Abstract: FR-PO203

Chronic Kidney Dysfunction Impairs Experimental Arteriovenous Fistula Healing

Session Information

Category: Hypertension

  • 1103 Vascular Biology and Dysfunction

Authors

  • Orii, Makoto, Massachusetts Genaral Hospital, Boston, Massachusetts, United States
  • Cui, Jie, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Jhajj, Harkamal Singh, Massachusetts General Hospital, Boston, Massachusetts, United States
  • McCarthy, Jason, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Jaffer, Farouc Amin, Massachusetts General Hospital, Boston, Massachusetts, United States
Background

Thrombosis and neointimal hyperplasia are major causes of arteriovenous fistula (AVF) failure in chronic kidney disease (CKD) patients. Here, we utilize in vivo molecular imaging characterize fibrin deposition after AVF creation in CKD mice.

Methods

CKD was induced in C57BL/6 mice using daily adenine gavage(50mg/kg). Serial blood sampling was performed to measure the creatinine (Cr) and BUN. Fourteen days after adenine (n=3) or PBS gavage (n=6), AVF were created using an end-to-side internal jugular vein and carotid artery anastomosis. AVF blood flow was measured 15 minutes post-surgery (Transonic). Molecular imaging of fibrin deposition on AVF was enabled using fluorophore-labeled peptide (FTP11-Cym7). On day 7 after AVF creation, a 150 nmol/kg IV bolus of FTP11-Cym7 was administered. Forty-five minutes after FTP11 injection, fibrin deposition was imaged in vivo using epifluorescence microscopy. Mice were then sacrificed at day 14. AVF vein wall thickness area (WTA), vein outflow area (OA), and patent area (PA) were measured using picrosirius red staining. The fibrin target-to-background ratio (TBR) was calculated as mean signal intensity (MSI) of the fistula divided by the MSI of the control vein. Regions-of-interest were defined as areas between the anastomosis and 960μm away from the anastomosis.

Results

The BUN/Cr values on day 14 and 28 after adenine administration were 93±24/1.3±0.4 mg/dl and 94±6/0.6±0.1 mg/dl, respectively (p<0.001 vs. PBS). AVF blood flow immediately after AVF surgery were similar between CKD and PBS groups (1.44±0.25ml/min vs 1.22±0.19 ml/min, p=0.5). The in vivo day 7 fibrin deposition after AVF creation (FTP11-Cym7 TBR) was significantly higher in CKD mice (p<0.0001 vs. PBS mice). The vein WTA, OA, and PA was also significantly lower in CKD group (p<0.0001 vs. PBS).

Conclusion

Compared to non-CKD subjects, CKD impairs AVF healing, as indicated by greater fibrin deposition and reduced outward remodeling.

Funding

  • Other NIH Support