{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:13:24Z","timestamp":1792541604828,"version":"4.5.0"},"reference-count":128,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:p>The global incidence of CKD continues to rise, with type 2 diabetes as a major contributor. At any stage of CKD, patients with concurrent CKD and type 2 diabetes are at heightened cardiovascular risk and have a greater likelihood of dying from cardiovascular causes than progressing to kidney failure. Consequently, the use of \u201cfour pillars\u201d of CKD therapy, including renin-angiotensin system inhibitors, sodium-glucose cotransporter 2 inhibitor, nonsteroidal mineralocorticoid receptor antagonists, and glucagon-like peptide-1 receptor agonists, has been advocated to reduce cardiovascular-kidney risk. Although these therapies can mitigate cardiovascular and kidney events when used individually, the residual risks of these events remain high across major clinical trials testing these therapies separately as well as in real-world clinical settings. This raises the question about when to optimally initiate these therapies, including strategies that start these agents in rapid sequence, or even simultaneously, to reduce long-term risk, thereby mirroring best practices with rapid titration schedules in patients with heart failure. However, initiating all four therapies simultaneously in the setting of CKD has not yet been tested due to lack of data on safety and tolerability in this high-risk population. Data regarding the safety profile of rapid sequence initiation remain limited. Therefore, our aim was to review the existing evidence on the safety profiles of guideline-recommended therapies and discuss the challenges associated with rapid sequence initiation of these treatments in patients with CKD.<\/jats:p>","DOI":"10.1681\/asn.0000000752","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T17:00:09Z","timestamp":1746550809000},"page":"2061-2076","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":23,"title":["Rapid and Simultaneous Initiation of Guideline-Directed Kidney Therapies in Patients with CKD and Type 2 Diabetes"],"prefix":"10.1681","volume":"36","author":[{"given":"Ahmed Mustafa","family":"Rashid","sequence":"first","affiliation":[{"name":"Baylor Scott and White Research Institute, Baylor Scott and White Health, Dallas, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Shahzeb","family":"Khan","sequence":"additional","affiliation":[{"name":"Baylor Scott and White Research Institute, Baylor Scott and White Health, Dallas, Texas"},{"name":"Baylor Scott and White: The Heart Hospital Plano, Plano, Texas"},{"name":"Department of Medicine, Baylor College of Medicine, Temple, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David Z.I.","family":"Cherney","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Toronto General Hospital, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankit","family":"Mehta","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Baylor University Medical Center, Dallas, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janani","family":"Rangaswami","sequence":"additional","affiliation":[{"name":"Department of Medicine, Veterans Affairs Medical Center, Washington, DC"},{"name":"Division of Nephrology, George Washington University School of Medicine and Health Sciences, Washington, DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7222-4666","authenticated-orcid":false,"given":"Tariq","family":"Shafi","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Baylor Scott and White Health, Temple, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javed","family":"Butler","sequence":"additional","affiliation":[{"name":"Baylor Scott and White Research Institute, Baylor Scott and White Health, Dallas, Texas"},{"name":"Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,5,6]]},"reference":[{"issue":"3","key":"B1-20251121","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1111\/jdi.13355","article-title":"Changing epidemiology of chronic kidney disease as a result of type 2 diabetes mellitus from 1990 to 2017: estimates from Global Burden of Disease 2017","volume":"12","author":"Li","year":"2021","journal-title":"J Diabetes Investig."},{"issue":"3","key":"B2-20251121","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/j.kint.2018.04.011","article-title":"Analysis of the Global Burden of Disease study highlights the global, regional, and national trends of chronic kidney disease epidemiology from 1990 to 2016","volume":"94","author":"Xie","year":"2018","journal-title":"Kidney Int."},{"issue":"11","key":"B3-20251121","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1161\/CIRCULATIONAHA.120.050686","article-title":"Cardiovascular disease in chronic kidney disease: pathophysiological insights and therapeutic options","volume":"143","author":"Jankowski","year":"2021","journal-title":"Circulation."},{"issue":"5S","key":"B4-20251121","first-page":"S1","article-title":"KDIGO 2022 clinical practice guideline for diabetes management in chronic kidney disease","volume":"102","year":"2022","journal-title":"Kidney Int."},{"issue":"11","key":"B5-20251121","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.2337\/dci22-0034","article-title":"Management of hyperglycemia in type 2 diabetes, 2022. 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