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Variants, N-Acetylated Amino Acids, and Progression of CKD.

TitleVariants, N-Acetylated Amino Acids, and Progression of CKD.
Publication TypeJournal Article
Year of Publication2020
AuthorsLuo S, Surapaneni A, Zheng Z, Rhee EP, Coresh J, Hung AM, Nadkarni GN, Yu B, Boerwinkle E, Tin A, Arking DE, Steinbrenner I, Schlosser P, Köttgen A, Grams ME
JournalClin J Am Soc Nephrol
Date Published2020 Dec 31

BACKGROUND AND OBJECTIVES: Genetic variants in , a liver- and kidney-specific acetyltransferase encoding gene, have been associated with eGFR and CKD in European populations. Higher circulating levels of two -associated metabolites, N--acetylornithine and N-acetyl-1-methylhistidine, have been linked to lower eGFR and higher risk of incident CKD in the Black population. We aimed to expand upon prior studies to investigate associations between rs13538, a missense variant in , N-acetylated amino acids, and kidney failure in multiple, well-characterized cohorts.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted analyses among participants with genetic and/or serum metabolomic data in the African American Study of Kidney Disease and Hypertension (AASK; =962), the Atherosclerosis Risk in Communities (ARIC) study (=1050), and Bio, an electronic health record-linked biorepository (=680). Separately, we evaluated associations between rs13538, urinary N-acetylated amino acids, and kidney failure in participants in the German CKD (GCKD) study (=1624).

RESULTS: Of 31 N-acetylated amino acids evaluated, the circulating and urinary levels of 14 were associated with rs13538 (

CONCLUSIONS: We demonstrate significant associations between an gene variant and 14 N-acetylated amino acids, five of which had circulation levels that were associated with kidney failure.

Alternate JournalClin J Am Soc Nephrol
PubMed ID33380473
PubMed Central IDPMC7792648
Grant ListR01 DK108803 / DK / NIDDK NIH HHS / United States