Sequential Cohort Analysis After Liver Transplantation Shows de Novo Extended Release Tacrolimus Is Safe, Efficacious, and Minimizes Renal Dysfunction

Abstract

Background. The use of once-daily extended-release tacrolimus (ERT) is associated with improved long-term graft and patient survival when compared with twice-daily tacrolimus (BDT), but the underlying reasons for differential survival are unclear. The aim of the study was to compare clinical outcomes known to impact on posttransplant survival for de novo BDT and ERT in liver transplantation (LT) recipients. Methods. We conducted a single-center, prospective sequential cohort analysis of adult patients undergoing LT during a change in protocol from de novo BDT to ERT, with a 6-month post-LT follow-up. Results. A total of 160 transplanted patients were evaluated; 82 were in the BDT group and 78 were in the ERT group. The cohorts were matched for standard variables and a similar proportion in each group received induction interleukin-2 receptor antibody (36% and 31%). There were no significant differences in the measured outcomes of patient and graft survival, biopsy-proven acute rejection episodes, post LT diabetes, and toxicity. A significantly lower number of patients developed chronic kidney disease Stage3–4 in the ERT cohort compared with BDT cohort. In patients with pre-LT renal dysfunction who received antibody induction, estimated glomerular filtration rate decreased significantly in the BDT but not the ERT group. Conclusions. We show that once-daily ERT is as safe and efficacious as BDT in de novo LT but optimally conserves renal function post-LT.

A Systematic Review of the Literature on Chronic Kidney Disease Following Liver Transplantation

“…When information was available, ≥78.1% of patients were White; the exception was Chauhan et al, in which 36.3–43.3% of patients across study arms were White [ 20 ]. The primary diseases at baseline varied between studies and study arms ( Table 4 ), but included alcoholism or ethanol abuse (23.1–71.4% across 3 studies [ 23 , 24 , 29 ]) hepatitis C virus infection (0–41.8% in 11 studies [ 7 , 19 , 20 , 22 – 26 , 28 – 30 ]), and hepatocellular carcinoma (2.3–63.6% in 10 studies [ 7 , 19 – 22 , 24 , 27 – 30 ]).…”

“…Mean GFR/eGFR decreased numerically over time in at least 1 study arm from 6 publications where data were reported according to study arm [ 19 , 22 – 24 , 26 , 27 ]. Where mean data were available, eGFR ranged from 71.4 to 119.6 mL/min/1.73 m 2 (means within CKD stage 2 to stage 1) across studies at baseline, from 76.0 to 85.2 mL/min/1.73 m 2 (CKD stage 2) at 6 months [ 22 , 26 , 27 ], and was 77.2 and 79.1 mL/min/1.73 m 2 (CKD stage 2) in 2 studies at 12 months [ 24 , 26 ].…”

“…Five studies reported the prevalence of CKD (it was unclear if these were new cases after transplantation), and Lim et al reported the incidence of new-onset CKD [ 7 , 19 , 22 , 24 , 26 , 28 ] ( Table 6 ). Of the 2 studies reporting the prevalence of CKD at baseline and follow-up, there was an increase in the proportion of patients with CKD [ 7 ].…”

“…Defining CKD as stage 3a or higher (GFR/eGFR <60 mL/min/1.73 m 2 ), 5.4–32.6% of patients had CKD at 6 months across 3 study arms in 2 studies ( Table 6 ) [ 19 , 22 ]. Across 3 study arms in 2 studies, 23.2–36.8% of patients had CKD at 12 months, with the highest proportion reported in patients with post-transplantation AKI ( Table 6 ) [ 26 , 28 ].…”

“…Ten studies reported data for patient deaths ( Table 7 ) [ 7 , 19 , 20 , 22 , 23 , 26 – 30 ]. The incidence of patient deaths at 6 months was generally between 0% and 3.8%, with the exception of the sotrastaurin arms of Pascher et al, in which death rates of up to 14.3% were cited ( Table 7 ) [ 30 ].…”