Kidney Week

Abstract: SA-PO1169

Cardiac Dysfunction in C57Bl/6J Mice with CKD: Comparison of Dietary Adenine and 5/6 Nephrectomy Models

Session Information

• CKD: Mechanisms - 3
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2303 CKD (Non-Dialysis): Mechanisms

Authors

• Zhao, Yitong, Division of Nephrology, Department of Medicine, University of California-Irvine, Irvine, California, United States

Yitong Zhao, PhD

• Yang, Karen, University of California Riverside School of Medicine, Riverside, California, United States

Karen Yang

• Wu, Hongmei, Division of Nephrology, Department of Medicine, University of California-Irvine, Irvine, California, United States

Hongmei Wu

• Liu, Han, Division of Nephrology, Department of Medicine, University of California-Irvine, Irvine, California, United States

Han Liu, MS

• Velez, Leandro, University of California Irvine Department of Biological Chemistry, Irvine, California, United States

Leandro Velez, PhD

• Kim, Jin Kyung, Division of Cardiology, Department of Medicine, University of California-Irvine, Irvine, California, United States

Jin Kyung Kim, MD, PhD

• Seldin, Marcus, University of California Irvine Department of Biological Chemistry, Irvine, California, United States

Marcus Seldin, PhD

• Lau, Wei Ling, Division of Nephrology, Department of Medicine, University of California-Irvine, Irvine, California, United States

Wei Ling Lau, MD, FASN

Background

Cardiovascular disease (CVD) is the leading cause of death among patients with chronic kidney disease (CKD). Gut-derived uremic toxins contribute to vascular injury and cardiomyopathy in CKD. In this study, we compared echocardiogram parameters between dietary adenine and 5/6 nephrectomy CKD models and examined associations with gut-derived uremic toxins stratified by sex.

Methods

Male and female adult C57Bl/6J mice were randomly assigned to control, adenine-induced CKD and 5/6 nephrectomy CKD groups. Echocardiography was performed on all mice at 5 weeks after CKD induction. Serum creatinine, cystatin C and gut-derived uremic toxins (trimethylamine N-oxide, TMAO; indoxyl sulfate, IS; and p-cresyl sulfate, pCS) were analyzed at study termination. Data was analyzed using two-way ANOVA and Spearman correlation analysis.

Results

Serum markers of kidney dysfunction (creatinine and cystatin C) were significantly elevated in both CKD models. TMAO was significantly increased in adenine CKD mice, IS was elevated in both CKD models, and pCS was increased in the nephrectomy group. Left ventricular volume was increased in nephrectomy animals. Cardiac output (CO) was decreased in male CKD animals from both models compared to male controls, and ejection fraction (EF) was decreased in male 5/6 nephrectomy mice (figure). Female controls had lower CO than male counterparts, and female CKD animals were not significantly different from female controls in terms of CO and EF. In female animals, higher serum pCS and IS were positively correlated with increased left ventricular volume; higher pCS were inversely correlated with EF (r = -0.501, P<0.05). These associations were not seen in male animals.

Conclusion

Our work highlights sex differences in cardiac function and serum toxin levels in two established preclinical CKD models. Gut-derived uremic toxins may impact cardiorenal pathophysiology in female but not male CKD animals.