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  • Review Article
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An improved terminology and classification of Bartter-like syndromes

Nature Clinical Practice Nephrology volume 4, pages 560–567 (2008)Cite this article

Abstract

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 β-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.

Key Points

  • The timing and clinical presentation of hypokalemic distal convoluted tubule dysfunction and polyuric loop dysfunction differs markedly; patients with the former become symptomatic during childhood or later, whereas those with the latter can develop life-threatening symptoms in the perinatal period

  • As a consequence of generalized impairment of transcellular salt reabsorption in the distal convoluted tubule, there is a marked phenotypic overlap between the disorders currently classified as Bartter syndrome and Gitelman syndrome

  • Pharmacotyping provides the basis for a new terminology and classification of the various forms of salt-losing tubulopathy that are caused by defects in the distal convoluted tubule or loop of Henle

  • This new and more rational approach should help clinicians to avoid potentially harmful diagnostic and therapeutic experiments, such as treatment with potassium-saving or calcium-saving diuretics, which paralyze any compensatory mechanisms of salt and water homeostasis

  • Although less than ideal, inhibition of renal prostaglandin synthesis by NSAIDs (e.g. indometacin) remains the most appropriate therapeutic option for patients with a severe polyuric loop disorder

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Figure 1: Mechanisms of transcellular and paracellular salt and mineral transport in the distal nephron.

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Author notes

  1. Lazarettgarten 23, 76829 Landau, Germany seyberth@staff.uni-marburg.de

Authors and Affiliations

  1. HW Seyberth is Professor Emeritus of Pediatrics and Former Director of the Center for Pediatric and Adolescent Medicine at Philipps University in Marburg, Germany.,

    Hannsjörg W Seyberth

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Seyberth, H. An improved terminology and classification of Bartter-like syndromes. Nat Rev Nephrol 4, 560–567 (2008). https://doi.org/10.1038/ncpneph0912

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