Excisional wound healing is delayed in a murine model of chronic kidney disease

PLoS One. 2013;8(3):e59979. doi: 10.1371/journal.pone.0059979. Epub 2013 Mar 25.

Abstract

Background: Approximately 15% of the United States population suffers from chronic kidney disease (CKD), often demonstrating an associated impairment in wound healing. This study outlines the development of a surgical murine model of CKD in order to investigate the mechanisms underlying this impairment.

Methods: CKD was induced in mice by partial cauterization of one kidney cortex and contralateral nephrectomy, modifying a previously published technique. After a minimum of 6-weeks, splinted, dorsal excisional wounds were created to permit assessment of wound healing parameters. Wounds were harvested on postoperative days (POD) 0, 3, 7, and 14 for histological, immunofluorescent, and quantitative PCR (qPCR).

Results: CKD mice exhibited deranged blood chemistry and hematology profiles, including profound uremia and anemia. Significant decreases in re-epithelialization and granulation tissue deposition rates were found in uremic mice wounds relative to controls. On immunofluorescent analysis, uremic mice demonstrated significant reductions in cellular proliferation (BrdU) and angiogenesis (CD31), with a concurrent increase in inflammation (CD45) as compared to controls. CKD mice also displayed differential expression of wound healing-related genes (VEGF, IL-1β, eNOS, iNOS) on qPCR.

Conclusions: These findings represent the first reported investigation of cutaneous healing in a CKD animal model. Ongoing studies of this significantly delayed wound healing phenotype include the establishment of renal failure model in diabetic strains to study the combined effects of CKD and diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Disease Models, Animal
  • Granulation Tissue / pathology
  • Inflammation / genetics
  • Inflammation / metabolism
  • Inflammation / pathology
  • Kidney Glomerulus / pathology
  • Male
  • Mice
  • Neovascularization, Physiologic
  • Renal Insufficiency, Chronic / genetics
  • Renal Insufficiency, Chronic / metabolism
  • Renal Insufficiency, Chronic / pathology*
  • Time Factors
  • Wound Healing*

Grant support

This work was supported by internal funds within the Division of Plastic Surgery at Northwestern University Feinberg School of Medicine. None of the authors have any financial disclosures or commercial associations that may pose a conflict of interest with any information presented in this manuscript. The funders were involved in study design, data collection and analysis, decision to publish, and preparation of the manuscript.