Recent insights into sodium and potassium handling by the aldosterone-sensitive distal nephron: a review of the relevant physiology

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In recent years, our understanding of the physiology of the aldosterone-sensitive distal nephron (ASDN) has greatly advanced thanks to the discovery of the complex with-no-lysine kinase (WNK) signaling and the molecular characterization of the epithelial sodium channel (ENaC). A series of studies, initially focused on rare tubulopathies such as Gordon and Liddle syndromes, eventually led to a partial elucidation of the so-called “aldosterone paradox”, the traditional explanation of the physiology of such disparate conditions such as hyperkalemia and low effective arterial blood volume. The physiology of the ASDN is herein illustrated in light of the novel acquisitions in an easy-to-understand fashion, with the aim of giving the practicing nephrologist a solid “first glance” into this exciting but challenging field. Focus is on ion channels and transporters, their regulation by key hormones such as aldosterone and angiotensin II, and dietary implications.

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Epithelial sodium channel


With no lysine kinase


Aldosterone-sensitive distal nephron


Angiotensin II


Distal convoluted tubule


Connecting tubule


Collecting duct


The late portion of the distal convoluted tubule


Cortical collecting duct


Mineralocorticoid receptor


11β-Hydroxysteroid dehydrogenase type 2


The early portion of the distal convoluted tubule


Sodium chloride cotransporter


Sodium-driven chloride bicarbonate exchanger


Ste20-like proline–alanine rich kinase


Oxidative stress responsive kinase 1


Kelch-like 3


Cullin 3


Neural precursor cell expressed developmentally down-regulated protein 4-2


Renal outer medullary potassium channel


Big potassium channels


Inward-rectifier potassium channel 4.1/5.1


Chloride channel, kidney b


Angiotensin II receptor type 1


Serum and glucocorticoid-regulated kinase 1


Flow-induced potassium secretion


Bartter syndrome


Gitelman syndrome


Thick ascending limb of the loop of Henle


Sodium–potassium–chloride cotransporter 2


Calcium-sensing receptor


Transient receptor potential cation channel subfamily V


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The authors would like to thank Prof. G. Capasso and F. Trepiccione for their useful comments and suggestions.

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Correspondence to Enrico Fiaccadori.

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Rossi, G.M., Regolisti, G., Peyronel, F. et al. Recent insights into sodium and potassium handling by the aldosterone-sensitive distal nephron: a review of the relevant physiology. J Nephrol (2020) doi:10.1007/s40620-019-00684-1

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  • NCC
  • WNK
  • ENaC
  • ROMK
  • ASDN