Charcoal

Chronic Kidney Disease (CKD) and Colorectal Cancer (CRC) share a profound epidemiological link, supported by Mendelian randomization studies suggesting causality. This review articulates a refined Gut-Kidney Axis, focusing on the pathophysiology of indole-derived uremic toxins. CKD-induced dysbiosis drives hepatic synthesis and systemic accumulation of indoxyl sulfate, which is proposed to promote carcinogenesis via Aryl Hydrocarbon Receptor (AhR) and Akt signaling, ultimately upregulating c-Myc and EGFR. We propose a two-compartment model: while systemic indoxyl sulfate reflects the total gut indole pool (mainly from planktonic bacteria), adherent bacteria like Fusobacterium nucleatum may create high-concentration indole hotspots within the tumor microenvironment. Clinically, we advocate for protein-independent DNA methylation biomarkers (SEPT9, SDC2) to avoid renal confounding. Furthermore, we propose a novel diagnostic panel integrating serum indoxyl sulfate (systemic load) and urinary indoxyl sulfate (gut production) to guide therapy. Therapeutically, targeting upstream drivers (AhR/Akt) may bypass resistance to anti-EGFR therapies in KRAS-mutated tumors. We also discuss the repurposing of the oral adsorbent AST-120 and emerging bacteriophage therapies as strategies to disrupt this oncogenic axis. This review offers a comprehensive framework for stratified management of CKD-associated CRC.

To examine the effects of the oral uremic toxin absorbent AST-120 on the concentration of free and protein-bound indoxyl sulphate (IS) and to assess the effects of serum albumin in end-stage kidney disease (ESKD) patients undergoing hemodialysis.

The study enrolled 37 ESKD patients who initiated hemodialysis at the Shirasagi Hospital. Serum free and bound IS concentrations were measured before the first of 4 hemodialysis sessions and after the last hemodialysis 7 days later. The cohort contained a subgroup of patients in whom AST-120 treatment (6 g/day) was discontinued immediately prior to the first hemodialysis and a subgroup not treated with AST-120. Clinical characteristics were obtained from electronic medical records.

Discontinuation in AST-120 treatment prior to dialysis resulted in marked but highly variable increases in IS concentrations, measured 7 days later, where the efficiency of dialysis of IS was dependent on the serum albumin concentration.

The observation that the percentage change in IS concentration was significantly higher after discontinuation of AST-120 compared to those not receiving AST-120 was unexpected as was the finding of a high inter-patient variability in IS concentrations before and after hemodialysis. The effects of a discontinuation in AST-120 administration can be interpreted as a rebound in the systemic absorption of indole precursors, but the source of variability in IS concentrations was unclear. Although there are important limitations in this investigation, the report presents valid and valuable data on free and albumin-bound IS concentrations during hemodialysis and AST-120 treatment as well as measurements of serum albumin concentrations in the group of largely elderly subjects.

AST-120 in ESKD patients has profound effects on the disposition of IS. There are important sources of variability having a possible marked effect on the concentration of IS in patients with chronic kidney disease. Discontinuing AST-120 treatment before hemodialysis, a practice in Japan to avoid the "off-label" administrations of the agent, will result in high and variable concentrations of uremic toxins such as IS. The consequences of this effect will include progression of the disease and the occurrence of cardiovascular and neurological degeneration.