{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T06:12:14Z","timestamp":1793081534004,"version":"4.5.0"},"reference-count":165,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["DK142878"],"award-info":[{"award-number":["DK142878"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["DK112042; DK132690"],"award-info":[{"award-number":["DK112042; DK132690"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["DK139291"],"award-info":[{"award-number":["DK139291"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder and a leading cause of kidney failure worldwide. Disease progression is driven by cyst expansion, tubular injury, and maladaptive metabolic and hemodynamic changes. Tolvaptan remains the only US Food and Drug Administration\u2013approved disease-modifying therapy, however its tolerability and safety profile highlight the need for additional strategies. Sodium-glucose cotransporter 2 inhibitors (SGLT2is), initially developed for glycemic control, have demonstrated robust kidney-protective and cardioprotective effects across diverse patient populations, including those without diabetes. By lowering intraglomerular pressure, metabolic reprogramming, and attenuating hypoxic microenvironment and inflammation, SGLT2is target mechanisms that are relevant to ADPKD. However, concerns that SGLT2i may provoke osmotic diuresis and activate vasopressin led to systematic exclusion of patients with ADPKD from pivotal outcome trials. The 2025 Kidney Disease Improving Global Outcomes ADPKD guidelines explicitly advise against the use of SGLT2i for slowing kidney function decline in ADPKD. In this review, we examine mechanistic intersections between SGLT2i and ADPKD pathophysiology, summarize available preclinical and early clinical data, and discuss ongoing large trials designed to address safety and efficacy of SGLT2i in patients with ADPKD. We also highlight the importance of genetic heterogeneity, as most ongoing trials are enriched for rapid progressors carrying\n                      <jats:italic toggle=\"yes\">PKD1<\/jats:italic>\n                      or\n                      <jats:italic toggle=\"yes\">PKD2<\/jats:italic>\n                      pathogenic variants, while other genotypes such as\n                      <jats:italic toggle=\"yes\">DNAJB11<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">ALG8<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">ALG9<\/jats:italic>\n                      , often associated with greater interstitial fibrosis, are underrepresented. Substratification of patients by genotype, risk of progression, and comorbidities will be essential to guide precision application of SGLT2i. Whether SGLT2i can ultimately be positioned as an adjunctive or standalone therapy for ADPKD remains unresolved.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.0000000943","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T17:00:41Z","timestamp":1762794041000},"page":"861-880","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":9,"title":["Sodium-Glucose Cotransporter 2 Inhibitors in Autosomal Dominant Polycystic Kidney Disease"],"prefix":"10.1681","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5143-1670","authenticated-orcid":false,"given":"Marie Therese","family":"Bou Antoun","sequence":"first","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Jacksonville, Florida"},{"name":"Mayo Clinic Florida PKD Center of Excellence, Jacksonville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul Hamid","family":"Borghol","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Jacksonville, Florida"},{"name":"Mayo Clinic Florida PKD Center of Excellence, Jacksonville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5801-0702","authenticated-orcid":false,"given":"Levon","family":"Souvalian","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Jacksonville, Florida"},{"name":"Mayo Clinic Florida PKD Center of Excellence, Jacksonville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6047-8792","authenticated-orcid":false,"given":"Mohamad","family":"Hadla","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Jacksonville, Florida"},{"name":"Mayo Clinic Florida PKD Center of Excellence, Jacksonville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0353-2515","authenticated-orcid":false,"given":"Georges","family":"Abboud","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Jacksonville, Florida"},{"name":"Mayo Clinic Florida PKD Center of Excellence, Jacksonville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4925-2677","authenticated-orcid":false,"given":"Ahmad","family":"Ghanem","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Jacksonville, Florida"},{"name":"Mayo Clinic Florida PKD Center of Excellence, Jacksonville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0581-1211","authenticated-orcid":false,"given":"Fadi George","family":"Munairdjy Debeh","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Jacksonville, Florida"},{"name":"Mayo Clinic Florida PKD Center of Excellence, Jacksonville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1300-7989","authenticated-orcid":false,"given":"Jean Marc","family":"Mardirossian","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Jacksonville, Florida"},{"name":"Mayo Clinic Florida PKD Center of Excellence, Jacksonville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4568-8967","authenticated-orcid":false,"given":"Mahdi","family":"Salih","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Nephrology and Transplantation, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6016-4715","authenticated-orcid":false,"given":"Pranav S.","family":"Garimella","sequence":"additional","affiliation":[{"name":"Division of Nephrology-Hypertension, University of California, La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9211-2063","authenticated-orcid":false,"given":"Volker","family":"Vallon","sequence":"additional","affiliation":[{"name":"Division of Nephrology-Hypertension, University of California, La Jolla, California"},{"name":"Department of Pharmacology, University of California, La Jolla, California"},{"name":"VA San Diego Healthcare System, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3949-5720","authenticated-orcid":false,"given":"Fouad T.","family":"Chebib","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Jacksonville, Florida"},{"name":"Mayo Clinic Florida PKD Center of Excellence, Jacksonville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"issue":"1","key":"B1-20260525","doi-asserted-by":"crossref","first-page":"2492374","DOI":"10.1080\/0886022X.2025.2492374","article-title":"Autosomal dominant polycystic kidney disease: an overview of recent genetic and clinical advances","volume":"47","author":"Borghol","year":"2025","journal-title":"Ren 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(Lausanne)."},{"issue":"1","key":"B26-20260525","doi-asserted-by":"crossref","first-page":"R75","DOI":"10.1152\/ajpregu.00357.2011","article-title":"Acute and chronic effects of SGLT2 blockade on glomerular and tubular function in the early diabetic rat","volume":"302","author":"Thomson","year":"2012","journal-title":"Am J Physiol Regul Integr Comp Physiol."},{"issue":"1","key":"B27-20260525","doi-asserted-by":"crossref","first-page":"F207","DOI":"10.1152\/ajprenal.00120.2019","article-title":"Knockout of Na(+)-glucose cotransporter SGLT1 mitigates diabetes-induced upregulation of nitric oxide synthase NOS1 in the macula densa and glomerular hyperfiltration","volume":"317","author":"Song","year":"2019","journal-title":"Am J Physiol Renal Physiol."},{"issue":"1","key":"B28-20260525","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.kint.2019.09.023","article-title":"Do sodium-glucose cotransporter-2 inhibitors affect renal hemodynamics by different mechanisms in type 1 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