Pathophysiologic approach in genetic hypokalemia: An update

Ann Endocrinol (Paris). 2023 Apr;84(2):298-307. doi: 10.1016/j.ando.2022.11.005. Epub 2023 Jan 10.

Abstract

The pathophysiology of genetic hypokalemia is close to that of non-genetic hypokalemia. New molecular pathways physiologically involved in renal and extrarenal potassium homeostasis have been highlighted. A physiological approach to diagnosis is illustrated here, with 6 cases. Mechanisms generating and sustaining of hypokalemia are discussed. After excluding acute shift of extracellular potassium to the intracellular compartment, related to hypokalemic periodic paralysis, inappropriate kaliuresis (>40mmol/24h) concomitant to hypokalemia indicates renal potassium wasting. Clinical analysis distinguishes hypertension-associated hypokalemia, due to hypermineralocorticism or related disorders. Genetic hypertensive hypokalemia is rare. It includes familial hyperaldosteronism, Liddle syndrome, apparent mineralocorticoid excess,11beta hydroxylase deficiency and Geller syndrome. In case of normo- or hypo-tensive hypokalemia, two etiologies are to be considered: chloride depletion or salt-wasting tubulopathy. Diarrhea chlorea is a rare disease responsible for intestinal chloride depletion. Due to the severity of hypokalemic metabolic alkalosis, this disease can be misdiagnosed as pseudo-Bartter syndrome. Gitelman syndrome is the most frequent cause of genetic hypokalemia. It typically associates renal sodium and potassium wasting, hypomagnesemia, conserved chloride excretion (>40mmol/24h), and low-range calcium excretion (urinary Ca/creatinine ratio<0.20mmol/mmol). Systematic analysis of hydroelectrolytic disorder and dynamic hormonal investigation optimizes indications for and orientation of genotyping of hereditary salt-losing tubulopathy.

Keywords: Chloride depletion; Hypermineralocorticism; Hypokalemia; Kidney; Salt-wasting tubulopathy.

Publication types

  • Review

MeSH terms

  • Bartter Syndrome* / complications
  • Bartter Syndrome* / diagnosis
  • Bartter Syndrome* / genetics
  • Chlorides / urine
  • Humans
  • Hyperaldosteronism* / complications
  • Hyperaldosteronism* / diagnosis
  • Hyperaldosteronism* / genetics
  • Hypertension* / complications
  • Hypokalemia* / etiology
  • Hypokalemia* / genetics
  • Potassium

Substances

  • Chlorides
  • Potassium