Session Time: 3:15pm-4:45pm
Presentation Time: 4:27pm-4:39pm
- Impact on Graft Histology of Steroid Withdrawal versus Standard Immunosuppression: Randomized, Parallel Group, Controlled Clinical Trial in Low Immunological Risk Kidney Transplant Patients
- Evolution of CCR4highCD4+ Subpopulations in Renal Graft Blood After Steroid Withdrawal: A Prospective, Randomized, Controlled Study in Parallel Groups. Preliminary Results.
*Purpose: Whether steroid withdrawal can modulate the subclinical inflammatory response after a kidney transplant is unknown.
*Methods: We undertook a controlled multicenter clinical trial involving 105 patients (77 male, aged 53.4±12.4 years) with low immunological risk and stable renal function. The patients, who all received a first kidney transplant, were randomized in the third post-transplant month to receive either triple therapy (Group A: steroids+Tac+MMF, n=52) or immunosuppression without steroids (Group B: Tac+MMF, n=53) after a graft biopsy that showed subclinical inflammatory lesions (borderline) in 14 Group A and 16 Group B patients. At three and 24 months post-transplant (coinciding with the protocol biopsies) measurements were made by flow cytometry of the lymphocyte subpopulations of CD4+CD25+ IL-7Ra highCXCR3 (Th1), CD4+ CD25+ IL-7Ra highCCR4 (Th2), CD4+CD16+, CD8DR+, effector (CD4+CD25+ IL-7Ra high) and regulatory (CD4+ CD25+ IL-7Ra low) cells obtained from peripheral blood and by fine-needle aspiration puncture (FNAP) from the graft.
*Results: Although we observed no differences in the lymphocyte subpopulations between patients with and without subclinical inflammation (borderline) at the third month post-transplant, we saw a significant correlation between the CD4+ CD25+ IL-7Ra low obtained by FNAP and tubulitis (r=0.272; P=0.009) and interstitial inflammation (r=0.414; P=0.0001), as well as between CXCR3highCD4+ and interstitial inflammation (r=0.349; P=0.037). Whereas the CD4+CD16+ obtained by FNAP at the third month showed a positive correlation with the chronic lesions (ct+ci+cv+cg) seen at 24 months post-transplant (r=0.374; P=0.038), the regulatory subpopulations CCR4highCD4+ showed an inverse correlation with the interstitial inflammation (r=-0.431; P=0.007) and the tubulitis (r=-0.436; P=0.007) in the 24-month biopsy. We also noted a tendency to a greater increase in CXCR3highCD4+/CCR4highCD4, especially CCR4highCD4+, in those patients who continued not to receive steroids. No differences were seen in the other subpopulations between the two groups at 24 months post-transplant. There was a significant direct correlation between the CXCR3highCD4+ subpopulations and the interstitial inflammation (r=0.396; P=0.017). Finally, the CD14+CD16+ showed a significant increase in FNAP versus peripheral blood at three and 24 months post-transplant in patients with and without borderline lesions (P=0.005), though this was more accentuated in those without steroids.
*Conclusions: A greater infiltration of the graft by lymphocyte subpopulations involved in the immune response could predict in the medium term the appearance of chronic lesions in patients with a low immunological risk and stable renal function.
To cite this abstract in AMA style:Sanchez TVazquez, Caballero A, Alonso-Titos J, Lopez V, Sola E, Cabello M, Vilchez EGutierrez, Martínez-Esteban M, Esteban PRuiz, Delgado J, Hernandez D. Steroid Withdrawal and Lymphocyte Subsets in Graft Capillary Blood versus Peripheral Blood in Low Immunological Risk Kidney Transplant Patients: Randomized, Parallel Group, Controlled Clinical Trial [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/steroid-withdrawal-and-lymphocyte-subsets-in-graft-capillary-blood-versus-peripheral-blood-in-low-immunological-risk-kidney-transplant-patients-randomized-parallel-group-controlled-clinical-trial/. Accessed April 20, 2021.
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