title: A novel therapeutic effect of statins on nephrogenic diabetes insipidus.
abstract: Statins competitively inhibit hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase, resulting in reduced plasma total and low-density lipoprotein cholesterol levels. Recently, it has been shown that statins exert additional 'pleiotropic' effects by increasing expression levels of the membrane water channels aquaporin 2 (AQP2). AQP2 is localized mainly in the kidney and plays a critical role in determining cellular water content. This additional effect is independent of cholesterol homoeostasis, and depends on depletion of mevalonate-derived intermediates of sterol synthetic pathways, i.e. farnesylpyrophosphate and geranylgeranylpyrophosphate. By up-regulating the expression levels of AQP2, statins increase water reabsorption by the kidney, thus opening up a new avenue in treating patients with nephrogenic diabetes insipidus (NDI), a hereditary disease that yet lacks high-powered and limited side effects therapy. Aspects related to water balance determined by AQP2 in the kidney, as well as standard and novel therapeutic strategies of NDI are discussed.
authors.affiliation: Department of Biomedical Sciences and Human Oncology, Internal Medicine, University Medical School, Bari, Italy.
authors.forename: Leonilde
authors.initials: L
authors.lastname: Bonfrate
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Procino
authors.forename: David Q-H
authors.initials: DQ
authors.lastname: Wang
authors.forename: Maria
authors.initials: M
authors.lastname: Svelto
authors.forename: Piero
authors.initials: P
authors.lastname: Portincasa
mesh_terms: D000818:Animals; D051399:Aquaporin 2 / Q000378:metabolism; D018500:Diabetes Insipidus, Nephrogenic / Q000188:drug therapy*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism
chemical_list: D051399:Aquaporin 2; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: HMG-CoA; apical membrane; aquaporin; cholesterol-lowering drugs; hypercholesterolaemia; kidney; nephrogenic diabetes insipidus; vasopressin; water channels