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

Abstract

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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Abbreviations

ENaC:

Epithelial sodium channel

WNK:

With no lysine kinase

ASDN:

Aldosterone-sensitive distal nephron

AII:

Angiotensin II

DCT:

Distal convoluted tubule

CNT:

Connecting tubule

CD:

Collecting duct

DCT2:

The late portion of the distal convoluted tubule

CCD:

Cortical collecting duct

MR:

Mineralocorticoid receptor

11BHSD2:

11β-Hydroxysteroid dehydrogenase type 2

DCT1:

The early portion of the distal convoluted tubule

NCC:

Sodium chloride cotransporter

NDCBE:

Sodium-driven chloride bicarbonate exchanger

SPAK:

Ste20-like proline–alanine rich kinase

OSR1:

Oxidative stress responsive kinase 1

KLHL3:

Kelch-like 3

CUL3:

Cullin 3

Nedd4-2:

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

ROMK:

Renal outer medullary potassium channel

BK:

Big potassium channels

Kir4.1/5.1:

Inward-rectifier potassium channel 4.1/5.1

CLCNKB:

Chloride channel, kidney b

AT1R:

Angiotensin II receptor type 1

SGK-1:

Serum and glucocorticoid-regulated kinase 1

FIKS:

Flow-induced potassium secretion

BS:

Bartter syndrome

GS:

Gitelman syndrome

TAL:

Thick ascending limb of the loop of Henle

NKCC2:

Sodium–potassium–chloride cotransporter 2

CaSR:

Calcium-sensing receptor

TRPV5:

Transient receptor potential cation channel subfamily V

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Acknowledgements

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 33, 431–445 (2020). https://doi.org/10.1007/s40620-019-00684-1

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Keywords

  • NCC
  • WNK
  • ENaC
  • ROMK
  • ASDN