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Related Experiment Video

Updated: Jan 22, 2026

A Rapid Method for Modeling a Variable Cycle Engine
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Intrafamilial Variability of ADPKD.

Matthew B Lanktree1,2, Elsa Guiard1,2, Weili Li3

  • 1Division of Nephrology, University Health Network, Toronto, Ontario, Canada.

Kidney International Reports
|July 19, 2019
PubMed
Summary

Autosomal dominant polycystic kidney disease (ADPKD) shows significant kidney disease severity differences within families. This study found intrafamilial discordance in at least 12% of ADPKD families, irrespective of gene mutation.

Keywords:
ADPKDgeneticspolycystic kidney disease

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Area of Science:

  • Nephrology
  • Genetics
  • Epidemiology

Background:

  • Autosomal dominant polycystic kidney disease (ADPKD) is characterized by variable kidney disease severity among affected relatives.
  • Understanding intrafamilial discordance is crucial for comprehending ADPKD progression.

Purpose of the Study:

  • To systematically investigate the prevalence and clinical characteristics of intrafamilial kidney disease severity discordance in a large ADPKD cohort.
  • To identify factors associated with intrafamilial variability in ADPKD.

Main Methods:

  • Analysis of the extended Toronto Genetic Epidemiology Study of Polycystic Kidney Disease (eTGESP) cohort (1390 patients, 612 families).
  • Comprehensive PKD1 and PKD2 mutation screening.
  • Assessment of kidney disease severity using estimated glomerular filtration rate (eGFR) decline, age at end-stage renal disease (ESRD) onset, and Mayo Clinic Imaging Classification (MCIC).
  • Total kidney volume measured by MRI in 500 patients.

Main Results:

  • 20% of patients had mild ADPKD, and 33% had severe ADPKD based on defined criteria.
  • Intrafamilial discordance (mild and severe cases within the same family) was observed in 12% of families (43/371).
  • Discordance frequency was similar across different genes (PKD1, PKD2, no mutation) and mutation types.
  • Discordance was more prevalent in larger families, affecting 30% of those with over 5 affected members.

Conclusions:

  • Significant intrafamilial kidney disease discordance affects at least 12% of ADPKD families.
  • This variability exists regardless of the specific gene mutation or mutation class.
  • Further research into genetic and environmental modifiers is needed to understand ADPKD progression mechanisms.