Comparison of the efficacy of low-dosage versus standard-dosage tacrolimus after kidney transplantation by programming renal biopsies

Objective To evaluate the effect and safety of modest tacrolimus(FK506) reduction by programming renal biospies.Methods A prospective,randomized,open study was designed and forty-eight recipients undergoing firstly cadaveric renal transplantation were divided randomly into two groups: low dose tacrolimus group(Lo-FK506 group,n=24) and standard dose tacrolimus group(St-FK506 group,n=24).The recipients in both groups were treated with triple immunosuppression regimen including mycophenolate mofetil(MMF),FK506 and adrenal cortex hormone.The FK506 blood trough concentration of St-FK506 group was maintained at 10-12 ng/ml in the first three months after study entry,and then at 8-10 ng/ml after three months.The FK506 blood trough concentration of Lo-FK506 group was maintained at 8-10 ng/ml in the first two months after study entry,3-7 ng/ml in third month,3-5 ng/ml after 3 months.All patients were followed up for one year.The FK506 blood trough concentration,renal function[serum creatinine(Scr),endogenous creatinine clearance rate(Ccr)],fasting blood glucose,glycosylated hemoglobin,seralbumin and blood fat were examined and recorded regularly.At the same time,acute rejection(AR) occurrence,pathological damage index score and chronic allograft damage index(CADI)of recipients were evaluated by using renal graft biopsy(FNA) at month 3 and 12 post-transplantation.The 1-year survival rate of patients /grafts and the incidence of adverse event were observed.Results One year follow-up post-transplantation,FK506 blood trough concentration in the Lo-FK506 group was lower compared with St-FK506 group(P0.01),but most of the patients reached the target level.The level of Ccr in Lo-FK506 group was higher than that of St-FK506 group[(83±14) ml / min vs(62 ±16) ml/min,P0.05].The level of glucose was lower in Lo-FK506 group than that of St-FK506 group(P0.05).According to the results of programming renal biopsies,interstitial fibrosis,tubular atrophy and glomerulosclerosis score were also lower in Lo-FK506 group(all in P0.05).The incidence,severity of AR as well as 1-year survival rates of patient /graft was similar in both groups(P0.05).The incidence of pulmonary infection and de novo diabetes one year posttransplant was significantly lower in Lo-FK506 group compared with St-FK506 group(P0.05 and P0.01 respectively).Conclusion It is reliable and helpful to evaluate the efficacy of modest tacrolimus reduction by programming renal biopsies and to find the chronic pathological changes of transplanted grafts.Modest reduction of the FK506 blood trough concentration in the early stage after transplantation is good for kidney grafts and recipients without increasing the risk of rejection.