TABLE 5.
Consensus recommendations: diagnostics
| Screening |
| • We recommend regular screening of kidney transplant recipients for BKPyV replication to identify patients for treatment of probable/presumptive/biopsy-proven BKPyV-nephropathy (strong, A) |
| • We recommend screening kidney transplant recipients for plasma BKPyV loads monthly until mo 9, then every 3 mo until 2 y posttransplantation (strong, B; Figure 1) |
| • If plasma BKPyV-DNA loads are 1000–10 000 c/mL (or equivalent), we suggest confirmatory testing within 2–3 wk (weak, B) |
| • In kidney transplant recipients with sustained plasma BKPyV-DNA loads >1000 c/mL (or equivalent), we suggest monitoring BKPyV-DNAemia every 2–4 wk to assess dynamics and response to the intervention (weak, D) |
| • In kidney transplant recipients requiring increased immunosuppression or antirejection therapy, we suggest resuming monthly screening for BKPyV-DNAemia for the next 3 mo (weak, D) |
| • In resource-limited settings, we recommend using urine cytology for decoy cells as the minimal screening approach (strong, B) at similar time points to the above (weak, D) |
| • If blood sampling is not available or considered inappropriate for screening, we suggest measuring urine BKPyV-DNA loads by QNAT at similar time points as recommended above (weak, D) |
| • If urine decoy cells or urine BKPyV-DNA loads of >10 million copies/mL (or equivalent) are detected, we recommend measuring plasma BKPyV-DNA loads to guide clinical management (strong, B) |
| • For combined kidney/solid organ transplants, including pancreas, we suggest extending screening for BKPyV-DNAemia every 3 mo up to 36 mo posttransplant (weak, C) |
| • For non-kidney solid organ transplant recipients, we recommend to not routinely screen for BKPyV-DNAemia (strong, B) |
| • For non-kidney solid organ transplant recipients presenting with declining renal function, in the absence of other reasons for the renal compromise, we suggest testing for BKPyV-DNAemia and looking for BKPyV-nephropathy if a renal biopsy is performed (weak, C) |
| Laboratory testing |
| • We recommend that the same specimen type and assay be used in the same diagnostic laboratory to avoid uncertainty because of assay variability when monitoring the dynamics of BKPyV-DNAemia (strong, B) |
| • We recommend using QNAT assays that target conserved BKPyV genome sequences to permit the detection of all genotypes and variants (strong, C) |
| • We recommend using QNAT assays with a short amplicon size of <150 bp to avoid significant underquantification (strong, C) |
| • We recommend that clinical virology laboratories serving transplantation programs participate in external quality assurance programs for quantitative BKPyV-DNA load testing (strong, C) |
| Statements |
| • Further data are needed: |
| - before pretransplant BKPyV serology of donor or recipient can be recommended for risk stratifying kidney transplant recipients for posttransplant BKPyV-DNAemia/-nephropathy |
| - before pretransplant BKPyV-specific CMI measurement can be recommended for routine clinical use to predict posttransplant BKPyV-DNAemia/-nephropathy |
| - before posttransplant BKPyV serology can be recommended for routine clinical use to predict the course of BKPyV-DNAemia/-nephropathy |
| - before posttransplant BKPyV-specific CMI can be recommended for routine clinical use to predict the course of posttransplant BKPyV-DNAemia/-nephropathy |
| - before posttransplant BKPyV-specific CMI can be used to safely guide changes in immunosuppression |
| - before recommendations can be made as to how best to screen for BKPyV-associated urothelial carcinoma in kidney transplant recipients with ongoing BKPyV-DNAemia/-nephropathy |
| Future directions |
| ➢ Develop commutable international standards for BKPyV-DNA loads (plasma, whole blood, urine, and tissue) based on defined molecular sequences and copy numbers of early and late viral gene regions |
| ➢ Better define optimal intervals for screening and monitoring using relevant assays, minimizing additional diagnostics without compromising outcomes |
| ➢ Evaluate the utility of donor and recipient BKPyV serostatus, serotype, and neutralizing antibody pretransplantation and posttransplant |
| ➢ Evaluate the role of BKPyV serotype/genotypes and mutants in increasing the rate, severity, and duration of BKPyV-DNAemia/-nephropathy |
| ➢ Identify BKPyV-specific CMI assays and thresholds pretransplant and posttransplant to predict protection from BKPyV-DNAemia/-nephropathy posttransplant |
BKPyV, BK polyomavirus; CMI, cell-mediated immunity; QNAT, quantitative nucleic acid testing.