Open AccessA novel therapeutic effect of statins on nephrogenic diabetes insipidus
Author(s) -
Bonfrate Leonilde,
Procino Giuseppe,
Wang David Q.H.,
Svelto Maria,
Portincasa Piero
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12422
Subject(s) - aquaporin 2 , nephrogenic diabetes insipidus , reabsorption , endocrinology , medicine , kidney , homeostasis , cholesterol , chemistry , hmg coa reductase , diabetes insipidus , aquaporin , reductase , water channel , biochemistry , enzyme , mechanical engineering , engineering , inlet
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 ( AQP 2). AQP 2 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 AQP 2, 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 AQP 2 in the kidney, as well as standard and novel therapeutic strategies of NDI are discussed.