This Review outlines a terminology and classification of Bartter-like syndromes that is based on the underlying causes of these inherited
salt-losing tubulopathies and is, therefore, more clinically relevant than the classical definition. Three major types of
salt-losing tubulopathy can be defined: distal convoluted tubule dysfunction leading to
hypokalemia (currently known as Gitelman or
Bartter syndrome), the more-severe condition of polyuric loop dysfunction (often referred to as antenatal Bartter or hyperprostaglandin E syndrome), and the most-severe condition of combined loop and distal convoluted tubule dysfunction (antenatal Bartter or hyperprostaglandin E syndrome with sensorineural
deafness). These three subtypes can each be further subdivided according to the identity of the defective ion transporter or channel: the
sodium-chloride cotransporter NCCT or the
chloride channel ClC-Kb in distal convoluted tubule dysfunction; the
sodium-potassium-chloride cotransporter NKCC2 or the renal outer medullary
potassium channel in loop dysfunction; and the
chloride channels ClC-Ka and ClC-Kb or their beta-subunit Barttin in combined distal convoluted tubule and loop dysfunction. This new classification should help clinicians to better understand the pathophysiology of these syndromes and choose the most appropriate treatment for affected patients, while avoiding potentially harmful diagnostic and therapeutic approaches.