Abstract: TH-PO434
Association Between PKD1 Truncating Mutations and Accelerated eGFR Decline in ADPKD Patients: Implications for Early Identification and Intervention
Session Information
- Genetic Diseases: Cystic - Therapeutic Investigations and Prognosis
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Cystic
Authors
- Ali, Hamad, Kuwait University Health Sciences Centre, Safat, Kuwait
- Alahmad, Barrak, Harvard University, Cambridge, United States
- Bahbahani, Yousif, Dasman Diabetes Institute, Kuwait City, Kuwait
- Senum, Sarah R., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Abu-Farha, Mohamed, Dasman Diabetes Institute, Kuwait City, Kuwait
- Abubaker, Jehad, Dasman Diabetes Institute, Kuwait City, Kuwait
- Al-Mulla, Fahd, Dasman Diabetes Institute, Kuwait City, Kuwait
- Harris, Peter C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
Background
ADPKD severity varies due to allelic and genic heterogeneity. Identifying patients at risk of rapid disease progression may improve outcomes. This study aims to explore the association between PKD1 types (truncating vs. non-truncating) mutations & rate of eGFR decline in ADPKD patients.
Methods
This study followed up 42 PKD1-ADPKD patients with clinically & genetically confirmed diagnoses for an average of 6.6±3.8 years. Renal function tests were performed annually, and eGFR was calculated using the CKD-EPI Creatinine Equation (2021).
Results
Patients with PKD1 truncating mutations had a more rapid rate of eGFR decline per year (-4.7 ml/min/1.73 m2 per year) compared to patients with PKD1 non-truncating mutations (-3.5 ml/min/1.73 m2 per year) (P<0.001).
Conclusion
This study highlights the association between PKD1 truncating mutations & a more rapid rate of eGFR decline in ADPKD patients. Identifying patients with potential rapid disease progression may aid in early intervention & better disease management to improve outcomes.
Analysis of ADPKD progression per PKD1 mutation type
| Effect Estimate | 95% CI | P | |
| Truncated vs. Non-Truncated (a) | |||
| Creatinine (mmol/L) | 184.6 | 57.1 - 312.1 | 0.007 |
| Urea (mmol/L) | 5.9 | 1.0, 10.7 | 0.022 |
| eGFR (ml/min/1.73 m2) | -19.2 | -38.9, 0.42 | 0.063 |
| Rate of eGFR (ml/min/1.73 m2) decline per year (b) | |||
| PKD1 Truncating mutation | -4.7 | -5.0, -4.4 | <0.001 |
| PKD1 Non-truncating mutation | -3.5 | -4.0,-3.1 | <0.001 |
a estimated from mixed effects model adjusted for sex, age at visit, and birth year b estimated from stratified mixed effects models adjusted for sex and birth year. P-value of interaction was obtained from an interaction term.
A non-linear estimation of eGFR change through a smooth interaction between age at visit and mutation type.
Funding
- Government Support – Non-U.S.