Observational Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Mar 24, 2015; 5(1): 19-25
Published online Mar 24, 2015. doi: 10.5500/wjt.v5.i1.19
Conversion from calcineurin inhibitors to mTOR inhibitors stabilizes diabetic and hypertensive nephropathy after liver transplant
José M Álamo, Claudia Olivares, Lydia Barrera, Luis M Marín, Gonzalo Suarez, Carmen Bernal, Juan Serrano, Jordi Muntané, Francisco J Padillo, Miguel A Gómez
José M Álamo, Unit of Liver Transplantation, Department of Surgery, University of Seville, 41013 Seville, Spain
José M Álamo, Miguel A Gómez, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, (CIBEREH o Ciberehd), Instituto de Salud Carlos III, 08036 Barcelona, Spain
Claudia Olivares, Lydia Barrera, Luis M Marín, Gonzalo Suarez, Carmen Bernal, Juan Serrano, Jordi Muntané, Francisco J Padillo, Department of General Surgery, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville 41013, Spain
Author contributions: Álamo JM, Olivares C, Barrera L, Marín LM, Suarez G, Bernal C and Serrano J substantially contributed to the conception and design, acquisition, analysis and interpretation of data; Muntané J and Padillo FJ contributed to drafting the article and revising it critically for important intellectual content; Álamo JM and Gómez MA contributed to the final approval of the version to be published.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: José M Álamo, Professor Assistant, Unit of Liver Transplantation, Department of Surgery, University of Seville, Manuel Siurot Av., 41013 Seville, Spain. jmalamom@hotmail.com
Telephone: +34-95-5012317 Fax: +34-95-5012317
Received: January 6, 2014
Peer-review started: January 6, 2014
First decision: January 23, 2014
Revised: September 22, 2014
Accepted: October 28, 2014
Article in press: October 29, 2014
Published online: March 24, 2015
Processing time: 442 Days and 11.3 Hours
Abstract

AIM: To investigate if conversion to the mammalian target of rapamycin inhibitors (mTORi) improves renal function in diabetic and/or hypertensive liver transplant patients immunosuppressed with tacrolimus or cyclosporine.

METHODS: The study included 86 liver graft recipients immunosuppressed with mTORi treatment after orthotopic liver transplantation (OLT), including all liver recipients with worsening renal function before conversion to mTORi (n = 55 patients) and recipients with normal renal function who converted to mTORi for other reasons (n = 31 patients). We identified patients with diabetes mellitus (n = 28), arterial hypertension (n = 27), proteinuria (n = 27) and all three factors (n = 8) (some patients have hypertension and diabetes and no proteinuria). The primary endpoint was evolution in renal function defined as the development in plasma creatinine as a function of diabetes mellitus (DM), hypertension (HT) or proteinuria. We required elevated serum creatinine for at least two weeks to define renal dysfunction.

RESULTS: Only patients that converted because of renal failure with plasma creatinine levels > 1.5 mg/dL showed an improvement of renal function (2.14 to 1.77 mg/dL) (P = 0.02). Patients with DM showed no improvement of serum creatinine levels (1.31 mg/dL to 1.37 mg/dL) compared with non DM patients (1.31 mg/dL to 1.15 mg/dL) (P = 0.01), HT patients (1.48 mg/dL to 1.5 mg/dL) with non HT patients (1.21mg/dL to 1.08 mg/dL) and patients with proteinuria (1.44 mg/dL to 1.41 mg/dL) and no proteinuria (1.31 mg/dL to 1.11 mg/dL).

CONCLUSION: In OLT recipients with diabetes or hypertensive nephropathy, conversion to mTORi does not improve renal function but stabilizes plasma levels of creatinine. Proteinuria is not a contraindication to conversion to mTORi; it also stabilizes renal function. Conversion to mTORi should only be avoided in patients with diabetes, hypertension and proteinuria.

Keywords: Mammalian target of rapamycin inhibitors; Liver transplant; Renal dysfunction; Hypertension; Diabetes

Core tip: These results could be useful in choosing an immunosuppressant regimen in liver transplant recipients, especially in patients with diabetes mellitus and/or arterial hypertension with proteinuria and possibly renal dysfunction.