Kidney Res Clin Pract.  2022 May;41(3):275-287. 10.23876/j.krcp.21.279.

Claudins in kidney health and disease

• Jo Ch
• Kim S
• Kim GH

• KMID: 2531756
• DOI: http://doi.org/10.23876/j.krcp.21.279

Abstract

Claudins are strategically located to exert their physiologic actions along with the nephron segments from the glomerulus. Claudin-1 is normally located in the Bowman’s capsule, but its overexpression can reach the podocytes and lead to albuminuria. In the proximal tubule (PT), claudin-2 forms paracellular channels selective for water, Na+, K+, and Ca2+. Claudin-2 gene mutations are associated with hypercalciuria and kidney stones. Claudin-10 has two splice variants, -10a and -10b; Claudin-10a acts as an anion-selective channel in the PT, and claudin-10b functions as a cation-selective pore in the thick ascending limb (TAL). Claudin-16 and claudin-19 mediate paracellular transport of Na+, Ca2+, and Mg2+ in the TAL, where the expression of claudin-3/16/19 and claudin-10b are mutually exclusive. The claudin-16 or -19 mutation causes familial hypomagnesemia with hypercalciuria and nephrocalcinosis. Claudin- 14 polymorphisms have been linked to increased risk of hypercalciuria. Claudin-10b mutations produce HELIX syndrome, which encompasses hypohidrosis, electrolyte imbalance, lacrimal gland dysfunction, ichthyosis, and xerostomia. Hypercalciuria and magnesuria in metabolic acidosis are related to downregulation of PT and TAL claudins. In the TAL, stimulation of calcium-sensing receptors upregulates claudin-14 and negatively acts on the claudin-16/19 complex. Claudin-3 acts as a general barrier to ions in the collecting duct. If this barrier is disturbed, urine acidification might be impaired. Claudin-7 forms a nonselective paracellular channel facilitating Cl– and Na+ reabsorption in the collecting ducts. Claudin-4 and -8 serve as anion channels and mediate paracellular Cl– transport; their upregulation may contribute to pseudohypoaldosteronism II and salt-sensitive hypertension.

Keyword

Claudinopathy; Collecting duct; Electrolytes; Glomerulus; Proximal tubule; Thick ascending limb