Kidney Week 2025 Annual Meeting-Renin-Angiotensin System and Kidney Function: Mechanisms, Insights, and Implications

Video Transcription

Video Summary

This session on the renin–angiotensin system (RAS) highlighted how renin-producing juxtaglomerular (JG) cells and ACE2 shape kidney vascular structure, renin release, and responses to injury.<br /><br />Dr. Ariel Gomez described renin cell “plasticity”: during homeostatic threats, vascular smooth muscle–lineage cells can re-express renin, but chronic overstimulation (including genetic deletion of RAS components or long-term RAS blockade) can drive maladaptive fate changes. In mouse models and limited human nephrectomy samples from patients on ARBs, prolonged renin pathway disruption was associated with concentric arteriolar hypertrophy, matrix deposition, vessel obstruction, periglomerular fibrosis, and kidney dysfunction that may appear only after pathology is established. Renin-lineage cells contributed directly to diseased arterioles, and kidneys showed hyperinnervation, potentially driven by renin-cell expression of neurotrophins such as NGF.<br /><br />Dr. Rose Hill presented evidence that the mechanosensitive ion channel Piezo2 is highly expressed in renin cells and links mechanical forces to intracellular calcium signaling. Conditional Piezo2 deletion reduced in vivo calcium oscillations in renin cells, increased renal and plasma renin, raised ACE2 activity, and produced marked hyperfiltration. Blocking the Mas receptor (implicating Ang-(1–7) signaling downstream of ACE2) rescued the elevated GFR. Across volume challenges, Piezo2 acted as a “brake” on renin: impaired renin suppression during hypervolemia and exaggerated induction during hypovolemia.<br /><br />Dr. Daniel Batlle focused on ACE2 biology and therapeutics. Recombinant, truncated ACE2 proteins can be filtered into the kidney, lower Ang II, and improve outcomes in high–Ang II states (including a renin-transgenic model with vascular “onion-skinning” reminiscent of scleroderma renal crisis) and in transplant ischemia-reperfusion injury. Unlike ACE inhibitors, recombinant ACE2 did not raise renin or lower aldosterone in short-term studies.<br /><br />Dr. Suzanne Gurley reviewed ACE2 knockout and kidney cross-transplant data: global ACE2 loss exaggerates Ang II–induced hypertension, but isolating ACE2 loss to kidney alone did not reproduce the full phenotype because soluble ACE2 from outside the kidney can be filtered into urine. Proximal tubule–specific ACE2 deletion caused an early spike in Ang II hypertension and altered sodium-handling pathways (including ENaC regulation), supporting a protective proximal-tubule ACE2 role during Ang II stress, while ACE2 effects may differ across AKI models.

Asset Subtitle

Moderator(s): Jordana Cohen, Mohammad Saleem

Presentation(s):

Fate of Renin Cells in Health and Disease - Roberto Ariel Gomez
Renin Control by Mechanosensors: Role of PIEZO2 - Rose Hill
Angiotensin-Converting Enzyme 2 and Its Role in Kidney Function and Diseases - Daniel Batlle
Angiotensin-Converting Enzyme 2 in Hypertension and Diabetic Kidney Disease - Susan Gurley

Meta Tag

Date 11/6/2025

Pathway 1 Hypertension and Cardiorenal Disorders

Session ID 507274

Keywords

renin–angiotensin system

juxtaglomerular (JG) cells

renin cell plasticity

vascular smooth muscle lineage

RAS blockade

angiotensin receptor blockers (ARBs)

concentric arteriolar hypertrophy

periglomerular fibrosis

kidney hyperinnervation

nerve growth factor (NGF)

Piezo2 mechanosensitive ion channel

intracellular calcium oscillations

ACE2 activity

Ang-(1–7) Mas receptor signaling

recombinant soluble ACE2 therapy