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J Clin Pharmacol. 2018 Nov 2. doi: 10.1002/jcph.1334. [Epub ahead of print]

Effects of Conversion From Calcineurin Inhibitors to Sirolimus or Everolimus on Renal Function and Possible Mechanisms in Liver Transplant Recipients.

Author information

1
Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
2
Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
3
Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
4
School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
5
Liver Transplant Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
6
Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan.

Abstract

Mammalian targets of rapamycin inhibitors (mTORIs), including sirolimus and everolimus, are used for minimizing calcineurin inhibitors after liver transplantation. However, head-to-head randomized comparisons of these 2 mTORIs are lacking. We assessed the differences in renoprotection and possible mechanisms between sirolimus and everolimus in liver transplant recipients. For this prospective cohort study, we recruited liver transplant recipients whose regimens were switched from tacrolimus to sirolimus or everolimus at a Taiwan medical center. Serial changes in estimated glomerular filtration rate (eGFR), urinary N-acetyl-β-D-glucosaminidase, neutrophil gelatinase-associated lipocalin, 8-hydroxy-2'-deoxyguanosine, and transforming growth factor-β1 during 1 year after mTORI conversion were compared within and between groups. In the 61 patients analyzed, no significant change in eGFR occurred within 12 months after conversion in both mTORI groups. Among patients with baseline eGFR <60 mL/min/1.73 m2 , eGFR improved at 6 months and 1 year after conversion (+12.3 and +12.0 mL/min/1.73 m2 , both P < .05). Urinary N-acetyl-β-D-glucosaminidase decreased in both sirolimus and everolimus groups at 6 months (-68.7 ± 137.6 and -62.0 ± 92.4 U/g creatinine, both P < .05), and the reduction of urinary neutrophil gelatinase-associated lipocalin was significant in the sirolimus group (-4345.1 ± 7763.5 ng/g creatinine; P < .05). Neither transforming growth factor-β1 nor 8-hydroxy-2´-deoxyguanosine changed significantly. In conclusion, the renoprotective effect of mTORI conversion was significant in liver transplant recipients with renal insufficiency, which was similar for sirolimus and everolimus, in the first year and may be associated with ameliorated tubular injury. Available evidence remains insufficient to determine which mTORI conversion therapy is more effective in renoprotection in the long run.

KEYWORDS:

chronic kidney disease; liver transplantation; mTOR inhibitor; renal preservation; urinary biomarkers

PMID:
30387865
DOI:
10.1002/jcph.1334

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