Journal article
Area Under Trough Concentrations of Tacrolimus as a Predictor of Progressive Renal Impairment After Liver Transplantation
Transplantation, Vol.103(12), pp.2539-2548
2019
PMID: 31107827
Abstract
Background.
Tacrolimus minimization is usually restricted to patients with pretransplant renal impairment, and this strategy could result into worse renal outcomes after liver transplantation (LT).
Methods.
A consecutive cohort of 455 LT patients receiving tacrolimus-based immunosuppression was studied (2008–2013). Cumulative exposure to tacrolimus was calculated as the area under curve of trough concentrations (AUCtc). Patients were stratified as tacrolimus minimization, conventional, or high exposure, according to the thresholds based in the COMMIT consensus. Estimated glomerular filtration rates (eGFR) were assessed by the Modification of Diet in Renal Disease formula (MDRD-4) up to 5 years after LT.
Results.
Seventy patients (15.4%) had pretransplant eGFR < 60 mL/min, which was associated with increased mortality rates, particularly within the first 5 years post-LT (31.4% versus 17.5%; Breslow P = 0.010). After LT, there was an abrupt eGFR decline within the first 3 months (median 18.6 mL/min; P < 0.001), further decreasing up to 12 months (additional 3 mL/min), without any improvement thereafter. According to AUCtc, 33.7% of patients received tacrolimus minimization, 44.8% conventional exposure, and 21.5% high exposure. Conventional/high exposure to tacrolimus resulted in a more pronounced eGFR decline within the first 3 months when compared with minimization (23.3 mL/min versus 9.5 mL/min; P < 0.001). This gap was even higher in patients with initially preserved renal function. Tacrolimus AUCtc was an independent predictor of eGFR decline within the first 3 months after controlling for potential confounders.
Conclusions.
AUCtc is a surrogate of cumulative exposure to tacrolimus and may be helpful for routine dose adjustments. Tacrolimus minimization should be universally attempted after LT to preserve renal function.
Details
- Title
- Area Under Trough Concentrations of Tacrolimus as a Predictor of Progressive Renal Impairment After Liver Transplantation
- Authors
- Manuel Rodríguez-Perálvarez (Author) - Hospital Universitario Reina SofíaMarta Guerrero (Author) - Royal Free HospitalLaura De Luca (Author) - Royal Free HospitalBeatriz Gros (Author) - Hospital Universitario Reina SofíaDouglas Thorburn (Author) - Royal Free HospitalDavid Patch (Author) - Royal Free HospitalMaría D Aumente (Author) - Hospital Universitario Reina SofíaRachel Westbrook (Author) - Royal Free HospitalRocío Fernández (Author) - Hospital Universitario Reina SofíaVíctor Amado (Author) - Hospital Universitario Reina SofíaPatricia Aguilar (Author) - Hospital Universitario Reina SofíaJose Luis Montero (Author) - Hospital Universitario Reina SofíaJames O'Beirne (Author) - Royal Free HospitalJavier Briceño (Author) - Hospital Universitario Reina SofíaEmmanuel Tsochatzis (Author) - Royal Free HospitalManuel De la Mata (Author) - Hospital Universitario Reina Sofía
- Publication details
- Transplantation, Vol.103(12), pp.2539-2548
- Publisher
- Lippincott Williams & Wilkins
- DOI
- 10.1097/TP.0000000000002760
- ISSN
- 1534-6080
- PMID
- 31107827
- Organisation Unit
- School of Health and Behavioural Sciences - Legacy; University of the Sunshine Coast, Queensland
- Language
- English
- Record Identifier
- 99609708202621
- Output Type
- Journal article
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- Domestic collaboration
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- Immunology
- Surgery
- Transplantation
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