Characterization of Kidney and Liver Cystic Phenotype Associated with GANAB Using Advanced Imaging Biomarkers.

BACKGROUND

Monoallelic pathogenic variants in GANAB cause autosomal dominant cystic kidney and liver disease, but quantitative imaging phenotypes remain incompletely defined.

METHODS

We performed a retrospective study of 16 individuals with GANAB variants and available abdominal imaging. Deep learning-based cyst segmentation quantified kidney and liver volumes and cyst metrics, including height-adjusted total kidney volume (htTKV), height-adjusted total liver volume, total cyst number (TCN), and height-adjusted total cyst volume.

RESULTS

Hepatic involvement was common, with polycystic liver disease present in most individuals with varying severity (liver TCN range 22-219). Kidney involvement was more heterogeneous (htTKV range 153-858 mL/m; kidney TCN range 3-42). Individuals with kidney TCN <20 had preserved kidney function and slower annual estimated glomerular filtration rate (eGFR) decline (median -1.68 mL/min/1.73 m2) compared with those with kidney TCN ≥20 (-2.8 mL/min/1.73 m2/year); no individual progressed to kidney failure during follow-up. Hypertension occurred in 50%. Intracranial aneurysms were identified in 3 of 6 screened individuals, including two from a family with known aneurysmal disease.

CONCLUSIONS

Quantitative imaging reveals a phenotypic spectrum in ADPKD-GANAB, ranging from liver-predominant cystic disease with minimal kidney involvement to a phenotype with higher kidney cyst burden and faster eGFR decline. Establishing robust genotype-phenotype relationships in this rare disease will require larger, aggregated cohorts with standardized imaging and systemic extrarenal screening.