Abstract: FR-PO182

Impaired Cutaneous Wound Healing in a Rodent Model of Uremia

Session Information

  • Mitochondriacs and More
    November 03, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Chronic Kidney Disease (Non-Dialysis)

  • 308 CKD: Mechanisms of Tubulointerstitial Fibrosis

Authors

  • Duraisingham, Sai Krishna, Queen Mary University , London, United Kingdom
  • Kieswich, Julius Edward, Queen Mary University , London, United Kingdom
  • Harwood, Steven Michael, Queen Mary University , London, United Kingdom
  • Yaqoob, Muhammad M., Queen Mary University , London, United Kingdom
Background

Patients with CKD develop a multitude of skin changes associated with the duration and severity of renal failure. Additionally, causative comorbidities such as peripheral vascular disease and diabetes directly impact on wound healing. In clinical practice, poor healing contributes to prolonged hospital stays, a susceptibility to infective complications and significant morbidity, including a considerable negative psychological impact. For these reasons finding methods to assess wound healing in uremia will be valuable.

Methods

We developed a rodent model of excisional wound healing. Animals were maintained in a temperature controlled facility with a 12h light/dark cycle. After 2 weeks acclimatization, 6 week old male Wistar rats were fed a diet of standard rat chow supplemented with 0.75% adenine and given water ad libitum for 4 weeks to establish uremia. Healthy controls were fed standard chow. Survival, growth rate and well-being were monitored during the experimental period. Under inhaled 1.5% Isoflurane anesthesia a 30μl subcutaneous injection of Buprenorphine 0.3mg/ml was administered before creating bilateral 5mm full thickness dorsal punch biopsies with a Stiefel Biopsy Punch. Recovery from anesthesia was observed before returning animals to cages. Measurements of the wounds were taken on subsequent days. At day 3 and 7, half the animals were sacrificed under Ketamine and Xylazine anesthesia. Blood samples obtained by cardiac puncture were centrifuged for plasma and organs were harvested for histology or for protein and RNA analysis. Wounds were excised and bisected, one semicircle section was stored in formalin, the other snap frozen under liquid nitrogen. Experiments were conducted under our UK Home Office license after institutional approval.

Results

This model successfully established a uremic state with no premature deaths, excess bleeding or infected wounds observed. Serum urea was significantly higher in the uremic group at both day 3 and 7 (p<0.01) as was serum creatinine (p<0.02). Percentage of the wound area healed compared to day 0, was significantly greater in the control group at day 3 and day 7 (p<0.02 and p<0.001).

Conclusion

We have developed a novel rodent model with low complication rates to study factors contributing to delayed wound healing in uremia. Moreover, we have demonstrated a delay in healing in the uremic state.