BACKGROUND This post hoc analysis of data from the prospective OSAKA study evaluated the efficacy and safety of prolonged- and immediate-release tacrolimus in patients who received kidneys from extended-criteria (ECD) and standard-criteria (SCD) donors. MATERIAL AND METHODS Within the ECD and SCD groups, patients were randomized to one of 4 tacrolimus-based regimens (initial dose): Arm 1, immediate-release tacrolimus (0.2 mg/kg/day); Arm 2, prolonged-release tacrolimus (0.2 mg/kg/day); Arm 3, prolonged-release tacrolimus (0.3 mg/kg/day); Arm 4, prolonged-release tacrolimus (0.2 mg/kg/day) plus basiliximab. All patients received mycophenolate mofetil and bolus corticosteroids; Arms 1-3 also received tapered corticosteroids. ECDs met the definition: living/deceased donors aged ≥60 years, or 50-60 years with ≥1 other risk factor, and donation after circulatory death. Primary composite endpoint: graft loss, biopsy-confirmed acute rejection or renal dysfunction by Day 168. Outcomes were compared across treatment arms with the chi-squared or Fisher's exact test. RESULTS A total of 1198 patients were included in the analysis (ECD: n=620 [51.8%], SCD: n=578 [48.2%]). Patients with kidneys from ECDs were older versus SCDs (mean age, 55.7 vs. 44.5 years, p<0.0001). A higher proportion of patients with kidneys from ECDs versus SCDs met the primary composite endpoint (56.8% vs. 32.4%, p<0.0001). However, no statistically significant differences in clinical outcomes or the incidence of treatment-emergent adverse events were seen between treatment arms within each donor group. CONCLUSIONS Worse outcomes were experienced in patients who received kidneys from ECDs versus SCDs. Prolonged-release tacrolimus provided similar graft survival to the immediate-release formulation, with a manageable tolerability profile.

Department of General Visceral and Transplantation Surgery Hannover Medical School Hannover Germany

Department of Nephrology and Organ Transplantation CHU Rangueil Paul Sabatier University INSERM U10403 Toulouse France

Department of Nephrology Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Nephrology University Hospital Center of Nice Nice France

Department of Nephrology University Medical Center Regensburg Regensburg Germany

Department of Transplantology and Surgery District Public Hospital Poznań Poland

Formerly Astellas Pharma GmbH Munich Germany

Medical Affairs Astellas Pharma Global Development Inc Northbrook IL USA

Nicolaus Copernicus University College of Medicine Bydgoszcz Poland

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Nankivell BJ, Kuypers DRJ. Diagnosis and prevention of chronic kidney allograft loss. Lancet. 2011;378:1428–37. PubMed

Gondos A, Döhler B, Brenner H, Opelz G. Kidney graft survival in Europe and the United States: Strikingly different long-term outcomes. Transplantation. 2013;95:267–74. PubMed

Lamb KE, Lodhi S, Meier-Kriesche H-U. Long-term renal allograft survival in the United States: A critical reappraisal. Am J Transplant. 2011;11:450–62. PubMed

Collins MG, Chang SH, Russ GR, McDonald SP. Outcomes of transplantation using kidneys from donors meeting expanded criteria in Australia and New Zealand, 1991 to 2005. Transplantation. 2009;87:1201–9. PubMed

Rao PS, Ojo A. The alphabet soup of kidney transplantation: SCD, DCD, ECD – Fundamentals for the practicing nephrologist. Clin J Am Soc Nephrol. 2009;4:1827–31. PubMed

Aubert O, Kamar N, Vernerey D, et al. Long term outcomes of transplantation using kidneys from expanded criteria donors: Prospective, population based cohort study. BMJ. 2015;351:h3557. PubMed PMC

Tedesco Silva H, Yang HHC, Meier-Kriesche H-U, et al. Long-term follow-up of a phase III clinical trial comparing tacrolimus extended-release/MMF, tacrolimus/MMF, and cyclosporine/MMF in de novo kidney transplant recipients. Transplantation. 2014;97:636–41. PubMed PMC

Ekberg H, Bernasconi C, Tedesco-Silva H, et al. Calcineurin inhibitor minimization in the Symphony study: Observational results 3 years after transplantation. Am J Transplant. 2009;9:1876–85. PubMed

Albano L, Banas B, Klempnauer JL, et al. OSAKA trial: A randomized, controlled trial comparing tacrolimus QD and BD in kidney transplantation. Transplantation. 2013;96:897–903. PubMed PMC

Arns W, Citterio F, Campistol JM. ‘Old-for-old’ – New strategies for renal transplantation. Nephrol Dial Transplant. 2007;22:336–41. PubMed

Isakova T, Xie H, Messinger S, et al. Inhibitors of mTOR and risks of allograft failure and mortality in kidney transplantation. Am J Transplant. 2013;13:100–10. PubMed PMC

Ferrer F, Mota A, Alves R, et al. Renal transplantation with expanded criteria donors: The experience of one Portuguese center. Transplant Proc. 2009;41:791–93. PubMed

Lai Q, Pretagostini R, Poli L, et al. Delayed graft function decreases early and intermediate graft outcomes after expanded criteria donor kidney transplants. Transplant Proc. 2009;41:1145–48. PubMed

Metzger RA, Delmonico FL, Feng S, et al. Expanded criteria donors for kidney transplantation. Am J Transplant. 2003;3(Suppl 4):114–25. PubMed

Frutos MA, Sola E, Mansilla JJ, et al. Expanded criteria donors for kidney transplantation: Quality control and results. Transplant Proc. 2006;38:2371–73. PubMed

La Manna G, Comai G, Cappuccilli ML, et al. Prediction of three-year outcome of renal transplantation from optimal donors versus expanded criteria donors. Am J Nephrol. 2013;37:158–66. PubMed

Ekberg H, Tedesco-Silva H, Demirbas A, et al. Reduced exposure to calcineurin inhibitors in renal transplantation. N Engl J Med. 2007;357:2562–75. PubMed