Rituximab and Monitoring Strategies for Late Antibody-Mediated Rejection After Kidney Transplantation

Abstract

Background. There is limited information on treatment strategies and monitoring strategies for late antibody-mediated rejection (ABMR) after kidney transplantation. Methods. In this observational and nonrandomized study, we compared 78 patients diagnosed with late ABMR (>3 months after transplant) who were treated with standard of care steroids/IVIG (n = 38) ± rituximab (n = 40) at our center between March 1, 2013 and December 31, 2016. All patients had follow-up biopsy and donor-specific antibodies (DSA) monitoring within 3 to 12 weeks. Results. Patients had biopsy 7.3 ± 7 years after transplant and were followed for 15.9 ± 9.6 months after ABMR was diagnosed. Both treatment strategies were associated with a significant decline in DSA, microvascular inflammation (peritubular capillaritis + glomerulitis), and C4d Banff scores. In univariate regression analyses, rituximab, estimated glomerular filtration rate (eGFR), Banff i, t, v, chronicity (interstitial fibrosis + tubular atrophy + fibrous intimal thickening + allograft glomerulopathy) scores on the first biopsy, and eGFR and Banff v score on follow-up biopsy were associated with graft loss. Multivariate analyses retained only rituximab (hazard ratio, 0.23; 95% confidence interval, 0.06-0.84; P = 0.03) and eGFR at follow-up biopsy (0.84; 95% confidence interval, 0.76-0.92; P < 0.001) as significant predictors of graft loss. Kaplan-Meier analyses demonstrated that the benefit associated with rituximab was apparent after 1 year (15% vs 32% graft loss, P = 0.02). Conclusion. Treatment of late ABMR with steroids/IVIG ± rituximab was effective in reducing DSA and microcirculation inflammation. The addition of rituximab was associated with better graft survival. Follow-up biopsies could be considered in the management of acute rejection to monitor the effect of therapy. Randomized studies on the best therapeutic options for ABMR are needed.