A PILOT STUDY OF SWITCHING CSA TO LOW DOSE OF TACROLIMUS ON CHRONIC ALLOGRAFT NEPHROPATHY AFTER KIDNEY TRANSPLANTATION

Abstract

P178 Aims: The two principal factors implicated in late kidney allograft failure are chronic allograft nephropathy(CAN) and death of the patient with a functioning graft (mainly from cardiovascular causes). CAN is the leading cause of graft failure. Both nonimmunological and immunological mechanisms contribute to this pathology. Tacrolimus is a new, high-potential immunosuppressive agent, possible strategies to stabilize or improve allograft function in patients with already established CAN are the addition of mycophenolate mofetil and conversion from cyclosporine to tacrolimus. Methods: A total of 58 cadaveric kidney transplants were performed at CHAO YANG HOSPITAL from 1998-2000,these patients were first grafts. All recipients received CsA-based triple immunosuppressive regimen. The mean age was 36±14 years, 0.5 to 7.5years after operation. The patients with abnormal grafted renal function after operation and chronic renal allograft nephropathy proved pathologically were collected. A cyclosporine based regimen was converted to a tacrolimus-based regimen. Recipients began to received tacrolimus-based triple immunosuppressive regimen (tacrolimus + MMF +prednisone) after 12 hours discontinuation of CsA. The initial dosage of tacrolimus ranged from 0.04 mg/kg/d to 0.07mg/kg/d,. Dosage adjustments were based on whole blood trough levels. The targeting whole blood trough levels was 8-10ng/ml within 6 months after operation, 5-7 ng/ml after 6 months operation. The dosage of MMF was 1500mg/day. Fellow up at least twelve months. Monitoring the slope of serum creatinine and GFR(ml/min/1.73m2) and 24-hours urine protein output and blood pressure and lipid before and after twelve months of switching CsA to Tacrolimus. Results: The result are shown in Fig 1, 2 and Table 1. The 58 patients of serum creatinine level decreased from 387.5 ±49.7mmol/l to 165.1±56.2mmol/L(p<0.01), 185.1±48.2mmol/L, 180.1±51.2mmol/L. The slope of serum creatinine were from-1.35±1.3 to 2.43±1.7(p<0.05), 2.33±1.5, 2.45±1.5,The result are shown in Fig 2. GFR (ml/min/1.73m2) were from 38.79±2.25 to 49.21±3.19 (p<0.05), 47.21±3.38, 43.37±2.54,24-hours urine protein output were from 4.3±0.8g to 1.9±0.5g(p<0.05), 1.7±0.8g,1.8±0.6g,Cholesterol were from 288±46 mg/dL to 159±55 mg/dL, 169±39 mg/dL,152±47mg/dL, Triglyceride were from 308±56 mg/dL to 217±48 mg/dL, 197±52 mg/dL, 201±43 mg/dL,MAP were from 126±39 mmHg to 90±25 mmHg, 95±38 mmHg, 87±40 mmHg before and after 12,24,36 months of switching CsA to Tacrolimus. The patients survival rates were 100%(58/58),96.5%(56/58), 94.8%(55/58) at 1 year,2 year,3 year respectively. Graft function recovered in 38 cases,improved in 11 recipients, stabilized in 6 patients. Therapy failed in 3 cases and begin hemodialysis. 3 recipients withdrawn from the study because of liver toxicity. The incidence of acute rejection in our study was 10.34%(6/58) after 1 years fellow up. Adverse events in our study were bilirubinemia3.45% (2/58), tremor17.24%(10/58). None of all the patients developed new-onset insulin-dependent Diabetes Mellitus. Conclusions: Many investigators have noted that CAN is the mainly factor of the late kidney allograft failure. Our reports cited that Tacrolimus+MMF is better than CsA in delaying kidney transplant function,(1) Combine Tacrolimus and MMF treatment results in a low incidence of biopsy-confirmed rejection.(2) Tacrolimus reduced TGF-β transforming.(3)Tacrolimus requred less antihypertension,antihyperlipid therapy.(4)To the extent that MMF gives clinicans confidence to reduce the CNI (calcineurin inhibitor) this minimized drug-related toxicities.(5)Mycophenolate mofetil is more bioavailable when used with tacrolimus, compared with cyclosporine, probably because cyclosporine reduces MMF’s bioavailability. The use of a lower dose of MMF in combination with Tacrolimus as maintenance therapy may decrease the incidence of adverse effects while maintaining efficacy. In summary, in this study we demonstrated that conversion from cyclosporine to tacrolimus based regimen was an effective and safe alternative for delaying the course of renal function induced by Chronic Allograft Nephropathy after kidney transplantation.