Randomized Sirolimus-based early calcineurin inhibitor reduction in liver transplantation: impact on renal function.

Buchholz, Bettina M, Ferguson, James W, Schnitzbauer, Andreas A, Nightingale, Peter, Schlitt, Hans J, Geissler, Edward K and Mirza, Darius F (2019) Randomized Sirolimus-based early calcineurin inhibitor reduction in liver transplantation: impact on renal function. Transplantation. ISSN 1534-6080.

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Official URL: https://insights.ovid.com/crossref?an=00007890-900...



The long-term use of calcineurin inhibitors (CNI) after liver transplantation (LT) is associated with nephrotoxicity.


5-year follow-up data was retrieved from the randomized controlled multicenter SiLVER trial. Standard CNI-based mTOR-free immunosuppression (group A, n=264) was compared to a 50 % reduction of CNI and introduction of the mTOR inhibitor Sirolimus within 4 to 6 weeks after LT (group B, n=261).


Median MELD at LT was low with 10 (7 - 15) (group A) and 11 (8 - 15) (group B) in the intention-to-treat approach. CNI dose and CNI trough were reduced by 20% and 8% (group A) versus 55% and 56% (group B) at 3 months post transplantation. Renal function was preserved at 3 months after LT in the Sirolimus arm [eGFR 74 (57-95) versus 67 (55-85) ml/min/1.73m, p=0.004] but was similarly impaired thereafter compared to group A. The per protocol analysis identified LT recipients in group B with concomitant early CNI minimization and Sirolimus treatment ≥ year 1 with significantly superior eGFR and lowest rate of chronic kidney disease (≥ stage 3) from year 1 onwards until study end. Competing risk factors for renal disease (arterial hypertension, fat metabolism disorder and hyperglycemia) were not associated with worse kidney function.


Prevention of CNI nephrotoxicity by Sirolimus-based early CNI minimization protects renal function only short-term after LT in the intention-to-treat analysis of this low MELD cohort. Yet, selected LT recipients compliant with early CNI minimization and Sirolimus maintenance achieved better long-term renal outcomes compared to real-world practice.

Item Type: Article
Subjects: WI Digestive system. Gastroenterology
WJ Urogenital system. Urology
Divisions: Emergency Services > Renal
Planned IP Care > General Surgery
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Depositing User: Mrs Yolande Brookes
Date Deposited: 04 Oct 2019 13:14
Last Modified: 04 Oct 2019 13:14
URI: http://www.repository.uhblibrary.co.uk/id/eprint/2446

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