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Updated: Jun 9, 2026
Spectral Karyotyping to Study Chromosome Abnormalities in Humans and Mice with Polycystic Kidney Disease
Published on: February 3, 2012
Microvascular aberrations found in human polycystic kidneys are an early feature in a Pkd1 mutant mouse model
Daniyal J Jafree1,2,3, Charith Perera4, Mary Ball1
1Developmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.
Abstract:
Therapies targeting blood vessels hold promise for autosomal dominant polycystic kidney disease (ADPKD), the most common inherited disorder causing kidney failure. However, the onset and nature of kidney vascular abnormalities in ADPKD are poorly defined. Accordingly, we employed a combination of single-cell transcriptomics; three-dimensional imaging with geometric, topological and fractal analyses; and multimodal magnetic resonance imaging with arterial spin labelling to investigate aberrant microvasculature in ADPKD kidneys. Within human ADPKD kidneys with advanced cystic pathology and excretory failure, we identified a molecularly distinct blood microvascular subpopulation, characterised by impaired angiogenic signalling and metabolic dysfunction, differing from endothelial injury profiles observed in non-cystic human kidney diseases. Next, Pkd1 mutant mouse kidneys were examined postnatally, when cystic pathology is well established, but before excretory failure. An aberrant endothelial subpopulation was also detected, concurrent with reduced cortical blood perfusion. Disorganised kidney cortical microvasculature was also present in Pkd1 mutant mouse fetal kidneys when tubular dilation begins. Thus, aberrant features of cystic kidney vasculature are harmonised between human and mouse ADPKD, supporting early targeting of the vasculature as a strategy to ameliorate ADPKD progression.
Insights
Aberrant blood vessels in autosomal dominant polycystic kidney disease (ADPKD) are identified early, even before kidney failure. Targeting these abnormal kidney vasculature early may help slow ADPKD progression.
Area of Science:
- Nephrology
- Vascular Biology
- Genetics
Background:
- Autosomal dominant polycystic kidney disease (ADPKD) is a leading inherited cause of kidney failure.
- Vascular abnormalities in ADPKD are not well understood, hindering targeted therapies.
- Understanding kidney microvasculature is crucial for developing effective ADPKD treatments.
Purpose of the Study:
- To define the onset and characteristics of aberrant kidney vasculature in ADPKD.
- To investigate molecular and structural changes in ADPKD microvasculature.
- To explore early therapeutic strategies targeting kidney blood vessels in ADPKD.
Main Methods:
- Single-cell transcriptomics to identify distinct endothelial cell populations.
- 3D imaging with geometric, topological, and fractal analyses for microvasculature structure.
- Multimodal MRI with arterial spin labeling to assess kidney blood flow.
- Analysis of human ADPKD kidneys and Pkd1 mutant mouse models (fetal and postnatal).
Main Results:
- A unique blood microvascular subpopulation with impaired angiogenic signaling and metabolic dysfunction was found in human ADPKD kidneys.
- Similar aberrant endothelial subpopulations and reduced cortical blood perfusion were observed in Pkd1 mutant mouse kidneys.
- Disorganized kidney microvasculature was present in fetal Pkd1 mutant kidneys, coinciding with early tubular dilation.
Conclusions:
- Aberrant kidney vasculature features in ADPKD are conserved between humans and mouse models.
- These vascular abnormalities are detectable early in ADPKD development.
- Early targeting of the aberrant vasculature presents a promising strategy to ameliorate ADPKD progression.
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