Gitelman syndrome: consensus and guidance from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Kidney Int. 2017 Jan;91(1):24-33. doi: 10.1016/j.kint.2016.09.046.

Abstract

Gitelman syndrome (GS) is a rare, salt-losing tubulopathy characterized by hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria. The disease is recessively inherited, caused by inactivating mutations in the SLC12A3 gene that encodes the thiazide-sensitive sodium-chloride cotransporter (NCC). GS is usually detected during adolescence or adulthood, either fortuitously or in association with mild or nonspecific symptoms or both. The disease is characterized by high phenotypic variability and a significant reduction in the quality of life, and it may be associated with severe manifestations. GS is usually managed by a liberal salt intake together with oral magnesium and potassium supplements. A general problem in rare diseases is the lack of high quality evidence to inform diagnosis, prognosis, and management. We report here on the current state of knowledge related to the diagnostic evaluation, follow-up, management, and treatment of GS; identify knowledge gaps; and propose a research agenda to substantiate a number of issues related to GS. This expert consensus statement aims to establish an initial framework to enable clinical auditing and thus improve quality control of care.

Keywords: SLC12A3; hypokalemic metabolic alkalosis; hypomagnesemia; salt-losing tubulopathy; thiazide-sensitive sodium-chloride cotransporter.

MeSH terms

  • Angiotensin Receptor Antagonists / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Bartter Syndrome / blood
  • Bartter Syndrome / diagnosis*
  • Bartter Syndrome / genetics
  • Bartter Syndrome / urine
  • Calcium / urine
  • Chloride Channels / genetics
  • Chondrocalcinosis / etiology*
  • Chondrocalcinosis / prevention & control
  • Consensus Development Conferences as Topic
  • Diagnosis, Differential
  • Dietary Supplements*
  • Genetic Testing
  • Gitelman Syndrome / complications
  • Gitelman Syndrome / diagnosis*
  • Gitelman Syndrome / drug therapy*
  • Gitelman Syndrome / genetics
  • Humans
  • Hypokalemia / blood
  • Hypokalemia / genetics
  • Magnesium / administration & dosage
  • Magnesium / blood
  • Magnesium / therapeutic use
  • Mutation
  • Phenotype
  • Potassium / administration & dosage
  • Potassium / blood
  • Potassium / therapeutic use
  • Practice Guidelines as Topic
  • Quality of Life
  • Rare Diseases / genetics
  • Sodium Chloride, Dietary / therapeutic use
  • Solute Carrier Family 12, Member 3 / genetics
  • Ultrasonography

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Anti-Inflammatory Agents, Non-Steroidal
  • CLCNKB protein, human
  • Chloride Channels
  • SLC12A3 protein, human
  • Sodium Chloride, Dietary
  • Solute Carrier Family 12, Member 3
  • Magnesium
  • Potassium
  • Calcium