# Clinical and Transcriptomic Characteristics of Aortic Stenosis in Patients Undergoing Haemodialysis

## TL;DR

This study finds that patients on hemodialysis with aortic stenosis have unique clinical and genetic features, including immune and bone-related gene activity, which may explain their faster disease progression.

## Contribution

The study identifies novel gene expression patterns and immune cell infiltration in aortic stenosis patients undergoing hemodialysis.

## Key findings

- HD patients showed distinct clinical features like lower BMI and higher inflammatory markers.
- RNA sequencing revealed 35 upregulated and 30 downregulated genes in HD aortic valves.
- Immune response and ossification genes were upregulated, with increased macrophage infiltration in HD patients.

## Abstract

Patients with aortic stenosis (AS) undergoing haemodialysis (HD) often experience more rapid disease progression and poorer prognosis than non-dialysis patients; however, the underlying mechanisms remain unclear. This study aimed to elucidate clinical and molecular differences between HD and non-HD patients with AS, focusing on transcriptomic profiling of resected aortic valves.

We retrospectively analysed 183 patients with severe AS who underwent surgical aortic valve replacement at the University of Yamanashi Hospital from February 2015 to May 2024. Among them, 34 patients were receiving maintenance HD, while 149 were not. Clinical data, echocardiographic findings, and CT-based valve calcification were assessed. RNA sequencing was conducted on aortic valve specimens from 5 HD and 4 non-HD patients. Differentially expressed genes were identified, followed by enrichment analysis and immune cell profiling using CIBERSORTx.

Haemodialysis patients exhibited lower body mass index, a higher prevalence of ischaemic heart disease, elevated C-reactive protein and B-type natriuretic peptide levels, and impaired diastolic function compared to non-HD patients. RNA sequencing revealed 35 upregulated and 30 downregulated genes in HD valves. Enrichment analysis demonstrated that genes involved in immune response and ossification were upregulated in aortic valves from HD patients. CIBERSORTx analysis suggested increased macrophage infiltration. Comparison with public datasets identified HD- associated gene signatures.

Patients with AS on HD exhibited distinct clinical features and gene expression profiles. Upregulation of immune and ossification-related genes, alongside macrophage infiltration, suggests a key role for immune response in AS progression among HD patients.

Chronic kidney disease (CKD) is a major global public health concern, with an estimated global prevalence of 9.1%.