Mycophenolate Mofetil Enhances the Negative Effects of Sirolimus and Tacrolimus on Rat Kidney Cell Metabolism

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Feb 6

PMID 24497939

Citations 2

Authors

Jelena Klawitter

Jost Klawitter

Volker Schmitz

Touraj Shokati

Ekaterina Epshtein

Joshua M Thurman

Uwe Christians

Affiliations

Soon will be listed here.

Abstract

Background And Purpose: Mycophenolate mofetil (MMF) per se is not known to have negative effects on the kidney. MMF alone or in combination with sirolimus, can be the basis of calcineurin inhibitor (CNI)-free, kidney sparing drug protocols. However, long-term outcomes in patients on MMF/SRL seem to be inferior to those treated with regimens that include the CNI tacrolimus (TAC) due to an increased risk of allo-immune reactions. Interestingly, potential enhancement of the negative effects of SRL and TAC on the kidney by MMF has never been considered.

Experimental Approach: It was our aim to study the effects of TAC, SRL and MMF alone and evaluate their interactions when combined on the rat kidney. For this purpose we used a comprehensive molecular marker approach including measurements of urinary 8-isoprostane concentrations (oxidative stress marker) and changes of urinary metabolite patterns ((1)H-NMR spectroscopy) and comparing these markers to renal function (glomerular filtration rate (GFR)) and morphologic alterations (histology).

Key Results: While MMF alone did not impact GFR, its interaction with SRL and TAC led to a significant decrease of rats' renal function. The decline went in parallel with a significant increase in urinary isoprostane concentrations and an enhancement of negative effects on urinary metabolite patterns.

Conclusions: In broad summary, the present study showed that MMF may enhance the negative effects of TAC on kidney function and may even display nephrotoxic properties when combined with SRL.

Citing Articles

Protective effect of mycophenolate mofetil against nephrotoxicity and hepatotoxicity induced by tacrolimus in Wistar rats.

Ferjani H, El Arem A, Bouraoui A, Achour A, Abid S, Bacha H J Physiol Biochem. 2016; 72(2):133-44.

PMID: 26746208 DOI: 10.1007/s13105-015-0451-7.

Everolimus and sirolimus in transplantation-related but different.

Klawitter J, Nashan B, Christians U Expert Opin Drug Saf. 2015; 14(7):1055-70.

PMID: 25912929 PMC: 6053318. DOI: 10.1517/14740338.2015.1040388.

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