{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T18:37:35Z","timestamp":1768415855044,"version":"3.49.0"},"reference-count":12,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,8,8]],"date-time":"2017-08-08T00:00:00Z","timestamp":1502150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"No funding was received for this study."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2018,1]]},"abstract":"\n Individual patients show a large variation in their response to renin\u2010angiotensin\u2010aldosteron system (\n RAAS<\/jats:styled-content>\n ) inhibition (\n RAASi<\/jats:styled-content>\n ), both in surrogates such as albuminuria and in hard renal outcomes. Sodium\u2010glucose co\u2010transporter 2 inhibitors (\n SGLT<\/jats:styled-content>\n 2) have been shown to lower albuminuria and to confer cardiovascular and, possibly, renal protection. To establish whether individual therapy resistance to\n RAASi<\/jats:styled-content>\n can be overcome by adding an\n SGLT<\/jats:styled-content>\n 2 inhibitor, we assessed individual albuminuria responses in patients exposed to both\n RAASi<\/jats:styled-content>\n and the\n SGLT2<\/jats:styled-content>\n inhibitor dapagliflozin. We used data from a randomized controlled cross\u2010over trial designed to assess the albuminuria\u2010lowering effect of 6\u2010week treatment with dapagliflozin 10\u2009mg\/d. We extracted from the electronic medical records data on the albuminuria response upon initiation of\n RAASi<\/jats:styled-content>\n before the trial period, and analysed individual albuminuria responses to\n RAASi<\/jats:styled-content>\n and to dapagliflozin. We retrieved data on\n RAASi<\/jats:styled-content>\n for 26 patients (age, 62\u2009years [SD, 8]; female gender, 6 [23%]; 24\u2010hour urinary albumin excretion, 521 [187\u2010921] mg\/24\u2009h). The mean albuminuria\u2010lowering response to\n RAASi<\/jats:styled-content>\n was 26.5% (range, \u221276.1% to 135.1%). The addition of dapagliflozin res in a further reduction of 34.9%, (range, \u221283.9 to 94.2). Interestingly, the albuminuria response to\n RAASi<\/jats:styled-content>\n significantly correlated with the response to dapagliflozin (\n P<\/jats:styled-content>\n earson correlation coefficient, 0.635 [95%\n CI<\/jats:styled-content>\n , 0.328\u20100.821];\n P<\/jats:italic>\n \u2009<\u2009.001), indicating that patients who did not respond to\n RAASi<\/jats:styled-content>\n also did not respond to dapagliflozin. We concluded that individual therapy resistance to\n RAASi<\/jats:styled-content>\n cannot be overcome with the addition of a completely different class of drugs,\n SGLT2<\/jats:styled-content>\n inhibitors. These data suggest that the individual drug response is an intrinsic individual characteristic, possibly unrelated to the type of intervention, unless the mode of action of dapagliflozin on albuminuria is through the\n RAAS<\/jats:styled-content>\n .\n <\/jats:p>","DOI":"10.1111\/dom.13057","type":"journal-article","created":{"date-parts":[[2017,7,7]],"date-time":"2017-07-07T09:44:07Z","timestamp":1499420647000},"page":"224-227","source":"Crossref","is-referenced-by-count":17,"title":["Does\n SGLT<\/scp>\n 2 inhibition with dapagliflozin overcome individual therapy resistance to\n RAAS<\/scp>\n inhibition?"],"prefix":"10.1111","volume":"20","author":[{"given":"Sergei","family":"Petrykiv","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University of Groningen, University Medical Center Groningen Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gozewijn D.","family":"Laverman","sequence":"additional","affiliation":[{"name":"Department of Nephrology Ziekenhuisgroep Twente Almelo and Hengelo The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dick","family":"de Zeeuw","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University of Groningen, University Medical Center Groningen Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3126-3730","authenticated-orcid":false,"given":"Hiddo J. L.","family":"Heerspink","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University of Groningen, University Medical Center Groningen Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,8,8]]},"reference":[{"key":"e_1_2_6_2_1","volume-title":"IDF Diabetes Atlas","author":"International Diabetes Federation","year":"2013"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2011.861"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s001250050140"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12655"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2002.00536.x"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.57.s75.6.x"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.021887"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1515920"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12936"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008030292"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13217"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(15)00424-6"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fdom.13057","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dom.13057","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/dom.13057","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.13057","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T04:58:16Z","timestamp":1761886696000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/10.1111\/dom.13057"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,8]]},"references-count":12,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,1]]}},"alternative-id":["10.1111\/dom.13057"],"URL":"https:\/\/doi.org\/10.1111\/dom.13057","archive":["Portico"],"relation":{},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,8]]}}}