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 Ranst; Geert Verbeke; Maarten Coemans; Maarten Naesens

doi:10.1016/j.kint.2023.07.025

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

Kidney Int. 2023 Nov;104(5):1018-1034. doi: 10.1016/j.kint.2023.07.025. Epub 2023 Aug 19.

Authors

Evert Cleenders¹, Priyanka Koshy², Elisabet Van Loon³, Katrien Lagrou⁴, Kurt Beuselinck⁵, Graciela Andrei⁶, Marta Crespo⁷, Katrien De Vusser³, Dirk Kuypers³, Evelyne Lerut², Kris Mertens⁸, Olga Mineeva-Sangwo⁶, Parmjeet Randhawa⁹, Aleksandar Senev¹⁰, Robert Snoeck⁶, Ben Sprangers¹¹, Claire Tinel⁸, Amaryllis Van Craenenbroeck³, Jan van den Brand⁸, Marc Van Ranst¹², Geert Verbeke¹³, Maarten Coemans¹, Maarten Naesens¹⁴

Affiliations

¹ Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven, Leuven, Belgium; Department of Public Health and Primary Care, Leuven Biostatistics and Statistical Bioinformatics Centre, KU Leuven, Leuven, Belgium.
² Department of Imaging and Pathology, University Hospitals Leuven, Leuven, Belgium.
³ Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven, Leuven, Belgium; Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium.
⁴ Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical Microbiology, KU Leuven, Leuven, Belgium.
⁵ Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical Microbiology, KU Leuven, Leuven, Belgium; Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium.
⁶ Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, KU Leuven, Leuven, Belgium.
⁷ Department of Nephrology, Hospital del Mar Medical Research Institute (IMIM), Hospital del Mar, Barcelona, Spain.
⁸ Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven, Leuven, Belgium.
⁹ Division of Transplantation Pathology, the Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center-Montefiore Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
¹⁰ Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven, Leuven, Belgium; Histocompatibility and Immunogenetics Laboratory, Belgian Red Cross-Flanders, Mechelen, Belgium.
¹¹ Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium; Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Molecular Immunology, KU Leuven, Leuven, Belgium.
¹² Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Clinical and Epidemiological Virology, KU Leuven, Leuven, Belgium.
¹³ Department of Public Health and Primary Care, Leuven Biostatistics and Statistical Bioinformatics Centre, KU Leuven, Leuven, Belgium.
¹⁴ Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven, Leuven, Belgium; Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium. Electronic address: [email protected].

PMID: 37598855
DOI: 10.1016/j.kint.2023.07.025

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.

Keywords: biopsy; kidney transplantation; polyomavirus nephropathy; screening.