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Higher circulating levels of two\n                      <jats:italic toggle=\"yes\">NAT8<\/jats:italic>\n                      -associated metabolites, N-\n                      <jats:italic toggle=\"yes\">\u03b4<\/jats:italic>\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                      <jats:italic toggle=\"yes\">NAT8<\/jats:italic>\n                      , N-acetylated amino acids, and kidney failure in multiple, well-characterized cohorts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, setting, participants, &amp; measurements<\/jats:title>\n                    <jats:p>\n                      We conducted analyses among participants with genetic and\/or serum metabolomic data in the African American Study of Kidney Disease and Hypertension (AASK;\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =962), the Atherosclerosis Risk in Communities (ARIC) study (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =1050), and Bio\n                      <jats:italic toggle=\"yes\">Me<\/jats:italic>\n                      , an electronic health record\u2013linked biorepository (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =680). Separately, we evaluated associations between rs13538, urinary N-acetylated amino acids, and kidney failure in participants in the German CKD (GCKD) study (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =1624).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 31 N-acetylated amino acids evaluated, the circulating and urinary levels of 14 were associated with rs13538 (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.05\/31). Higher circulating levels of five of these N-acetylated amino acids, namely, N-\n                      <jats:italic toggle=\"yes\">\u03b4<\/jats:italic>\n                      -acetylornithine, N-acetyl-1-methylhistidine, N-acetyl-3-methylhistidine, N-acetylhistidine, and N2,N5-diacetylornithine, were associated with kidney failure, after adjustment for confounders and combining results in meta-analysis (combined hazard ratios per two-fold higher amino acid levels: 1.48, 1.44, 1.21, 1.65, and 1.41, respectively; 95% confidence intervals: 1.21 to 1.81, 1.22 to 1.70, 1.08 to 1.37, 1.29 to 2.10, and 1.17 to 1.71, respectively; all\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      values &lt;0.05\/14). None of the urinary levels of these N-acetylated amino acids were associated with kidney failure in the GCKD study.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We demonstrate significant associations between an\n                      <jats:italic toggle=\"yes\">NAT8<\/jats:italic>\n                      gene variant and 14 N-acetylated amino acids, five of which had circulation levels that were associated with kidney failure.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.2215\/cjn.08600520","type":"journal-article","created":{"date-parts":[[2020,12,30]],"date-time":"2020-12-30T11:31:06Z","timestamp":1609327866000},"page":"37-47","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":47,"title":["NAT8 Variants, N-Acetylated Amino Acids, and 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