Claudins in Renal Physiology and Pathology

Abstract

Claudins are integral proteins expressed at the tight junctions of epithelial and endothelial cells. In the mammalian kidney, every tubular segment express a specific set of claudins that give to that segment unique properties regarding permeability and selectivity of the paracellular pathway. So far, 3 claudins (10b, 16 and 19) have been causally traced to rare human syndromes: variants of CLDN10b cause HELIX syndrome and variants of CLDN16 or CLDN19 cause familial hypomagnesemia with hypercalciuria and nephrocalcinosis. The review summarizes our current knowledge on the physiology of mammalian tight junctions and paracellular ion transport, as well as on the role of the 3 above-mentioned claudins in health and disease. Claudin 14, although not having been causally linked to any rare renal disease, is also considered, because available evidence suggests that it may interact with claudin 16. Some single-nucleotide polymorphisms of CLDN14 are associated with urinary calcium excretion and/or kidney stones. For each claudin considered, the pattern of expression, the function and the human syndrome caused by pathogenic variants are described.

Comparison of renal histopathology and gene expression profiles between severe COVID-19 and bacterial sepsis in critically ill patients

“…4d). In the kidney, Claudin-1, Claudin-5 and Occludin have a key role in mediating paracellular permeability to solutes [20,21]. However, the mRNA levels of these molecules in COVID-19 and bacterial sepsis were comparable to control individuals (Fig.…”

Incidental chronic kidney disease in an obese child with high myopia: Answers

“…Although this variant has not been described in the 1000 Genomes database and has a low minor allele frequency of 0.0035 in ExAC, the in silico predictions were damaging by MutationTaster, Sorting Intolerant From Tolerant (SIFT), and Likelihood Ratio Test (LRT). The variant has been mapped to exon 4 and lies in the TM4 domain of the claudin channel [6] (Fig. 1).…”

“…The final pathogenesis resulting in stage 5 CKD includes glomerulosclerosis, interstitial fibrosis, and tubular atrophy [6].…”

“…The progression to CKD in patients with CLDN19 mutations is earlier than that with CLDN16 and they have a poorer kidney survival. The only treatment for the kidney failure is kidney replacement therapy [6,7].…”

Pathophysiological aspects of the thick ascending limb and novel genetic defects: HELIX syndrome and transient antenatal Bartter syndrome

“…The complexes formed by claudins along the cell membranes act primarily as pore or barrier structures, defining permeability and selectivity of the paracellular space and the transepithelial electrical resistance [9]. The claudins 3, 10b, 14, 16, and 19 are heterogeneously expressed in different portions of the TAL [10,11,12]. In the inner stripe of the outer medulla (ISOM), claudin-10b is the only claudin present, whereas in the outer stripe of the outer medulla (OSOM) and in the cortex, claudins have a mosaic pattern of expression with tight junctions expressing either claudin-10b or claudins 3, 16, and 19 [13,14].…”