{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:33:23Z","timestamp":1788431603884,"version":"build-2803163510"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","funder":[{"DOI":"10.13039\/100001296","name":"PKD Foundation","doi-asserted-by":"publisher","award":["241G20a"],"award-info":[{"award-number":["241G20a"]}],"id":[{"id":"10.13039\/100001296","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Baltimore PKD Research and Clinical Core Center Pilot and Feasibility Program","award":["P30DK090868"],"award-info":[{"award-number":["P30DK090868"]}]},{"name":"Zell Family Foundation"},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["K01 DK103678"],"award-info":[{"award-number":["K01 DK103678"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R03 DK103678"],"award-info":[{"award-number":["R03 DK103678"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["5T32DK007135-46"],"award-info":[{"award-number":["5T32DK007135-46"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>On the basis of earlier observations, we evaluated the association between overweight and obesity and rapid progression of autosomal dominant polycystic kidney disease in participants in the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO) 3:4 trial. More importantly, we also determined whether efficacy of tolvaptan was attenuated in individuals with baseline overweight or obesity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, setting, participants, &amp; measurements<\/jats:title>\n                    <jats:p>\n                      A total of 1312 study participants with relatively early-stage autosomal dominant polycystic kidney disease (mean eGFR 78\u00b122 ml\/min per 1.73 m\n                      <jats:sup>2<\/jats:sup>\n                      ) who were at high risk of rapid progression were categorized by body mass index (BMI; calculated using nonkidney weight) as normal weight (18.5\u201324.9 kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ;\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =670), overweight (25.0\u201329.9 kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ;\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =429), or obese (\u226530 kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ;\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =213). Linear and multinomial logistic regression models were used to determine the association of baseline overweight and obesity with change in total kidney volume (TKV) over the 3-year study period.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In fully adjusted models, higher BMI was associated with greater annual percent change in TKV (difference of 1.20 [95% confidence interval (95% CI), 0.85 to 1.55] per five-unit higher BMI). Overweight and obesity were associated with higher odds of annual percent change in TKV of \u22657% versus &lt;5% (overweight: odds ratio, 2.04 [95% CI, 1.45 to 2.87]; obese: odds ratio, 4.31 [95% CI, 2.83 to 6.57] versus normal weight). eGFR decline did not differ according to BMI (fully adjusted difference in decline of \u22120.95 [95% CI, \u22122.32 to 0.40] ml\/min per 1.73 m\n                      <jats:sup>2<\/jats:sup>\n                      per year per five-unit higher BMI). The three-way interaction (treatment\u00d7time\u00d7BMI group) was not statistically significant in linear mixed models with an outcome of TKV (log-transformed estimated coefficient comparing the treatment effect for overweight versus normal weight: 0.56% [95% CI, \u22120.70% to 1.84%] per year;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.38; obese versus normal weight: 0.07% [95% CI, \u22121.47% to 1.63%] per year;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.93) or eGFR (estimated coefficient comparing overweight versus normal weight: \u22120.07 [95% CI, \u22120.95 to 0.82] ml\/min per 1.73 m\n                      <jats:sup>2<\/jats:sup>\n                      per year;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.88; obese versus normal weight: 0.22 [95% CI, \u22120.93 to 1.36] ml\/min per 1.73 m\n                      <jats:sup>2<\/jats:sup>\n                      per year;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.71).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Overweight and particularly obesity are strongly and independently associated with kidney growth, but not eGFR slope, in the TEMPO 3:4 trial, and tolvaptan efficacy is irrespective of BMI categorization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial registry name and registration number:<\/jats:title>\n                    <jats:p>Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO) 3:4, NCT00428948<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2215\/cjn.16871020","type":"journal-article","created":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T16:35:14Z","timestamp":1623429314000},"page":"908-915","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":77,"title":["Overweight and Obesity and Progression of ADPKD"],"prefix":"10.2215","volume":"16","clinical-trial-number":[{"clinical-trial-number":"nct00428948","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct00283686","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct00428948","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03342742","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9364-3256","authenticated-orcid":false,"given":"Kristen L.","family":"Nowak","sequence":"first","affiliation":[{"name":"University of Colorado Anschutz Medical Campus, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5701-1240","authenticated-orcid":false,"given":"Cortney","family":"Steele","sequence":"additional","affiliation":[{"name":"University of Colorado Anschutz Medical Campus, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berenice","family":"Gitomer","sequence":"additional","affiliation":[{"name":"University of Colorado Anschutz Medical Campus, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenchyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development and Commercialization, Princeton, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development and Commercialization, Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel B.","family":"Chonchol","sequence":"additional","affiliation":[{"name":"University of Colorado Anschutz Medical Campus, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2021,6]]},"reference":[{"key":"B1-20241015","doi-asserted-by":"crossref","first-page":"577","DOI":"10.2215\/CJN.13291019","article-title":"Metabolic reprogramming in autosomal dominant polycystic kidney disease: Evidence and therapeutic potential","volume":"15","author":"Nowak","year":"2020","journal-title":"Clin J Am Soc Nephrol"},{"key":"B2-20241015","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1038\/nm.3092","article-title":"Defective glucose metabolism in polycystic kidney disease identifies a new therapeutic strategy","volume":"19","author":"Rowe","year":"2013","journal-title":"Nat 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