Kidney Week 2025 Annual Meeting-How to Combat AKI: Control Damage or Promote Repair?

Video Transcription

Video Summary

The session “How to Combat AKI,” moderated by David Basil (Indiana University) and Shana Bradford (Northwestern), featured four talks on mechanisms and potential interventions in acute kidney injury (AKI).<br /><br />Andreas Linkermann (Heidelberg University) focused on regulated cell death in renal tubules, emphasizing “cell death propagation” along tubules and arguing ferroptosis is often the dominant driver in AKI compared with necroptosis or pyroptosis (the latter more relevant to infiltrating immune cells). He presented data from isolated tubule models showing ferroptosis inhibition can halt propagation. He also described a diabetic mouse model (dominant-negative GIP receptor in β-cells) that develops nodular glomerulosclerosis and exhibits markedly increased tubular susceptibility to ferroptosis. Mechanistically, hyperglycemia induces TXNIP, suppressing thioredoxin reductase activity and lowering the ferroptosis threshold; modern ferroptosis inhibitors are being tested for therapeutic benefit.<br /><br />Carolyn Susztak (University of Pennsylvania) discussed how genetic mapping and single-cell atlases identify injured “failed-repair” proximal tubule states that promote inflammation and fibrosis after AKI. She highlighted a GWAS-nominated gene, TET2, where epithelial deletion worsened fibrosis, not primarily through methylation changes but via impaired homologous recombination DNA repair, micronuclei formation, and activation of cytosolic DNA sensing (cGAS–STING). Blocking this pathway reduced fibrosis, suggesting innate nucleic-acid sensing links injury to chronic disease.<br /><br />Zheng Dong (Medical College of Georgia) reviewed “organelle stress” (nucleus, mitochondria, ER, Golgi, stress granules) as coordinated determinants of tubular injury, repair, and progression, emphasizing mitochondrial dynamics/mitophagy and persistent stress responses that sustain inflammation.<br /><br />Shuyoshi Inoue (Nagasaki University) presented optogenetic control of autonomic pathways. Selective stimulation of vagal afferent or efferent fibers, C1 neurons, and renal sympathetic nerves protected against ischemia-reperfusion AKI via neuroimmune mechanisms involving the spleen and cholinergic anti-inflammatory pathways. He also described noninvasive abdominal ultrasound stimulation activating vagal afferents and suppressing systemic inflammation, highlighting translational potential.

Asset Subtitle

Moderator(s): David Basile, Shayna Bradford

Presentation(s):

Targeting Cell Death in AKI - Andreas Linkermann
DNA Damage Repair in AKI - Katalin Susztak
Organelle Stress During AKI - Zheng Dong
Optogenetic Rescue: A Bright Solution for Kidney Injury - Tsuyoshi Inoue

ASN thanks the Japanese Society of Nephrology (JSN) and JSN Ambassador, Dr. Tsuyoshi Inoue.

Meta Tag

Date 11/6/2025

Pathway 1 AKI and Critical Care

Pathway 2 Kidney Biology and Physiology

Session ID 507269

Keywords

acute kidney injury (AKI)

regulated cell death

ferroptosis

cell death propagation

renal tubule injury

TXNIP

thioredoxin reductase

diabetic nephropathy

nodular glomerulosclerosis

failed-repair proximal tubule state

TET2

cGAS–STING pathway

tubulointerstitial fibrosis

mitochondrial dynamics and mitophagy

vagus nerve stimulation