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

INTRODUCTION 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. METHODS In this open-label multicenter randomized controlled trial (VIPAR), participants with biopsy-proven chronic active AMR, were assigned to six doses (1g/kg/month) of IVIG or no-IVIG. The primary endpoint 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. RESULTS 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. CONCLUSION IVIG therapy was associated with stabilization in allograft histology and eGFR in kidney transplant recipients with chronic active AMR.