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

Abstract

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.