Donor Specific Antibody (DSA) Formation in Tacrolimus-Based, Mycophenolate vs mTOR Immunosuppression Regimens.

Abstract

The influence of mTOR inhibition upon DSA formation and later clinical events is controversial, with small reports suggesting a higher rate of DSA with mTOR but experimental data suggesting potential inhibitory signaling pathways. Prior clinical studies did not include regimens with tacrolimus (TAC) and/or prednisone (P) with adequate controls. We compared de novo DSA formation (DSA+) rates between two common immunosuppression regimens (TAC/MPA/P vs. lower exposure TAC/mTOR/P) and clinical outcomes Methods: 66 kidney and SPK recipients on TAC (lo)/mTOR/P (36 with everolimus, 30 with sirolimus) from hospital discharge were compared in a case-control study to 132 patients on TAC/MPA/P, matched for age, gender, race, and type/timing of transplant from 2007-2012. DSA assessment was performed prospectively at time of transplant and at 1, 6, 12, and 24 months post-transplant using single antigen beads. We compared de novo DSA formation ( ≥500 MFI), proteinuria, GFR and acute rejection (AR) between the two groups. Results: With a mean follow up of 796 days, TAC (lo)/mTOR had a higher proportion DSA+ at all time points but did not meet statistical significance. By one year, DSA+ rates were 35% with TAC (lo)/mTOR vs 28% with TAC/MPA (OR 1.37; 95% CI 0.69-2.75; p= 0.37) There was no significant difference between the two arms when comparing clinical outcomes, including GFR at 12 months, proteinuria at 12 months and AR at 12 months.Table: No Caption available.When comparing Sirolimus vs Everolimus, there was no significant difference in DSA formation or clinical outcomes. Neither the type of DSA (class I vs class II) nor strength of DSA (MFI) were significantly different among groups. Comparing those that formed DSA vs those that did not, GFR was not different at 1 year but proteinuria was significantly higher in DSA+ vs DSA- (0.35 vs 0.17g/d, p=0.03). Conclusion:In kidney and SPK transplant patients on TAC/prednisone regimens, mTOR inhibition was associated with similar rates of DSA formation compared to MPA. Our study did not demonstrate a difference in GFR, proteinuria or acute rejection at one year between the two arms. mTOR therapy is neither protective nor permissive in DSA formation or downstream clinical surrogates of antibody-mediated injury. DISCLOSURES:Wiseman, A.: Other, Novartis, consultant, Tolera, consultant, Astellas, consultant.