Does hypokalaemia cause nephropathy? An observational study of renal function in patients with Bartter or Gitelman syndrome

QJM. 2011 Nov;104(11):939-44. doi: 10.1093/qjmed/hcr095. Epub 2011 Jun 25.


Background: Hypokalaemic nephropathy has been described in patients with chronic potassium depletion; it is a condition in which proximal tubular vacuolization and interstitial fibrosis occur, resulting in a decline in glomerular filtration rate (GFR) and, in some cases, renal failure. It has been described in patients with chronic diarrhoea, eating disorders, laxative abuse and primary hyperaldosteronism; also occasionally in Bartter syndrome (BS), in which severe hypokalaemia accompanies significant renal sodium and water losses, though rarely in Gitelman syndrome (GS), in which there is equally severe hypokalaemia, but only modest sodium losses.

Aim: We hypothesized that hypokalaemic nephropathy may not be due to potassium depletion per se, but persistently elevated circulating levels of aldosterone, possibly with superimposed episodes of renal hypoperfusion.

Design and methods: We searched UK and European data sets to retrospectively compare serum and urinary parameters in patients with GS and BS.

Results: The patients with GS often had lower serum potassium concentrations than patients with BS, but the BS patients had significantly higher serum creatinine concentrations and lower estimated GFRs (eGFR). BS patients had significantly higher fractional excretions of sodium compared with GS patients, as well as higher plasma renin activities and serum aldosterone levels.

Conclusion: These findings show that in genetically confirmed cases of BS and GS, the degree of hypokalaemia (as an index of chronic potassium depletion) does not correlate with GFR, and that on-going sodium and water losses, and consequent secondary hyperaldosteronism, may play a more important role in the aetiology of hypokalaemic nephropathy.

MeSH terms

  • Adult
  • Aldosterone / blood
  • Bartter Syndrome / complications
  • Bartter Syndrome / physiopathology*
  • Creatinine / blood
  • Female
  • Gitelman Syndrome / complications
  • Gitelman Syndrome / physiopathology*
  • Glomerular Filtration Rate
  • Humans
  • Hypokalemia / complications
  • Hypokalemia / physiopathology*
  • Male
  • Potassium / blood
  • Renin / blood
  • Retrospective Studies
  • Sodium / urine


  • Aldosterone
  • Sodium
  • Creatinine
  • Renin
  • Potassium