Genetic diagnosis and treatment of hereditary renal tubular disease with hypokalemia and alkalosis

J Nephrol. 2023 Mar;36(2):575-591. doi: 10.1007/s40620-022-01428-4. Epub 2022 Aug 22.


Renal tubules play an important role in maintaining water, electrolyte, and acid-base balance. Renal tubule dysfunction can cause electrolyte disorders and acid-base imbalance. Clinically, hypokalemic renal tubular disease is the most common tubule disorder. With the development of molecular genetics and gene sequencing technology, hereditary renal tubular diseases have attracted attention, and an increasing number of pathogenic genes related to renal tubular diseases have been discovered and reported. Inherited renal tubular diseases mainly occur due to mutations in genes encoding various specific transporters or ion channels expressed on the tubular epithelial membrane, leading to dysfunctional renal tubular reabsorption, secretion, and excretion. An in-depth understanding of the molecular genetic basis of hereditary renal tubular disease will help to understand the physiological function of renal tubules, the mechanism by which the kidney maintains water, electrolyte, and acid-base balance, and the relationship between the kidney and other systems in the body. Meanwhile, understanding these diseases also improves our understanding of the pathogenesis of hypokalemia, alkalosis and other related diseases and ultimately promotes accurate diagnostics and effective disease treatment. The present review summarizes the most common hereditary renal tubular diseases (Bartter syndrome, Gitelman syndrome, EAST syndrome and Liddle syndrome) characterized by hypokalemia and alkalosis. Further detailed explanations are provided for pathogenic genes and functional proteins, clinical manifestations, intrinsic relationship between genotype and clinical phenotype, diagnostic clues, differential diagnosis, and treatment strategies for these diseases.

Keywords: Bartter syndrome; EAST syndrome; Gitelman syndrome; Hypokalemic metabolic alkalosis; Liddle syndrome.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkalosis* / diagnosis
  • Alkalosis* / genetics
  • Alkalosis* / therapy
  • Bartter Syndrome* / diagnosis
  • Bartter Syndrome* / genetics
  • Bartter Syndrome* / therapy
  • Humans
  • Hypokalemia* / etiology
  • Hypokalemia* / genetics
  • Kidney Diseases* / complications
  • Water


  • Water