REN and chronic kidney disease: For instance, the gut microbial metabolites p-cresyl sulfate and indoxyl sulfate accumulation in the circulation results in increased intestinal permeability [15], and the systemic inflammation in blood vessels, endothelial dysfunction [44], insulin resistance [45], and activation of the renin–angiotensin–aldosterone system [46], may induce or aggravate the progress of CKD.