UCLA

Background: Intravenous immunoglobulin (IVIG) is used alone and in combination with other therapies in desensitization regimens to modulate anti-human leukocyte antigen (HLA) donor-specific antibody (DSA) and facilitate transplantation of sensitized patients; however, the risk of acute antibody mediated rejection (ABMR) remains high (40-60%) and long-term graft survival remains unclear.

Objective: The aim of the study is to evaluate the impact of a single high dose IVIG protocol on the incidence of acute rejection and long-term graft survival in living donor kidney transplant (LDKT) recipients with preformed HLA DSA.

Methods: We retrospectively evaluated 663 adult (LDKT) recipients transplanted at our institution with and without preformed DSA between 2005-2013 with median follow-up of 5 years. We analyzed recipients with preformed DSA that received a single high dose of IVIG (2g/kg) at the time of transplant according to DSA Class (I, II or both) and compared them to each other and to DSA negative patients and patients with historic DSA (detected  6 months preceding transplantation). Rates of acute rejection and renal allograft survival were compared between groups.

Results: In a cohort of 663 LDKT, 72 (11%) had pre-formed HLA DSA to either Class I, Class II HLA molecules, or both with mean fluorescence intensity (MFI) < 6000 detected within 6 months of transplantation (DSA+), while another 9 (1.4%) of patients had detectable DSA on a sample that preceded transplant date by  6 months (historic DSA+). Any type of rejection occurred in 150/663 (23%) of the cohort with a statistically significant difference between DSA negative and historic DSA positive patients (20%) and DSA positive patients (39%) (p < 0.01). Similarly, AMR on for-cause biopsy was found in 7% of DSA negative and historic DSA positive patients and 29% in DSA positive patients (p < 0.01). The incidence of ACR alone was not statistically different between the groups. In a cox-regression analysis only age (which had a minimal effect) and DSA positivity were associated with increased hazard ratio of acute rejection and graft failure.

Conclusion: Single-dose IVIG given at the time of transplant can facilitate living donation in recipients with preformed DSA with acceptable acute rejection and graft failure rates. However, the risk is not completely mitigated by this regimen.