Data from: Cardiac dysfunction in C57Bl/6J mice with chronic kidney disease shows sex-specific effects: Comparison of dietary adenine and 5/6 nephrectomy models

Background Cardiovascular disease (CVD) is the leading cause of death
among patients with chronic kidney disease (CKD). Rodent models are widely
used to study uremic CVD pathophysiology. We compared cardiac function
parameters in male and female animals from 2 established mouse CKD models
and examined associations between gut-derived uremic toxins and
echocardiogram findings. 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 age 17 weeks (5
weeks after CKD induction). Serum creatinine, cystatin C and gut-derived
uremic toxins were analyzed at study termination, and RNA sequencing of
left ventricle tissue was performed and analyzed. Results Markers of
kidney dysfunction were elevated in both CKD models. The gut-derived
uremic toxin indoxyl sulfate (IS) was increased in both CKD models, while
trimethylamine N-oxide (TMAO) was increased in adenine CKD mice and
p-cresyl sulfate (pCS) in nephrectomy animals. Left ventricular volume was
increased in nephrectomy animals. Cardiac output (CO) was decreased in
male CKD animals from both models compared to controls, and ejection
fraction (EF) was decreased in male 5/6 nephrectomy mice. Female controls
had lower stroke volume (SV) and CO than male counterparts. No significant
changes in CO or EF were observed in female CKD groups. Higher serum pCS
and IS positively correlated with increased left ventricular volume;
higher pCS inversely correlated with EF in females but not males.
Transcriptomics of cardiac tissue revealed sex-based variations in matrix
metalloproteinase and mitochondrial pathways associated with cardiac
dysfunction. Conclusions Our work highlights sex differences in cardiac
function and serum chemistries in two established preclinical CKD models.
Gut-derived uremic toxins may significantly impact cardiorenal
pathophysiology in female but not male CKD animals.