Session Time: 6:00pm-7:00pm
Presentation Time: 6:25pm-6:30pm
*Purpose: BK viremia (BKV) after kidney transplantation (KT) poses significant risk for BK virus-associated nephropathy (BKVN) and impacts graft survival. Conventional treatment involves reduction of immunosuppression therapy (IST) 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. We report safety and efficacy of leflunomide use for the eradication of BKV and prevention of BKVN in pediatric kidney transplant recipients (KTRs).
*Methods: We describe a multi-center experience with leflunomide for management of BKV over a 10-year period in pediatric KTRs. All patients prescribed leflunomide from 01/2010 – 10/2019 were included in this retrospective chart review and followed from initiation until 1 year following leflunomide completion. Data collected included leflunomide and IST dosing (mg/kg), metabolite trough values (mcg/mL), adverse drug reactions (ADRs), BKV status, renal function, and biopsy data.
*Results: 83 pediatric KTR [mean age at KT: 11 years (SD 6.2)] were treated with leflunomide and followed for a mean of 24.4 (12 – 87) months post-BKV diagnosis. BKV was successfully eradicated in 77 (93%) KTR including all 7 (8.4%) with BKN on initial biopsy. Median time from KT to BKV was 6.8 (0 – 76.7) months. Following leflunomide initiation, median time to BKV eradication was 75 (5 – 885) days and to 50% reduction in viremia was 30 (5 – 300) days. IST was reduced from a mean mycophenolate (MMF) dose of 538mg/m2/day (SD 349) to 316mg/m2/day (SD 316) and to mean tacrolimus troughs of 4.3-8.1 ng/mL (SD 2.6, 3.4). 79% KTR received maintenance steroids pre-diagnosis and 69.4% post-diagnosis. 24% of subjects received additional therapies (e.g. cidofovir, IVIG). On univariate linear regression, leflunomide troughs (mean 32.3 mcg/mL, SD 15.1) were associated with decreased time to BK eradication (B 5.84, p = 0.004), whereas MMF dosing and steroid use were not. No grafts were lost to BKV or BKN. Estimated glomerular filtration rate (eGFR) was mildly reduced 1-year post BKV diagnosis (78.3, SD 30.0 vs. 72.0, SD 34.2; p = 0.047). Within 1 year of BKV diagnosis, biopsy proven acute rejection (BPAR) occurred in 19 (23.2%) KTR (30.4% cellular, 8.7% humoral, 4.3% mixed). On linear regression, reduced MMF dosing, blood BK PCR at diagnosis, steroid use, and leflunomide trough were not associated with increased BPAR. DSA at 1-year follow-up was associated with increased BPAR (slope 1.37, p = 0.026). Minimal ADRs were reported (10% gastrointestinal, 7.2% hematologic, 2.4% other).
*Conclusions: Leflunomide is a promising adjunctive treatment for BKV eradication along with IST reduction and does not appear to increase risk for BPAR or graft loss. Moreover, treatment is associated with minimal ADRs.
To cite this abstract in AMA style:Aldieri A, Chandran M, Matossian D, Magella B, Lazear D, Bock M, Blanchette E. Leflunomide Therapy for Treatment of Bk Viremia in Pediatric Kidney Transplant Recipients [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/leflunomide-therapy-for-treatment-of-bk-viremia-in-pediatric-kidney-transplant-recipients/. Accessed June 18, 2021.
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