Clinical efficacy and safety of conversion from cyclosporine A to tacrolimus-based regimen for different pathological types of chronic allograft nephropathy patients / 中国组织工程研究

ABSTRACT

BACKGROUND: Recent studies have suggested that conversion from cyclosporine A (CsA) to tacrolimus (FK 506)-based regimen can improve renal allograft function and survival rate. But little is known about whether the conversion from CsA to tacrolimus(FK 506) plus mycophenolate mofetil (MMF)-based regimen exhibits the same or similar clinical efficacy. OBJECTIVE: To investigate the clinical efficacy and safety of converting CsA to FK506 plus MMF in treatment of different types of chronic allograft nephropathy (CAN). DESIGN, TIME AND SETTING: An observational and controlled trial was performed at the Center for Organ Transplantation, Zhujiang Hospital, Southern Medical University from January 2005 to October 2007. PARTICIPANTS: Fifteen-nine enrolled patients received CsA-based regimen after renal allografting. Following pathological confirm and typing, all patients were assigned to two groups: CAN with chronic rejection (CR, n = 31) and CAN without chronic rejection (non-CR, n = 28). FK 56 was purchased from Fujisawa Pharmaceutical Company, Ltd., Japan. MMF was sourced from Shanghai Roche Pharmaceutical Co., Ltd., China. METHODS: When patients were diagnosed CAN, the CsA regimen was conversed to FK506 plus MMF regimen. FK506 initiated at a dose of 0.08 mg/kg per day and then was adjusted to achieve steady-state whole blood trough levels of approximately 5-8 μg/L. MMF was used at a fixed dosage, 1.0 g/d, twice a day, only if relative adverse events occurred. All patients were followed up at least 6 months. MAIN OUTCOME MEASURES: Serum creatinine(Scr), total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), 24-h proteinuria, glomerular filtration rate (GFR), and complications. RESULTS: All initial 59 patients were included in the final analysis. At 6 months after regimen conversion, the levels of Scr, TC, TG, LDL, and 24-hour proteinuria were significantly reduced in non-CR, in particular CR, groups, compared with prior to conversion (P< 0.05). GFR was markedly increased in both the CR and non-CR groups (P< 0.05). In the CR group, 20 patients obtained improved results, 7 got stable results, and 4 showed ineffective results. The effective rate of regimen conversion was 64.5% and 32.1% in the CR and non-CR groups, respectively, and significant difference existed between the two groups (P < 0.05). Compared with prior to conversion, the incidence of hypertension and hyperlipemia was significantly decreased after regimen conversion (P< 0.05). There was no significant difference in diabetes mellitus, opportunistic infection, and malignancy between prior to and after regimen conversion. CONCLUSION: FK506 plus MMF-based regimen can markedly improve the function of renal graft of CAN, in particular CR, patients.