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The effect of de novo DSA detected at the time of acute cellular rejection (ACR) and the response of DSA levels to rejection therapy on renal allograft survival were analyzed. Kidney transplant patients with acute rejection underwent DSA testing at rejection diagnosis with DSA levels quantified using Luminex single-antigen beads. Fifty-two patients experienced acute rejection with 16 (31%) testing positive for de novo DSA. Median follow-up was 27.0 +/- 17.4 months postacute rejection. Univariate analysis of factors influencing allograft survival demonstrated significance for African American race, DGF, cytotoxic PRA >20% (current) and/or >50% (peak), de novo DSA, C4d and repeat transplantation. Multivariate analysis showed only de novo DSA (6.6-fold increased allograft loss risk, p = 0.017) to be significant. Four-year allograft survival was higher with ACR (without DSA) (100%) than mixed acute rejection (ACR with DSA/C4d) (65%) or antibody-mediated rejection (35%) (p < 0.001). Patients with >50% reduction in DSA within 14 days experienced higher allograft survival (p = 0.039). De novo DSAs detected at rejection are associated with reduced allograft survival, but prompt DSA reduction was associated with improved allograft survival. DSA should be considered a potential new end point for rejection therapy.

Elimination of corticosteroid-related morbidity has been a goal of transplant clinicians from the earliest days of renal transplantation more than 50 years ago. Over the past decade, this goal has begun to be realized. Herein, we describe our efforts to eliminate corticosteroid therapy from maintenance immunosuppression-efforts that have spanned 15 years and have included design and conduct of five multicenter trials and over ten single center trials with over 650 patients at the University of Cincinnati. These efforts have led to a near complete elimination of corticosteroid-related morbidity, and, importantly, a more precise definition of the risk/benefit assessments of corticosteroid withdrawal in individual patient populations, which has allowed individualization and tailoring of corticosteroid-free immunosuppression.