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Kidney Week

Abstract: FR-PO493

Autosomal Dominant Polycystic Kidney Disease Results in Increased Flow in Murine Arteriovenous Fistulas

Session Information

  • Dialysis: Vascular Access
    November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Dialysis

  • 803 Dialysis: Vascular Access

Authors

  • Laboyrie, Suzanne, Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands
  • Peters, Dorien J.M., Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands
  • Bijkerk, Roel, Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands
  • De vries, Margreet R., Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands
  • Rotmans, Joris I., Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands
Background

Autosomal dominant polycystic kidney disease (ADPKD) is a renotubular disease caused by mutations in the PKD1-gene. ADPKD is the most common monogenic kidney disorder, affecting 10% of end-stage kidney disease (ESKD) patients. The arteriovenous fistula (AVF) is the gold standard of hemodialysis vascular access, although non-maturation due to inadequate vascular remodeling is a major limitation of these conduits. Polycystins are expressed in endothelial and vascular smooth muscle cells, and involved in production of extracellular matrix supporting the vessel wall and mechanosensation. In the present study, we investigated whether reduced expression of Pkd1 impacts vascular remodeling in a murine model of AVF failure.

Methods

Unilateral jugular-carotid AVFs were created in adult B6OlaPkd1nl/nl mice and wild-type litter mates. Blood pressure was measured using a tail cuff, before and six days after AVF-surgery. Flow volume was measured weekly over three weeks post-AVF creation using doppler ultrasound. After three weeks, the mice were sacrificed and AVFs were used for histological analysis and collagen analysis through multiphoton microscopy. Longitudinal flow data was analyzed using Mixed-effects model, histological data using the Mann-Whitney U test.

Results

B6OlaPkd1nl/nl mice show signs of renal failure, with cystic kidneys and elevated blood urea levels throughout the study. Pkd1nl/nl mice had elevated mean arterial blood pressure at both timepoints compared to WT mice (1.2 and 1.3 fold increase in ADPKD mice). Whereas arterial flow was comparable in both groups before surgery, AVF flow in Pkd1nl/nl mice was consistently higher post-AVF creation (1.9 fold difference, p=0.0002, at all time points). There was no difference in luminal area between the two groups, nor aneurysm formation in the afferent artery. Histological analysis revealed a reduction of collagen deposition in the venous outflow tract in Pkd1nl/nl mice at 21 days post-surgery.

Conclusion

AVFs in mice with ADPKD are characterized by a higher flow and reduced collagen deposition in the venous outflow tract, when compared to wild type mice. Clinical studies should reveal if ADPKD patients have better primary patency rates of their AVFs compared to patients with other causes of ESKD.