Kidney Week 2025 Annual Meeting-Therapeutics in AKI: From Bench to Bedside, Including the Burton D. Rose, MD, Endowed Lectureship

Video Transcription

Video Summary

The session opened with Dr. Benjamin Humphreys (Washington University) presenting multi-omic studies of acute kidney injury (AKI) identifying a “failed repair” proximal tubule (PT) state marked by VCAM1, inflammatory/fibrotic programs, and NF-κB/RELA motif activity. Single-nucleus ATAC-seq time courses suggested divergent PT trajectories after injury, with a key branch point around day 2. Human single-cell RNA/ATAC data revealed similar VCAM1+ PT cells even in “healthy” kidneys, resembling scattered tubular cells and increasing with age and CKD. Computational network modeling predicted transcriptional drivers of failed repair, including NFAT5 and CREB5; knockdown studies reduced VCAM1 and inflammatory/ECM genes (NFAT5) or altered proliferation/apoptosis programs (CREB5). Lineage tracing indicated some VCAM1+ cells can revert and contribute to repair. Additional analysis suggested genomic instability (e.g., loss of Y chromosome) enriched in PT-VCAM1 cells, raising therapeutic caution.<br /><br />Dr. Katerina Kapustana (Northwestern) discussed hypoxia and tryptophan metabolism in AKI. Hypoxic or prolyl-hydroxylase inhibitor “preconditioning” protected against ischemia-reperfusion injury and converged on tryptophan–kynurenine pathway metabolites. IDO knockout abolished hypoxia protection, rescued by kynurenine supplementation, implicating kynurenine/derivatives and NAD-related pathways. Hypoxic “post-conditioning” after AKI also improved recovery and induced tryptophan metabolites. 3-hydroxyanthranilic acid reduced ferroptosis and inflammatory CCL2 in tubular cells, linking metabolic signaling to repair and longevity biology.<br /><br />Dr. Giovanni Landoni highlighted a large RCT (~3,500 cardiac surgery patients) showing intravenous amino acid infusion reduced AKI (including AKI stage 3) and appeared cost-effective; he emphasized short, pharmacologic dosing (≤48 hours; ~24 hours if treating established AKI) and practical implementation.<br /><br />The Bertrand Rose lecture by Prof. Marlies Ostermann reviewed remote ischemic preconditioning (RIPC). Mechanistic work suggests humoral/neuronal mediators (e.g., nitric oxide; cell-cycle arrest pathways such as HMGB1-related signaling). Meta-analyses indicate RIPC may reduce AKI after cardiac surgery, particularly with volatile anesthesia; propofol and beta-blockers may blunt effects. Evidence is less supportive in major non-cardiac surgery (including the large PRINCE trial), but a recent angiography study suggested possible benefit.

Asset Subtitle

Moderator(s): Sherry Mansour, Ravindra Mehta

Presentation(s):

Epigenetic Reprogramming in AKI - Benjamin Humphreys
Angiopoietin-Tie2 Signaling in Ischemic AKI - Pinelopi Kapitsinou
Intravenous Amino Acids for Kidney Protection in Cardiac Surgery - Giovanni Landoni
Delayed Remote Ischemic Preconditioning: Extending the Window for AKI Protection: The Burton D. Rose, MD, Endowed Lectureship - Marlies Ostermann

ASN gratefully acknowledges Wolters Kluwer (publisher of UpToDate), the Beth Israel Deaconess Medical Center Department of Medicine Foundation, the Rose Family, and several of Dr. Rose's colleagues for supporting this lectureship.

Meta Tag

Date 11/8/2025

Pathway 1 AKI and Critical Care

Pathway 2 Kidney Biology and Physiology

Session ID 507287

Keywords

acute kidney injury (AKI)

multi-omics

proximal tubule failed repair

VCAM1-positive tubular cells

NF-κB/RELA signaling

single-nucleus ATAC-seq

single-cell RNA-seq

tubular cell trajectories day 2 branch point

NFAT5 transcription factor

CREB5 transcription factor

genomic instability loss of Y chromosome

hypoxia preconditioning

tryptophan–kynurenine pathway

indoleamine 2,3-dioxygenase (IDO)

remote ischemic preconditioning (RIPC)