Kidney Week 2025 Annual Meeting-AKI Progression and Resolution: Cellular and Molecular Insights

Video Transcription

Video Summary

This ASN Kidney Week session, “AKI, Progression and Resolution: Cellular and Molecular Insights,” featured multiple talks on mechanisms that determine kidney recovery versus progression to CKD and on systemic consequences of AKI.<br /><br />Sena Zeynep Cetin presented single-cell RNA-seq of urine-derived cells from AKI patients at peak injury and follow-up, showing distinct cellular/endotype patterns: recovery associated with developmental distal tubular signatures and reduced inflammation, while non-recovery resembled CKD with injured tubular states, immune infiltration, and pathway shifts (e.g., oxidative phosphorylation up in non-recovery; inflammatory signaling up in CKD).<br /><br />Vivian Huang described how ischemia-reperfusion induces persistent mitochondrial DNA mutations that worsen AKI-to-CKD transition. Using a Polg “mutator” model, she linked higher mtDNA mutation burden to greater damage and fibrosis, identified suppression of purine metabolism and AK4, and showed adenosine can restore ATP-related protection. Human CKD biopsies and UK Biobank analyses associated mitochondrial mutation burden/heteroplasmy with lower eGFR and future AKI risk.<br /><br />Zhangzi Peng reported TRIM16 as protective in AKI by promoting clearance of damaged lysosomes in tubular cells through K63-linked ubiquitination of the SNARE YKT6, enabling ATG5-independent “lysosome–lysosome” fusion and quality control.<br /><br />Runzi Ni showed macula densa–specific NOS1 deletion exacerbates mild ischemic AKI by enhancing tubuloglomerular feedback, causing severe GFR loss, hypoxia/apoptosis, and early profibrotic signaling; haptoglobin emerged as a severity biomarker, and restoring NOS1β activity via alkalinization was discussed.<br /><br />Li Hong Chen demonstrated diurnal variation in ischemia-reperfusion injury mediated by a proximal tubule BMAL1–REV-ERBα–CSF1 axis that regulates macrophage infiltration; REV-ERBα activation reduced injury.<br /><br />Additional talks linked LILRB3 variants to monocyte-driven inflammation, CpG-ODN preconditioning to septic AKI protection via IL-17/G-CSF and splenic LSK mobilization, gut microbiome–dependent trafficking of intestinal T cells to injured kidney via CXCR6, and kidney-released osteopontin (not uremia) driving hippocampal monocyte recruitment and anxiety-like behavior after AKI via CCL2.

Asset Subtitle

Moderator(s): Craig Brooks, Sarah Huen

Presentation(s):

Single-Cell Transcriptomic Phenotypes of Kidney Recovery and Nonrecovery Following Acute Injury - Sena Cetin
Persistent Injury-Induced Mitochondrial DNA Variants Compromise Kidney Function by Suppressing Nucleotide Biosynthesis - Huihui Huang
TRIM16 Protects Against AKI by Promoting the Clearance of Damaged Lysosomes in Tubular Cells via Ubiquitinating YKT6 - Zhangzhe Peng, Chen Yang
Enhanced Tubuloglomerular Feedback by Specific Deletion of Macula Densa NOS1 Enhances AKI by Activating Inflammatory and Fibrogenic Factors - Runze Ni
Circadian Bmal1/Rev-erbα/CSF-1 Axis in Proximal Tubules Modulates Macrophage-Driven Diurnal Variation in Renal Ischemia-Reperfusion Injury - Lihong Chen
LILRB3 Missense Variants Promote Monocyte-Mediated Inflammation in AKI - Weijia Zhang
Cytosine-Phosphate-Guanine (CpG)-Oligodeoxynucleotides Confer Protection Against Septic AKI by Enhancing LSK Cell Mobilization in the Spleen - Ryutaro Shida
Trafficking of Intestinal Peyer Patches Immune Cells to Kidneys: Novel Mechanism by Which Gut Microbiome Modulates AKI - Shishir Patel
Neuroinflammation and Neurological Dysfunction After AKI Is Driven by Kidney-Released Osteopontin and Not Uremia - Poornima Dilhani Ekanayake Weerasinghe Mudiyanselage

Note: Continuing education credits are not being offered for this session.

Meta Tag

Date 11/6/2025

Pathway 1 AKI and Critical Care

Session ID 519812

Keywords

acute kidney injury (AKI)

AKI-to-CKD transition

kidney recovery vs non-recovery endotypes

urine single-cell RNA sequencing

tubular injury and immune infiltration

mitochondrial DNA mutations and heteroplasmy

Polg mutator model

purine metabolism and adenosine protection

TRIM16-mediated lysosome quality control

K63-linked ubiquitination of YKT6

macula densa NOS1 and tubuloglomerular feedback

circadian BMAL1–REV-ERBα–CSF1 axis

gut microbiome–kidney immune trafficking (CXCR6)