Influence of conversion from cyclosporin A to tacrolimus on chronic allograft nephropathy / 中国组织工程研究

ABSTRACT

BACKGROUND: The introduction of cyclosporin A (CsA) has greatly enhanced the early survival rate of kidney graft, but the long-term graft survival rate is still limited. Whether tacrolimus prevents chronic allograft nephropathy (CAN) and prolongs survival time is now becoming a hot spot in field of renal transplantation.OBJECTIVE: To investigate the feasibility and safety of converting CsA to tacrolimus (FK506) in preventing progression of CAN. DESIGN: Observation and controlled trial.SETTING: Department of Urological Organ Transplantation, Center of Organ Transplantation, the Second Xiangya Hospital, Central South University.PARTICIPANTS: A total of 73 patients who had received kidney transplantation at the Department of Urological Organ Transplantation, Center of Organ Transplantation, the Second Xiangya Hospital of Central South University from April 2001 to October 2005, and had been diagnosed as CAN by graft biopsy (42 male patients and 31 female patients; age ranged 19-69 years), were enrolled in the study approved by the ethics committee of this hospital after their written informed consents. CsA soft capsules (Hangzhou Zhongmei Huadong Pharmaceutical Limited Company or Huabei Pharmaceutical Limited Company); mycophenolate mofetil capsules (Shanghai Roche Pharmaceutical Limited Company); prednisone acetate tablets (Second Xiangya Hospital of Central South University); tacrolimus capsules (Fujisawa Pharmaceutical Limited Company).METHODS: Seventy-three patients voluntarily participated in CsA group (n =30) or FK506 group (n =43). The two groups were homogenous regarding patients' sex, age and general data (P > 0.05). Patients in the CsA group were continued on their initial immunosuppression protocol, which consisted of CsA, mycophenolate mofetil and prednisone acetate. In the FK506 group, CsA was stopped, and FK506 was started at a dose of 0.08-0.1 mg/(kg·d) 24 hours later, twice daily, administered 2 hours after breakfast and supper. Three days later, the blood trough concentration of FK506 was tested and adjusted to a target range of 5-8μg/L. FK506 dosage adjustment was based on the blood trough concentration, serum creatinine (SCr) and its side effects. All 73 patients were treated for 12 months. MAIN OUTCOME MEASURES: SCr, glomerular filtration rate (GFR), 24-hour urine protein excretion, serum total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL) and the toxic side effects of calcineurin inhibitors (incidences of tremor, hyperglycemia and hypertension) were monitored during a follow-up of over 12 months. RESULTS: A total of 73 patients were involved in the result analysis.①12 months after conversion, the level of SCr was statistically reduced and GFR levels were markedly elevated in the FK506 group compared with the CsA group (P < 0.01). TC, TG and LDL levels in the FK506 group were significantly lower than those in the CsA group (P < 0.01).②Compared with the CsA group, the incidence of tremor was obviously increased [30% (9/30), 5% (2/43), P < 0.01] and the incidence of hypertension was obviously decreased [56% (24/43), 83% (25/30), P < 0.05] in the FK506 group.CONCLUSION: Conversion from CsA to FK506 can postpone renal dysfunction, reduce proteinuria and improve hyperlipidemia. FK506 treatment is an effective therapy in slowing the progression of CAN.