Kidney Week

Abstract: FR-PO0123

A Case Series Highlighting Overlap Between PKD-Spectrum Disease and COL4-Related Nephropathies

Session Information

• Hereditary Glomerular and Tubulointerstitial Kidney Diseases
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1202 Genetic Diseases of the Kidneys: Non-Cystic (Complex and Non-Cystic Monogenic)

Authors

• Abuelsamen, Tamer, University of Utah Health, Salt Lake City, Utah, United States

Tamer Abuelsamen, MD

• Sameh, Ahmed, University of Utah Health, Salt Lake City, Utah, United States

Ahmed Sameh, MD, MBChB

• Ludwig, Micah Joseph, Duke University Hospital, Durham, North Carolina, United States

Micah Joseph Ludwig, MD

• Mekki, Ossama, University of Utah Health, Salt Lake City, Utah, United States

Ossama Mekki, MD

• Al-Rabadi, Laith, University of Utah Health, Salt Lake City, Utah, United States

Laith Al-Rabadi, MD

• Sparks, Matthew A., Duke University Hospital, Durham, North Carolina, United States

Matthew A. Sparks, MD, FASN

Background

Autosomal dominant polycystic kidney disease (ADPKD) and collagen 4 (COL4)-related nephropathies are traditionally considered distinct disorders. Genomic testing increasingly identifies patients harboring variants in both disease spectrums, resulting in accelerated or atypical presentations.

Methods

We analyzed 4 new patients with concurrent PKD-spectrum and COL4A3–A5 genetic variants. A structured literature review identified 7 additional cases, yielding a cohort of 11 patients.Clinical and genetic data defined genotype–phenotype relationships

Results

Variants involved PKD1, GANAB, and IFT140, with COL4A3–A5 mutations distributed across COL4A3 (5/11, 45%), COL4A5 (4/11, 36%), and COL4A4 (2/11, 18%), including truncating, splice-site, missense, and in-frame deletion classes. Five truncating PKD1 variants were identified, including two in the novel cohort, suggesting enrichment of loss-of-function alleles. Phenotypes were classified as PKD-dominant (27%) and mixed (73%), without isolated COL4-dominant presentations.Hematuria occurred in 83%, proteinuria in 75% (nephrotic range in 25%), and sensorineural hearing loss (SNHL) in 50%. Early-onset disease was prominent, with mean age at presentation of 30.7 years, 42% presenting before age 25, and kidney failure in 50%, with cases before age 20. Initial diagnosis was frequently anchored to ADPKD; however glomerular or extrarenal features prompted reconsideration of COL4-related disease. Discordant features included cystic phenotypes with disproportionate proteinuria, hematuria, and SNHL

Conclusion

Kidney cysts may obscure COL4-related nephropathy while hematuria, proteinuria, and extrarenal features may obscure ADPKD. This bidirectional overlap supports broader genomic testing in patients with discordant features. Coexisting ADPKD-spectrum and COL4A3–A5 variants may drive earlier-onset disease, disproportionate proteinuria, and accelerated kidney failure compared with either disorder alone

Figure. Clinical and genetic overlap between PKD-spectrum disease and COL4-related nephropathies in the combined cohort

Funding

• Private Foundation Support