No Significant Influence of Reduced Initial Tacrolimus Dose on Risk of Underdosing and Early Graft Function in Older and Overweight Kidney Transplant Recipients

• Published in: Transplantation proceedings Vol. 50; no. 6; pp. 1755 - 1759
• Main Authors: Krzyżowska, K., Kolonko, A., Giza, P., Chudek, J., Więcek, A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2018
• Subjects: Aged; Delayed Graft Function - epidemiology; Delayed Graft Function - prevention & control; Female; Graft Rejection - epidemiology; Graft Rejection - prevention & control; Humans; Immunosuppression - methods; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - adverse effects; Incidence; Kidney Transplantation; Male; Middle Aged; Overweight; Risk; Tacrolimus - administration & dosage; Tacrolimus - adverse effects
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2018.02.108

Nowadays, a reduced initial daily dose of tacrolimus (Tac) (0.1–0.15 mg/kg) is recommended for the majority of kidney transplant recipients (KTRs). The aim of the study was to analyze the safety of such a regimen, including the risk of first inadequately low Tac blood level, acute rejection (AR) occurrence, or early graft dysfunction. In 2011, we introduced a modified (0.1–0.15 mg/kg/d) initial Tac dosing regimen in older (>55 years) and/or overweight KTRs. To assure the safety of this protocol, we monitored the risk of inadequately low blood Tac level (<6 ng/mL) and incidence of AR or delayed graft function (DGF). The historical cohort with the higher Tac dosing regimen (0.2 mg/kg/d, n = 208) served as a control group. The mean Tac daily dose in 78 KTRs (group with reduced dosing) was 0.133 (95% confidence interval [CI], 0.130–0.136) mg/kg and was significantly lower than the standard, previously prescribed dose of 0.195 (95% CI, 0.194–0.197) mg/kg. Of note, induction therapy was employed twice more often in the reduced Tac dosing group. The dose reduction resulted in a slight, nonsignificant decrease in first Tac trough level. The percentages of patients with first Tac troughs <6 ng/mL (5.1% vs 4.8%), AR (6.4% vs 5.8%), and DGF (25.6% vs 31.2%) were similar in the reduced and standard dosing groups. The currently recommended reduction in Tac initial dosing does not increase the risk of inadequate immunosuppression and does not affect the early graft function. Regardless of Tac dose reduction, there is still a substantial risk of Tac overdosing in older or overweight KTRs. •The safety of reduced initial tacrolimus dose was studied.•Only older and overweight kidney recipients were included in this study.•No differences in tacrolimus levels a <6 ng/mL or early graft function were noted.