Abstract: FR-PO0086
CDK4/6 Inhibitor Abemaciclib Arrests and Reverses Kidney Cystic Progression in Preclinical ADPKD Model
Session Information
- ADPKD and Cystic Kidney Disease - 2
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Cystic (Monogenic)
Authors
- Cao, Yingshu, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Sun, Xiaobo, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Huang, Yan, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Ji, Biyun, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Gao, Yue, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Liang, Yan, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Patel, Vishal, Southwestern University, Georgetown, Texas, United States
- Harris, Peter C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Ling, Kun, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Hu, Jinghua, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- He, Kai, Mayo Clinic Minnesota, Rochester, Minnesota, United States
Background
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder and is characterized by progressive renal cyst formation 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. The ciliary Ciliary polycystins are central to ADPKD pathogenesis. We previously demonstrated that a specific cilia base-localized pool of CDK6 at cilia base restricts ciliary polycystin abundance by suppressing axonemal polyglutamylation. However, whether CDK6 inhibition can restore polycystin function and suppress ADPKD progression in vivo remains unknown.
Methods
Abemaciclib was tested in vitro using 3D cyst assays and ex vivo metanephric organ cultures. In vivo efficacy of early- and late-stage intervention were assessed in F1(129/B6) Pkd1R3277C/R3277C (Pkd1RC/RC) mice receiving daily oral Abemaciclib. Tolvaptan severed as therapeutic control. Cyst burden, renal fibrosis, kidney function, and primary cilia of renal epithelial cells were analyzed at study endpoints.
Results
CDK6 was prominently upregulated in cyst-lining cells in both human and murine PKD kidneys. At doses substantially lower than those used in cancer patientsoncology, Abemaciclib robustly suppressed cyst growth in vitro and ex vivo. In vivo, long-term early treatment arrested cyst expansion and preserved renal function cyst progression more effectively than Tolvaptan without detectable toxicity. Remarkable, Llate intervention produced sex-specific effects: cyst growth was largely halted halted cyst growth in female mice and , whereas reversed established cyst progressions regressed in males. Mechanistically, Abemaciclib restored axonemal polyglutamylation, increased ciliary polycystin levels, and suppressed proliferative signaling.
Conclusion
Abemaciclib has superior therapeutic efficacy and tolerability compared with Tolvaptan. , largely driven by CDK6 inhibition–mediated restoration of axonemal polyglutamylation and increased ciliary polycystin abundance. Restoration of axonemal polyglutamylation and increased ciliary polycystin dosageThese findings support selective CDK6 inhibition represent as a promising and safer promising therapeutic potentialstrategy for ADPKD.
Acknowledgment
We thank Dr. Feng Qian at the Maryland PKD Core Center at University of Maryland for providing the polyclonal PC2 antibody and IMCD3 PC1-flag FlpIn cells.
Funding
- NIDDK Support