Acute Cellular Rejection and Polyoma (Videos Available)

Monday July 02, 2018 from 09:45 to 11:15

Room: N-102

316.1 DSA plus TCMR leads to poor outcomes in renal allograft recipients and this is markedly exacerbated by non-adherence (Video Available)

Award Winner

Dominik Chittka, United States has been granted the TTS Young Investigator Scientific Award

Dominik Chittka, United States

Postdoctoral Associate
Starzl Transplant Institute
University of Pittsburgh

Abstract

DSA plus TCMR Leads to Poor Outcomes in Renal Allograft Recipients and this is Markedly Exacerbated by Non-Adherence

Dominik Chittka1, Aravind Cherukuri1, Akhil Sharma1, Rajil Mehta1, Sundaram Hariharan1, David M Rothstein1.

1Thomas E. Starzl Transplant Institute, University of Pittsburgh, Pittsburgh, PA, United States

Introduction: Post-transplant DSA is strongly associated with poor renal allograft outcomes but has limited predictive value. In this prospective study, we aimed to risk-stratify patients with early post-transplant DSA to allow timely identification of individuals at-risk for poor clinical outcomes.
Methods: Patients were screened for DSA at 0, 1, 3, 6, 9 & 12 months and analyzed in relation to protocol biopsies at 3 and 12 months and any for-cause biopsies within the first year.
Results: 294/ 372 patients transplanted between 01/2013 and 11/2014 with at least one biopsy in the first post-transplant year were included in the analysis. The immunosuppressive regimen was Thymoglobulin induction followed by MPA and Tacrolimus as maintenance therapy. 67/294 (22.8%) of these patients developed DSA. Of these, 76% were detected within the first 3 months with 58% being persistent. DSA was associated with significantly increased rates of subclinical and clinical TCMR (58%) compared to patients lacking DSA (33%; p<0.0001). Importantly, presence of DSA was associated with higher Banff grade TCMR (Fig. 1A) and with a higher rate of concomitant AMR (10.4% vs. 1.8%, p=0.003). In 77% of patients with both DSA and TCMR, DSA was detected at the same time or prior to TCMR. Patients with DSA and TCMR had significantly worse chronic allograft histological changes at 1 year (Fig. 1B) and significantly increased graft loss or impending graft loss (eGFR<30ml/min with >30% decline from baseline) at 4 years when compared to the others, including patients with TCMR or DSA alone (Fig. 1C). In a multivariate Cox model, younger recipient age, Class I HLA mismatch, DGF and poor adherence (defined by a high intra-patient CNI variability (>35%)) were independently associated with DSA plus TCMR. Of these, non-adherence, which is potentially modifiable, further risk stratified patients with DSA plus TCMR. In fact, >70% of nonadherent patients with DSA plus TCMR have already lost their grafts or showed impending graft loss by 4 years, whereas patients with DSA plus TCMR who were adherent had outcomes relatively comparable to the other patient groups (Fig. 1D).
Conclusion: Thus, early post-transplant DSA is associated with increased TCMR which in turn leads to poor graft outcomes, particularly in nonadherent patients. Strategies to address non-adherence in patients with DSA plus TCMR should be explored to improve long-term graft outcomes.

Deutsche Forschungsgesellschaft (DFG). American Society of Transplantation (AST).



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