The Use of an Adenine Diet to Induce Uremic Cardiac Hypertrophy in Mice

Over 90% of patients with chronic kidney disease (CKD) will develop cardiac hypertrophy and approximately half of them will die from cardiovascular disease. Recently, our lab and others have shown that uremic toxins like fibroblast growth factor 23 can directly induce pathological cardiac hypertrophy. While the understanding of the mechanisms responsible for cardiac hypertrophy in uremia is improving, there is a strong need to establish a simple, non‐surgical, and reproducible mouse model of uremic cardiac hypertrophy. An adenine diet has been shown to cause nephropathy and uremia; however, the link between ingestion of adenine and uremic cardiac hypertrophy has not been established. The objective of the present study was to develop a mouse model of dietary adenine‐induced uremia that results in cardiac hypertrophy. Thirty CD1 mice were randomly divided into two groups and fed for 12 weeks: 1) a control group (CON, n=15) fed standard feed, and 2) an adenine (0.2–0.15%) diet intervention group (AD, n=15). The percentage of adenine was adjusted weekly based on temporal assessments of blood urea nitrogen (BUN) to ensure initiation and maintenance of renal injury. Throughout the protocol, the BUN in AD mice was significantly elevated (~80 mg/dl) compared to that of the controls (~30 mg/dl). Post‐intervention, serum levels of BUN (+118%), creatinine (+72%), and phosphate (+107%) were significantly higher in the AD mice. Kidney mass/body mass ratio was significantly lower (−38%) in AD mice, suggesting renal atrophy. The AD mice also had increased heart mass/body mass ratio (+25%) and increased ventricular wall thickness, consistent with hypertrophy. Our data suggests that over 12 weeks, the induction of uremia in the AD group resulted in cardiac hypertrophy. Adenine diet fed mice may be a suitable model to study novel therapeutic treatments to prevent or treat the development of cardiac hypertrophy during uremia. Support or Funding Information University of Memphis Faculty Research Grant to CDT; Honors Summer Research Fellowship, University of Memphis Helen Hardin Honors Program to EMA