Renin cells are crucial for the regulation of blood pressure and fluid electrolyte homeostasis. We have recently shown that renin cells possess unique chromatin features at regulatory regions throughout the genome that may determine the identity and memory of the renin phenotype. The 3-D structure of chromatin may be equally important in the determination of cell identity and fate. CCCTC-binding factor (Ctcf ) is a highly conserved chromatin organizer that may regulate the renin phenotype by controlling chromatin structure. We found that Ctcf binds at several conserved DNA sites surrounding and within the renin locus, suggesting that Ctcf may regulate the transcriptional activity of renin cells. In fact, deletion of Ctcf in cells of the renin lineage led to decreased endowment of renin-expressing cells accompanied by decreased circulating renin, hypotension, and severe morphological abnormalities of the kidney, including defects in arteriolar branching, and ultimately renal failure. We conclude that control of chromatin architecture by Ctcf is necessary for the appropriate expression of renin, control of renin cell number and structural integrity of the kidney.

Chronic kidney disease (CKD) has emerged as a global public health problem. Although the incidence and prevalence of CKD vary from one country to another, the estimated worldwide prevalence is 8–16%. The complications associated with CKD include progression to end-stage renal disease (ESRD), mineral and bone disorders, anaemia, cognitive decline and elevated all-cause and cardiovascular (CV) mortality. As a result of progressive nephron loss, patients with late-stage CKD are permanently exposed to uraemic toxins. These toxins have been classified into three groups as a function of the molecular mass: small water-soluble molecules, middle molecules and protein-bound uraemic toxins. The compounds can also be classified according to their origin (i.e. microbial or not) or their protein-binding ability. The present review will focus on the best-characterized protein-bound uraemic toxins, namely indoxylsulfate (IS), indole acetic acid (IAA) and p -cresylsulfate (PCS, a cresol metabolite). Recent research suggests that these toxins accelerate the progression of CV disease, kidney disease, bone disorders and neurological complications. Lastly, we review therapeutic approaches that can be used to decrease toxin levels.