| Title: |
#2084 Biologic effect evaluation of de novo long-term release tacrolimus on metabolizer phenotype and T cell composition after kidney transplantation |
| Authors: |
Aberger, Simon; Schuller, Max; Artinger, Katharina; Mooslechner, Agnes Anna; Gashi, Aferdita; Pfeifer, Verena; Prietl, Barbara; Kirsch, Alexander H; Rosenkranz, Alexander; Eller, Kathrin |
| Source: |
Nephrology Dialysis Transplantation ; volume 39, issue Supplement_1 ; ISSN 0931-0509 1460-2385 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2024 |
| Description: |
Background and Aims Kidney transplantation (KTX) is the current treatment of choice in patients with kidney failure. Since immunosuppressive medication to prevent acute rejection is still needed in high doses with frequent adverse events, new strategies to achieve risk-appropriate personalization of immunosuppression are needed. Calcineurin inhibitors are the cornerstone of T cell suppression, currently available in different release formulations including once daily long-term release tacrolimus (LCPT) and regular twice daily immediate release tacrolimus (IRT). Little is known about the temporal evolution of tacrolimus metabolism potentially influencing T cell composition and clinical endpoints between different tacrolimus formulations after KTX. Method To evaluate the influence of de novo LCPT on clinical endpoints, metabolizer phenotype and immune cell composition after KTX, subgroup analysis of a single-center, prospective, observational cohort study including 32 patients started on LCPT (0.1 mg/kg) and 55 patients started on IRT (0.1 mg/kg) was conducted. Peripheral blood mononuclear cells were isolated from whole blood samples drawn before KTX, 2 months and 12 months after KTX for flow cytometry analysis. Study visits were simultaneously conducted to obtain tacrolimus dosing, plasma levels, acute rejection and infection incidence. Statistical analysis was done using GraphPad Prism (v10), accepting significance for p < 0.05, and flow cytometry analysis was done using FlowJo (v10) software. Results The cohort represented KTX recipients with a median age of 60 years and similar distributions of gender, HLA-mismatches and induction therapy. Clinical outcome data showed a trend towards lower acute rejection rate, lower serum-creatinine values and increased incidence of BK-viremia in LCPT treated patients. Rejection rate was associated with a fast-metabolizer phenotype (HR 3.9; 1.1-6.8, p < 0.01) and HLA mismatch > 3 (HR 4.0; 1.2-7.3, p < 0.01) while this effect was blunted in ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1093/ndt/gfae069.1689 |
| Availability: |
https://doi.org/10.1093/ndt/gfae069.1689; https://academic.oup.com/ndt/article-pdf/39/Supplement_1/gfae069-1689-2084/57794262/gfae069-1689-2084.pdf |
| Rights: |
https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model |
| Accession Number: |
edsbas.6005815D |
| Database: |
BASE |