Original Article

Clinical and Experimental Nephrology

, Volume 17, Issue 5, pp 743-749

First online:

Excess fluid distribution affects tacrolimus absorption in peritoneal dialysis patients

  • Tadashi SofueAffiliated withDivision of Nephrology and Dialysis, Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University Email author 
  • , Masashi InuiAffiliated withDepartment of Urology, Faculty of Medicine, Kagawa University
  • , Hideyasu KiyomotoAffiliated withDivision of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine
  • , Kumiko MoriwakiAffiliated withDivision of Nephrology and Dialysis, Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University
  • , Taiga HaraAffiliated withDivision of Nephrology and Dialysis, Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University
  • , Kazunori YamaguchiAffiliated withDepartment of Pharmacy, Kagawa University Hospital
  • , Noriyasu FukuokaAffiliated withDepartment of Pharmacy, Kagawa University Hospital
  • , Kazuko BannoAffiliated withShiga Pharmaceutical Association Proof Center
  • , Akira NishiyamaAffiliated withDepartment of Pharmacology, Faculty of Medicine, Kagawa University
    • , Yoshiyuki KakehiAffiliated withDepartment of Urology, Faculty of Medicine, Kagawa University
    • , Masakazu KohnoAffiliated withDivision of Nephrology and Dialysis, Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University

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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.

Keywords

Peritoneal dialysis Excess fluid distribution Tacrolimus pharmacokinetics Living-donor kidney transplantation