Chronic kidney disease as an active driver of digestive tract tumors: mechanistic insights and emerging management strategies

Digestive tract tumors (DTT), particularly gastric cancer (GC) and colorectal cancer (CRC), remain among the leading causes of cancer-related morbidity and mortality worldwide. Accumulating epidemiological evidence indicates that patients with chronic kidney disease (CKD) exhibit a significantly increased risk of developing gastrointestinal malignancies and experience worse clinical outcomes. However, the biological mechanisms underlying this association have not been comprehensively synthesized. In this review, we integrate clinical and experimental evidence to delineate how CKD functions as a systemic pro-tumorigenic condition rather than a passive comorbidity. We highlight three interrelated mechanistic axes linking CKD to DTT: (i) persistent systemic inflammation and oxidative stress, (ii) metabolic and endocrine dysregulation driven by uremic toxin accumulation, vitamin D deficiency, and mineral imbalance, and (iii) immune perturbations associated with dialysis modalities and post-transplant immunosuppression. These processes converge to disrupt gastrointestinal barrier integrity, reshape the gut microbiota, impair antitumor immune surveillance, and promote malignant transformation and tumor progression. Importantly, we discuss how CKD-specific interventions, including dialysis strategies, kidney transplantation, dietary management, and modulation of gut microbiota, may further modify gastrointestinal cancer risk. Finally, we propose CKD-oriented preventive and screening strategies for GC and CRC, emphasizing the need for risk stratification based on renal function, proteinuria, and metabolic profiles. By framing CKD as an active driver of gastrointestinal carcinogenesis, this review provides a novel integrative framework that synthesizes interconnected mechanistic pathways and explicitly links them to CKD-specific clinical management strategies, a translational perspective that informs early detection, prevention, and integrated care of DTT in patients with CKD.