Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall D1
Purpose: To demonstrate that a pharmacodynamics assay using Real Time (RT)-PCR to measure residual expression (RE) of nuclear factor of activated T cell (NFAT)-dependent cytokines in kidney transplant recipients (KTR) can be used to adjust Tacrolimus (Tac) & may predict infectious complications better than trough levels.
Methods: This was a single center, randomized, controlled trial. Study population included stable KTR on Tac, mycophenolic acid, & prednisone with no prior rejection episodes & a normal 6 month protocol biopsy. At enrollment, expression of cytokines IL-2, IFN-γ, & GM-CSF were measured by RT- PCR at T0 (pre dose) & T1.5 (1.5 h post Tac dose, C max concentration). RE of each gene was calculated as T1.5/T0 x 100. Mean residual expression (MRE) was the average RE of the 3 genes. In the INT, the daily dose of Tac was reduced by 15% if the MRE was <20% & was increased by 15% if the MRE was > 60%. KTR in the control arm (CTL) had their dose adjusted based on trough levels. In the INT arm, MRE was re-measured at 6 months post enrollment & a second adjustment was made. The Mann-Whitney U test was used for comparison of medians.
Results: 40 KTR, 20 randomized to the INT arm & 20 to the CTL arm were enrolled.There was no SS difference in renal function at enrollment (eGFR 79 ml/min/1.73m2 INT (CI 71.2-85.1) vs 79.5 CTL (CI 68.6-88.9) P =0.87. There was no SS difference in Tac trough levels: 9.9 [micro]g/L (CI 8.6-11.2 ) INT and 9.1 [micro]g/L (CI 7.8-10.4) CTL, P= 0.22 .The Median MRE INT was 41.4 (CI 32.5-54.3) vs. 25.3 (CI 20.8-35) in CTL, P=0.03. Tac trough levels did not correlate with baseline MRE (Spearman 0.08 P=0.62). There was no SS difference INT vs CTL re: infections (P=0.33), hospitalizations (P=1) malignancies (P=1) rejections (P=1) eGFR (P=0.33), or death at 1 year(P=1). In KTR whose Tac dose was never adjusted (N= 5 INT and 4 CTL arm), KTR with infections had a SS lower MRE at enrollment c/w those without infections (MRE 22.5 (CI 19.5-29.6) vs 47.4 (CI 23.7-67.4) P=0.03. This not true for tac trough levels (P=0.46).
Conclusions: Our study suggests that NFAT- regulated gene expression better predicts the biologic activity of tac, with a low MRE predicting infectious complications post- transplant better than trough levels. Larger prospective studies are needed to assess the role of this novel immune monitoring assay in KTR.
CITATION INFORMATION: Webber A, Tatapudi V, Leung C, Vincenti F. NFAT-Regulated Cytokine Gene Expression for Immune Monitoring in Kidney Transplant Recipients – A Randomized Controlled Trial. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Webber A, Tatapudi V, Leung C, Vincenti F. NFAT-Regulated Cytokine Gene Expression for Immune Monitoring in Kidney Transplant Recipients – A Randomized Controlled Trial. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/nfat-regulated-cytokine-gene-expression-for-immune-monitoring-in-kidney-transplant-recipients-a-randomized-controlled-trial/. Accessed August 15, 2020.
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