Kidney Week

Abstract: TH-PO391

Cerebrovascular Function in Early-Stage Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Session Information

• Genetic Diseases of the Kidneys: Cystic - I
  November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1101 Genetic Diseases of the Kidneys: Cystic

Authors

• Steele, Cortney, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States

Cortney Steele,

• Oh, Ester, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States

Ester Oh,

• Struemph, Taylor, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States

Taylor Struemph,

• Farmer-Bailey, Heather, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States

Heather Farmer-Bailey,

• Gitomer, Berenice Y., University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States

Berenice Y. Gitomer,

• Chonchol, Michel, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States

Michel Chonchol,

• Nowak, Kristen L., University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States

Kristen L. Nowak,

Background

Cerebrovascular dysfunction, characterized by reduced cerebrovascular reactivity, cerebral hypoperfusion, and increased pulsatile flow within the brain precedes the onset of dementia and is linked to cognitive dysfunction. PKD has been described to increase risk of dementia as compared to propensity score matched controls, and intracranial aneurysms are also more prevalent in patients with ADPKD. However, cerebrovascular function has not been previously characterized in patients with ADPKD.

Methods

Using Transcranial Doppler, we compared middle cerebral artery (MCA) blood flow-velocity response to hypercapnia (normalized for blood pressure and end-tidal CO₂; a measure of cerebrovascular reactivity) and MCA pulsatility index (PI; a measure of cerebrovascular stiffness) in patients with early-stage ADPKD vs. age-matched healthy controls. We also administered the NIH cognitive toolbox (cognitive function) and measured carotid-femoral pulse-wave velocity (CFPWV; aortic stiffness).

Results

Fifteen participants with ADPKD (9F, 27±4 yrs [mean±s.d.], estimated glomerular filtration rate [eGFR]: 106±22 ml/min/1.73m²) were compared to 15 healthy controls (8F, 29±4 yrs, eGFR: 107±11 ml/min/1.73m²). MCA PI was unexpectedly lower in ADPKD (0.71±0.07) vs. controls (0.82±0.02 A.U.; p<0.001); however, normalized MCA blood flow-velocity response to hypercapnia did not differ between groups 2.0±1.2 vs. 2.1±0.8 %Δ/mmHg; p=0.85). Lower PI was associated with a lower crystalized composite score, which persisted after adjustment for age, sex, eGFR, and education (β = 0.55, p<0.01); the crystallized composite score (adjusted for education) was lower in ADPKD (109.9±11.7) vs. controls (118.0±8.7; p<0.05). There was no association of PI with CFPWV (which was greater in the ADPKD group), suggesting PI reflects vascular properties other than arterial stiffness in this population (r=0.01, p=0.96).

Conclusion

PI is lower in early-stage ADPKD, with preservation of cerebrovascular reactivity to hypercapnia. Low PI could be a risk factor for aneurysms in APKD, as low MCA PI and carotid PI are associated with the presence of aneurysms in a population of middle-aged/older healthy adults. Follow-up research on this observation is merited.

Funding

• NIDDK Support