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Pre-Transplant Evaluation of KSORTSM to Assess Risk for Rejection in Highly Sensitized Patients.

S. Nandoe,1 S. Roedder,3 S. Hsieh,1 T. Sigdel,1 P. Lindner,4 J. Ekberg,4 J. Alberu,5 F. Vincenti,1 M. Sarwal.1

1UCSF, San Francisco, CA
2Immucor, Norcross, GA
3Gothenburg University, Gothenburg, Sweden
4Salvador Zubiran, Mexico City, Mexico

Meeting: 2017 American Transplant Congress

Abstract number: 87

Keywords: Gene expression, Highly-sensitized, Kidney transplantation, Rejection

Session Information

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

Location: E351

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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).

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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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