Kidney Volume and Molecular Processes are Dynamic in ADPKD

Area of Science:

• Nephrology
• Genetics
• Molecular Biology

Background:

• Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by cyst formation in the kidneys.
• While initial cystogenesis is understood, mechanisms driving ADPKD progression and disease timing remain unclear.
• Understanding these dynamics is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the dynamic nature of kidney biological processes in ADPKD progression.
• To compare disease progression in mouse models with human ADPKD phenotypes.
• To identify potential therapeutic targets and biomarkers for ADPKD.

Main Methods:

• Longitudinal analysis of kidney volume and function in human ADPKD cohorts and Pkd1RC/RC mice.
• Transcriptomic profiling (mRNA-seq) of Pkd1RC/RC mouse kidneys at various disease stages.
• Comparison of mouse model data with existing ADPKD models and human ADPKD data.

Main Results:

• Kidney volume increases in most ADPKD patients, with varying growth rates by class and age.
• Pkd1RC/RC mouse kidney changes correlate with human Class 1C ADPKD progression.
• Kidney transcriptomic profiles in Pkd1RC/RC mice evolve dynamically and share similarities with other ADPKD models and human ADPKD.

Conclusions:

• ADPKD kidney phenotypes are highly dynamic throughout disease progression.
• Different therapeutic strategies may be required for distinct ADPKD disease stages.
• Identified pathways offer potential for biomarker discovery in human ADPKD.