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-cr..., Animal models
All animal studies were approved by the Animal Research Committee, University of California, Irvine (UCI) under protocol AUP-21-157. Animals were maintained at the UCI vivarium in accordance with the policies instituted by the American Association for Accreditation of Laboratory Animal Care. Male and female C57Bl/6J mice aged between 8-10 weeks were purchased from the Jackson Laboratory (Bar Harbor, ME) and were randomly assigned to control vs adenine-induced CKD. Mice in adenine groups were fed a 0.2% adenine diet for 18 days, followed by 2 weeks on regular chow and then a second 1-week period on adenine diet to maintain CKD . Age-matched male and female 5/6 nephrectomized mice were purchased from the Jackson Laboratory. The initiation timepoint of uremia was considered to be after 18 days of adenine diet (adenine-CKD model) or 14 days post-surgery (5/6 nephrectomy model). Echocardiography was performed at 5 weeks after uremia induction at age 18 weeks (n=8 per group). Ta..., , # 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

[https://doi.org/10.5061/dryad.zcrjdfnps](https://doi.org/10.5061/dryad.zcrjdfnps)

## Description of the data and file structure

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. Fastq files obtained from sequencing were inspected via FastQC then aligned to the current mouse genome build (mm10) using STAR. Counts matrices were then generated from aligned BAM files using summarizeOverlaps (Genomicfeatures) and differential expression was performed using DESeq2 with false discovery rate (FDR) adjuste...,