The Urinary Polyomavirus-Haufen Test: A Highly Predictive Non-Invasive Biomarker to Distinguish “Presumptive” from “Definitive” Polyomavirus Nephropathy: How to Use It—When to Use It—How Does It Compare to PCR Based Assays?
Abstract
:1. Introduction
2. Main Body
2.1. PyV-Haufen—Definition and Characteristics
2.2. Urinary PyV-Haufen Assays: A Qualitative, Quantitative and Comparative Test Analysis
2.2.1. PyV-Haufen Testing: Qualitative Assay
- Group 1, no PyV activation: 581/809 patients (72%):
- Decoy cell analysis negative or with no more than one positive decoy-test(cut-off for positive test ≥10 decoy cells per ThinPrep cytology preparation);
- BKPy-viremia undetectable or always less than 250 viral copies/mL plasma;
- No “definitive” PyVN in all available biopsies.
- Group 2, PyV activation with positive decoy-cell tests: 37/809 patients (5%):
- Decoy cell analysis positive with two or more positive decoy-tests(cut-off for positive test ≥10 decoy cells per ThinPrep cytology preparation);
- BKPy-viremia undetectable or always less than 250 viral copies/mL plasma;
- No “definitive” PyVN in all available biopsies.
- Group 3, PyV activation with low level BKPy-viremia: 78/809 patients (10%):
- Decoy cell test positive or negative;
- BKPy-viremia between 250 and 9999 viral copies/mL plasmain one or more tests, and no test ≥104 viral copies/mL plasma;
- No “definitive” PyVN in all available biopsies.
- Group 4, PyV activation with high level BKPy-viremia: 32/809 patients (4%):
- Decoy cell tests positive or negative;
- BKPy-viremia variable with at least one test ≥104 viral copies/mL plasma;
- No “definitive” PyVN in all available biopsies.
- Group 5, biopsy proven “definitive” PyVN: 81/809 patients (10%):
- Decoy cell tests positive or negative;
- BKPy-viremia variable;
- Biopsy diagnosis of PyVN in all patients.
2.2.2. PyV-Haufen Testing: Quantitative Assay
2.3. Urinary PyV-Haufen Testing: Clinical Indications
2.4. Urinary PyV-Haufen Testing: Technical Guidelines and Recommendations
2.4.1. Urine Collection and Storage
2.4.2. Grid Preparation for EM and Negative Staining Protocols
2.4.3. PyV-Haufen Detection by EM: Best Practice Recommendations
3. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
Abbreviations
BKPyV- | BK-polyomavirus strain |
EM- | (transmission) electron microscopy |
LM- | (standard) light microscopy |
PCR- | (quantitative) polymerase chain reaction |
PyV- | polyomavirus |
Pvl- | histologic Banff score of intra renal polyomavirus load levels ranging from “0” (no PyV detected) to “3” (marked PyV load with >10% infected renal tubules) |
PyVN- | polyomavirus nephropathy (biopsy proven definitive renal disease) |
UNC | The University of North Carolina at Chapel Hill. |
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Groups N (Patients in Group) | PyV-Haufen Positive N (%) | PyV Haufen Negative N (%) | N Patients Tested for PyV-Haufen |
---|---|---|---|
Group 1 N = 581 No PyV activation | 1 (6) | 16 (94) | 17 |
Group 2 N = 37 PyV activation with positive decoy-cell tests | 0 (0) | 24 (100) | 24 |
Group 3 N = 78 PyV activation with low level BKPy-viremia | 1 (2) | 56 (98) | 57 |
Group 4 N = 32 PyV activation with high level BKPy-viremia | 0 (0) | 31 (100) | 31 |
Group 5 N = 81 Biopsy proven “definitive” PyVN | 80 (99) | 1 (1) | 81 |
N Patients tested | 82 | 128 | 210 |
Test | Patients with “Definitive” PyVN N 2 | Patients with “Definitive” PyVN -and- Positive Test 3 N | Sensitivity (%) | Patients without “Definitive” PyVN N | Patients without “Definitive” PyVN -and- Negative Test 4 N | Specificity (%) |
---|---|---|---|---|---|---|
Urine cytology/Decoys | ||||||
≥2 tests with ≥10 cells | 60 | 30 | 50 | 114 | 62 | 54 |
BKPy-viremia by PCR | ||||||
≥104 viral copies/mL | 61 | 40 | 66 | 102 | 82 | 80 |
≥250 viral copies/mL | 61 | 59 | 97 | 102 | 33 | 32 |
Urinary PyV-Haufen | 64 | 64 | 100 | 118 | 116 | 98 |
Test Marker (At Time of Index Biopsy) | Statistic | PyVN Disease Class (In Index Biopsy) | |||
---|---|---|---|---|---|
Class 1 | Class 2 | Class 3 | p-Value * | ||
PyV Haufen | Median | 416.5 | 1411 | 7881 | <0.001 |
(number/mL urine) | IQR | 282–451 | 903–3104 | 6732–9030 | |
N | 32 | 39 | 2 | ||
BKPy-viremia | Median | 1.39 | 2.74 | 11.83 | 0.098 |
(×104 viral copies/mL) | IQR | 0.31–3.48 | 0.59–10.02 | 2.52–21.13 | |
N | 27 | 35 | 2 | ||
BKPy-viruria | Median | 0.82 | 5.70 | 3.84 | 0.086 |
(×108 viral copies/mL) | IQR | 0.28–14.90 | 0.80–20.70 | 3.60–4.08 | |
N | 29 | 38 | 2 |
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Nickeleit, V.; Davis, V.G.; Thompson, B.; Singh, H.K. The Urinary Polyomavirus-Haufen Test: A Highly Predictive Non-Invasive Biomarker to Distinguish “Presumptive” from “Definitive” Polyomavirus Nephropathy: How to Use It—When to Use It—How Does It Compare to PCR Based Assays? Viruses 2021, 13, 135. https://doi.org/10.3390/v13010135
Nickeleit V, Davis VG, Thompson B, Singh HK. The Urinary Polyomavirus-Haufen Test: A Highly Predictive Non-Invasive Biomarker to Distinguish “Presumptive” from “Definitive” Polyomavirus Nephropathy: How to Use It—When to Use It—How Does It Compare to PCR Based Assays? Viruses. 2021; 13(1):135. https://doi.org/10.3390/v13010135
Chicago/Turabian StyleNickeleit, Volker, Vicki G. Davis, Bawana Thompson, and Harsharan K. Singh. 2021. "The Urinary Polyomavirus-Haufen Test: A Highly Predictive Non-Invasive Biomarker to Distinguish “Presumptive” from “Definitive” Polyomavirus Nephropathy: How to Use It—When to Use It—How Does It Compare to PCR Based Assays?" Viruses 13, no. 1: 135. https://doi.org/10.3390/v13010135