Date: Sunday, April 30, 2017
Session Name: Concurrent Session: Predicting Tolerance and Rejection
Session Time: 2:30pm-4:00pm
Presentation Time: 3:30pm-3:42pm
Study purpose: To investigate the kSORTSM molecular expression assay for immune risk assessment in renal transplant (tx) recipients prior to tx for correlation of pre-tx kSORT risk scores with sensitization and post-tx rejection risk.
Methods: 52 pre-kidney tx peripheral blood (PB) PaxGene samples were collected from 31 highly sensitized (cPRA>50) patients from the PRISM (prospective, UCSF) and TITRATE (single-center, RCT NCT02581436) trials, and from 21 non-sensitized patients from the SAILOR trial (multi-center RCT; NCT02083991). Sensitization (cPRA>80% in 74% patients) was caused by previous tx (13.7%), blood transfusions (1.96%), childbirths (13.7%), or combinations of these (29.4%). For kSORTSM total RNA was extracted, reverse transcribed, analyzed by QPCR for 17 kSORT genes and evaluated using customized software kSAS™ to generate immune risk scores for rejection: High- (HR), Low- (LR), Indeterminate-Risk (IR). ANOVA, Student T-, and Chi-Square-tests were used for group comparisons. Binary logistic regression analyses were used for correlating patient clinical and demographic variables with kSORT risk scores.
Results: Mean recipient age was 52.2+/-13.1; 57.7% were female. 46 patients (88%) had post-tx protocol (30) or for-cause (16) biopsies showing acute rejection (AR, n=20), borderline rejection (n=3), or no rejection (n=23) on average 91.9+/-111.7, 133+/-77, and 78.5+/-111 days post-tx. 15.4% sensitized patients developed de-novo donor specific antibodies. Pre-tx kSORT predicted HR/LR in 11/41 patients; IR was not predicted. Sensitization and pre-tx cPRA were the only significantly correlated variables with pre-tx kSORT by multivariate logistic regression (p=0.004, p=0.03). HR pre-tx kSORT was more often in sensitized patients (10/11; p=0.02) irrespective of sensitization cause, and LR pre-tx kSORT was more often in 1st graft recipients (36/41; p=0.03). More sensitized patients with post-tx AR (n=14) had HR pre-tx kSORT (9/14; p=0.019). De-novo sensitization was not associated with AR (p=0.44). Compared to pre-tx cPRA (AUC=0.73, p=0.11), pre-tx kSORT was a better predictor of AR in sensitized patients (AUC=0.95, p=0.01).
Conclusion: The molecular expression assay kSORT appears to correlate to pre-tx sensitization status and higher risk of post-tx AR and may be a useful adjunct to define overall pre-tx immunological risk profiles.
CITATION INFORMATION: Nandoe S, Roedder S, Hsieh S, Sigdel T, Lindner P, Ekberg J, Alberu J, Vincenti F, Sarwal M. Pre-Transplant Evaluation of KSORTSM to Assess Risk for Rejection in Highly Sensitized Patients. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Nandoe S, Roedder S, Hsieh S, Sigdel T, Lindner P, Ekberg J, Alberu J, Vincenti F, Sarwal M. Pre-Transplant Evaluation of KSORTSM to Assess Risk for Rejection in Highly Sensitized Patients. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/pre-transplant-evaluation-of-ksortsm-to-assess-risk-for-rejection-in-highly-sensitized-patients/. Accessed December 9, 2019.
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