ATC Abstracts

American Transplant Congress abstracts

Nuclear Factor of Activated T-Cells Post-Renal Transplant.

1Translational Pharmacology Research Center, School of Pharmacy, Buffalo
2Biostatistics, School of Public Health, Buffalo
3Flow Cytometry Laboratory, Roswell Park Cancer Institute, Buffalo
4Medicine, School of Medicine, University at Buffalo, Buffalo.

Meeting: 2016 American Transplant Congress

Abstract number: D235

Keywords: , , ,

Session Information

Date: Tuesday, June 14, 2016

Session Name: Poster Session D: Poster Session II: Kidney Complications-Other

Session Time: 6:00pm-7:00pm

 Presentation Time: 6:00pm-7:00pm

Location: Halls C&D

Background: Nuclear Factor of Activated T-cells (NFAT1) is a transcription factor regulating the expression of key targets involved with cellular immune function. Calcineurin is a phosphatase that regulates the nuclear translocation necessary for NFAT activation and targeted by calcineurin inhibitors such as tacrolimus (TAC) for immunosuppression in renal transplant recipients (RTR). TAC doses are individualized using therapeutic drug monitoring (TDM) of extracellular troughs due to PK variability. We assessed nuclear NFAT1 localization as a pharmacodynamic (PD) marker with TAC PK.

Methods:We enrolled 47 (25 males; 22 females) stable RTR > 6 months post-transplant receiving TAC and mycophenolic acid. NFAT activation was measured at TAC trough (0 hour) and 4 hour after drug (post-peak) in CD4 and CD8 lymphocytes. Baseline nuclear localization of NFAT (unstimulated) and localization following ex-vivo exposure to PMA/Ionomycin (stimulated) generating an Rd value was assessed by flow cytometry based image analysis. Concurrent steady-state 12-hour PK studies determined lean body weight (LBW) adjusted TAC clearance(CL) and dose-adjusted area under the concentration time curve 0-12hrs(AUC0-12).

Results: Female RTR had higher nuclear NFAT translocation in CD4 and CD8 cells when adjusted for race(*) with more rapid TAC CL and higher doses. No association of NFAT Rd translocation to TAC troughs or CL were found with a trend noted with AUC0-12/Dose (P=0.08).

Mean(SD) Males Females P Values
eGFR[ml/min/1.73m2] 56.4(17.9) 46.3(13.2) 0.034
TAC Dose[mg] 2.8(1.3) 3.4(1.9) NS
TAC Dose[mg/weight] 0.03(0.02) 0.04(0.02) 0.023
TAC Trough[ng/ml] 6.74(1.47) 6.74(1.47) NS
Tac CL/LBW  0.36(0.18) 0.58(0.32) 0.003
NFAT Rd CD4+[0hr] 0.46(0.55) 0.72(0.57) 0.088*
NFAT Rd CD4+[4hr] 0.36(0.58) 0.73(0.64) 0.041*
NFAT Rd CD8+[0hr] 0.79(0.65) 1.04(0.61) 0.182*
NFAT Rd CD8+[4hr] 0.69(0.59) 1.04(0.67) 0.052

Conclusion: These data suggest a gender difference in NFAT nuclear translocation in CD4 and CD8 cells and may be reflective of intracellular tacrolimus concentrations. Extracellular tacrolimus troughs alone may not adequately guide TDM of TAC immunosuppression.

CITATION INFORMATION: Tornatore K, Attwood K, McGuire O, O'Loughlin K, Venuto R, Minderman H. Nuclear Factor of Activated T-Cells Post-Renal Transplant. Am J Transplant. 2016;16 (suppl 3).

To cite this abstract in AMA style:

Tornatore K, Attwood K, McGuire O, O'Loughlin K, Venuto R, Minderman H. Nuclear Factor of Activated T-Cells Post-Renal Transplant. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/nuclear-factor-of-activated-t-cells-post-renal-transplant/. Accessed January 25, 2021.

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