Journal Article

No change in insulin sensitivity in renal transplant recipients converted from standard to once-daily prolonged release tacrolimus

Karsten Midtvedt, Trond Jenssen, Anders Hartmann, Nils Tore Vethe, Stein Bergan, Kjerstin Havnes and Anders Åsberg

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 26, issue 11, pages 3767-3772
Published in print November 2011 | ISSN: 0931-0509
Published online April 2011 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfr153
No change in insulin sensitivity in renal transplant recipients converted from standard to once-daily prolonged release tacrolimus

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Background. New-onset diabetes after transplantation may be associated with the use of tacrolimus (Tac) causing impaired insulin release or reduced insulin sensitivity. Such effects have not been studied in renal transplant recipients receiving traditional twice-daily tacrolimus (TacBID) and then compared to the new once-daily prolonged release formulation of tacrolimus (TacOD).

Methods. We performed a prospective crossover study of 20 stable non-diabetic renal transplant recipients. All patients underwent one hyperglycaemic clamp on TacBID (3.8 ±2.2 mg/day) and a new clamp 4–6 weeks after a 1:1 mg/day switch to TacOD (4.0 ±2.8 mg/day).

Results. Tac trough concentrations decreased from 6.6 ± 2.9 to 5.4 ± 1.4 μg/mL (P = 0.037) and Tac max from 21.3 ± 8.4 to 15.2 ± 3.5 μg/L (P = 0.001). Tac AUC0–24 was reduced from 265 ± 112 to 218 ± 47 μg × h/L (P = 0.12). The hyperglycaemic clamp did not detect any change in insulin sensitivity index after conversion [0.26 ± 0.21 versus 0.26 ± 0.25 μmol/min/kg/(pmol/L insulin), P = 0.99] nor any change in first (334 ± 274 versus 353 ± 248 μIU × min/mL, P = 0.41) or second phase insulin secretion (224 ± 155 versus 263 ± 210 μIU × min/mL/mmol glucose, P = 0.60) on TacBID versus TacOD.

Conclusions. Conversion from standard TacBID to TacOD on a 1:1 mg basis is safe. In spite of a reduced Tac exposure, there was no change in insulin release or sensitivity in renal transplant recipients.

Keywords: insulin secretion and sensitivity; once-daily tacrolimus; renal transplantation

Journal Article.  4274 words.  Illustrated.

Subjects: Nephrology

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