title: Salt handling in the distal nephron: lessons learned from inherited human disorders.
abstract: The molecular basis of inherited salt-losing tubular disorders with secondary hypokalemia has become much clearer in the past two decades. Two distinct segments along the nephron turned out to be affected, the thick ascending limb of Henle's loop and the distal convoluted tubule, accounting for two major clinical phenotypes, hyperprostaglandin E syndrome and Bartter-Gitelman syndrome. To date, inactivating mutations have been detected in six different genes encoding for proteins involved in renal transepithelial salt transport. Careful examination of genetically defined patients ("human knockouts") allowed us to determine the individual role of a specific protein and its contribution to the overall process of renal salt reabsorption. The recent generation of several genetically engineered mouse models that are deficient in orthologous genes further enabled us to compare the human phenotype with the animal models, revealing some unexpected interspecies differences. As the first line treatment in hyperprostaglandin E syndrome includes cyclooxygenase inhibitors, we propose some hypotheses about the mysterious role of PGE(2) in the etiology of renal salt-losing disorders.
authors.affiliation: MD, Univ. Children's Hospital, Philipps-Univ., Deutschhausstrasse 12, D-35037 Marburg, Germany. seyberth@staff.uni-marburg.de).
authors.forename: Nikola
authors.initials: N
authors.lastname: Jeck
authors.forename: Karl P
authors.initials: KP
authors.lastname: Schlingmann
authors.forename: Stephan C
authors.initials: SC
authors.lastname: Reinalter
authors.forename: Martin
authors.initials: M
authors.lastname: Kömhoff
authors.forename: Melanie
authors.initials: M
authors.lastname: Peters
authors.forename: Siegfried
authors.initials: S
authors.lastname: Waldegger
authors.forename: Hannsjörg W
authors.initials: HW
authors.lastname: Seyberth
mesh_terms: D004232:Diuretics / Q000494:pharmacology; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007674:Kidney Diseases / Q000235:genetics* / Q000503:physiopathology*; D008138:Loop of Henle / Q000378:metabolism; D008297:Male; D009399:Nephrons / Q000502:physiology*; D012492:Salts / Q000378:metabolism
chemical_list: D004232:Diuretics; D012492:Salts