Abstract: FR-PO0058
Renal Cyst Decortication for Tuberous Sclerosis Complex Polycystic Kidney Disease
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
- Bissler, John J., The University of Tennessee Health Science Center College of Medicine, Memphis, Tennessee, United States
- Reddi, Kiran Kumar, The University of Tennessee Health Science Center College of Medicine, Memphis, Tennessee, United States
- Batchelor, Dinah, The University of Tennessee Health Science Center College of Medicine, Memphis, Tennessee, United States
- Kumar, Prashant, Old Dominion University, Norfolk, Virginia, United States
- Hanna, Christian, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
- Chishti, Aftab S., University of Kentucky, Lexington, Kentucky, United States
- Cadnapaphornchai, Melissa A., The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
Background
Renal cystic disease is an important but underrecognized cause of morbidity in tuberous sclerosis complex (TSC). While mammalian target of rapamycin complex 1 (mTORC1) inhibition effectively treats TSC associated angiomyolipomata, no approved therapy exists for severe TSC associated renal cystic disease, particularly the polycystic phenotype seen in TSC2/PKD1 contiguous gene deletion. Increasing evidence suggests that cystogenesis in TSC involves non–cell autonomous mechanisms, including aberrant extracellular vesicle (EV) signaling, and that established cysts may function as autonomous disease-driving structures.
Methods
We conducted a pilot study of children and young adults with TSC associated polycystic kidney disease undergoing robot assisted bilateral renal cyst decortication. Clinical outcomes included blood pressure, antihypertensive medication burden, microalbuminuria, and estimated glomerular filtration rate (eGFR). Intracystic pressures were measured intraoperatively. Cyst fluid was analyzed for EV content and molecular characteristics using electron microscopy, particle analysis, Western blotting, and RNA profiling. Renal MRI was assessed longitudinally.
Results
Fourteen patients undergoing seventeen procedures were evaluated. Decortication resulted in sustained reductions in total kidney volume normalized to height (mean reduction 345 mL/m; p = 0.0004), preservation of renal parenchyma, and stable eGFR. Despite a 25–50% reduction in antihypertensive medications, systolic blood pressure decreased significantly (mean −10.4 mmHg; p = 0.032). Intracystic pressures were markedly elevated, particularly in hypertensive patients. Cyst fluid contained abundant small EVs with a distinct epithelial molecular signature.
Conclusion
These findings support a two stage model of TSC renal cystic disease in which early mTORC1 responsive cysts evolve into pressurized, possibly EV mediated, autonomous lesions that drive hypertension and renal injury. Renal cyst decortication reduces cyst pressure, improves blood pressure control, and preserves renal structure, providing a mechanistically informed therapeutic strategy for advanced TSC associated polycystic kidney disease.
Acknowledgment
This work was supported by the Federal Express Chair of Excellence, The Children's Foundation Research Center, and St. Jude Children's Research Hopsital.
Funding
- Private Foundation Support