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A Low Tacrolimus Concentration/Dose Ratio Increases the Risk for the Development of Acute Calcineurin Inhibitor-Induced Nephrotoxicity.

Abstract：

:Fast tacrolimus metabolism is linked to inferior outcomes such as rejection and lower renal function after kidney transplantation. Renal calcineurin-inhibitor toxicity is a common adverse effect of tacrolimus therapy. The present contribution hypothesized that tacrolimus-induced nephrotoxicity is related to a low concentration/dose (C/D) ratio. We analyzed renal tubular epithelial cell cultures and 55 consecutive kidney transplant biopsy samples with tacrolimus-induced toxicity, the C/D ratio, C0, C2, and C4 Tac levels, pulse wave velocity analyses, and sublingual endothelial glycocalyx dimensions in the selected kidney transplant patients. A low C/D ratio (C/D ratio < 1.05 ng/mL×1/mg) was linked with higher C2 tacrolimus blood concentrations (19.2 ± 8.7 µg/L vs. 12.2 ± 5.2 µg/L respectively; p = 0.001) and higher degrees of nephrotoxicity despite comparable trough levels (6.3 ± 2.4 µg/L vs. 6.6 ± 2.2 µg/L respectively; p = 0.669). However, the tacrolimus metabolism rate did not affect the pulse wave velocity or glycocalyx in patients. In renal tubular epithelial cells exposed to tacrolimus according to a fast metabolism pharmacokinetic profile it led to reduced viability and increased Fn14 expression. We conclude from our data that the C/D ratio may be an appropriate tool for identifying patients at risk of developing calcineurin-inhibitor toxicity.

journal_name

J Clin Med

journal_title

Journal of clinical medicine

authors

Thölking G,Schütte-Nütgen K,Schmitz J,Rovas A,Dahmen M,Bautz J,Jehn U,Pavenstädt H,Heitplatz B,Van Marck V,Suwelack B,Reuter S

doi

10.3390/jcm8101586

subject

Has Abstract

pub_date

2019-10-02 00:00:00

issue

10

issn

2077-0383

pii

jcm8101586

journal_volume

8

pub_type

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