplantation
  • polyomavirus nephropathy
  • screening

ASJC Scopus subject areas

  • Nephrology

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