{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T02:02:32Z","timestamp":1793325752739,"version":"4.5.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2017,3,14]],"date-time":"2017-03-14T00:00:00Z","timestamp":1489449600000},"content-version":"vor","delay-in-days":333,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Background: Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by multitudes of expanding renal cysts associated with mononuclear interstitial infiltrates. Monocyte chemotactic protein-1 is produced in the kidneys and excreted in the urine (uMCP1) of these patients in increased amounts. In the TEMPO 3:4 trial, tolvaptan slowed the rate of increase in total kidney volume (TKV) and the rate of decline in estimated glomerular filtration rate (eGFR). In a sub-analysis, we determined whether tolvaptan administration for up to 3 years changed the urinary excretion of MCP-1 referenced to creatinine in 869 treated subjects compared with 438 placebo subjects.<\/jats:p>\n                  <jats:p>Methods: Treatment group differences of uMCP1 at 0.75, 12, 24 and 36 months were evaluated by ANCOVA with factor of treatment and covariate baseline.<\/jats:p>\n                  <jats:p>Results: At baseline, mean uMCP1 was 429 \u00b1 224 pg\/mg in the tolvaptan and 434 \u00b1 233 pg\/mg in the placebo groups, \u223c4-fold greater than normal. Log uMCP1 associated positively with log TKV (r = 0.2645, P &amp;lt; 0.0001) and negatively with eGFR (r = \u22120.1555 P &amp;lt; 0.0001) and fasting urine osmolality (r = \u22120.1933, P &amp;lt; 0.0001). Tolvaptan reduced uMCP1 13.8 \u00b1 4.4% (P &amp;lt; 0.0001) below placebo-treated subjects at 24 months and 14.4 \u00b1 3.7% (P &amp;lt; 0.0001) at 36 months, and to the same extent in females and males. The effect of tolvaptan on uMCP1 excretion at 36 months extended across CKD Stage 1 (11.1 \u00b1 6.4%, P = 0.0595), CKD 2 (13.9 \u00b1 5.4%, P = 0.0050) and CKD 3 (21.4 \u00b1 8.0%, P = 0.0020).<\/jats:p>\n                  <jats:p>Conclusion: Tolvaptan, administered for 3 years to patients with ADPKD, caused a sustained reduction in the urinary excretion of MCP-1 relative to placebo.<\/jats:p>","DOI":"10.1093\/ndt\/gfw060","type":"journal-article","created":{"date-parts":[[2016,4,15]],"date-time":"2016-04-15T20:33:55Z","timestamp":1460752435000},"page":"969-975","source":"Crossref","is-referenced-by-count":13,"title":["Tolvaptan suppresses monocyte chemotactic protein-1 excretion in autosomal-dominant polycystic kidney disease"],"prefix":"10.1093","volume":"32","author":[{"given":"Jared J.","family":"Grantham","sequence":"first","affiliation":[{"name":"The Kidney Institute 1 , Kansas University Medical Center, Kansas City, KS 66160 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arlene B.","family":"Chapman","sequence":"additional","affiliation":[{"name":"2 University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Blais","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development and Commercialization, Inc. 3 , Rockville, MD 20850 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank S.","family":"Czerwiec","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development and Commercialization, Inc. 3 , Rockville, MD 20850 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Devuyst","sequence":"additional","affiliation":[{"name":"University of Zurich 4 , Z\u00fcrich 8057 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron T.","family":"Gansevoort","sequence":"additional","affiliation":[{"name":"University of Groningen 5 , Groningen, GR 9713 GZ ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiji","family":"Higashihara","sequence":"additional","affiliation":[{"name":"Kyorin University 6 , Kyorin, Tokyo 181-8611 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly","family":"Krasa","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development and Commercialization, Inc. 3 , Rockville, MD 20850 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development and Commercialization, Inc. 3 , Rockville, MD 20850 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development and Commercialization, Inc. 3 , Rockville, MD 20850 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald D.","family":"Perrone","sequence":"additional","affiliation":[{"name":"Tufts Medical Center 7 , Boston, MA 02111 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente E.","family":"Torres","sequence":"additional","affiliation":[{"name":"Mayo Clinic 8 , Rochester, MN 55901 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the TEMPO 3:4 Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,4,15]]},"reference":[{"key":"2025102312494079600_GFW060C1","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1056\/NEJMcp0804458","article-title":"Clinical practice. 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