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

  • Giovanni Maria Rossi
  • Giuseppe Regolisti
  • Francesco Peyronel
  • Enrico FiaccadoriEmail author
Review
  • 45 Downloads

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.

Keywords

NCC WNK ENaC ROMK ASDN 

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

Notes

Acknowledgements

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

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical approval

This article does not contain any studies with animals or human participants performed by any of the authors.

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Copyright information

© Italian Society of Nephrology 2020

Authors and Affiliations

  1. 1.UO Nefrologia, Azienda Ospedaliero-Universitaria ParmaParmaItaly
  2. 2.Dipartimento di Medicina e ChirurgiaUniversità di ParmaParmaItaly

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