Kidney Week

Abstract: TH-PO0164

Factors Associated with Kidney Failure in a Large Population of Patients with ADPKD and PKD1 Truncating Variants: A Multicenter Study

Session Information

• ADPKD and Cystic Kidney Disease - 1
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1201 Genetic Diseases of the Kidneys: Cystic (Monogenic)

Authors

• Elbarougy, Doaa E., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Doaa E. Elbarougy, MBChB

• Senum, Sarah R., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Sarah R. Senum, MS

• Sandford, Richard N., University of Cambridge, Cambridge, England, United Kingdom

Richard N. Sandford, MD

• Perrone, Ronald D., Tufts Medical Center, Boston, Massachusetts, United States

Ronald D. Perrone, MD, FASN

• Demoulin, Nathalie, Cliniques universitaires Saint-Luc, Brussels, Belgium

Nathalie Demoulin, MD

• Peters, Dorien J.M., Leids Universitair Medisch Centrum, Leiden, ZH, Netherlands

Dorien J.M. Peters, PhD

• Yu, Alan S.L., The University of Kansas Medical Center, Kansas City, Kansas, United States

Alan S.L. Yu, MBChB

• Torres, Vicente E., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Vicente E. Torres, MD, PhD

• Rahbari-Oskoui, Frederic F., Emory University School of Medicine, Atlanta, Georgia, United States

Frederic F. Rahbari-Oskoui, MD, MS, FASN

• Chapman, Arlene B., The University of Chicago, Chicago, Illinois, United States

Arlene B. Chapman, MD

• Gitomer, Berenice Y., University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Berenice Y. Gitomer, PhD

• Cornec-Le Gall, Emilie, Centre Hospitalier Regional et Universitaire de Brest, Brest, Brittany, France

Emilie Cornec-Le Gall, MD, PhD

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

Peter C. Harris, PhD

Background

Progression to kidney failure (KF) in ADPKD varies by genotype, with PKD1 truncating (T) variants associated with the most severe disease. We evaluated whether clinical factors further stratify risk within this high-risk subgroup.

Methods

We analyzed 2660 participants in the multicenter ADPKD Modifier Study with PKD1-T variants, representing a predominantly White cohort. Data were self-reported through questionnaires. The primary outcome was time to KF. Multivariable Cox proportional hazards models adjusted for sex, birth year, BMI category, and PKD1 truncating variant class (frameshift, nonsense, canonical splice-site) were used to evaluate clinical exposures.

Results

Urologic events were associated with increased risk of KF, including frequent urinary tract infections, hematuria, and nephrolithiasis (Figure 1). Hypertension was a strong predictor of KF, particularly with earlier age of onset. Use of ACE inhibitor/angiotensin receptor blocker (ACEI/ARB) therapy was associated with lower risk compared with other blood pressure medications, whereas greater comorbidity burden (e.g., diabetes mellitus, gout) was associated with substantially increased risk. In univariate analyses, male sex and obesity were also associated with higher risk of KF.
Kaplan–Meier analysis showed differences in kidney survival across PKD1-T variant classes, with canonical splice-site variants associated with earlier progression to KF compared with frameshift and nonsense variants (Figure 2).

Conclusion

In a genetically homogeneous population with PKD1-T variants, clinical factors provide important prognostic information beyond genotype and may help guide earlier risk stratification and intervention.

Funding

• NIDDK Support