Early withdrawal of cyclosporine A improves 1-year kidney graft structure and function in sirolimus-treated patients
- 15 April 2003
- journal article
- clinical trial
- Published by Wolters Kluwer Health in Transplantation
- Vol. 75 (7) , 998-1003
- https://doi.org/10.1097/01.tp.0000057240.95073.35
Abstract
BACKGROUND:\ud Chronic allograft nephropathy (CAN) represents the most common cause of late graft loss. Nephrotoxicity from chronic use of calcineurin inhibitors (CNI) has the potential to contribute to CAN. The present investigation aimed to evaluate the impact of early CNI withdrawal on kidney graft function and structure at 1 year in sirolimus (SRL)-treated patients.\ud METHODS:\ud Forty consecutive kidney transplant recipients were initially treated with corticosteroids, cyclosporine A (CsA), and SRL (2 mg/day). After 3 months, patients were randomly assigned to either continue the same treatment (group I) or to withdraw CsA and continue SRL (group II). All patients underwent kidney graft biopsy immediately after graft reperfusion (0-hr biopsy) and 12 months after engraftment.\ud RESULTS:\ud Baseline graft biopsy showed a higher degree of renal damage in group II patients (total score, 4+/-1.6 vs. 2+/-0.9; P<0.05). Twelve months after engraftment, CAN was diagnosed in 55% of all patients, of whom 64% were in group I and 36% in group II. CAN lesions were scored as moderate to severe in 90% of group I patients but only 32% of group II patients (P<0.05). A vascular score greater than or equal to 2 occurred in 90% of group I patients and in 38% of group II patients (P<0.05). At 1 year, group I patients showed a significantly worse kidney graft function (serum creatinine, 2.0+/-0.3 vs. 1.3+/-0.3 mg/dL; creatinine clearance, 54+/-14 vs. 66+/-17 mL/min; both P<0.002).\ud CONCLUSIONS:\ud These results suggest that early withdrawal of CsA is a safe option, which allows a significant reduction of chronic histologic damage, particularly vascular injury, of cadaveric kidney allograftsKeywords
This publication has 25 references indexed in Scilit:
- Reliability of chronic allograft nephropathy diagnosis in sequential protocol biopsiesKidney International, 2002
- SIROLIMUS ALLOWS EARLY CYCLOSPORINE WITHDRAWAL IN RENAL TRANSPLANTATION RESULTING IN IMPROVED RENAL FUNCTION AND LOWER BLOOD PRESSURE1,2,10Transplantation, 2001
- MECHANISMS OF NEPHROTOXICITYTransplantation, 2000
- Improved Graft Survival after Renal Transplantation in the United States, 1988 to 1996New England Journal of Medicine, 2000
- Nephrotoxicity of immunosuppressive drugs: Long-term consequences and challenges for the futureAmerican Journal of Kidney Diseases, 2000
- Rapamune® (RAPA, rapamycin, sirolimus): mechanism of action immunosuppressive effect results from blockade of signal transduction and inhibition of cell cycle progressionClinical Biochemistry, 1998
- Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexesCell, 1991
- SYNERGISTIC INTERACTIONS OF CYCLOSPORINE AND RAPAMYCIN TO INHIBIT IMMUNE PERFORMANCES OF NORMAL HUMAN PERIPHERAL BLOOD LYMPHOCYTES IN VITROTransplantation, 1991
- RAPAMYCIN, A POTENT IMMUNOSUPPRESSIVE DRUG FOR VASCULARIZED HEART, KIDNEY, AND SMALL BOWEL TRANSPLANTATION IN THE RATTransplantation, 1991
- RAPAMYCIN FOR IMMUNOSUPPRESSION IN ORGAN ALLOGRAFTINGThe Lancet, 1989