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Individuals were followed up for 9.0\u2009\u00b1\u20095.0\u00a0years until their first sign of progression of diabetic nephropathy, end-stage kidney disease or study end. Cox regressions were performed on the entire study population (overall progression), on 1999 individuals with normoalbuminuria and 347 individuals with macroalbuminuria at baseline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Seven urinary metabolites were associated with overall progression after adjustment for baseline albuminuria and chronic kidney disease stage (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20098\u2009\u00d7\u200910\n                      <jats:sup>\u22124<\/jats:sup>\n                      ): leucine (HR 1.47 [95% CI 1.30, 1.66] per 1-SD creatinine-scaled metabolite concentration), valine (1.38 [1.22, 1.56]), isoleucine (1.33 [1.18, 1.50]), pseudouridine (1.25 [1.11, 1.42]), threonine (1.27 [1.11, 1.46]) and citrate (0.84 [0.75, 0.93]). 2-Hydroxyisobutyrate was associated with overall progression (1.30 [1.16, 1.45]) and also progression from normoalbuminuria (1.56 [1.25, 1.95]). Six amino acids and pyroglutamate were associated with progression from macroalbuminuria.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\/interpretation<\/jats:title>\n                    <jats:p>Branched-chain amino acids and other urinary metabolites were associated with the progression of diabetic nephropathy on top of baseline albuminuria and chronic kidney disease. We found differences in associations for overall progression and progression from normo- and macroalbuminuria. These novel discoveries illustrate the utility of analysing urinary metabolites in entire population cohorts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1007\/s00125-021-05584-3","type":"journal-article","created":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T18:03:19Z","timestamp":1634925799000},"page":"140-149","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Urinary metabolite profiling and risk of progression of diabetic nephropathy in 2670 individuals with type 1 diabetes"],"prefix":"10.1007","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8293-6982","authenticated-orcid":false,"given":"Stefan","family":"Mutter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0672-554X","authenticated-orcid":false,"given":"Erkka","family":"Valo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viljami","family":"Aittom\u00e4ki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian","family":"Nybo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lassi","family":"Raivonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3999-0390","authenticated-orcid":false,"given":"Lena M.","family":"Thorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3354-7454","authenticated-orcid":false,"given":"Carol","family":"Forsblom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4322-6942","authenticated-orcid":false,"given":"Niina","family":"Sandholm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5832-0221","authenticated-orcid":false,"given":"Peter","family":"W\u00fcrtz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4055-6954","authenticated-orcid":false,"given":"Per-Henrik","family":"Groop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,22]]},"reference":[{"issue":"9","key":"5584_CR1","doi-asserted-by":"publisher","first-page":"2449","DOI":"10.2337\/diabetes.53.9.2449","volume":"53","author":"V Harjutsalo","year":"2004","unstructured":"Harjutsalo V, Katoh S, Sarti C, Tajima N, Tuomilehto J (2004) Population-based assessment of familial clustering of diabetic nephropathy in type 1 diabetes. 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