The development of a reliable surrogate endpoint for allograft survival after AMR treatment is a current unmet need in clinical transplantation (FDA AMR Workshop). We investigated the clinical, histological and immunological determinants of allograft survival in patients with active AMR receiving standard-of-care treatment in a prospective observational study.

We prospectively enrolled consecutive kidney transplant recipients with biopsy-proven active AMR diagnosed between 2007 and 2013 in two Paris transplant centers. All study patients received standardized treatment including plasmaphereses (x4), high-dose intravenous immune globulins (2 g/kg) repeated every 3 weeks for 3 rounds and rituximab (375 mg per square meter of body-surface area). Patients were systematically assessed at the time of diagnosis and 3 months post-treatment for clinical data (eGFR and proteinuria), histological characteristics (allograft biopsy) and circulating anti-HLA DSA characteristics (specificity, HLA class, mean fluorescence intensity [MFI] and C1q-binding capacity).

We included 291 patients with biopsy-proven acute or chronic active AMR who received standard-of-care treatment. The 5-year allograft survival after AMR diagnosis was 69.5% (95% CI: 62.7-75.2). Post-treatment independent determinants of allograft loss included eGFR (HR=0.97, 95% CI: 0.96-0.98, p<0.001), microvascular inflammation (g+ptc) score (HR=1.2, 95% CI: 1.0-1.3, p=0.035), allograft glomerulopathy (cg) score (HR=1.4, 95% CI: 1.1-1.8, p=0.004) and complement-binding capacity of DSA (HR=5.2, 95% CI: 3.3-8.3, p<0.001). On the basis of these predictors, we built a composite risk score for allograft loss after AMR treatment that showed a good predictive capacity: c-statistic, 0.77 (1000 bootstrap 95% CI: 0.71-0.84). For centers that do not use C1q-binding assay, we replaced C1q-binding assessment by the MFI of the highest rank anti-HLA DSA. The predictive capacity of the MFI-based score was 0.74 (95% CI: 0.68-0.81).

A systematic clinical, histological and immunological evaluation of the response to treatment at 3-month post-AMR allows to identify patients at high risk of allograft loss. We defined a post-AMR treatment composite score with a good performance to predict allograft loss. Further studies should validate this score on different independent cohorts.

CITATION INFORMATION: Viglietti D, Loupy A, Duong Van Huyen J, Verine J, Zeevi A, Legendre C, Glotz D, Lefaucheur C. Composite Score to Define the Risk of Allograft Loss After Standard-of-Care Treatment of Antibody-Mediated Rejection in Kidney Transplantation. Am J Transplant. 2016;16 (suppl 3).

« Back to 2016 American Transplant Congress