From Discovery to Translation: Characterization of C-Mannosyltryptophan and Pseudouridine as Markers of Kidney Function

Peggy Sekula, Katja Dettmer, Franziska C. Vogl, Wolfram Gronwald, Lisa Ellmann, Robert P. Mohney, Kai Uwe Eckardt, Karsten Suhre, Gabi Kastenmüller, Peter J. Oefner, Anna Köttgen

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Using a non-targeted metabolomics platform, we recently identified C-mannosyltryptophan and pseudouridine as non-traditional kidney function markers. The aims of this study were to obtain absolute concentrations of both metabolites in blood and urine from individuals with and without CKD to provide reference ranges and to assess their fractional excretions (FE), and to assess the agreement with their non-targeted counterparts. In individuals without/with CKD, mean plasma and urine concentrations for C-mannosyltryptophan were 0.26/0.72 μmol/L and 3.39/4.30 μmol/mmol creatinine, respectively. The respective concentrations for pseudouridine were 2.89/5.67 μmol/L and 39.7/33.9 μmol/mmol creatinine. Median (25th, 75th percentiles) FEs were 70.8% (65.6%, 77.8%) for C-mannosyltryptophan and 76.0% (68.6%, 82.4%) for pseudouridine, indicating partial net reabsorption. Association analyses validated reported associations between single metabolites and eGFR. Targeted measurements of both metabolites agreed well with the non-targeted measurements, especially in urine. Agreement for composite nephrological measures FE and urinary metabolite-to-creatinine ratio was lower, but could be improved by replacing non-targeted creatinine measurements with a standard clinical creatinine test. In summary, targeted quantification and additional characterization in relevant populations are necessary steps in the translation of non-traditional biomarkers in nephrology from non-targeted discovery to clinical application.

Original languageEnglish
Article number17400
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 1 Dec 2017

    Fingerprint

ASJC Scopus subject areas

  • General

Cite this

Sekula, P., Dettmer, K., Vogl, F. C., Gronwald, W., Ellmann, L., Mohney, R. P., Eckardt, K. U., Suhre, K., Kastenmüller, G., Oefner, P. J., & Köttgen, A. (2017). From Discovery to Translation: Characterization of C-Mannosyltryptophan and Pseudouridine as Markers of Kidney Function. Scientific Reports, 7(1), [17400]. https://doi.org/10.1038/s41598-017-17107-5