Microemulsion cyclosporin formulation, in contrast to the old formulation, widens the T lymphocyte subsets differences between stable and acute rejection of kidney transplants

• Published in: Nephrology, dialysis, transplantation dialysis, transplantation, 2001-06, Vol.16 (6), p.1256-1261
• Main Authors: Oliveira, José G. G., Ramos, João P., Xavier, Paula, Sampaio, Susana, Magalhães, Maria C., Mendes, Armando A., Pestana, Manuel
• Format: Article
• Language: English
• Subjects: Antigens, CD - analysis; Biological and medical sciences; Biopsy, Needle; Chronic Disease; cyclosporin formulation; Cyclosporine - blood; Cyclosporine - therapeutic use; Emulsions; fine‐needle aspiration biopsy; Graft Rejection - immunology; Graft Rejection - pathology; graft‐infiltrating lymphocytes; Humans; Immunomodulators; Immunosuppressive Agents - blood; Immunosuppressive Agents - therapeutic use; Kidney Transplantation - immunology; Kidney Transplantation - pathology; Medical sciences; Neoral; peripheral blood lymphocytes; Pharmacology. Drug treatments; Receptor-CD3 Complex, Antigen, T-Cell - analysis; Retrospective Studies; Sandimmune; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/16.6.1256

Background. The new cyclosporin (CsA) formulation, Neoral®, has different pharmacokinetics compared with Sandimmune® (SIM). Larger area under the curve (AUC) values with equivalent trough blood values are reached when Neoral is administered at equivalent doses to SIM. Previously, we showed a great diagnostic reliability when using cytofluorometric analysis from fine‐needle aspiration biopsy (FNAB) samples. We investigated possible changes brought about by Neoral on lymphocyte subsets and the repercussions on the activation score cut‐off for acute rejection, defined under SIM treatment. Methods. Of 63 patients that received SIM, 40 remained rejection‐free and 23 suffered one episode of rejection. Of 52 patients that received Neoral, 38 remained rejection‐free. Peripheral blood lymphocytes (PBL) and lymphocytes from FNAB taken on days 7 and 14 post‐transplantation and on the first day of acute rejection were analysed by flow cytometry. Results. Trough blood CsA levels were not different between SIM and Neoral treatments. Among rejection‐free patients, a significant down‐regulation of CD3DR and of CD8DR expression on both graft‐infiltrating lymphocytes (GIL) and PBL, and significant up‐regulation of naïve T cells on GIL were observed with Neoral. These changes were followed by a significant down‐regulation of the activation score with Neoral. Conversely, within the acute rejection group, the activation score was significantly higher with Neoral than with SIM. The activation score performed equally well in Neoral transplants compared with what we had reported with SIM. Conclusions. Our study indicates that Neoral elicits stronger immunosuppressive effects in stable patients, which eventually should translate into better clinical efficiency. However, when acute rejection supervenes, the treatment breakthrough seems stronger with Neoral. Cytofluorometric studies from FNAB samples showed that diagnostic reliability was maintained at a high level under Neoral therapy.