CLINICAL IMMUNOSUPPRESSION - KIDNEY EARLY

V. Sumethkul¹, S. Wongpraphairot,¹, P. Tankee¹, S. Jirasiritham^2
1Medicine, Ramathibodi Hospital, Bangkok/THAILAND, ²Surgery, Ramathibodi Hospital, Bangkok/THAILAND

Body: Introduction. CsA nephrotoxicity is an important cause of chronic allograft dysfunction. Clinical information concerning the impact of very early CsA dose reduction in kidney transplant recipients is limited. The objective of this study is to determine the long term outcomes of very early CsA dose reduction. This is synchronized with de novo everolimus and low dose corticosteroid therapy. Material and method. De novo kidney transplant recipients are prospectively investigated with informed consent. All received CsA (target C0 250-350 ng/ml) and prednisolone as initial therapy. CsA dosage is reduced by 50 % at day 7^th post transplantation. Everolimus is concomitantly started at the day of CsA reduction with a target trough level of 3-8 ng/ml. After nadir serum creatinine is achieved, CsA is gradually reduced to maintain C0 at 50-100 ng/ml. Full pharmacokinetic studies of everolimus and CsA was studied at the period of 4-8 weeks after CsA reduction. Ten blood samples of everolimus and CsA level are drawn ( predose, 0.5, 1, 1.5, 2, 3, 4, 6, 9 and 12 hours). Primary end point is patient and graft survival rate. Secondary end point is renal function as determined by MDRD GFR. No patient receive induction therapy. Results. There are 10 patients being enrolled (8 living related and 2 deceased donors). Four patients have diabetes mellitus as the cause of ESRD. Mean HLA mismatch is 2.4 ± 1.07 antigens. Mean follow up duration is 51.2 ± 3.45 months. Nadir serum creatinine is 1.03 ± 0.33 mg/dl. Mean initial GFR is 97.97± 23.36 ml/min. At the time of pharmacokinetic study, mean trough everolimus is 4.95±1.56 ng/ml (range 3.06-7.56). Mean Cmax of everolimus is 15.4±4.6 ng/ml. Time to Cmax of everolimus is 1.5±0.3 hr. Mean AUC of everolimus is 90.48±16.83 ng·hr/ml. Mean CsA trough level and AUC is 100.30±42.72 and 3449±1402 ng/ml. At last follow up, mean dose of CsA is 75 ± 24 mg/day, mean trough CsA level is 85±29 ng/ml, mean dose of everolimus is 1.275 ± 0.25 mg/day, mean everolimus level is 6.68± 2.0 ng/ml, mean serum creatinine is 1.2 ± 0.43 mg/dl. GFR at 1 year, 3 year and last follow up is 82 ± 25, 80 ± 21 and 80 ± 25 ml/min. Serum cholesterol and triglyceride change from 184±50 and 97±66 at base line to 225 ± 43 and 142 ± 74 mg/dl at last visit. Seventy percent of patients require lipid lowering drug by statins. Acute rejection occurs in one patient (10%) and is treated successfully by pulse methylprednisolone. One patient develops mild degree interstitial lung disease that requires everolimus dose reduction. Post transplant DM develops in three patients (30%). Recurrence Ig A nephropathy develops in two patient (20%). No patients have delay graft function, impair wound healing and lymphocele. Patient and graft survival is 100 %. Conclusion. Very early CsA dose reduction synchronized with de novo everolimus therapy is associated with good long term patient and graft survival in kidney transplant recipients. This intervention is associated with very good MDRD GFR at 4 years.

Disclosure: All authors have declared no conflicts of interest.