{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T18:38:16Z","timestamp":1777055896519,"version":"3.51.4"},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,5,28]],"date-time":"2015-05-28T00:00:00Z","timestamp":1432771200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004522","name":"Top Institute Pharma","doi-asserted-by":"publisher","award":["T6-503"],"award-info":[{"award-number":["T6-503"]}],"id":[{"id":"10.13039\/501100004522","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Angiotensin receptor blockers (ARBs) are renoprotective and targeted to blood pressure. However, ARBs have multiple other (off\u2010target) effects which may affect renal outcome. It is unknown whether on\u2010target and off\u2010target effects are congruent within individuals. If not, this variation in short term effects may have important implications for the prediction of individual long term renal outcomes. Our aim was to assess intra\u2010individual variability in multiple parameters in response to ARBs in type 2 diabetes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Changes in systolic blood pressure (SBP), albuminuria, potassium, haemoglobin, cholesterol and uric acid after 6 months of losartan treatment were assessed in the RENAAL database. Improvement in predictive performance of renal outcomes (ESRD or doubling serum creatinine) for each individual using ARB\u2010induced changes in all risk markers was assessed by the relative integrative discrimination index (RIDI).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>SBP response showed high variability (mean \u20135.7 mmHg, 5<jats:sup>th<\/jats:sup> to 95<jats:sup>th<\/jats:sup> percentile \u201336.5 to +24.0 mmHg) between individuals. Changes in off\u2010target parameters also showed high variability between individuals. No congruency was observed between responses to losartan in multiple parameters within individuals. Using individual responses in all risk markers significantly improved renal risk prediction (RIDI 30.4%, <jats:italic>P<\/jats:italic> &lt; 0.01) compared with using only SBP changes. Results were successfully replicated in two independent trials with irbesartan, IDNT and IRMA\u20102.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In this <jats:italic>post hoc<\/jats:italic> analysis we showed that ARBs have multiple off\u2010target effects which vary between and within individuals. Combining all ARB\u2010induced responses beyond SBP provides a more accurate prediction of who will benefit from ARB therapy. Prospective trials are required to validate these findings.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.12655","type":"journal-article","created":{"date-parts":[[2015,4,15]],"date-time":"2015-04-15T03:43:15Z","timestamp":1429069395000},"page":"678-686","source":"Crossref","is-referenced-by-count":37,"title":["The renal protective effect of angiotensin receptor blockers depends on intra\u2010individual response variation in multiple risk markers"],"prefix":"10.1111","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2577-4876","authenticated-orcid":false,"given":"Bauke","family":"Schievink","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":"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"}]},{"given":"Hans\u2010Henrik","family":"Parving","sequence":"additional","affiliation":[{"name":"Department of Medical Endocrinology, Rigshospitalet University of Copenhagen  Copenhagen"},{"name":"Department of Medical Endocrinology, Rigshospitalet, HEALTH Aarhus University  Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Rossing","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center, Gentofte, NNF Center for Basic Metabolic Research University of Copenhagen, Copenhagen, HEALTH Aarhus University  Aarhus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiddo Jan","family":"Lambers Heerspink","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University of Groningen University Medical Center Groningen  Groningen the 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