Leflunomide as adjunct therapy for BK viremia management in pediatric kidney transplant recipients

Background BK viremia after kidney transplantation (KT) poses significant risk for BK virus‐associated nephropathy and impacts graft survival. Conventional treatment involves reduction of immunosuppression, which in turn may increase risk for rejection. To address this dilemma, use of anti‐viral the...

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Published in:Pediatric transplantation 2024-03, Vol.28 (2), p.e14724-n/a
Main Authors: Aldieri, Alexandra, Chandran, Mary, Matossian, Debora, Hariprasad, Aparna, Magella, Bliss, Lazear, Danielle, Blanchette, Eliza, Benz, Eric, Bock, Margret
Format: Article
Language:English
Subjects:
Biopsy
Calcineurin Inhibitors
Child
Dosage
Eradication
Graft rejection
Humans
Immunosuppression
Immunosuppressive agents
Immunosuppressive Agents - therapeutic use
Kidney Transplantation
Leflunomide
Leflunomide - therapeutic use
Mycophenolic acid
Nephritis, Interstitial
Nephropathy
Patients
pediatric kidney transplant
Pediatrics
Regression analysis
Retrospective Studies
Transplants & implants
Viremia
Viremia - drug therapy
virus
Viruses
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Summary:Background BK viremia after kidney transplantation (KT) poses significant risk for BK virus‐associated nephropathy and impacts graft survival. Conventional treatment involves reduction of immunosuppression, which in turn may increase risk for rejection. To address this dilemma, use of anti‐viral therapy with immunosuppressive properties such as leflunomide is an attractive option. Methods We performed a multi‐center, retrospective chart review to report tolerability and effectiveness of leflunomide use for the eradication of BK viremia and prevention of BK virus‐associated nephropathy in pediatric KT recipients. Results Seventy patients prescribed leflunomide were included and were followed up from initiation until 1 year following leflunomide completion. BK viremia was eradicated in 64 (91.4%) patients including 8 of 11 with nephropathy (BKVN) on initial biopsy. Reduced anti‐proliferative medication (AP) dosing was not associated with increase in biopsy proven rejection (BPAR). However, complete discontinuation of AP during leflunomide therapy was associated with increase in BPAR in uni‐ and multivariate logistic regression, as was targeted reduction in calcineurin inhibitor (CNI) trough goals. One graft was lost to BKVN. There was no significant association found between time to BK eradication and leflunomide trough concentration, mycophenolate dose reduction, or steroid use (univariate logistic regression). Few leflunomide adverse drug reactions (ADR) were reported (most commonly: gastrointestinal, hematologic). Conclusion Leflunomide is a promising adjunctive treatment to immunosuppression reduction for BK virus eradication with minimal ADR. AP reduction, not discontinuation, and judicious reduction in CNI trough goals with close monitoring, is a promising strategy for treatment of BK viremia with concomitant use of leflunomide therapy. Leflunomide is a promising adjunctive treatment for BK virus eradication and prevention of BK nephropathy, along with IS reduction, particularly anti‐proliferative immunosuppression reduction, without significant risk for the development of biopsy‐proven rejection in pediatric kidney transplant recipients. Given the significant risk for the development of biopsy‐proven rejection with complete AP discontinuation and CNI reduction in our study cohort, we suggest anti‐proliferative reduction, not discontinuation, and judicious reduction in CNI trough goals with close monitoring as a strategy for treatment of BK viremia wit
ISSN:1397-3142
1399-3046
DOI:10.1111/petr.14724