Hypokalaemic salt-losing tubulopathies: an evolving story

Bartter syndrome, first described in 1962 [1], is a group of closely related hereditary tubulopathies. All variants of the syndrome share several clinical characteristics including renal salt wasting, hypokalaemic metabolic alkalosis, hyperreninaemic hyperaldosteronism with normal blood pressure, and hyperplasia of the juxtaglomerular apparatus [2–4]. All forms of the syndrome are transmitted as autosomal recessive traits. Three distinct clinical phenotypes have been distinguished, including antenatal Bartter syndrome, classic Bartter syndrome and Gitelman syndrome (Table 1). Recently, however, phenotypic overlap has been noted, and additional variants of Bartter syndrome have been described (Table 1, Figure 1), thereby expanding the clinical spectrum of the syndrome and providing further insight into the pathophysiological mechanisms underlying this complex disorder. Over the past decade, the breakthrough in molecular biology and molecular genetics has produced the tools to investigate various forms of Bartter syndrome at the molecular level. As a result, exciting discoveries have been made and the underlying molecular defects in these variants have been defined. The molecular studies of Bartter syndrome have been important not only in clarifying the genetic basis of this tubulopathy, but also in providing new and important insight into the function of specific transport proteins and into the physiology of renal tubular reclamation of solutes. Phenotypes