Chronic kidney disease (CKD) has become a prevalent health condition, affecting roughly 14.3 % of people globally (Liu, 2024; Glassock et al., 2017). This disease imposes substantial economic burdens on both individuals and healthcare systems while significantly diminishing patients' quality of life. Nearly all forms of CKD ultimately progress to renal tubulointerstitial fibrosis (He et al., 2025; Zeng et al., 2025b). The underlying molecular pathways driving this fibrotic process remain incompletely characterized. The elucidation of these mechanisms is essential for developing novel treatment approaches.

Growing research indicates that renal tubular epithelial cells (RTECs), the predominant cellular component of kidney tubules, are intimately linked to overall kidney health. These cells serve as critical mediators of CKD pathogenesis, orchestrating interstitial inflammation and fibrotic changes. NLRP3 belongs to the NOD-like receptor family of pattern recognition receptors (Islamuddin and Qin, 2024). Multiple investigations have demonstrated that elevated expression of NLRP3 and caspase-1 correlates with kidney fibrosis in CKD patients (Tian et al., 2023), suggesting that the NLRP3 inflammasome contributes to fibrotic processes. Additional research has documented increased NLRP3 inflammasome activation in unilateral ureteral obstruction (UUO) and 5/6-nephrectomized mouse models (Hung et al., 2024; Liao et al., 2024). Studies have also shown that anti-IL-1β treatment reduces inflammatory responses in lung and serum while ameliorating kidney fibrosis in mice (Guo et al., 2016). Collectively, these findings indicate that the NLRP3 inflammasome drives inflammatory cascades and contributes to early-stage renal fibrosis. Additionally, our research revealed that the NLRP3 inflammasome modulates mitochondrial function and cell death in cisplatin-induced acute kidney injury models (Luo et al., 2022).

IS is a toxin with such a high binding affinity for proteins that approximately 97 % of that in the body is protein-bound (Rocchetti et al., 2021). This protein modification can compromise normal protein function, potentially resulting in cellular metabolism dysfunction. In patients with CKD, accumulated IS can reach concentrations up to 80 times higher than that found in healthy individuals (Pieniazek et al., 2021). IS within the human body originates from tryptophan metabolism through the indolic pathway (Miao et al., 2024b), which produces both IS and indole-3-acetic acid (IAA) (Addi et al., 2018). These metabolic end products and their intermediates, including kynurenine, quinolinic acid, and kynurenic acid, are all categorized as protein-binding uremic toxins (Rocchetti et al., 2021). At high concentrations, IS has been shown to exert pro-inflammatory and pro-oxidative effects, contributing to the development and progression of comorbidities in patients with CKD (Corradi et al., 2024; Miao et al., 2024a). Despite advances in current therapies, there remains a critical need for safe and effective interventions that can halt or reverse renal damage (Zhao et al., 2024). Recent attention has turned to CH, a hydrogen-enriched coral material with potent antioxidant and anti-inflammatory properties, as a potential renal-protective agent. The incorporation of hydrogen into hemodialysis solutions has been shown to reduce plasma levels of pro-inflammatory markers in hemodialysis patients (Iida et al., 2016) and hepatoprotective effects in alcoholic mice (Wu et al., 2022), suggesting its therapeutic significance for fiborsis disease. Therefore, this study aimed to elucidate the cellular mechanisms by which CH confers protection against renal injury, with a focus on its effects on oxidative stress and the NLRP3 inflammasome pathway in vitro and in vivo.