Urinary Polyomavirus Haufen Shedding Accurately Reflects Intrarenal Burden of Polyomavirus Nephropathy (PVN): Comparative Quantitative Analyses of Different Screening Techniques.
Harsharan Singh, Kozlowski Tomasz, True Karen, Vimal Derebail, Detwiler Randy, Adil Gasim, Volker Nickeleit. The University of North Carolina, Chapel Hill
Background: We previously defined a new, qualitative noninvasive test to accurately diagnose PVN, a common infectious complication in renal allografts. The test is based on the detection of three dimensional cast-like polyomavirus (PV) aggregates, "Haufen", in voided urine samples. Urinary Haufen-testing is highly accurate for PVN (positive and negative predictive values > 95%).
Aim: Quantitative assessment of urinary Haufen shedding, viremia and viruria (by PCR, urine cytology) was performed and correlated with intrarenal signs of PV replication/PVN (viral detection by immunohistochemistry: SV40-T antigen). Hypothesis: In comparison to conventional screening techniques, the degree of urinary Haufen shedding most accurately reflects the extent of intrarenal PV replication and "viral burden".
Design: Quantitative analysis of urinary Haufen shedding (number Haufen/mL), PCR assays (serum, urine), and quantitation of urinary decoy cell shedding (number decoy cells/ThinPrep® slide) were performed on 39 samples from 37 patients with concurrent biopsy proven PVN. Results were correlated with biopsy findings (PVN disease stage and number of cells / %tubules expressing SV40-T antigen). Statistics were performed using Kruskal Wallis testing with ties.
Results: Degree of intrarenal polyomavirus replication: The number of urinary Haufen/mL showed the tightest correlation with the number of SV40-T expressing cells (correlation coefficient (cc) 0.86) and with the percentage of affected tubules (cc 0.70) in allografts with PVN (in comparison: cc viremia by PCR: 0.45; cc viruria by PCR: 0.45; cc decoy cells: 0.01). PVN disease stages: Only the number of urinary Haufen/mL showed a significant correlation with PVN disease stages (p<0.0001). Neither the degree of viremia nor viruria and decoy cell shedding correlated with PVN disease stages.
Conclusions: Haufen-testing is the most accurate noninvasive technique to diagnose PVN, predict PVN disease stages, and also to monitor the degree of polyomavirus replication. It may help to better assess the effectiveness of anti-viral therapy during persistent disease.
Category: Kidney (does not include tumors)
Monday, February 28, 2011 2:45 PM
Platform Session: Section H, Monday Afternoon