Kidney Week 2025 Annual Meeting-Kidney Disease with Diabetes: Translational Science Breakthroughs

Video Transcription

Video Summary

This Kidney Disease with Diabetes Translational Science Breakthroughs session opened with announcements about recording and strict 10-minute talk limits. Presentations focused on new tools and mechanisms in diabetic kidney disease (DKD) and cardiorenal-metabolic (CKM) disease.<br /><br />UTMB/Rush presented SeqStain, a high-plex spatial “-omics” immunofluorescence approach using antibodies linked to fluorescent DNA tags that can be gently removed with DNase, preserving tissue architecture across many staining cycles (>25 markers). They showed complete and even selective de-staining via restriction sites, enabling reference markers for alignment, and demonstrated mapping of immune neighborhoods (mouse spleen) and detailed human kidney compartment markers. In DKD tissue, SeqStain detected reduced epithelial/structural markers and increased inflammatory/vascular markers, though a question raised potential marker non-specificity across cell types.<br /><br />Swansea University reported computational modeling of SGLT2 variants near inhibitor binding sites. Docking and molecular dynamics suggested several SNPs (notably E99 variants and T87A) may alter binding for dapagliflozin/canagliflozin/empagliflozin, but frequencies are unclear and experimental validation is needed.<br /><br />A Netherlands group used a multifactorial CKM mouse model (obesity/diabetes + uninephrectomy + high-fat diet + hypertension) to compare therapies. Dapagliflozin and semaglutide both lowered glucose and slowed GFR decline; semaglutide improved survival, reduced weight, albuminuria, renal fibrosis, and cardiac measures more robustly.<br /><br />Japanese groups discussed salt-loaded diabetic rats showing limited ACE inhibitor response and benefits from mineralocorticoid receptor antagonism (finerenone) plus endothelin receptor antagonism, and another study linking MR activation in macrophages to TRPC5-mediated calcium influx and NLRP3 inflammasome activation, with finerenone reducing inflammation/fibrosis in DKD mice.<br /><br />Additional talks proposed that diabetic mesenchymal stromal cells are intrinsically pro-inflammatory but can be “reset” by healthy MSC secretome, and that early DKD may feature increased angiogenesis correlated with fibrosis and immune proximity (challenging rarefaction-only models). Mount Sinai showed hyperfiltration induces endothelial KLF2, while diabetes/inflammation suppresses it; SGLT2 inhibition restored KLF2 in DKD mice. Finally, a Korean team reported elevated asprosin in DKD; anti-asprosin antibody improved metabolic parameters and kidney injury via AMPK–SIRT1–mTOR signaling, with PTPRD as a candidate renal receptor.

Asset Subtitle

Moderator(s): Paulo Caceres, Thomas Coffman

Presentation(s):

Stratifying Diabetic Kidney Disease Through Spatialomic Analysis with SeqStain - Sowmya Gurusamy Kamaraj, Prathyushasai Machineni
Computational Analysis of Inhibitor Binding in SGLT2 Variants - Aled Lloyd
Treatment with Either SGLT2 Inhibitors or GLP-1 Receptor Agonists Rescues GFR Decline in a Multifactorial Cardiovascular-Kidney-Metabolic Syndrome Mouse Model - Arianne Van Koppen
Additive Antihypertensive and Renoprotective Effects of a Mineralocorticoid Receptor Antagonist Combined with an Endothelin Receptor Type A-Selective Antagonist in Salt-Loaded Spontaneously Diabetic Torii Rats - Takahiro Shirozu
Mineralocorticoid Receptor-TRPC5 Axis Drives Macrophage-Mediated Inflammation in Diabetic Kidney Disease - Masafumi Wada
Optimal Repair of Diabetic Kidney Disease Could Be Facilitated by Repair of Dysfunction Intrinsic to Mesenchymal Stromal Cells (MSCs) from Patients with Diabetes - Christof Westenfelder
Angiogenesis: A Profibrotic Factor in Kidney Disease Progression? - Mohammad Sohail
Regulation of KLF2 Expression in Glomerular Endothelial Cells by Glomerular Hyperfiltration - Fang Zhong
Elucidating Asprosin's Role as an Intracellular Metabolism Regulator in Diabetic Kidney Disease - Yaeni Kim

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

Meta Tag

Date 11/8/2025

Pathway 1 Diabetic Kidney Disease

Session ID 519830

Keywords

diabetic kidney disease (DKD)

cardiorenal-metabolic (CKM) disease

SeqStain high-plex spatial omics

multiplex immunofluorescence DNA-tag antibodies

spatial tissue profiling kidney compartments

SGLT2 variants SNP docking molecular dynamics

SGLT2 inhibitors dapagliflozin canagliflozin empagliflozin

multifactorial CKM mouse model uninephrectomy hypertension high-fat diet

GLP-1 receptor agonist semaglutide renal outcomes

mineralocorticoid receptor antagonism finerenone

endothelin receptor antagonists in DKD

macrophage MR activation TRPC5 calcium influx NLRP3 inflammasome

endothelial KLF2 hyperfiltration and SGLT2i restoration

asprosin anti-asprosin antibody AMPK–SIRT1–mTOR PTPRD receptor