Tadashi Sofue1, Masashi Inui2, Hideyasu Kiyomoto3, Kumiko Moriwaki4, Taiga Hara4, Kazunori Yamaguchi5, Noriyasu Fukuoka5, Kazuko Banno6, Akira Nishiyama7, Yoshiyuki Kakehi2, Masakazu Kohno4. 1. Division of Nephrology and Dialysis, Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-Cho, Kita-Gun, Kagawa, 761-0793, Japan. sofue@med.kagawa-u.ac.jp. 2. Department of Urology, Faculty of Medicine, Kagawa University, Kagawa, Japan. 3. Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan. 4. Division of Nephrology and Dialysis, Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-Cho, Kita-Gun, Kagawa, 761-0793, Japan. 5. Department of Pharmacy, Kagawa University Hospital, Kagawa, Japan. 6. Shiga Pharmaceutical Association Proof Center, Kusatsu, Japan. 7. Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Abstract
BACKGROUND: Excess fluid distribution is a common disorder in peritoneal dialysis (PD) patients. Tacrolimus malabsorption may also occur in PD patients, and may lead to acute allograft rejection after transplantation. The purpose of this study was to evaluate the relationship between tacrolimus pharmacokinetics and excess fluid distribution according to pre-transplant dialysis modality. METHODS: We retrospectively analyzed 41 adult living-donor kidney transplantations, including nine PD patients and 32 hemodialysis (HD) patients. We examined tacrolimus pharmacokinetics in the peri-operative period and determined the association between the tacrolimus absorption rate and body weight reduction. The absorption efficacy of tacrolimus was evaluated as the dose-normalized tacrolimus absorption rate. Tacrolimus concentrations in PD effluent were measured by high-performance liquid chromatography. RESULTS: The tacrolimus absorption rate on the day before kidney transplantation tended to be lower in PD patients than in HD patients; however, the rate improved after kidney transplantation and was similar in both groups of patients. The peak tacrolimus concentration time was later in PD patients than in HD patients. The body weight reduction after kidney transplantation was greater in PD patients than in HD patients, and was significantly associated with the change in tacrolimus absorption rate (p=0.04, r=0.32). Only 0.002% of the oral tacrolimus dose was removed by PD itself. CONCLUSION: Excess fluid distribution in PD patients appears to contribute to tacrolimus malabsorption rather than PD itself. We should consider the risk of tacrolimus malabsorption in patients with possible excess fluid distribution, particularly in PD patients.
BACKGROUND: Excess fluid distribution is a common disorder in peritoneal dialysis (PD) patients. Tacrolimus malabsorption may also occur in PDpatients, and may lead to acute allograft rejection after transplantation. The purpose of this study was to evaluate the relationship between tacrolimus pharmacokinetics and excess fluid distribution according to pre-transplant dialysis modality. METHODS: We retrospectively analyzed 41 adult living-donor kidney transplantations, including nine PDpatients and 32 hemodialysis (HD) patients. We examined tacrolimus pharmacokinetics in the peri-operative period and determined the association between the tacrolimus absorption rate and body weight reduction. The absorption efficacy of tacrolimus was evaluated as the dose-normalized tacrolimus absorption rate. Tacrolimus concentrations in PD effluent were measured by high-performance liquid chromatography. RESULTS: The tacrolimus absorption rate on the day before kidney transplantation tended to be lower in PDpatients than in HDpatients; however, the rate improved after kidney transplantation and was similar in both groups of patients. The peak tacrolimus concentration time was later in PDpatients than in HDpatients. The body weight reduction after kidney transplantation was greater in PDpatients than in HDpatients, and was significantly associated with the change in tacrolimus absorption rate (p=0.04, r=0.32). Only 0.002% of the oral tacrolimus dose was removed by PD itself. CONCLUSION: Excess fluid distribution in PDpatients appears to contribute to tacrolimus malabsorption rather than PD itself. We should consider the risk of tacrolimus malabsorption in patients with possible excess fluid distribution, particularly in PDpatients.
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