The gut-renal axis: link between plasma levels of intestinally generated uraemic toxins and gut microbiome profiles in consecutive stages of chronic kidney disease.

Chronic kidney disease (CKD) is characterised by the accumulation of a myriad of uraemic retention compounds. Cardiovascular disease (CVD) is the major cause of death in CKD patients. Many pathophysiological effects of uraemic retention compounds on cell types of the cardio-vascular system have been demonstrated over the past decade, hence the name "uraemic toxins". Many of these compounds indicated as most toxic by in vitro, in vivo and clinical association (phenolic and indolic compounds) are generated in the colon and are very difficult to remove by dialysis therapy. For early stage prevention of CVD in CKD and in addition to dialysis therapy at the end stage, an important alternative strategy could thus target a decrease in the primary generation of these toxins. To reach this goal, the current project envisages to link the composition and stability of the intestinal microbiome in CKD patients to plasma levels of protein-bound uraemic toxins such as pcresyl sulfate and indoxyl sulfate in CKD patients. This will be achieved through a series of comparative analyses (a) between CKD patients and healthy controls, (b) during different stages of the disease (i.e. CKD1-5) and (c) between CKD5D patients either on haemo- or peritoneal dialysis. The ultimate goal of this project is to reveal measures to alter the intestinal generation, resulting in lowering circulating levels of these uraemic toxins, aiming at decreasing cardiovascular morbidity and mortality in CKD patients.