A randomized controlled trial of intravenous immunoglobulin vs standard of care for the treatment of chronic active antibody-mediated rejection in kidney transplant recipients.

Abstract

Chronic active antibody-mediated rejection (AMR) is the leading cause of death-censored kidney allograft loss, with no proven treatments. While intravenous immunoglobulin (IVIG) has been used in certain cases, its efficacy is unknown. In this open-label multicenter randomized controlled trial (VIPAR), participants with biopsy-proven chronic active AMR, were assigned to six doses (1 g/kg/month) of IVIG or no-IVIG. The primary end point was the difference in slopes of the chronic allograft damage index (CADI) scores between groups, across four allograft biopsies (baseline, three, six and 12 months). Secondary outcomes, assessed at baseline, three, six and 12 months, included change in estimated glomerular filtration rate (eGFR), change in donor-specific anti-HLA antibodies (DSA), allograft and patient survival, and change in intra-graft mRNA expression. Fifteen participants were randomized to each arm. Their median age was 54.3 years, 22 were male and mean eGFR was 43.3 ml/min/1.73m². Participants in the no-IVIg group experienced a significant increase in mean CADI (+0.28/month, 95% confidence interval 0.14 to 0.41), while the IVIG group did not (-0.004/month, -0.13 to 0.12). Over two years, eGFR significantly declined more rapidly in the no-IVIG group (-1.1 ml/min/month, -1.5 to -0.7 ml/min/month) than the IVIG group (-0.4 ml/min/month, -0.8 to 0.03 ml/min/month). Differences in patient and allograft survival were not evident by 12 months. Intra-graft expression of 59 genes (mostly B-cell related) reduced with IVIG relative to no-IVIG. IVIG therapy was associated with stabilization in allograft histology and eGFR in kidney transplant recipients with chronic active AMR. Registered at https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=347495 with study number ACTRN12612000252819.