Mycophenolate Mofetil Enhances the Negative Effects of Sirolimus and Tacrolimus on Rat Kidney Cell MetabolismReportar como inadecuado




Mycophenolate Mofetil Enhances the Negative Effects of Sirolimus and Tacrolimus on Rat Kidney Cell Metabolism - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

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 1H-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.



Autor: Jelena Klawitter , Jost Klawitter , Volker Schmitz , Touraj Shokati, Ekaterina Epshtein, Joshua M. Thurman, Uwe Christians

Fuente: http://plos.srce.hr/



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