Higher tacrolimus trough levels on days 2–5 post‐renal transplant are associated with reduced rates of acute rejection

Abstract

We analyzed the association between whole-blood trough tacrolimus (TAC) levels in the first days post-kidney transplant and acute cellular rejection (ACR) rates. Four hundred and sixty-four consecutive, deceased-donor kidney transplant recipients were included. All were treated with a combination of TAC, mycophenolate mofetil and prednisolone. Patients were analyzed in four groups based on quartiles of the mean TAC on days 2 and 5 post-transplant: Group 1: median TAC 11 ng/mL (n = 122, range 2-13.5 ng/mL), Group 2: median 17 ng/mL (n = 123, range 14-20 ng/mL), Group 3: median 24 ng/mL (n = 108, range 20.5-27 ng/mL) and Group 4: median 33.5 ng/mL (n = 116, range 27.5-77.5 ng/mL). A graded reduction in the rates of ACR was observed for each incremental days 2-5 TAC. The one-yr ACR rate was 24.03% (95% CI 17.26-32.88), 22.20% (95% CI 15.78-30.70), 13.41% (95% CI 8.15-21.63) and 8.69% (95% CI 4.77-15.55) for Groups 1-4, respectively (p = 0.003). This study suggests that higher early TACs are associated with reduced rates of ACR at one yr.

Clinical efficacy and pharmacokinetics of tacrolimus in children with steroid-resistant nephrotic syndrome

“…Desirable C 0 in pediatric transplants are 10-12 ng/ml in the immediate post-transplant and 5-10 ng/ml thereafter to prevent rejection [14][15][16][17]. Taking a cue from the transplant data, most studies target tacrolimus levels between 5 and 10 ng/ml in children with SRNS [2,3].…”

The interactions of age, sex, body mass index, genetics, and steroid weight-based doses on tacrolimus dosing requirement after adult kidney transplantation

“…The magnitude of the prednisone effect is maximum when high intravenous doses are employed in first post-transplant days, resulting in an increase in tacrolimus clearance [26,49]. Clinicians should be aware that the increase in tacrolimus exposure and the risk of excessively high trough levels when the steroid dose is subsequently reduced does exist for all patients, but is especially high for slow metabolizers.…”

Validation of Tacrolimus Equation to Predict Troughs Using Genetic and Clinical Factors

“…Mean trough concentrations in the first week post-transplant have been shown to be significantly different between rejectors and nonrejectors [28,29]. Assuring that all patients are within the therapeutic target in the early post-transplant period would improve therapy [29].…”