Purpose: New onset diabetes after transplantation (NODAT) is a common metabolic complication which affects long-term patient survival and graft outcomes. Most of the immunosuppressive drugs are associated with NODAT. The 24-month (M) results from the ELEVATE study evaluated the impact of early conversion of standard calcineurin inhibitor (sCNI) to everolimus (EVR)-based regimen on NODAT in kidney transplant recipients (KTxR).

Methods: ELEVATE (NCT01114529) was a 24M, multicenter, open-label study in de novo KTxR, randomized at 10-14 weeks after Tx, to convert from sCNI to EVR (N=360; C₀ 6-10 ng/mL) or continue on sCNI (N=357; TAC: n=231, C₀ 5-10 ng/mL and cyclosporine [CsA]: n=126, C₀ 100-250 ng/mL), with mycophenolic acid and steroids. NODAT was considered if any of these conditions were met: diabetes mellitus (DM) reported as AE, random glucose ≥11 mmol/L, DM as a reason for medication, two consecutive fasting glucose readings ≥7 mmol/L, or two HbA1c ≥6.5%. Here, we present incidence of NODAT and efficacy and safety outcomes at M24.

Results: Of 157 KTxR who had HbA1c levels between 5.7-6.4% at randomization, 55 (35.0%) patients developed NODAT; the incidence was similar in EVR and sCNI, but higher in TAC vs CsA (Table). Mean HbA1c was comparable across arms. The probability of developing NODAT was similar in EVR and sCNI arm (Table). Incidence of tBPAR in KTxR with NODAT (Table) was comparable to that observed in patients without NODAT (EVR 11.5% vs sCNI 8.3%; P=0.182). Mean proteinuria (g/24 h) in KTxR with NODAT vs without NODAT was 0.46 vs 0.35, 0.21 vs 0.16, and 0.18 vs 0.34 in EVR, TAC, and CsA arms, respectively. Incidence of AEs/infection leading to treatment discontinuation was higher in EVR vs sCNI arm in patients with NODAT (11.1% vs 7.1%) and without NODAT (24.6% vs 8.5%).

Conclusion: 1) The probability of developing of NODAT after switch to EVR was similar to continued CNI treatment; however, the incidence of NODAT was higher in TAC vs CsA. 2) Post-transplant outcomes were similar in patients with or without NODAT.

CITATION INFORMATION: Holdaas H, Chadban S, de Fijter J, Rostaing L, Mancilla U, Lopez P, Bader G, Cruzado J, van der Giet M. Effect of Everolimus-Based Immunosuppressive Regimen on New Onset of Diabetes After Kidney Transplantation – A 24 Month Subanalysis from the ELEVATE Study. Am J Transplant. 2017;17 (suppl 3).

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