Kidney Transplant Research Today is a free monthly online journal that collates and summarizes the latest research about Kidney Transplant, including details on risks, prognosis, procedure, surgery, organ donation.

Monitoring biological action of rapamycin in renal transplantation.

Leogrande D, Teutonico A, Ranieri E, Saldarelli M, Gesualdo L, Schena FP, Di Paolo S

Department of Emergency and Organ Transplants, Division of Nephrology, Dialysis and Transplantation, University of Bari, Policlinico, Bari.

BACKGROUND: Inhibition of P70S6 kinase (P70(S6K)) phosphorylation in activated T cells is 1 of the major mechanisms by which rapamycin exerts its immunosuppressive action. STUDY DESIGN: Observational cohort study. SETTINGS & PARTICIPANTS: 2 different groups of kidney transplant recipients at a single center: 30 transplant recipients converted from mycophenolic acid and low-dose prednisone plus cyclosporine A to mycophenolic acid and low-dose prednisone plus rapamycin therapy for chronic allograft nephropathy (group 1) and 16 recipients of suboptimal organs converted from tacrolimus plus rapamycin to rapamycin therapy alone after 3 months (group 2). PREDICTOR: Exposure to rapamycin therapy and rapamycin trough levels. OUTCOMES & MEASUREMENTS: Basal and stimulated phosphorylation of P70(S6K) was measured by using Western blotting in patients' peripheral-blood mononuclear cells before and 6 to 11 months after conversion to rapamycin-based therapy. Kinase activation was attained in vivo by means of intravenous insulin injection. RESULTS: The potency of rapamycin inhibition of P70(S6K) phosphorylation varied among patients (RAPA blood concentration required to achieve 50% inhibition of P70(S6K) activation for mitogen-activated kinase, 3.14 to 12.14 ng/mL) and failed to correlate with drug trough levels. The combination of tacrolimus and rapamycin limited the inhibitory effect of the latter drug on P70(S6K) activation. LIMITATIONS: Need for additional studies exploring the relationship between P70(S6K) activity and kidney graft outcome. Exclusion of patients with diabetes. CONCLUSIONS: Long-term rapamycin treatment inhibits P70(S6K) phosphorylation in peripheral-blood mononuclear cells without significant correlation with rapamycin trough levels. By measuring in vivo the biological action of rapamycin, the assay may provide potentially relevant information for the clinical management of rapamycin-treated patients.

Published 30 July 2007 in Am J Kidney Dis, 50(2): 314-25.
Full-text of this article is available online (may require subscription).

© 2004-2008 Kidney Transplant Research Today. All Rights Reserved.