{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:02:50Z","timestamp":1787166170757,"version":"build-2736575974"},"reference-count":9,"publisher":"S. Karger AG","issue":"6","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am J Nephrol"],"published-print":{"date-parts":[[2022]]},"abstract":"<b><i>Introduction:<\/i><\/b> In autosomal dominant polycystic kidney disease (ADPKD) patients, predicting renal disease progression is important to make a prognosis and to support the clinical decision whether to initiate renoprotective therapy. Conventional markers all have their limitations. Metabolic profiling is a promising strategy for risk stratification. We determined the prognostic performance to identify patients with a fast progressive disease course and evaluated time-dependent changes in urinary metabolites. <b><i>Methods:<\/i><\/b> Targeted, quantitative metabolomics analysis (<sup>1<\/sup>H NMR-spectroscopy) was performed on spot urinary samples at two time points, baseline (<i>n<\/i> = 324, 61% female; mean age 45 years, SD 11; median eGFR 61 mL\/min\/1.73 m<sup>2<\/sup>, IQR 42\u201388; mean years of creatinine follow-up 3.7, SD 1.3) and a sample obtained after 3 years of follow-up (<i>n<\/i> = 112). Patients were stratified by their eGFR slope into fast and slow progressors based on an annualized change of &#x3e; \u22123.0 or \u2264 \u22123.0 mL\/min\/1.73 m<sup>2<\/sup>\/year, respectively. Fifty-five urinary metabolites and ratios were quantified, and the significant ones were selected. Logistic regression was used to determine prognostic performance in identifying those with a fast progressive course using baseline urine samples. Repeated-measures ANOVA was used to analyze whether changes in urinary metabolites over a 3-year follow-up period differed between fast and slow progressors. <b><i>Results:<\/i><\/b> In a single urinary sample, the prognostic performance of urinary metabolites was comparable to that of a model including height-adjusted total kidney volume (htTKV, AUC = 0.67). Combined with htTKV, the predictive value of the metabolite model increased (AUC = 0.75). Longitudinal analyses showed an increase in the myoinositol\/citrate ratio (<i>p<\/i> &#x3c; 0.001) in fast progressors, while no significant change was found in those with slow progression, which is in-line with an overall increase in the myoinositol\/citrate ratio as GFR declines. <b><i>Conclusion:<\/i><\/b> A metabolic profile, measured at a single time point, showed at least equivalent prognostic performance to an imaging-based risk marker in ADPKD. Changes in urinary metabolites over a 3-year follow-up period were associated with a fast progressive disease course.<\/jats:p>","DOI":"10.1159\/000524851","type":"journal-article","created":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T17:00:32Z","timestamp":1653498032000},"page":"470-480","source":"Crossref","is-referenced-by-count":7,"title":["Change in Urinary Myoinositol\/Citrate Ratio Associates with Progressive Loss of Renal Function in ADPKD Patients"],"prefix":"10.1159","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6066-8614","authenticated-orcid":false,"given":"Shosha E.I.","family":"Dekker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0373-9372","authenticated-orcid":false,"given":"Aswin","family":"Verhoeven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3232-2293","authenticated-orcid":false,"given":"Daria","family":"Frey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darius","family":"Soonawala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorien J.M.","family":"Peters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8739-9875","authenticated-orcid":false,"given":"Oleg A.","family":"Mayboroda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan W.","family":"de Fijter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the DIPAK Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2022,5,25]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60601-1"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.00330705"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(94)92026-5"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1186\/s12882-015-0114-5"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1021\/ac051632c"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1990.265"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfu044"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfaa283"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1111\/j.1752-8062.2012.00437.x"}],"container-title":["American Journal of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/524851","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/524851","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T10:57:31Z","timestamp":1745405851000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000524851"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022]]},"references-count":9,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,7,12]]},"published-print":{"date-parts":[[2022,7,19]]}},"URL":"https:\/\/doi.org\/10.1159\/000524851","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.19861762","asserted-by":"subject"}]},"ISSN":["0250-8095","1421-9670"],"issn-type":[{"value":"0250-8095","type":"print"},{"value":"1421-9670","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022]]}}}