Thymoglobulin Induction Decreases risk of ABMR and Death in Kidney Recipients

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Abstract

Anti-thymocyte globulin (ATG) is currently the preferential induction treatment in kidney recipients at high risk for allograft rejection. However, no study has evaluated the benefits of this induction strategy in terms of patient survival.

We conducted a multicentric prospective study including unselected kidney recipients from 4 referral centers (2004-2014). We assessed the type of induction therapy (IL2R inhibitors or ATG) and the dose of ATG (mg/kg). All donor, recipient and transplant baseline characteristics were recorded. Patients were systematically screened for anti-HLA DSAs at the time of transplantation, at any clinical event and yearly. We considered all allograft biopsies (N=10,293) performed at 1-year post-transplant and for clinical indication.

4,696 kidney recipients were included, among whom 2,246 (48%) patients received ATG at a mean dose of 7.2±3.1 mg/kg and 2,450 (52%) patients received IL2R inhibitors. During a median follow-up post-transplant of 7.0 (IQR, 4.4-9.6) years, 680 patients were diagnosed with biopsy-proven ABMR within the first year post-transplant (14%) and 869 within the first 5 years post-transplant (19%). ATG induction was the main protective factor for ABMR occurrence at 1 year (adjusted HR=0.69; 95%CI=0.58-0.81) and at 5 years (HR=0.76, 95%CI=0.66-0.88), when adjusted for clinical, histologic and immunologic factors, with a dose-effect relationship. The protective effect of ATG was observed in patients receiving between 4.5 and 6.5 mg/kg (1-year HR=0.60, 95%CI=0.46-0.79 and 5-year HR=0.74 0.66-0.96), whereas no effect was observed in patients receiving less than 4.5 mg/kg. We generated a propensity score to match patients according to the induction treatment (ATG vs IL2R) with similar risk factors (Anti-HLA DSA at day 0, HLA mismatches, graft rank, donor’s age, type of donor and cold ischemia time). The matched sample was composed of 2,418 patients (1,209 in the ATG group and 1,209 in the IL2R group). Patients with pre-transplant DSAs receiving ATG (N=177, 7%) showed better patient survival at 5 years compared to patients with pre-transplant DSAs receiving IL2R inhibitors (N=175, 7%): 92% vs 84%, p=0.008, while those without pre-transplant DSAs (N=2,066 (85.44%)) had similar survival according to induction therapy (ATG: 88% vs IL2R: 89%).

ATG is the main protective factor for ABMR occurrence in kidney recipients and improves patient survival in recipients with pre-transplant anti-HLA DSAs, independent of patient age and comorbidities.

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