Bartter syndrome

Bartter syndrome is a group of inherited kidney disorders that impair salt reabsorption in the thick ascending limb of the loop of Henle. Salt wasting causes low potassium, metabolic alkalosis, and often increased renin and aldosterone.

Thick ascending limb: The nephron segment that reabsorbs sodium, potassium, and chloride while diluting tubular fluid. Most Bartter forms disrupt transport proteins that normally reclaim salt in this segment.
Nephron: The kidney's microscopic functional unit, comprising a filtering corpuscle and a tubule. Bartter syndrome arises from transport defects in a specific part of the nephron.
Urinary chloride: The concentration of chloride in urine, used to assess renal chloride handling and volume status. Persistently elevated urinary chloride supports ongoing renal salt loss rather than chloride-depleted alkalosis.
Bartter syndrome type 1: A severe Bartter subtype caused by pathogenic variants in SLC12A1, which encodes NKCC2. This subtype directly disrupts the principal sodium-potassium-chloride transporter of the thick ascending limb.
NKCC2: A sodium-potassium-chloride cotransporter on the apical membrane of thick ascending limb cells. Loss of NKCC2 function causes Bartter syndrome type 1.
Loop of Henle: The nephron's U-shaped segment that helps establish the concentration gradient used to concentrate urine. The thick ascending limb affected in Bartter syndrome is part of this loop.
Hypercalciuria: Excessive calcium excretion in urine. It is common in some Bartter subtypes and can contribute to nephrocalcinosis.
Bartter syndrome type 2: A severe Bartter subtype caused by pathogenic variants in KCNJ1, which encodes the ROMK potassium channel. Its channel defect limits potassium recycling required for thick ascending limb salt transport.
ROMK: A potassium channel that recycles potassium into the thick ascending limb's tubular lumen. ROMK defects impair NKCC2 activity and cause Bartter syndrome type 2.
Tubular reabsorption: Movement of water and solutes from kidney tubule fluid back into the blood. Bartter syndrome reduces reabsorption of sodium chloride in the loop of Henle.

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