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The use of tacrolimus (Tac) may be involved in the development of new-onset diabetes after transplantation (NODAT) in a dose-related manner. This study aimed to evaluate the effects of a standard twice-daily formulation of Tac (TacBID) vs. the once-daily slow-release formulation (TacOD) on the basal insulin resistance indexes (Homa and McAuley), and related metabolic parameters, in a cohort of kidney transplant patients. We retrospectively evaluated 20 stable renal transplant recipients who were switched from TacBID to TacOD. Blood levels of Tac were analyzed at one-month intervals from 6 months before to 8 months after conversion. Moreover, Homa and McAuley indexes, C-peptide, insulin, HbA1c, uric acid, triglycerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL)-cholesterol serum levels and their associations with Tac levels were evaluated. We observed a significant decrease in Tac exposure (8.5 ± 2 ng/mL, CV 0.23 vs. 6.1 ± 1.9 ng/mL, CV 0.31, TacBID vs. TacOD periods, p &lt, 0.001) and no significant changes in Homa (1.42 ± 0.4 vs. 1.8 ± 0.7, p &gt, 0.05) and McAuley indexes (7.12 ± 1 vs. 7.58 ± 1.4, p &gt, 0.05). Similarly, blood levels of glucose, insulin, HbA1c, lipids, and uric acid were unchanged between the two periods, while C-peptide resulted significantly lower after conversion to TacOD. These data suggest that in kidney transplant recipients, reduced Tac exposure has no significant effects on basal insulin sensitivity indexes and metabolic parameters.

Background Tacrolimus trough levels (TTL) during the first weeks after liver transplantation (LT) have been related with long-term renal function and hepatocellular carcinoma recurrence. Nevertheless, the significance of trough levels of tacrolimus during the early post-transplant period for the long-term outcome is under debate. Aim To evaluate the effect of TTL during the first month on the long-term outcomes after LT. Methods One hundred fifty-five LT recipients treated de novo with once-daily tacrolimus were retrospectively studied. Patients with repeated LT or combined transplantation were excluded as well as those who presented renal dysfunction prior to transplantation and/or those who needed induction therapy. Patients were classified into 2 groups according to their mean TTL within the first month after transplantation: ≤ 10 (n = 98) and > 10 ng/mL (n = 57). Multivariate analyses were performed to assess risk factors for patient mortality. Results Mean levels within the first month post-transplant were 7.4 ± 1.7 and 12.6 ± 2.2 ng/mL in the ≤ 10 and > 10 groups, respectively. Donor age was higher in the high TTL group 62.9 ± 16.8 years vs 45.7 ± 17.5 years (P = 0.002) whilst mycophenolate-mofetil was more frequently used in the low TTL group 32.7% vs 15.8% (P = 0.02). Recipient features were generally similar across groups. After a median follow-up of 52.8 mo (range 2.8-81.1), no significant differences were observed in: Mean estimated glomerular filtration rate (P = 0.69), hepatocellular carcinoma recurrence (P = 0.44), de novo tumors (P = 0.77), new-onset diabetes (P = 0.13), or biopsy-proven acute rejection rate (12.2% and 8.8%, respectively; P = 0.50). Eighteen patients died during the follow-up and were evenly distributed across groups (P = 0.83). Five-year patient survival was 90.5% and 84.9%, respectively (P = 0.44), while 5-year graft survival was 88.2% and 80.8%, respectively (P = 0.42). Early TTL was not an independent factor for patient mortality in multivariate analyses. Conclusion Differences in tacrolimus levels restricted to the first month after transplant did not result in significant differences in long-term outcomes of LT recipients.

Massimo Sabbatini,1 Gianluca Garofalo,1 Silvio Borrelli,2 Sossio Vitale,1 Massimiliano Torino,1 Domenico Capone,3 Luigi Russo,3 Antonio Pisani,1 Rosa Carrano,1 Riccardo Gallo,1 Stefano Federico11Nephrology, Department of Public Health, University Federico II of Naples, 2Department of Nephrology, Second University of Naples, 3Department of Neurosciences, Unit of Clinical Pharmacology, University Federico II of Naples, Naples, ItalyPurpose: The aim of this study was to determine the prevalence of nonadherence in a cohort of renal transplant recipients (RTRs) and to evaluate prospectively whether more intense clinical surveillance and reduced pill number enhanced adherence.Patients and methods: The study was carried out in 310 stable RTRs in whom adherence, life satisfaction, and transplant care were evaluated by specific questionnaires (time 0). The patients under tacrolimus (TAC; bis in die [BID]) were then shifted to once-daily TAC (D-TAC) to reduce their pill burden (Shift group) and were followed up for 6 months to reevaluate the same parameters. Patients on cyclosporin or still on BID-TAC constituted a time-control group.Results: The prevalence of nonadherence was 23.5% and was associated with previous rejection episodes (P

Introduction We assessed our clinical experience with de novo kidney transplant recipients from living donors who received once–daily tacrolimus (OD TAC). In addition, we investigated tacrolimus pharmacokinetics and compared the dose of tacrolimus in de novo kidney transplant patients treated with OD TAC or twice–daily tacrolimus (BD TAC). Material and methods Ten patients (3 ABO incompatible, 2 preemptive), who had received a living donor kidney transplant at our hospital since February, 2009, received OD TAC with mycophenolate mofetil, methylprednisolone, and basiliximab. OD TAC doses were adjusted to maintain tacrolimus trough levels in the range of 9–12 ng/mL. We assessed clinical and pharmacokinetic profiles. We compared average total daily dose of tacrolimus between the OD TAC and BD TAC groups. Results Patient survival and graft survival rates were 100% at 15.7 months. Acute rejection was not found clinically. The protocol biopsies (week 3 and month 3) did not reveal biopsy–proven acute rejection, either. No calcineurin inhibitor toxicity occurred. Doses in the OD TAC and BD TAC groups at week 3 posttransplant were 0.308 mg/kg/day and 0.149 mg/kg/day, respectively. Conclusions OD TAC appears to have efficacy and safety equivalent to that of BD TAC. However, a larger dose of OD TAC compared to that of BD TAC may be required during the early period after kidney transplantation.

Despite the therapeutic equivalence between twice-daily and once-daily tacrolimus, patient safety after conversion is still a concern. We reviewed 218 liver transplantation (LT) patients who converted twice-daily to once-daily tacrolimus between May 2011 and January 2014. Thirty (13.8%) patients had adverse events after conversion, with a liver function test (LFT) abnormality being the most common adverse event (n = 17). Despite the decrease in serum tacrolimus of > 30% after conversion, none of the patients who were converted to a dosage ratio (once-daily tacrolimus dosage: twice-daily tacrolimus dosage) > 1 had an LFT abnormality. Most patients with an LFT abnormality improved after increasing the once-daily tacrolimus dosage (n = 2), returned to a previous medication, and/or added another immunosuppressant (n = 15). One patient had acute cellular rejection, which improved after steroid pulse treatment, and another patient had graft failure. In patients with a dosage ratio ≤ 1, the conversion time within 5 years after LT was the only significant risk factor for an LFT abnormality after conversion (odds ratio: 11.850, 95% confidence interval: 1.321–106.325, P = 0.027). In conclusion, the dosage ratio and time after LT should be carefully considered during conversion from twice-daily to once-daily tacrolimus., Graphical Abstract