Kidney Week

Abstract: SA-PO0591

Autosomal Recessive PKD: Not Just for Kids, Long-Term Outcomes in Early vs. Late-Onset Disease

Session Information

• Cystic Kidney Diseases: Clinical Research
  November 08, 2025 | 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: Monogenic Kidney Diseases

Authors

• Borghol, Abdul Hamid, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Abdul Hamid Borghol, MD

• Potretzke, Theodora A., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Theodora A. Potretzke, 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

• Smith, Byron H., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Byron H. Smith, MS, PhD

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

Doaa E. Elbarougy, MBChB

• Thompson, Whitney, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Whitney Thompson, MD

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

Neera K. Dahl, MD, PhD, FASN

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

Vicente E. Torres, MD, PhD

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

Berenice Y. Gitomer, PhD

• Ong, Albert C., The University of Sheffield School of Medicine and Population Health, Sheffield, England, United Kingdom

Albert C. Ong, MD, PhD

• Chebib, Fouad T., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Fouad T. Chebib, MD, FASN

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

Peter C. Harris, PhD

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

Christian Hanna, MD, MS, FASN

Background

Autosomal recessive polycystic kidney disease (ARPKD) is a rare ciliopathy usually caused by biallelic PKHD1 variants. It is typically diagnosed in early childhood, though late-onset ARPKD are increasingly recognized with broader molecular testing, but long-term outcomes data is lacking.

Methods

This retrospective study compared early- and late-onset ARPKD in patients with biallelic PKHD1 pathogenic variants, using clinical and imaging data from 1961 to 2022 to evaluate long-term outcomes and phenotypic differences.

Results

Among 50 genetically confirmed ARPKD-PKHD1 patients, 27 had early-onset [median diagnosis age 0 yrs (IQR 0–2)] and 23 had late-onset disease [31 yrs (20–42)]; median follow-up was 22 yrs (8–32) vs. 15 yrs (6–25) (p = 0.46). Figure 1A illustrates that late-onset ARPKD presented with fewer renal and more hepatobiliary symptoms. Nephromegaly at diagnosis was less common, and over time, these patients had a lower lifetime incidence of hypertension and kidney failure (p < 0.05), but higher rates of ascending cholangitis and urinary stone disease (p < 0.05). Interestingly, the distribution of two non-truncating (2NT) versus non-truncating/truncating (NT/T) variants was similar between early- and late-onset cases (p = 0.15). In late-onset patients with serial imaging, height adjusted total kidney and liver volumes, and cyst counts showed variable progression, while eGFR decline was common; 11 of 14 (79%) had a final eGFR <60 ml/min/1.73m^² (Figure 1B–F).

Conclusion

Late-onset ARPKD often presents with hepatobiliary-dominant features, urinary stone disease, variable organ progression, and despite limited nephromegaly, gradual kidney function decline with risk of CKD ≥3 was common. These findings support recognizing late-onset ARPKD as a meaningful clinical subset, warranting long-term monitoring and broader diagnosis in adolescents and adults with unexplained hepatobiliary disease.

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025bf6aaxjq