Which Kidney Transplant Recipients Can Benefit from the Initial Tacrolimus Dose Reduction?

Abstract

Background Observational data suggest that the fixed initial recommended tacrolimus (Tc) dosing (0.2 mg/kg/day) results in supratherapeutic drug levels in some patients during the early posttransplant period. The aim of the study was to analyze a wide panel of patient-related factors and their interactions which increase the risk for first Tc blood level > 15 ng/ml. Materials and Methods We performed a retrospective analysis of 488 consecutive adult kidney transplant recipients who were initially treated with triple immunosuppressive regimen containing tacrolimus twice daily. The analysis included the first assessment of Tc trough blood levels and several demographic, anthropometric, laboratory, and comedication data. Results The multiple logistic regression analysis showed that age > 55 years, BMI > 24.6 kg/m2, blood hemoglobin concentration > 9.5 g/dl, and the presence of anti-HCV antibodies independently increased the risk for first Tc level > 15 ng/ml. The relative risk (RR) for first tacrolimus level > 15 ng/ml was 1.88 (95% CI 1.35–2.64, p < 0.001) for patients with one risk factor and 2.81 (2.02–3.89, p < 0.001) for patients with two risk factors. Conclusions Initial tacrolimus dose reduction should be considered in older, overweight, or obese kidney transplant recipients and in subjects with anti-HCV antibodies. Moreover, dose reduction of tacrolimus is especially important in patients with coexisting multiple risk factors.

A pharmacist-led intervention to improve kidney transplant recipient outcomes and identify patients at risk of highly variable trough tacrolimus levels: a cohort study

“…Consequently, changes in pharmacokinetic variables in obese patients might produce more linear kinetics and therefore lower intra-individual variations in drug levels. These mechanisms might also explain why obese patients in our study have lower tacrolimus dosages at discharge, and suggest the possible need to adjust dosages at treatment initiation, as already described 24–27. Also, our results show that male sex and young age were associated with out-of-range C min , as already reported by others 28–30.…”

Studying the Blood Trough Level of Tacrolimus on Patients after Kidney Transplant at the Uronephreulogical Department, Bach Mai Hospital, Vietnam

“…In our study, the mean BMI was 20,512 ± 2,898 kg/m 2 , 54.8% of patients had normal BMI and the proportion of overweight and obese patients was only 19.4%. This rate was lower than in the Kinga Krzyhowska's study (the proportion of overweight and obese patients were 43.2%) [16].…”

“…The mean age of the patients in this study was 34.70 ± 10.88 years old, lower than that of other studies conducted on kidney transplant patients. In the research of C. Staatz in a hospital, Australia (2001) [15] and Kinga Krzyhowska at Silesia Medical University (2018) [16], the average age of patients was 47 years old, or around 50 years old in the study of P. Stratta in 2012 [17]. Moreover, in our study, the number of patients over 60 years old was only recorded 2 cases.…”

Tacrolimus Exposure in Obese Patients: and A Case–Control Study in Kidney Transplantation

“…Finally, Krzy_ zowska et al demonstrated in a cohort of 488 KTRs (aged .55 years), BMI .24.6 kg/m 2 , and the presence of antibodies against HCV were independent risk factors for a first supratherapeutic tacrolimus trough level. 35 There is limited information available in the literature on the mechanisms that could explain these pharmacokinetic changes. The absorption step in the context of obesity has barely been studied.…”