The colon: an overlooked site for therapeutics in dialysis patients

Abstract

Morbidity and mortality related to chronic kidney disease remain unacceptably high, despite tremendous progress in its prevention and treatment. In an ongoing quest to improve outcome in chronic kidney disease patients, the colon might be an appealing, but largely underexplored, therapeutic target. A clear bi-directional functional relationship exists between the colon and kidney, also referred as to the colo-renal axis. Uremia has an important impact on the colonic microbiome. The microbiome, in turn, is an important source of uremic toxins, with p-cresyl sulfate and indoxyl sulfate as important prototypes. These co-metabolites accumulate in the face of a falling kidney function, and may accelerate the progression of renal and cardiovascular disease. Several therapeutic interventions, including prebiotics and adsorbants, specifically target these colon-derived uremic toxins originating from bacterial metabolism. As kidney function declines, the colon also gains importance in the homeostasis and disposal of potassium and oxalate. Their colonic secretion may be increased by drugs increasing the expression of cAMP and by probiotics (e.g., Oxalobacter formigenes).