Abstract

Optimizing antithymocyte globulin (rATG) dosage is critical for high immunological risk patients undergoing a repeat kidney transplant. This natural retrospective cohort study compared clinical outcomes of two successive cohorts of consecutive recipients of retransplants receiving 5 x 1 mg/kg (rATG-5, n = 100) or a single 3 mg/kg (rATG-3, n = 110) dose of rATG induction therapy. All patients had negative complement-dependent cytotoxicity crossmatch and no anti-HLA A, B, DR donor-specific antibodies (DSA). The primary endpoint was efficacy failure (first biopsy-proven acute rejection, graft loss, or death) at 12 months. There was no difference in the cumulative incidence of efficacy failure (18.0% vs. 21.8%, HR = 1.22, 95% CI 0.66-2.25), respectively. There were no differences in 3-years freedom from biopsy proven acute rejection, and patient, graft, and death-censored graft survivals. There were no differences in the incidence of surgical complications (25.0% vs. 18.2%; p 0.151), early hospital readmission (27.8% vs. 29.5%; p = 0.877) and CMV infections (49% vs. 40%; p = 0.190). There were also no differences in the incidence (59.6% vs. 58.7%, p = 0.897) and duration of delayed graft function but a stable difference in estimate glomerular filtration rate was observed from month 1 (54.7±28.8 vs. 44.1±25.3 ml/min/1.73 m2, p = 0.005) to month 36 (51.1±27.7 vs. 42.5±24.5, p = 0.019). Mean urinary protein concentration (month 36: 0.38±0.81 vs. 0.70±2.40 g/ml, p = 0.008) and mean chronic glomerular Banff score in for cause biopsies (months 4-36: 0.0±0.0 vs. 0.04±0.26, p = 0.044) were higher in the rATG-3 group. This cohort analysis did not detect differences in the incidence of efficacy failure and in safety outcomes at 12 months among recipients of kidney retransplants without A, B, and DR DSA, receiving induction therapy with a single 3 mg/kg rATG dose or the traditional 5 mg/kg rATG.

Highlights

  • The number of patients requiring repeat kidney transplants is increasing [1, 2]

  • HR = 1.22, 95% Confidence Interval (CI) 0.66–2.25. r-ATG: rabbit antithymocyte globulin; BPAR: biopsy proven acute rejection; ABMR: antibody mediated rejection; IQR: interquartile range; Treated acute rejection (tAR): treated acute rejection; AR: acute rejection; FSGS: focal and segmentar glomerulosclerosis; HR: hazard ratio; CI: confidence interval

  • Given the allocation policy and the large size of the local waiting list, 14% received a zero Human Leukocyte Antigen (HLA) A, B, DR mismatched and 73% zero HLA DR mismatched allografts, suggesting a further long-term benefit for this population [17, 18]

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Summary

Introduction

Besides the negative complement-dependent cytotoxicity (CDC) crossmatch, all patients undergoing kidney transplantation should not have pre-formed anti-HLA A, B and DR donor specific antibodies with mean fluorescence intensity (MFI) above 1500. This strategy is associated with a lower risk for early acute rejection and graft loss [11]. Our hypothesis was that in high immunological risk patients undergoing retransplantation without pre-formed HLA A, B, DR donor specific antibodies, the use of a single 3 mg/kg dose of rATG would provide comparable efficacy to the traditional 5 mg/kg dose, with possible safety benefits related to surgical complications, number of early hospital readmissions (EHR) and incidence of CMV infection

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