{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T16:08:21Z","timestamp":1789402101041,"version":"build-2803163510"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"abstract":"\n Background:<\/jats:title>\n \n Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited disorder leading to kidney failure. Tolvaptan, the only FDA-approved therapy, modestly slows disease progression but is limited by significant adverse effects, highlighting the need for more effective and better-tolerated treatments. Ciliary polycystins are central to ADPKD pathogenesis. We previously demonstrated that a cilia base-localized pool of CDK6 restricts ciliary polycystin abundance by suppressing axonemal polyglutamylation. However, whether CDK6 inhibition can restore polycystin function and suppress ADPKD progression\n in vivo<\/jats:italic>\n remains unknown.\n <\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n \n Abemaciclib was tested in\n in vitro<\/jats:italic>\n 3D cyst assays and\n ex vivo<\/jats:italic>\n metanephric organ cultures.\n In vivo<\/jats:italic>\n efficacy of early- and late-stage intervention were assessed in F1(129\/B6)\n Pkd1<\/jats:italic>\n R3277C\/R3277C<\/jats:sup>\n mice receiving daily abemaciclib. Tolvaptan served as a therapeutic control. Cyst burden, fibrosis in the kidneys, kidney function, and primary cilia of renal epithelial cells were analyzed at study endpoints.\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n CDK6 was prominently upregulated in cyst-lining cells in human and murine PKD kidneys. At doses substantially lower than those used in oncology, abemaciclib robustly suppressed cyst growth\n in vitro<\/jats:italic>\n and\n ex vivo<\/jats:italic>\n .\n In vivo<\/jats:italic>\n , long-term early treatment arrested cyst progression more effectively than tolvaptan without detectable toxicity. Late intervention largely halted cyst growth in females and reversed cyst progression in males. Mechanistically, abemaciclib restored axonemal polyglutamylation and increased ciliary polycystin levels.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n Abemaciclib has greater therapeutic efficacy and tolerability than tolvaptan in this preclinical model, largely driven by CDK6 inhibition\u2013mediated restoration of axonemal polyglutamylation and increased ciliary polycystin abundance.<\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.0000001269","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T16:00:50Z","timestamp":1789401650000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["CDK4\/6 Inhibitor Abemaciclib Arrests and Reverses Kidney Cyst Progression in Preclinical Models of Autosomal Dominant Polycystic Kidney Disease"],"prefix":"10.1681","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5488-0494","authenticated-orcid":false,"given":"Yingshu","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, 55905, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6342-0158","authenticated-orcid":false,"given":"Xiaobo","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, 55905, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0678-1795","authenticated-orcid":false,"given":"Yan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, 55905, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0694-0867","authenticated-orcid":false,"given":"Chuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, 55905, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9027-8150","authenticated-orcid":false,"given":"Biyun","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, 55905, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8618-0072","authenticated-orcid":false,"given":"Renee","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, 55905, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, 55905, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6195-0961","authenticated-orcid":false,"given":"Yan","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, 55905, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariana","family":"Aghevli","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, 55905, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, 55905, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2875-4659","authenticated-orcid":false,"given":"Vishal","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Nephrology, UT Southwestern Medical Center, Dallas, TX, 75390, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5304-6593","authenticated-orcid":false,"given":"Peter","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, 55905, USA."},{"name":"Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA."},{"name":"Robert M. and Billie Kelley Pirnie Translational Polycystic Kidney Disease Center, Mayo Clinic, Rochester, MN, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2388-5492","authenticated-orcid":false,"given":"Kun","family":"Ling","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, 55905, USA."},{"name":"Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA."},{"name":"Robert M. and Billie Kelley Pirnie Translational Polycystic Kidney Disease Center, Mayo Clinic, Rochester, MN, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghua","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, 55905, USA."},{"name":"Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA."},{"name":"Robert M. and Billie Kelley Pirnie Translational Polycystic Kidney Disease Center, Mayo Clinic, Rochester, MN, USA."},{"name":"Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Rochester, MN, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6405-8330","authenticated-orcid":false,"given":"Kai","family":"He","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, 55905, USA."},{"name":"Robert M. and Billie Kelley Pirnie Translational Polycystic Kidney Disease Center, Mayo Clinic, Rochester, MN, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,9,14]]},"container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.0000001269","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T16:00:50Z","timestamp":1789401650000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.0000001269"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,14]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1681\/asn.0000001269","relation":{},"ISSN":["1046-6673","1533-3450"],"issn-type":[{"value":"1046-6673","type":"print"},{"value":"1533-3450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,14]]},"assertion":[{"value":"2026-03-31","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-09","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}