Studies on the pathogenesis of hypokalemia in Gitelman's syndrome: role of bicarbonaturia and hypomagnesemia

Am J Nephrol. 1998;18(1):42-9. doi: 10.1159/000013303.


Objective: Hypokalemia and renal potassium (K) wasting are hallmarks of the group of disorders called Bartter's syndrome. The presence of hypomagnesemia and a low rate of excretion of calcium are currently used to characterize a subgroup of these patients as having Gitelman's syndrome (GS) in which the molecular lesion is a defect in the thiazide-sensitive NaCl cotransporter in the distal convoluted tubule. This study was undertaken to examine whether bicarbonaturia or hypomagnesemia exacerbates the kaliuresis in patients with GS.

Methods: Six patients with most of the diagnostic features of GS were examined. To examine the role of bicarbonaturia, the transtubular K concentration gradient (TTKG) was assessed before and after an oral load of NH4Cl which caused the urine pH to be < 6. To evaluate the role of hypomagnesemia, the TTKG was examined after an infusion of enough magnesium (Mg) to achieve normal levels of Mg in plasma for close to 24 h.

Results: The TTKG remained very high even when the pH of the urine was < 6.0. An infusion of Mg caused the TTKG to approach expected values for hypokalemia in 4 of 6 patients. The infusion of Mg was extended in 1 patient who had a sustained high TTKG for 24 h; the TTKG remained elevated for 96 h despite normal plasma Mg levels.

Conclusions: Bicarbonaturia does not play a critical role in maintaining the very high TTKG in these patients. The K wasting in 4 of 6 of these patients could largely be attributed to hypomagnesemia and/or Mg depletion. The plasma aldosterone level tended to be higher in patients who did not respond to the infusion of Mg. Therefore, these patients may not represent a homogeneous group with regard to the pathophysiology of their renal K wasting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Ammonium Chloride / pharmacology
  • Bartter Syndrome / blood
  • Bartter Syndrome / physiopathology*
  • Bartter Syndrome / urine
  • Bicarbonates / urine*
  • Child, Preschool
  • Female
  • Humans
  • Hydrogen-Ion Concentration
  • Hypokalemia / physiopathology*
  • Kidney Tubules / physiopathology
  • Magnesium / blood*
  • Magnesium Sulfate / administration & dosage
  • Magnesium Sulfate / pharmacology
  • Male
  • Potassium / metabolism
  • Syndrome


  • Bicarbonates
  • Ammonium Chloride
  • Magnesium Sulfate
  • Magnesium
  • Potassium