Juxtaglomerular apparatus-mediated homeostatic mechanisms: therapeutic implication for chronic kidney disease.
| Autor: | Higashihara E; Department of Urology, Kyorin University School of Medicine, Mitaka, Japan., Harada T; Department of Renal and Cardiovascular Research, Otsuka Pharmaceutical Co. Ltd, Tokushima, Japan., Fukuhara H; Department of Urology, Kyorin University School of Medicine, Mitaka, Japan. |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | Expert opinion on pharmacotherapy [Expert Opin Pharmacother] 2024 May; Vol. 25 (7), pp. 819-832. Date of Electronic Publication: 2024 May 22. |
| DOI: | 10.1080/14656566.2024.2357188 |
| Abstrakt: | Introduction: Juxtaglomerular apparatus (JGA)-mediated homeostatic mechanism links to how sodium-glucose cotransporter 2 inhibitors (SGLT2is) slow progression of chronic kidney disease (CKD) and may link to how tolvaptan slows renal function decline in autosomal dominant polycystic kidney disease (ADPKD). Area Covered: JGA-mediated homeostatic mechanism has been hypothesized based on investigations of tubuloglomerular feedback and renin-angiotensin system. We reviewed clinical trials of SGLT2is and tolvaptan to assess the relationship between this mechanism and these drugs. Expert Opinion: When sodium load to macula densa (MD) increases, MD increases adenosine production, constricting afferent arteriole (Af-art) and protecting glomeruli. Concurrently, MD signaling suppresses renin secretion, increases urinary sodium excretion, and counterbalances reduced sodium filtration. However, when there is marked increase in sodium load per-nephron, as in advanced CKD, MD adenosine production increases, relaxing Af-art and maintaining sodium homeostasis at the expense of glomeruli. The beneficial effects of tolvaptan on renal function in ADPKD may also depend on the JGA-mediated homeostatic mechanisms since tolvaptan inhibits sodium reabsorption in the thick ascending limb.The JGA-mediated homeostatic mechanism regulates Af-arts, constricting to relaxing according to homeostatic needs. Understanding this mechanism may contribute to the development of pharmacotherapeutic compounds and better care for patients with CKD. |
| Databáze: | MEDLINE |
| Externí odkaz: |
|