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Juxtaglomerular apparatus-mediated homeostatic mechanisms: therapeutic implication for chronic kidney disease

Eiji Higashihara1, Takeo Harada2, Hiroshi Fukuhara1

  • 1Department of Urology, Kyorin University School of Medicine, Mitaka, Japan.

Expert Opinion on Pharmacotherapy
|May 22, 2024
PubMed

Insights

The juxtaglomerular apparatus (JGA) mechanism influences how sodium-glucose cotransporter 2 inhibitors (SGLT2is) treat chronic kidney disease (CKD) and how tolvaptan affects autosomal dominant polycystic kidney disease (ADPKD). This understanding may improve kidney disease treatments.

Area of Science:

  • Nephrology
  • Pharmacology
  • Physiology

Background:

  • The juxtaglomerular apparatus (JGA) plays a crucial role in kidney homeostasis.
  • The JGA's function is linked to tubuloglomerular feedback and the renin-angiotensin system.
  • Sodium-glucose cotransporter 2 inhibitors (SGLT2is) and tolvaptan are key drugs in managing kidney diseases.

Purpose of the Study:

  • To explore the JGA-mediated homeostatic mechanism.
  • To assess the relationship between the JGA mechanism and the therapeutic effects of SGLT2is in chronic kidney disease (CKD).
  • To evaluate the potential link between the JGA mechanism and tolvaptan's benefits in autosomal dominant polycystic kidney disease (ADPKD).

Main Methods:

  • Review of clinical trials involving SGLT2is and tolvaptan.
  • Analysis of the JGA-mediated homeostatic mechanism, including tubuloglomerular feedback.
  • Examination of macula densa (MD) signaling in response to sodium load.

Main Results:

  • Increased sodium load to the macula densa (MD) triggers adenosine production, constricting the afferent arteriole (Af-art) to protect glomeruli.
  • MD signaling suppresses renin secretion and enhances sodium excretion, balancing filtration.
  • In advanced CKD, increased MD adenosine production may relax the afferent arteriole (Af-art), maintaining sodium balance at the glomeruli's expense.

Conclusions:

  • The JGA-mediated homeostatic mechanism is central to understanding SGLT2i efficacy in CKD.
  • Tolvaptan's renal benefits in ADPKD may involve JGA-mediated mechanisms due to its action on sodium reabsorption.
  • Further understanding of the JGA mechanism can guide the development of novel pharmacotherapies for kidney diseases.
Abstract

Keywords:
Autosomal dominant polycystic kidney diseasechronic kidney diseaseglomerular filtrationjuxtaglomerular apparatusrenin–angiotensin systemsodium-glucose transporter 2 inhibitortolvaptanvasopressin V2 receptor

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