Abstract: SA-PO586
Characterization of IFT140 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
- Ghanem, Ahmad, Mayo Clinic in Florida, Jacksonville, Florida, United States
- Munairdjy Debeh, Fadi George, Mayo Clinic in Florida, Jacksonville, Florida, United States
- Borghol, Abdul Hamid, Mayo Clinic in Florida, Jacksonville, Florida, United States
- Paul, Stefan N., Mayo Clinic in Florida, Jacksonville, Florida, United States
- Alkhatib, Bassel, Mayo Clinic in Florida, Jacksonville, Florida, United States
- Nader, Nay, Mayo Clinic in Florida, Jacksonville, Florida, United States
- Gregory, Adriana, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Yang, Hana, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Hanna, Christian, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Dahl, Neera K., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Kline, Timothy L., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Harris, Peter C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Chebib, Fouad T., Mayo Clinic in Florida, Jacksonville, Florida, United States
Background
Autosomal dominant polycystic kidney disease (ADPKD) is commonly caused by pathogenic variants in PKD1 and PKD2 genes. This study aims to characterize the phenotype of ADPKD-IFT140, the third most common pathogenic variant associated with milder ADPKD, and compare it with the phenotypes of nontruncating-PKD1 (PKD1NT) and PKD2 pathogenic variants.
Methods
In this retrospective cohort study, ADPKD patients with pathogenic variants in IFT140, 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 as shown in Figure.
Results
Of the included ADPKD patients (27 each in IFT140, PKD1NT, PKD2), 48% were male with a mean (±SD) age at imaging of 57.7 (±13.3) years. Imaging biomarkers analyses across the 3 groups is shown in Table. Although no significant difference was observed in total cyst volume (TCV) between the 3 groups, ADPKD-IFT140 patients were characterized by a smaller total number of cysts (median TCN: 42 in IFT140 vs. 277 in PKD2 vs 217 in PKD1NT, p<0.01) and larger average cyst volumes (median: 12.1 mL in IFT140 vs. 2.2 in PKD2 and 1.0 mL in PKD1NT, p<0.01). Furthermore, the cyst-parenchymal surface area was significantly smaller in the ADPKD-IFT140 group (median: 182.3 cm2 in IFT140 vs. 1222.4 cm2 in PKD2 and 678.3 cm2 in PKD1NT, p<0.01).
Conclusion
ADPKD-IFT140 patients develop enlarged kidneys with fewer but significantly larger cysts compared to ADPKD-PKD2 and ADPKD-PKD1NT.
Table
| IFT140 | PKD2 | PKD1NT1 | p-value | |
| Height-adjusted total kidney volume (htTKV) (mL/m), median (Q1-Q3) | 424.8 (263.7 - 858.7) | 915.8 (345.2 - 1402.1) | 448.0 (312.5 - 1141.1) | 0.13 |
| Total cyst volume (TCV) (mL), median (Q1-Q3) | 399.4 (110.7 - 1063.9) | 815.6 (217.9 - 1412.6) | 223.5 (83.4 - 1007.5) | 0.18 |
| Renal parenchymal volume (RPV) (mL), median (Q1 - Q3) | 384.9 (293.2 - 529.2) | 603.7 (393.5 - 1043.8) | 550.8 (412.5 - 1106.6) | <0.01 |
| Cyst-parenchymal surface area (CPSA) (cm2), median (Q1 - Q3) | 182.3 (100.3 - 382.4) | 1222.4 (421.3 - 1888.8) | 678.3 (347.4 - 1734.8) | <0.01 |
| Total cyst number (TCN), median (Q1 - Q3) | 42 (18 - 56) | 277 (121 - 614) | 217 (144 - 470) | <0.01 |
| Average cyst volume (mL), median (Q1 - Q3) | 12.1 (4.0 - 17.1) | 2.2 (0.9 - 3.4) | 1.0 (0.5 - 2.2) | <0.01 |
Figure: Advanced imaging biomarkers assessed using an automated cyst segmentation deep learning model.