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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The authors would like to thank Prof. G. Capasso and F. Trepiccione for their useful comments and suggestions.
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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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DOI: https://doi.org/10.1007/s40620-019-00684-1