Abstract: PO1525
PKD1 Compared with PKD2 Genotype and Cardiac Hospitalizations in the HALT-PKD Studies
Session Information
- Cystic Kidney Diseases: Mechanisms, Genetics, and Treatment
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1001 Genetic Diseases of the Kidneys: Cystic
Authors
- Steele, Cortney, University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado, United States
- You, Zhiying, University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado, United States
- Gitomer, Berenice Y., University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado, United States
- Brosnahan, Godela M., University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado, United States
- Harris, Peter C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Torres, Vicente E., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Abebe, Kaleab, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States
- Steinman, Theodore I., Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
- Yu, Alan S.L., University of Kansas Medical Center, Kansas City, Kansas, United States
- Perrone, Ronald D., Tufts Medical Center, Boston, Massachusetts, United States
- Braun, William E., Cleveland Clinic, Cleveland, Ohio, United States
- Chapman, Arlene B., University of Chicago Pritzker School of Medicine, Chicago, Illinois, United States
- Chonchol, Michel, University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado, United States
- Nowak, Kristen L., University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado, United States
Background
Polycystin 1 and 2 are expressed in vascular endothelial and vascular smooth muscle cells. While the hallmark of autosomal dominant polycystic kidney disease (ADPKD) is the development and continued growth of multiple renal cysts that ultimately result in loss of kidney function, cardiovascular complications are the leading cause of death. Although hypertension occurs earlier and more frequently in PKD1 vs. PKD2, both genotypes seem to confer equal risk of developing intracranial aneurysms. It is currently unknown if PKD1 vs. PKD2 confers a different risk of cardiovascular events.
Methods
864 individuals with ADPKD who participated in the 5-yr HALT-PKD study A or B and had genotype data with either a PKD1 or PKD2 mutation were included in this analysis. Since the number of cardiac events in the HALT-PKD studies was limited, we determined the association of genotype with the adverse cardiac event with the highest frequency (cardiac hospitalization; defined according to the Common Terminology Criteria for Adverse Events v.4.0 of the National Cancer Institution and adjudicated by an endpoints committee). The association of genotype with cardiac hospitalization was determined using logistic regression.
Results
Among the 864 included participants, individuals with the PKD1 genotype (84%) were slightly younger (42±10 vs. 46±10 yrs, p<0.0001) and had a slightly lower baseline estimated glomerular filtration rate (eGFR; 70±26 vs. 75±26 ml/min/1.73m2, p=0.06) vs. PKD2. Cardiac hospitalization (n=43) was more common in individuals with a PKD2 genotype (9.2%) compared to a PKD1 genotype (4.1%; p=0.01). After adjustment for age, sex, race, and study randomization, PKD2 was associated with an increased odds of cardiac hospitalization (OR; 2.14, 95% CI: 1.04-4.41 vs. PKD1). This association was slightly attenuated after further adjustment for cardiac history, systolic blood pressure, body mass index, and baseline estimated glomerular filtration rate (OR: 2.12, CI: 0.99-4.52).
Conclusion
In early- and late-stage participants in the HALT-PKD studies, PKD2 genotype was independently associated with increased odds of cardiac hospitalization.
Funding
- NIDDK Support