# Low serum free IL-18 is a novel potential marker for predicting infectious events in patients at dialysis initiation

**Authors:** Takashi Tawara-Iida, Joichi Usui, Itaru Ebihara, Takashi Ishizu, Masaki Kobayashi, Yoshitaka Maeda, Hiroaki Kobayashi, Kunihiro Yamagata, Hideko Nakamura, Hideko Nakamura, Kenji Takada, Koichi Kozaki, Satoshi Iwabuchi, Tadashi Iitsuka, Kenta Nishiki, Hideaki Takasaki, Takashi Takita, Masami Nakajima, Sumiko Honma, Youichi Akai, Genzou Ishizuka, Koichi Issiki, Takako Saito, Hitoshi Iwamoto, Akira Ohishi, Masakazu Ohtsuka, Atsushi Ono, Hidehiko Kashiwabara, Takuro Kanekawa, Naoaki Kanamori, Fumika Kaneda, Hiroshi Kikuchi, Masashi Kubo, Hiromi Kurosawa, Takeshi Shiraishi, Tatsuo Shiigai, Masayoshi Shima, Tokuo Takahashi, Hideki Matsukawa, Minoru Tokoi, Sadao Tsunematsu, Atsushi Tsuruta, Masao Deguchi, Masahiro Hayakawa, Makoto Hiroi, Nobuki Maeda, Takanobu Hoshino, Tetsu Yamaguchi, Kota Yamada, Takashi Ishizu, Atsushi Takeda, Ikuo Takahashi, Takamichi Yuhara, Tadashi Kondo, Syoji Ooba, Yasunobu Ogura, Hisaya Tachibana, Hiroshi Ookawa, Toshihiro Fujii

PMC · DOI: 10.1093/ckj/sfaf094 · 2025-04-09

## TL;DR

Low levels of free IL-18 in dialysis patients may predict a higher risk of severe infections.

## Contribution

Identifies low serum free IL-18 as a novel potential biomarker for predicting infectious events in dialysis patients.

## Key findings

- Low free IL-18 (<6.0 pmol/l) was independently associated with infectious events.
- Total IL-18 and IL-18BP showed no association with infectious events.
- Cumulative incidence of infections was significantly higher in the low free IL-18 group.

## Abstract

Compared to the general population, individuals who are undergoing hemodialysis are at a higher risk of contracting severe infectious diseases, and their mortality rate from infectious diseases is also higher. We investigated the serum free interleukin-18 [free state of interleukin-18 (IL-18)] concentration as a prognostic factor for hemodialysis patients' infection risk.

The Ibaraki Dialysis Initiation Cohort (iDIC) study is a multicenter prospective cohort investigation of patients undergoing a new initiation of dialysis in a local region of Japan. We performed a survival analysis of several events requiring hospitalization and compared the Kaplan–Meier curves of the “low” and “high” serum free IL-18 concentration groups. To adjust for confounding factors, we also performed a Cox proportional hazards analysis.

We analyzed the serum free IL-18 concentration of samples from 295 patients randomly selected from the blood sample bank of the iDIC study. The mean free IL-18 concentration was 8.7 ± 5.3 pmol/l. The cumulative incidence of infectious events was significantly higher in the low free IL-18 group (<6.0 pmol/l, log-rank test P < .01). The Cox proportional hazards analysis revealed that low serum free IL-18 (<6.0 pmol/l) was an independent factor associated with the development of infectious events. Total IL-18 and IL-18BP (binding protein) showed no association with infectious events.

A low serum free IL-18 concentration in the dialysis initiation period is a potential marker for predicting the development of severe infection in these patients.

## Linked entities

- **Proteins:** IL18 (interleukin 18), IL18BP (interleukin 18 binding protein)

## Full-text entities

- **Genes:** IL18 (interleukin 18) [NCBI Gene 3606] {aka IGIF, IL-18, IL-1g, IL1F4}, IL18BP (interleukin 18 binding protein) [NCBI Gene 10068] {aka FVH, IL18BPa}
- **Diseases:** infection (MESH:D007239), infectious diseases (MESH:D003141)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12044333/full.md

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Source: https://tomesphere.com/paper/PMC12044333