Kidney Week

Abstract: SA-PO587

Characterization of GANAB Phenotype in Patients with ADPKD Using Advanced Imaging Biomarkers

Session Information

• Cystic Kidney Diseases: Genetic Causes, Modifiers, and Extrarenal Manifestations
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1201 Genetic Diseases of the Kidneys: Cystic

Authors

• Munairdjy Debeh, Fadi George, Mayo Clinic in Florida, Jacksonville, Florida, United States

Fadi George Munairdjy Debeh, MD

• Rangarajan, Vineetha, Mayo Clinic in Florida, Jacksonville, Florida, United States

Vineetha Rangarajan, DO

• Ghanem, Ahmad, Mayo Clinic in Florida, Jacksonville, Florida, United States

Ahmad Ghanem, MD

• Borghol, Abdul Hamid, Mayo Clinic in Florida, Jacksonville, Florida, United States

Abdul Hamid Borghol, MD

• Paul, Stefan N., Mayo Clinic in Florida, Jacksonville, Florida, United States

Stefan N. Paul, MBBS

• Alkhatib, Bassel, Mayo Clinic in Florida, Jacksonville, Florida, United States

Bassel Alkhatib, MD

• Nader, Nay, Mayo Clinic in Florida, Jacksonville, Florida, United States

Nay Nader, MD

• Gregory, Adriana, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Adriana Gregory, MS

• Yang, Hana, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Hana Yang, PhD

• Hanna, Christian, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Christian Hanna, MD, MS

• Dahl, Neera K., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Neera K. Dahl, MD, PhD, FASN

• Kline, Timothy L., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Timothy L. Kline, MS, PhD

• Harris, Peter C., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Peter C. Harris, PhD

• Chebib, Fouad T., Mayo Clinic in Florida, Jacksonville, Florida, United States

Fouad T. Chebib, MD, FASN

Group or Team Name

• Chebib's Clinical Team.

Background

Autosomal dominant polycystic kidney disease (ADPKD), primarily caused by pathogenic variants in the PKD1 and PKD2 genes, is the most prevalent inherited kidney disorder leading to kidney failure. Rarely, other genes like GANAB can cause ADPKD with a lower risk of kidney failure. This study aims to characterize the renal and hepatic manifestations of ADPKD-GANAB and compare them with nontruncating-PKD1 (PKD1NT) and PKD2 pathogenic variants.

Methods

In this retrospective cohort study, ADPKD patients with pathogenic variants in GANAB, PKD2, or PKD1NT, and imaging prior to any event that may affect total kidney volume (TKV) were identified and matched by sex, age, and closest htTKV. Advanced imaging biomarkers were assessed using an automated cyst segmentation deep learning model.

Results

Of the included ADPKD patients (14 each in GANAB, PKD1NT, PKD2), 78% were female with a mean (±SD) age at imaging of 56 ±11.5 years. Imaging biomarkers analyses across the 3 groups is shown in Table. Median total liver volume and percentage of patients with >100 liver cysts were similar between the 3 groups. However, ADPKD-GANAB patients had a significantly lower htTKV (median: 214.5 in GANAB vs. 324 in PKD2 vs. 288.3 in PKD1NT, p=0.03), total cyst volume (TCV) (median: 4.1 in GANAB vs. 119 in PKD2 vs. 69.2 in PKD1NT, p=0.02), and total cyst number (TCN) (median: 12.5 in GANAB, vs. 145 in PKD2 vs 98 in PKD1NT, p<0.01).

Conclusion

Compared to ADPKD-PKDNT1 and ADPKD-PKD2, ADPKD-GANAB patients have similar hepatic manifestations, but milder renal manifestations characterized by significantly smaller kidneys with a fewer number of cysts. These findings suggest that GANAB pathogenic variants lead to a liver-dominant phenotype with milder renal cystic burden.

Table