Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Aug 5;1(7):e24.
doi: 10.1097/TXD.0000000000000536. eCollection 2015 Aug.

Medium-Term Renal Function in a Large Cohort of Stable Kidney Transplant Recipients Converted From Twice-Daily to Once-Daily Tacrolimus

Lluís Guirado  1 , Dolores Burgos  2 , Carme Cantarell  3 , Ana Fernández  4 , Antonio Franco  5 , Miguel Ángel Gentil  6 , Auxiliadora Mazuecos  7 , Josep Vicenç Torregrosa  8 , Ernesto Gómez Huertas  9 , Juan Carlos Ruiz  10 , Jaime Sánchez Plumed  11 , Javier Paul  12 , Ricardo Lauzurica  13 , Sofía Zárraga  14 , Antonio Osuna  15 , Carlos Jiménez  16 , Ángel Alonso  17 , Alberto Rodríguez  18 , Beatriz Bardají  19 , Domingo Hernández  2
Affiliations

Medium-Term Renal Function in a Large Cohort of Stable Kidney Transplant Recipients Converted From Twice-Daily to Once-Daily Tacrolimus

Lluís Guirado et al. Transplant Direct. .

Abstract

Background: There is some evidence pointing toward better renal function in kidney transplant recipients (KTR) treated with once-daily tacrolimus (QD-TAC) vs. twice-daily tacrolimus (BID-TAC).

Methods: This is an extension study of a 1-year, single arm prospective study of stable KTR who were converted from BID-TAC to QD-TAC (4.9 ± 4.0 years after transplantation) in Spanish routine clinical practice. Patient and graft survival, renal function, acute rejection episodes, and other analytic parameters were assessed at 24 and 36 months after conversion.

Results: A total of 1798 KTR were included in the extension study. Tacrolimus doses at 36 months were significantly lower compared to those at time of conversion (-0.2 mg/day; P = 0.023). Blood levels were lower than baseline during all the study (P < 0.001). Graft and patient survival at 3 years after conversion were 93.9% and 95.1%, respectively. Compared with baseline, the mean estimated glomerular filtration rate (eGFR) remained very stable at all timepoints (56.7 ± 19.8 vs 58.1 ± 24.6 mL/min per 1.73 m(2) at month 36; P = 0.623). Even when patients reinitiating dialysis were counted as eGFR = 0, the mean eGFR was very stable. In fact, a small but significant increase was observed at 36 months versus baseline (+0.1 mL/min per 1.73 m(2); P = 0.025). An increase in proteinuria was observed at 36 months versus baseline (+0.11 g/24 h; P < 0.001). Acute rejection rates were low during the study.

Conclusions: Conversion from BID-TAC to QD-TAC in a large cohort of stable KTR was safe and associated with a very stable renal function after 3 years. Comparative studies are warranted to assess the feasibility of such conversion.

PubMed Disclaimer

Conflict of interest statement

The authors declare no funding or conflicts of interest.

L.G. participated in the research design, the performance of the research, the data analysis and the writing of the article. D.B. participated in the performance of the research and the writing of the article. C.C. participated in the performance of the research and the writing of the article. A.F. participated in the performance of the research and the writing of the article. A.F. participated in the performance of the research and the writing of the article. M.Á.G. participated in the performance of the research and the writing of the article. A.M. participated in the performance of the research and the writing of the article. J.V.T. participated in the performance of the research and the writing of the paper. E.G.H. participated in the performance of the research and the writing of the article. J.C.R. participated in the performance of the research and the writing of the article. J.S.P. participated in the performance of the research and the writing of the article. J.P. participated in the performance of the research and the writing of the article. R.L. participated in the performance of the research and the writing of the article. S.Z. participated in the performance of the research and the writing of the article. A.O. participated in the performance of the research and the writing of the article. C.J. participated in the performance of the research and the writing of the article. Á.A. participated in the performance of the research and the writing of the article. A.R. participated in the performance of the research and the writing of the article. B.B. participated in the data analysis and the writing of the article. D.H. participated in the performance of the research and the writing of the article.

Figures

FIGURE 1
FIGURE 1
Patients' flowchart of the 3-year extension of the EVOLUTION study.
FIGURE 2
FIGURE 2
Mean (±SD) tacrolimus dose (mg/day) (A) and blood levels (ng/mL) (B). First QD-TAC: first determination under once-daily tacrolimus (normally at 10-14 days after conversion from twice-daily tacrolimus).
FIGURE 3
FIGURE 3
Mean (±SD) tacrolimus dose adjusted through concentrations ([ng/mL]/mg).
FIGURE 4
FIGURE 4
Patients with low (≤20) or high (>20) coefficient of variability of tacrolimus levels before (BID-TAC) and after the conversion (QD-TAC). CV indicates coefficient of variability.
FIGURE 5
FIGURE 5
Mean (±SD) estimated glomerular filtration rate (mL/min per 1.73 m2) censoring patients reinitiating hemodialysis (A) or counting patients reinitiating hemodialysis as having MDRD = 0 (B). HD indicates hemodialysis.
FIGURE 6
FIGURE 6
Mean (± SD) proteinuria (g/24 h).
See this image and copyright information in PMC

References

    1. Chisholm MA, Middleton MD. Modified-release tacrolimus. Ann Pharmacother. 2006; 40: 270– 275. - PubMed
    1. Alloway R, Steinberg S, Khalil K, et al. Conversion of stable kidney transplant recipients from a twice daily Prograf-based regimen to a once daily modified release tacrolimus-based regimen. Transplant Proc. 2005; 37: 867– 870. - PubMed
    1. Silva HT, Jr, Yang HC, Abouljoud M, et al. One-year results with extended-release tacrolimus/MMF, tacrolimus/MMF and cyclosporine/MMF in de novo kidney transplant recipients. Am J Transplant. 2007; 7: 595– 608. - PubMed
    1. Krämer BK, Charpentier B, Bäckman L, et al. Tacrolimus once daily (ADVAGRAF) versus twice daily (PROGRAF) in de novo renal transplantation: a randomized phase III study. Am J Transplant. 2010; 10: 2632– 2643. - PubMed
    1. Kuypers DR, Peeters PC, Sennesael JJ, et al. Improved adherence to tacrolimus once-daily formulation in renal recipients: a randomized controlled trial using electronic monitoring. Transplantation. 2013; 95: 333– 340. - PubMed