{
  "abstract": "Introduction Chronic kidney disease (CKD) affects 10–15% of the global population. CKD causes systemic inflammation (marked by elevated levels of C-reactive protein, interleukins and tumour necrosis factor-alpha) and CKD-associated cardiomyopathy characterised by increased left ventricular mass, diastolic and systolic dysfunction, profound cardiac fibrosis and atrial and ventricular arrhythmias. The mechanistic links between CKD induced systemic inflammation and cardiac remodelling are unclear, especially in early CKD stages. Therefore, we propose characterizing a CKD mouse model using an adenine-rich diet to compare structural and functional changes in CKD-related cardiomyopathy between early and late stages, and the link to inflammation and other systemic consequences of CKD.Methods 8–9-week-old C57BL/6 female and male mice were fed a normal chow or 0.15% adenine rich diet, for up to 7-weeks. Following the diet, blood levels of creatinine and urea were measured to assess kidney dysfunction. Inflammatory markers were sent to be analysed through an o-link panel, and urea and creatinine were analysed through IDEXX. Hearts were isolated for ex vivo cardiac electrophysiological testing and stored for future imaging.Results Significant and progressive increase in urea (5-week, p = 0.0053 and 7-week, p <0.0001) and creatinine (5-week, p = 0.0017 and 7-week, p <0.0001) levels were observed between control and adenine-fed mice, reflecting kidney dysfunction, see figure 1 and figure 2. O-link analysis revealed increases in circulating levels of several inflammatory markers, including interleukin-6, tumor necrosis factor-alpha and C-reactive protein. Although heart weights remained comparable between the two groups, histological evaluation revealed a significant increase in cardiac fibrosis across all chambers (p < 0.0001), rising from 1.35% in control mice, to 3.34% in adenine-fed mice. The right atria identified the largest increase in fibrosis, expanding from 2.16% in control mice to 4.16% in adenine-fed mice.Abstract BS47 Figure 1Indicators of kidney damage in adenine-fed mice. A.) Urea levels from normal chow 7-weeks, and adenine-fed mice at 5 and 7-weeks. 1-way ANOVA test results represented by significant values (p=0.0053 and p<0.0001). B.) Creatinine levels from normal chow 7-weeks, and adenine-fed mice at 5 and 7-weeks. 1-way ANOVA test results represented by significant values (p=0.0017 and p <0.0001)Abstract BS47 Figure 2O-link inflammatory and cytokine panel, showing percentage increase or decrease between control mice and adenine-fed miceConclusion The adenine-rich diet induced progressive CKD in this mouse model, which is associated with significant systemic inflammation and early cardiac remodelling characterised by increased fibrosis. Ongoing investigations into electrophysiological changes aim to further elucidate the mechanistic link between CKD-induced inflammation and cardiac dysfunction.",
  "authors": [
    {
      "affiliations": [
        "University of Birmingham, Birmingham, UK"
      ],
      "name": "Katie Tompkins"
    },
    {
      "affiliations": [
        "University of Birmingham, Birmingham, UK"
      ],
      "name": "Abbie Hayes"
    },
    {
      "affiliations": [
        "University of Birmingham, Birmingham, UK"
      ],
      "name": "Katie Bruce"
    },
    {
      "affiliations": [
        "University of Birmingham, Birmingham, UK"
      ],
      "name": "Rowan Hardy"
    },
    {
      "affiliations": [
        "University of Birmingham, Birmingham, UK"
      ],
      "name": "Michael Sagmeister"
    },
    {
      "affiliations": [
        "University of Birmingham, Birmingham, UK"
      ],
      "name": "Jonathan Townend"
    },
    {
      "affiliations": [
        "University of Birmingham, Birmingham, UK"
      ],
      "name": "Katja Gehmlich"
    },
    {
      "affiliations": [
        "University of Birmingham, Birmingham, UK"
      ],
      "name": "Christopher O’Shea"
    },
    {
      "affiliations": [
        "University of Birmingham, Birmingham, UK"
      ],
      "name": "Davor Pavlovic"
    }
  ],
  "title": "BS47 Inflammatory response in a clinically relevant progressive model of chronic kidney disease-associated cardiomyopathy",
  "uid": "7efc2833-59a2-53c0-9053-2a3bf80ade0a"
}