Metabolites related to eGFR: Evaluation of candidate molecules for GFR estimation using untargeted metabolomics

• Published in: Clinica chimica acta Vol. 489; pp. 242 - 248
• Main Authors: Titan, S.M., Venturini, G., Padilha, K., Tavares, G., Zatz, R., Bensenor, I., Lotufo, P.A., Rhee, E.P., Thadhani, R.I., Pereira, A.C.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-02-2019
• Subjects: CKD; GFR; Metabolomics; Metabolomics; CKD; GFR
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2018.08.037

Metabolomics can be used to identify novel metabolites related to renal function and that could therefore be used for estimating GFR. We evaluated metabolites replicated and related to eGFR in 3 studies (CKD and general population).
Metabolomics was performed by GC–MS. The Progredir Cohort (n = 454, class 3 and 4 CKD) was used as the derivation study and adjusted linear regression models on eGFR-CKDEPI were built. Bonferroni correction was applied for selecting metabolites to be independently validated in the Diabetic Nephropathy Study (n = 56, macroalbuminuric DN) and in the Baependi Heart Study (BHS, n = 1145, general population).
In the Progredir Cohort, 72 metabolites where associated with eGFR. Of those, 11 were also significantly associated to eGFR in the DN Study and 8 in the BHS. Four metabolites were replicated and significantly associated to eGFR in all 3 studies: d-threitol, myo-inositol, 4-deoxierythronic acid and galacturonic acid. In addition, pseudouridine was strongly correlated to eGFR only in the 2 CKD populations.
Our results demonstrate metabolites that are potential biomarkers of renal function: d-threitol, myo-inositol, 4-deoxierythronic acid, galacturonic acid and pseudouridine. Further investigation is needed to determine their performance against otherwise gold-standard methods, most notably among those with normal eGFR.
•Untargeted metabolomics can be used to investigate new biomarkers to disease and phenotypes;•We wanted to investigate molecules that can be possibly used as biomarkers of GFR in CKD;•GC–MS was used to select metabolites with top associations to eGFR in a CKD population;•Reproduction was tested in two other samples, one with CKD and the other from the general population;•Our results identified five candidate molecules for estimating GFR.