Endothelial dysfunction and microvascular abnormalities in autosomal dominant polycystic kidney disease

Series of 3D microcomputerized tomography images comparing the renal microvasculature of wild-type and Pkd1RC/RC mice at 1, 6 and 12 months of age. Progressive renal microvascular rarefaction in Pkd1RC/RC

Representative 3D microcomputerized tomography images of the renal microvasculature in wild-type and Pkd1RC/RC mice at 1, 6 and 12 months of age show progressive loss of the intrarenal microvascular network and vascular rarefaction in Pkd1RC/RC kidneys over time.

The lab studies the role of endothelial dysfunction and microvascular remodeling in the progression of autosomal dominant polycystic kidney disease. Endothelial dysfunction is one of the earliest manifestations of vascular injury and may contribute to progressive renal damage before measurable loss of kidney function occurs.

Using preclinical models and translational studies in patients with autosomal dominant polycystic kidney disease, the lab investigates how abnormalities in nitric oxide signaling, oxidative stress and vascular remodeling contribute to microvascular rarefaction and disease progression.

Areas of investigation include:

  • Intrarenal microvascular remodeling and capillary loss.
  • Endothelial dysfunction in early autosomal dominant polycystic kidney disease.
  • Longitudinal assessment of vascular function.
  • Noninvasive imaging of the renal microvasculature.
  • Relationship between vascular dysfunction and kidney structural disease severity.

The lab recently led the first longitudinal study in a slowly progressive, orthologous autosomal dominant polycystic kidney disease model and showed that intrarenal microvascular alterations occur early in preclinical autosomal dominant polycystic kidney disease and evolve over time. Similarly, the lab's collaborative work using ultrasound localization microscopy led to the first clinical study to noninvasively evaluate the intrarenal microvasculature in patients with autosomal dominant polycystic kidney disease.

Ultrasound localization microscopy-derived super-resolution images comparing the intrarenal microvasculature of a person with autosomal dominant polycystic kidney disease and an age- and sex-matched control. The figure includes morphology, bidirectional flow, flow velocity and flow direction maps, demonstrating altered cortical microvascular organization and vascular flow patterns in autosomal dominant polycystic kidney disease compared with the control kidney. Vessel morphology and velocity maps of the native kidney of a person with autosomal dominant polycystic kidney disease and an age-sex matched control

Pictured are representative ultrasound localization microscopy-derived super-resolution images of the intrarenal microvasculature in a person with autosomal dominant polycystic kidney disease (C-D and G-H) and an age- and sex-matched control (A-B and E-F). Morphology (A and C), including bidirectional (B and D), flow velocity (E and G) and flow direction (F and H) maps demonstrate altered cortical microvascular architecture in autosomal dominant polycystic kidney disease.

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