Abstract：
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
摘要：
■球旁体（JGA）介导的稳态机制与钠-葡萄糖协同转运蛋白2抑制剂（SGLT2is）如何减缓慢性肾脏疾病（CKD）的进展有关，并且可能与托伐普坦如何减缓常染色体显性多囊肾疾病（ADPKD）的肾功能下降有关。
■基于对肾小管肾小球反馈和肾素-血管紧张素系统的研究，假设了JGA介导的稳态机制。我们回顾了SGLT2is和托伐普坦的临床试验，以评估该机制与这些药物之间的关系。
■当钠对黄斑（MD）的负荷增加时，MD增加了腺苷的产生，收缩传入小动脉（Af-art）并保护肾小球。同时,MD信号抑制肾素分泌，增加尿钠排泄，和平衡减少钠过滤。然而,当每个肾单位的钠负荷明显增加时，与先进的CKD一样，MD腺苷产量增加，放松Af-art并以肾小球为代价维持钠稳态。托伐普坦对ADPKD中肾功能的有益作用也可能取决于JGA介导的稳态机制，因为托伐普坦抑制粗大的上行肢体中钠的重吸收。JGA介导的稳态机制调节Af-arts，根据体内平衡的需要收缩到放松。了解这种机制可能有助于药物治疗化合物的开发以及对CKD患者的更好护理。
■基于对肾小管肾小球反馈和肾素-血管紧张素系统的研究，假设了JGA介导的稳态机制。我们回顾了SGLT2is和托伐普坦的临床试验，以评估该机制与这些药物之间的关系。
■当钠对黄斑（MD）的负荷增加时，MD增加了腺苷的产生，收缩传入小动脉（Af-art）并保护肾小球。同时,MD信号抑制肾素分泌，增加尿钠排泄，和平衡减少钠过滤。然而,当每个肾单位的钠负荷明显增加时，与先进的CKD一样，MD腺苷产量增加，放松Af-art并以肾小球为代价维持钠稳态。托伐普坦对ADPKD中肾功能的有益作用也可能取决于JGA介导的稳态机制，因为托伐普坦抑制粗大的上行肢体中钠的重吸收。JGA介导的稳态机制调节Af-arts，根据体内平衡的需要收缩到放松。了解这种机制可能有助于药物治疗化合物的开发以及对CKD患者的更好护理。
