"Definitive" biopsy proven polyomavirus nephropathy (PyVN), usually caused by BK polyomavirus (BKPyV), remains a significant infection of kidney transplants. Diagnosis depends upon an allograft biopsy and outcome depends upon early intervention. Here, we report data on a non-invasive biomarker for PyVN, the urinary PyV-Haufen test. Test results were compared to those of conventional laboratory assays targeting PyV replication, i.e., BKPy-viremia, -viruria and urinary decoy cell shedding. Of 809 kidney transplant recipients, 228 (28%) showed PyV replication with decoy cell shedding and/or BKPy-viremia by quantitative PCR; only a subset of 81/228 (36%) showed "definitive" PyVN. Sensitivity and specificity for identifying patients with PyVN was: 100% and 98%, respectively, urinary PyV-Haufen test; 50% and 54%, respectively, urinary decoy cell shedding; 97% and 32%, respectively, BKPy-viremia with cut-off of >= 250 viral copies/mL; 66% and 80%, respectively, for BKPy-viremia >= 10(4) viral copies/mL. The PyV-Haufen test showed a very strong correlation with the severity of PyVN (Spearman's rho = 0.84) and the Banff PyVN disease classes (p < 0.001). In comparison, BKPy-viremia and -viruria levels by PCR displayed modest correlations with PyVN severity (Spearman's rho = 0.35 and 0.36, respectively) and were not significantly associated with disease classes. No association was found between decoy cell shedding and PyVN severity or disease classes. Pilot data demonstrated that PyVN resolution with decreasing Banff pvl-scores was reflected by a gradual decrease in PyV-Haufen shedding; such a tight association was not noted for BKPy-viremia. In conclusion, urinary PyV-Haufen testing is a highly specific, non-invasive method to accurately diagnose patients with "definitive" PyVN and to optimize patient management. Assay specifics are discussed.
