TABLE 7.
Consensus recommendations: management
| Reduction of immunosuppression (see Table 6 for detailed guidance) |
| • We recommend reducing maintenance immunosuppression as the primary treatment of sustained BKPyV-DNAemia/-nephropathy in kidney transplant patients without high immunologic risk or concurrent acute rejection (strong, B) |
| • We suggest reducing immunosuppression when BKPyV-DNAemia is between 1000–10 000 copies/mL (or equivalent) on 2 measurements within 2–3 wk (weak, B) |
| • We recommend reducing immunosuppression based on 1 measurement BKPyV-DNAemia >10 000 copies/mL (or equivalent) or if biopsy-proven BKPyV-nephropathy (strong, B) |
| • We recommend reducing immunosuppression for biopsy-proven BKPyV-nephropathy even if plasma BKPyV-DNA load results needed to confirm the diagnosis are still pending (strong, B) |
| • We suggest each transplant center to develop an institutional algorithm and standard operating procedure of how to reduce immunosuppression in patients with BKPyV-DNAemia (weak, D) |
| • There is insufficient data to evaluate the efficacy of switching to mTOR inhibitors for treating BKPyV-DNAemia or biopsy-proven BKPyV-nephropathy (no recommendation—statement only) |
| • We suggest to judiciously reincrease maintenance immunosuppression based on the individual immunologic risk after confirmed BKPyV-DNAemia clearance, with appropriate screening for BKPyV-DNAemia (weak, D) |
| • We suggest testing patients with persistent BKPyV-DNAemia despite the lowest acceptable immunosuppression for de novo DSA if there is evidence of renal dysfunction to assist decisions regarding kidney transplant biopsy (weak, D) |
| • For multiorgan transplant recipients, including kidney or non-kidney solid organ transplant recipients with BKPyV-DNAemia or biopsy-proven BKPyV-nephropathy, we suggest a careful reduction of immunosuppression as per above, with close clinical and laboratory monitoring, weighing the risks and benefits of rejection and graft loss (weak, D) |
|
Statement • In the absence of data defining the best treatment of acute rejection in patients with ongoing BKPyV-DNAemia/-nephropathy, most experts apply high-dose steroid therapy followed by resuming close monitoring of renal allograft function and at least monthly monitoring of BKPyV-DNAemia for the next 3 to 6 mo (expert opinion) • Depending on the clinical course, some experts consider a judicious increment of maintenance immunosuppression, whereas others consider decreasing immunosuppression as a second step, especially in cases experiencing a significant rise in BKPyV-DNAemia loads (expert opinion) |
|
mTOR inhibitor regimens • For kidney transplant recipients developing BKPyV-DNAemia or biopsy-proven BKPyV-nephropathy while receiving a combination of mTOR inhibitors and calcineurin inhibitors, there is insufficient data to guide the reduction of immunosuppression. |
| Possible approaches include |
| - to first reduce the dose of calcineurin inhibitor followed by a reduction of the dose of mTOR inhibitor if needed (expert opinion) |
| - to first switch to low-dose cyclosporine followed by a reduction of the dose of mTOR inhibitor if needed (expert opinion) |
|
Belatacept regimens • For kidney transplant recipients developing BKPyV-DNAemia or biopsy-proven BKPyV-nephropathy while receiving a belatacept-based regimen, there is insufficient data to guide the reduction of immunosuppression. |
| Possible approaches include |
| -to first reduce or discontinue the antimetabolite (expert opinion) |
| -to increase the interval of belatacept administration to every 6–8 wk (expert opinion) |
| -to switch to a low-level calcineurin-based or mTOR inhibitor–based immunosuppressive regimen (expert opinion) |
| Adjunctive therapies |
| • We suggest consideration of intravenous immunoglobulin administration as adjuvant therapy in kidney transplant recipients with insufficient response to reduced immunosuppression to facilitate viral clearance (weak, D) |
| • We suggest consideration of IVIG administration as adjuvant therapy to prevent acute rejection in recipients with high immunological risk when immunosuppression reduction is necessary to facilitate viral clearance (weak, D) |
| • We recommend to not use cidofovir to treat BKPyV-DNAemia/-nephropathy in kidney transplant recipients (strong, B) |
| • We recommend to not use leflunomide to treat BKPyV-DNAemia/-nephropathy (strong, B) |
| • We recommend to not use fluoroquinolones to prevent or treat BKPyV-DNAemia or BKPyV-nephropathy in kidney transplant recipients (strong, A) |
| • We recommend to not use statins to prevent or treat BKPyV-DNAemia or BKPyV-nephropathy in kidney transplant recipients (strong, A) |
| Future directions |
| ➢ Randomized controlled trials to evaluate the administration of IVIG to prevent or treat BKPyV-DNAemia/-nephropathy |
| ➢ Randomized controlled trials to evaluate the administration of BKPyV-neutralizing monoclonal antibodies to prevent or treat BKPyV-DNAemia/-nephropathy |
| ➢ Randomized controlled trials to evaluate the administration of adoptive virus-specific T cells to prevent or treat BKPyV-DNAemia/-nephropathy |
| ➢ Development of BKPyV vaccines to prevent or improve treatment responses of BKPyV-DNAemia/-nephropathy |
| ➢ Development of effective and safe antiviral therapies to prevent or treat BKPyV-DNAemia/-nephropathy |
BKPyV, BK polyomavirus; DSA, donor-specific antibody; mTOR, mammalian target of rapamycin.