Kidney Week

Abstract: FR-PO500

Impact of CKD on Arteriovenous Fistula Remodeling: Studies in a Murine Model of Autosomal Dominant Polycystic Kidney Disease

Session Information

• Dialysis Vascular Access
  October 25, 2024 | Location: Exhibit Hall, 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

Suzanne Laboyrie, MSc

• Peters, Dorien J.M., Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands

Dorien J.M. Peters, PhD

• Bijkerk, Roel, Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands

Roel Bijkerk, PhD

• de Klerk, Juliette A., Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands

Juliette A. de Klerk

• de Vries, Margreet R., Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands

Margreet R. de Vries, PhD

• Rotmans, Joris I., Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands

Joris I. Rotmans, MD, PhD

Background

The arteriovenous fistula (AVF) is the gold standard for hemodialysis vascular access, although inadequate vascular remodelling and intimal hyperplasia pose a major limitation. We utilised an autosomal dominant polycystic kidney disease (ADPKD) model, the most common hereditary cause of chronic kidney disease (CKD), to study the effect of CKD on AVFs. We hypothesized that CKD accelerates AVF failure.

Methods

Jugular-carotid AVFs were created in adult B6OlaPkd1^nl/nl (ADPKD) mice and B6OlaPkd1^+/+ litter mates. AVFs were harvested seven days post-surgery for bulk mRNA sequencing or three weeks post-surgery for histological analysis. We performed weekly AVF flow measurements using doppler ultrasound and assessed kidney morphology and function by histology and blood urea analysis. Blood pressure was measured using a tail cuff, before and six days after AVF-surgery. Longitudinal flow data was analysed using Mixed-effects model, histological data using the Mann-Whitney U test.

Results

Pkd1^nl/nl mice developed cystic kidneys and elevated blood urea levels (8.7 ± 2.8 mmol/L versus 24.0 ± 3.8 mmol/L) and higher mean arterial blood pressure (92 versus 113). AVF flow in Pkd1^nl/nl mice was consistently higher post-AVF creation (1.9-fold difference, p<0.001), with a 50% reduction in intimal hyperplasia and 30% increase in luminal AVF volume. RNA sequencing showed altered regulation of extracellular matrix in the venous ADPKD AVF, with reduced collagen deposition in the venous outflow tract.

Conclusion

Pkd1^nl/nl mice are a suitable model to study AVF remodeling in a CKD setting, resulting in enhanced luminal volume and higher AVF flow when compared to normotensive mice with healthy renal function.