Background: Loss of Medicare coverage for immunosuppression 3 years after kidney transplant may be associated with increased nonadherence. The goal of this study was to examine whether adherence declines 3 years after transplant and whether nonadherence late post-transplant is associated with 5-year allograft histology.

Methods: We retrospectively analyzed 1290 conventional kidney allografts transplanted at our center between 1/1/99 and 6/1/10. Adherence to tacrolimus (tac), cyclosporine (CSA), azathioprine (AZA), mycophenolate (MMF) and prednisone was examined using refill records from our Transplant Specialty Pharmacy. Average adherence between post-transplant years 1-3 and years 3-5 was calculated. Nonadherence was defined as <80% proportion of days covered. The relationship between nonadherence during post-transplant years 3-5 and 5-year renal allograft histology was examined. Specifically, interstitial fibrosis and inflammation (GIF+i), a histologic pattern associated with reduced allograft survival, was assessed.

Results: Transplant Specialty Pharmacy refill data up to 5 years post-transplant was available in 613 (47.5%) allografts. Among this cohort, recipient age was 53 ± 14 years, 60% were male, 94% were Caucasian and 29% were diabetic. Adherence to tac/CSA, AZA/MMF and prednisone declined 3-5 years post-transplant compared to 1-3 years post-transplant (-1%, -1%, -2%, respectively, p<0.0001 for all). During 3-5 years post-transplant, nonadherence to tac/CSA was 8%, nonadherence to AZA/MMF was 9% and nonadherence to prednisone was 17%. 400 patients (65%) had a renal allograft biopsy 5-years post-transplant, and prevalence of GIF+i was 8% (n=33). GIF+i was associated with 3-5 year nonadherence to tac/CSA, AZA/MMF and prednisone therapy (21% vs 7%, p=0.03; 28% vs 6%, p=0.0008; 20% vs 7%, p=0.009, respectively). These associations were independent of donor age, HLA mismatch and pre-transplant DSA. After adjusting for nonadherence to tac/CSA and prednisone therapy, only nonadherence to AZA/MMF remained significantly associated with GIF+i (OR 10.23, CI 1.45-73.82, p=0.02).

Discussion: Adherence to immunosuppression declines 3 years after kidney transplant. Nonadherence with immunosuppression late post-transplant is associated with allograft fibrosis and inflammation, a phenotype associated with poor allograft survival. Further efforts to improve long-term adherence after transplant are needed.

CITATION INFORMATION: Lorenz E, Smith B, Cosio F, Shah N, Groehler P, Verdick J, Park W, Stegall M. Long-Term Immunosuppression Adherence After Kidney Transplant and Relationship to Allograft Histology. Am J Transplant. 2017;17 (suppl 3).

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