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. 2020 Aug 10;236(3):1712–1729. doi: 10.1002/jcp.29997

Table 1.

Classification of Bartter syndromes

NKCC2 dysfunction Genes linked to phenotype Mechanisms of abnormal renal salt handling along the TALH
Primary NKCC2 (SLC12A1) Decreased Na+–K+–Cl− uptake via apical membranea
Secondary ROMK (KCNJ1) Decreased K+ secretion via apical membraneb
CLCNKB Decreased Cl− absorption via basolateral membranec
Barttin (BSND) Decreased Cl− absorption via basolateral membraned
CLCNKA+B Decreased Cl− absorption via basolateral membranee
Na+/K+ ATPase Decreased Na+ absorption from lack of ATPf
Tertiary CaSR Decreased expression/activity of ROMKg
MAGED2 Decreased expression of NKCC2h
UMOD Decreased expression of NKCC2i

Note: At least nine different defects have been associated with the hereditary forms of Bartter syndrome. They are classified here into primary NKCC2 dysfunction, where the defect is in NKCC2 itself, secondary NKCC2 dysfunction, where the defect is in another NKCC2‐dependent ion transport system, and tertiary NKCC2 dysfunction, where the defect is in a protein that regulates NKCC2 expression.

Abbreviations: CaSR, calcium‐sensing receptor; MAGED2, melanoma‐associated antigen D2; NKCC2, Na+–K+–Cl− cotransporter 2; TALH, thick ascending loop of Henle; UMOD, uromodulin (also known as Tamm–Horsfall protein).

a

Simon et al. (1996); Starremans et al. (2003); Vargas‐Poussou et al. (1998).

b

Finer et al. (2003); Peters et al. (2002); Simon et al. (1996).

c

Birkenhager et al. (2001); Kramer, Bergler, Stoelcker, and Waldegger (2008); Schlingmann et al. (2004); Scholl et al. (2006); Simon et al. (1997).

d

Birkenhager et al. (2001); Kramer et al. (2008); Schlingmann et al. (2004); Scholl et al. (2006); Simon et al. (1997).

e

Birkenhager et al. (2001); Kramer et al. (2008); Schlingmann et al. (2004); Scholl et al. (2006).

f

Dimke, Hoenderop, and Bindels (2009); Finsterer and Scorza (2017).

g

Gamba and Friedman (2009); Hebert, Brown, and Harris (1997); Watanabe et al. (2002).

h

Kleta and Bockenhauer (2018); Laghmani et al. (2016).

i

Mutig et al. (2011); Renigunta et al. (2011); Trudu et al. (2013).