# The Impact of Clinical Variables and Dialysis Modality on Kynurenine Pathway Enzymes Expression

## TL;DR

This study examines how kidney failure treatment and clinical factors affect enzymes in the kynurenine pathway, finding that dialysis type influences gene expression.

## Contribution

The study is the first to analyze KYN pathway enzyme gene expression in kidney failure patients undergoing different dialysis modalities.

## Key findings

- Ido, Kat1, and Kmo gene expression does not differ based on comorbidities, vascular access types, or diuresis in KFRT patients.
- HDF-treated patients show lower Kmo gene expression compared to HD-treated patients.
- Gene expression correlates with pre-dialysis metabolite concentrations and reduction ratios.

## Abstract

Chronic kidney disease (CKD) and kidney failure significantly reduce patients’ quality of life and markedly increase cardiovascular risk and overall mortality. Disturbed metabolism of tryptophan (Trp) through kynurenine (KYN) pathway was implicated as an important factor in kidney damage and its complications. However, the expression of genes coding crucial enzymes of KYN pathway was not examined so far. The goal of the present study was to analyze the expression of Ido (indoleamine-2,3-dioxygenase), Kat1 (kynurenine aminotransferase 1), Kat2 (kynurenine aminotransferase 2), and Kmo (kynurenine-3-monooxygenase) genes in patients undergoing kidney failure with kidney replacement therapy (KFRT) treatment with either hemodiafiltration (HDF) or hemodialysis (HD) in relation to selected clinical and dialysis parameters. Our data imply that Ido, Kat1, and Kmo gene expression does not differ between KFRT patients with analyzed comorbidities, vascular access types, or diuresis occurrence. However, Ido and Kmo gene expression correlated with pre-dialysis concentration or reduction ratio (RR) of selected metabolites. Interestingly, patients treated with HDF manifested lower Kmo gene expression in comparison with patients treated by HD. Our study suggests that epigenetic factors do not exert noticeable impact on the KYN pathway enzymes expression in patients with KFRT. The advantageous effect of HDF vs. HD towards the KYN pathway genes expression has potential therapeutic implications, as it may reflect superiority of the former method in KFRT patients.