Abstract: PO2028
Immunoreactivity of CD3+CD4+ in Stable Young, Middle Aged, and Elderly Kidney Transplant Recipients Receiving Maintenance Tacrolimus and Mycophenolic Acid Immunosuppression
Session Information
- Clinical Pharmacology, Pharmacokinetics, and Drug Toxicity in Kidney Diseases
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
- 1800 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
Authors
- Tornatore, Kathleen M., University at Buffalo, Buffalo, New York, United States
- Gundroo, Aijaz A., The Ohio State University, Columbus, Ohio, United States
- Chang, Shirley Shwu-Shiow, University at Buffalo, Buffalo, New York, United States
- Yonis, Mahfuz, University at Buffalo, Buffalo, New York, United States
- Attwood, Kris, Roswell Park Comprehensive Cancer Center, Buffalo, New York, United States
- Murray, Brian M., University at Buffalo, Buffalo, New York, United States
Background
Tacrolimus and mycophenolic acid are the standard of care in most stable kidney transplant recipients (KTR) at U.S. transplant centers. However, there are limited data that determine within subject immunophenotypic responses over the adult age range. This study examined ex vivo immunoreactivity of CD3+CD4+ lymphocytes in stable young, middle age and elderly KTR receiving tacrolimus and mycophenolic acid.
Methods
Fifteen stable KTR greater than 1 yr post-transplant completed a 12-hour study with serial collections at pre-dose (trough-0 hr), 4, 8 and 12 hours. The immune response potential was evaluated by Interleukin-2 (IL-2) and Interferon gamma (IFN-γ) production by CD3+CD4+ T cells after ex-vivo treatment with PMA/Ionomycin with Brefeldin-A. Data was represented as within individual, timed collection and the mean for all time points of ex-vivo stimulation by cell sub-populations stratified by young, middle age and elderly. Comparisons were made using Kruskal-Wallis test.
Results
Table summarizes the major findings. There were no group differences between tacrolimus and mycophenolic acid troughs with all tacrolimus troughs within the therapeutic range. Increased IFN-γ from CD3+CD4+ T cells was quantitated by ex vivo immunoreactivity in middle age recipients at the 4 and 8 hours during the 12-hr study period. No significant differences were noted for interleukin-2 quantitated from CD3+CD4+.
Conclusion
These data indicate increased IFN-γ from CD3+CD4+ T cells for ex vivo immunoreactivity over a 12-hr dosing interval in middle age KTR receiving long-term maintenance immunosuppression. Variable immunodynamics and the implications of intra- and interpatient variability in immunoreactivity across the range of adult KTR require further investigation of clinical and allograft outcomes.
| Young [21 to <45} | Middle Age [45 to<65] | Elderly [>65] | P Value | |
| Age (years) | 38.0(3.0) | 56.4(3.4) | 69.8(1.6) | 0.002 |
| Race [W=White; B=Black] | 2W/1B | 4W/3B | 4W/1B | 0.790 |
| e-GFR (ml/min) | 41.1 (12.5) | 60.3 (14.5) | 57.4 (14.3) | 0.158 |
| CD3+CD4+ IFN-γ+ at 0 hr [%gate] | 1.15(0.14) | 1.81(0.45) | 1.40(0.63) | 0.110 |
| CD3+CD4+ IFN-γ+ at 4 hr [%gate] | 0.74(0.36) | 2.33(0.76) | 1.24(0.35) | 0.013 |
| CD3+CD4+ IFN-γ+at 8 hr [%gate] | 0.66(0.31) | 2.37(1.16) | 1.48(0.97) | 0.037 |
| CD3+CD4+ IFN-γ+ at 12 hr [%gate] | 0.97(0.04) | 1.92(1.56) | 1.18 (0.60) | 0.064 |
| Mean CD3+CD4+ IFN-γ+[%gate] | 0.88(0.12) | 2.11(0.91) | 1.33(0.61) | 0.028 |
Funding
- Other NIH Support