Abstract:

Chronic end-stage renal disease （ESRD） represents a major challenge in modern nephrology. Its progression is closely associated with programmed cell death （PCD）， among which pyroptosis and ferroptosis play core regulatory roles. These PCD processes are regulated not only by genetic and pathological signals but also significantly dependent on nutritional status and metabolic energy supply. Although studies on the “nutrition-PCD-ESRD” axis have been increasing， relevant evidence remains fragmented and mechanistic understanding has not been unified. Accordingly， this review systematically summarized the molecular mechanisms of pyroptosis and ferroptosis in patients with ESRD and maintenance hemodialysis （MHD）. Pyroptosis contributes to irreversible kidney injury through a three-stage pathway： initiation， amplification， and propagation. Ferroptosis is driven by the core axis of iron overload， antioxidant imbalance， and lipid peroxidation amplification. Both pathways are key drivers of irreversible renal damage. This review further focused on the intervention effects of nutrients including zinc， vitamin D， ω-3 polyunsaturated fatty acids， selenium， vitamin E， L-carnitine， and dietary fiber by targeting key nodes of the above PCD pathways. It confirmed that nutritional interventions can delay disease progression through multiple pathways， such as inhibiting inflammasome activation， restoring antioxidant defense， and regulating iron metabolism. Meanwhile， current challenges in precision nutritional therapy were identified， including high patient heterogeneity， insufficient evidence strength， and limitations of single interventions. Future research directions were proposed， such as establishing a PCD-signature-based precise stratification system， developing multi-target synergistic intervention strategies， and strengthening supporting technologies. This review provided mechanistic evidence and translational ideas for nutritional intervention in ESRD/MHD patients， and offered a reference for basic research and clinical strategies.

Key words: ESRD, PCD, pyroptosis, ferroptosis, uremic microenvironment, disease-modifying nutritional strategies