Combined Phenotyping to Identify Kidney Transplants at Greatest Risk after Subclinical Acute Rejection

S. Park¹, R. Heilman², E. Poggio³, D. Taber⁴, L. Zhao¹, K. Guo¹, S. Kurian⁵, C. Rebello¹, S. Brietigam¹, M. Abecassis⁶, J. Friedewald¹

¹Northwestern University, Chicago, IL, ²Mayo Clinic, Scottsdale, AZ, ³Cleveland Clinic, Cleveland, OH, ⁴MUSC, Charleston, SC, ⁵Scripps, La Jolla, CA, ⁶University of Arizona, Tucson, AZ

Meeting: 2020 American Transplant Congress

Abstract number: A-317

Keywords: Genomic markers, Graft failure, Kidney transplantation, Rejection

Session Information

Session Name: Poster Session A: Biomarkers, Immune Assessment and Clinical Outcomes

Session Type: Poster Session

Date: Saturday, May 30, 2020

Session Time: 3:15pm-4:00pm

Presentation Time: 3:30pm-4:00pm

Location: Virtual

*Purpose: We hypothesize that the combination of protocol biopsy histology and gene expression profiles (GEP) for subclinical acute rejection (subAR) in the blood will improve predictive accuracy for clinical outcomes.

*Methods: Graft failure (GF) was assessed retrospectively in a previously studied patient cohort with paired samples (surveillance biopsy and GEP). GF was defined as death-censored graft loss, initiation of dialysis, or retransplant. We used Kaplan-Meier estimator to analyze the impact of 3-6month (3M) subAR on graft survival (GS) within 5-year (5Y) post KT. The primary endpoint was GF within 5Y in three groups: 1) both positive histology and GEP (+HIS+GEP) for subAR at 3M, 2) mixed (either negative histology and positive GEP (-HIS+GEP) for subAR or positive histology and negative GEP (+HIS-GEP) for subAR at 3M), 3) both negative histology and GEP(-HIS-GEP) for subAR at 3M. We also used a linear mixed effect model to assess the changes of estimated glomerular filtration rate (eGFR) beginning 4-month (4M) following up to 5Y post KT as a secondary outcome.

*Results: 186 patients were eligible for 5Y graft survival (GS) analysis classified as histology results paired with GEP at 3M, 1) +HIS+GEP (n=26), 2) mixed (n=22), 3) -HIS-GEP (n=138). GF occurred in 12 patients (6%) out of 186 at mean follow-up of 4.2 years. The overall GS was significantly lower in the +HIS+GEP group compared to the other two groups (p=0.002) (Fig). Baseline eGFR at 4M was 5.13 and 6.77 (mL/min/1.73m2) higher in the mixed (p=0.322) and the -HIS-GEP group (p=0.079), respectively, than the +HIS+GEP group. The annual changes of eGFR were -2.97 (CI [-3.88, -2.06]), -0.49 (CI [-1.34, 0.36], P<0.001) and -2.00 (CI [-2.39, -1.62], P=0.056) in the +HIS+GEP, the mixed, and the -HIS-GEP group, respectively. This trend was continued after adjusting age, sex, and race.

*Conclusions: 3M subAR classified with the combination of +HIS+GEP was significantly associated with lower GS at mean follow-up of 4.2 years. The eGFR showed the trend of faster decline in the +HIS+GEP group than other groups. This suggests the importance of early subAR classified by histology + GEP on graft outcomes.

To cite this abstract in AMA style:

Park S, Heilman R, Poggio E, Taber D, Zhao L, Guo K, Kurian S, Rebello C, Brietigam S, Abecassis M, Friedewald J. Combined Phenotyping to Identify Kidney Transplants at Greatest Risk after Subclinical Acute Rejection [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/combined-phenotyping-to-identify-kidney-transplants-at-greatest-risk-after-subclinical-acute-rejection/. Accessed May 16, 2025.

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