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

Buchholz, Bettina M and Ferguson, James W and Schnitzbauer, Andreas A and Nightingale, Peter and Schlitt, Hans J and 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...

Abstract

BACKGROUND

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

METHODS

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).

RESULTS

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.

CONCLUSIONS

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
Related URLs:
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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