Background: Polyomavirus nephropathy (PyVN) leads to kidney transplant dysfunction and loss. Since a definitive diagnosis requires an invasive kidney biopsy, a timely diagnosis is often hampered. In this clinical dilemma the PyV-haufen-test, centering around the detection of three-dimensional PyV aggregates in the urine, might provide crucial diagnostic information.
Methods: A multistep experimental design. Hypothesis: PyV-haufen form within the kidneys under high concentrations of uromodulin, a kidney specific protein; PyV-haufen are kidney-specific-disease-markers.
Results: Investigative step A showed colocalization of uromodulin with aggregated PyV (i) in ten kidneys with PyVN by immunohistochemistry, (ii) in urine samples containing PyV-haufen by electron microscopy/immunogold labeling (n = 3), and (iii) in urine samples containing PyV-haufen by immunoprecipitation assays (n = 4). Investigative step B: In in-vitro experiments only high uromodulin concentrations of ≥ 1.25 mg/mL aggregated PyV, as is expected to occur within injured nephrons. In contrast, in voided urine samples (n = 59) uromodulin concentrations were below aggregation concentrations (1.2 -19.6 µg/mL). Investigative step C: 0/11 (0%) uromodulin KO-/- mice with histologic signs of PyVN showed urinary PyV-haufen shedding compared to 10/14 (71%) WT+/+ mice.
Conclusion: PyV-haufen form within kidneys under high uromodulin concentrations. Thus, PyV-haufen detected in the urine are specific biomarkers for intra-renal disease, i.e. definitive PyVN.
Keywords: BK-polyomavirus; biomarker; diagnosis; haufen-test; infection; kidney; polyomavirus nephropathy; transplantation; urine.
© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.