Masahiro Iinuma

Chronopharmacokinetics of Tacrolimus in Kidney Transplant Recipients: Occurrence of Acute Rejection

The circadian variation of clinical pharmacokinetics of tacrolimus was studied using 16 adult renal transplant recipients 1 month after the operation. The recipients were administered tacrolimus twice a day (9 a.m. and 9 p.m.), and whole‐blood samples were obtained just prior to and 1, 2, 3, 6, 9, and 12 hours after oral administration. Histological specimens of transplant kidney were collected by an allograft core biopsy on day 28 after the transplantation. There were no circadian changes in the area under the concentration‐time curve (AUC0–12) (214 ng•h/mL during daytime vs. 223 ng•h/mL during nighttime) resulting from morning and night doses. A slight delay in mean residence time (MRT0–12) and time to the peak concentration (tmax) was found after night doses, but there was no statistical significance. Three patients (18.8%) had a clinical acute rejection (AR) episode 4 to 6 weeks after transplantation, and AUC0–12 at nighttime was significantly lower (18.4% on average) in patients with AR in comparison to those without AR. There was no statistical significance in maximum concentration (Cmax) or morning/night trough levels between patients with and without AR. In regard to the correlation between tacrolimus concentrations in each sampling time and AUC0–12, the morning trough concentrations were less predictable for daytime AUC0–12 (r2 = 0.125), but there was a weak correlation to nighttime AUC0–12 (r2 = 0.424). Tacrolimus concentrations at 2, 3, and 6 hours after the morning dose (C2, C3, and C6) had a good correlation against daytime AUC. The results of this study indicate that the variance on the clinical pharmacokinetics of tacrolimus between daytime and nighttime in renal transplant patients is not significant, while the lower nighttime AUC corresponded to the occurrence of AR.

Hand assisted retroperitoneoscopic living donor nephrectomy in elderly donors.

PURPOSE We assessed the influence of HARDN on residual donor kidney and allograft function, invasiveness and morbidity in elderly living donors. MATERIALS AND METHODS A total of 89 living donors underwent nephrectomy before September 2004 at our institution. The 18 donors who were 65 years or older included 4 of 27 with ODN and 14 of 62 with HARDN. RESULTS In older (65 years or older) donors mean operative time, mean blood loss and warm ischemia time in the HARDN group did not differ from those in the ODN group. None of the donors had major complications. Older donors with HARDN had a tendency toward a shorter hospital stay than those with ODN. Postoperative serum creatinine in older donors with HARDN was higher than that in younger donors with HARDN, while there was no difference in postoperative serum creatinine between older donors with HARDN and those with ODN. The frequency of allograft losses tended to be higher in older than in younger kidneys (4 of 18 vs 5 of 71, p = 0.054). However, most allograft losses did not seem to be related to surgical technique. CONCLUSIONS Although further studies, especially with long-term followup, are necessary, HARDN is suggested to be safe and minimally invasive surgery even in elderly donors and to be comparable to open surgery in terms of morbidity, the residual donor kidney and allograft function.