{'fraction_non_alphanumeric': 0.04501969611705121, 'fraction_numerical': 0.023072594259988744, 'mean_word_length': 5.045918367346939, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Consideration of the switch from twice‐daily to once‐daily tacrolimus in pediatric kidney transplant in daily clinical practice: Pharmacokinetic parameters, patient satisfaction and medical practices

To the editor, Major advances in pediatric kidney transplantation have been made in the last few years, in the fields of surgical techniques, immunosuppressive (IS) therapy, prevention and treatment of infectious, and neoplastic complications. Currently, one of the preventable causes of late acute rejection and graft loss is patient non-adherence to IS medication (1). The risk of graft failure is increased seven times in non-adherent subjects (2). Non-compliance is estimated at 30% in pediatric renal transplant recipients (RTR) and up to 70% in adolescents (3, 4). Conversion to oncedaily dose maintenance immunosuppression should improve adherence and thereby may result in better long-term renal allograft survival (5, 6). Tacrolimus (Tac) is one of the commonly used IS drugs in pediatric kidney transplantation. A prolonged-released formulation of Tac is now available to allow once-daily dosing (Tac-OD) and may improve adherence. Preliminary studies have shown an equivalence in pharmacokinetic parameters for twice-daily tacrolimus (Tac-TD) and Tac-OD in both adult and pediatric kidney and liver transplantations (7–9). Accordingly, a 1:1 mg conversion from Tac-TD to Tac-OD formulation has been recommended by the European Medicine Agency and the Canadian Society of Transplantation (10, 11). Nevertheless, pharmacokinetic results from recent clinical studies differ from the initial observations (12–15). We thought it might be interesting to disclose about our study concerning the switch to Tac-OD. The aims of this study were (i) to compare the Tac dosing before the switch, at the switch (M0), and six months later (M6), (ii) to assess patient adherence and satisfaction, (iii) to evaluate medical practices concerning the conversion from Tac-TD to Tac-OD in several French pediatric transplantation centers. Retrospectively, we included patients who were transplanted between 1992 and 2012, aged under 18 at transplantation, followed in the University Hospital of Lyon, Nantes, Robert Debr e, Toulouse and Tours, and in whom Tac-OD was introduced in relay from Tac-TD or Ciclosporin. Combined liver–kidney transplantation and patients who received straightaway Tac-OD post-transplantation were excluded. The values at M0 and M6 were compared with a Wilcoxon paired test. Data were expressed as medians and interquartile range (IQR). Two different questionnaires of about 10 simple questions were composed, one for the patients and the other for the pediatric nephrologists. Thirty-seven patients were included, with a median age of 14.7 yr old at the switch. The conversion from Tac-TD to Tac-OD was proposed to improve patient adherence in 51% of the cases and to decrease gastro-intestinal complications in 20%. The median time between transplantation and the introduction of Tac-OD was 45 months (1–232 months). Patients were converted to Tac-OD on a median ratio of 1:1 mg for their total daily dose (1:0.75 mg to 1:1.5 mg). Six months after conversion, a significant increase in Tac-OD dosing of +10% (IQR = 25%, [ 25 to +100%], p = 0.0119) was necessary to obtain appropriate residual blood concentrations (C0) (Fig. 1). Fifty-five percent of patients required an increase in Tac-OD dosing, 31% no change, and 14% a decrease. Eight graft rejections occurred after the switch (median delay of four months, from one to 20 months