Kidney Week 2025 Annual Meeting-Precision Medicine in Diabetic Kidney Disease: Biomarkers, Combination Therapies, and Treatment Response Prediction

Video Transcription

Video Summary

The transcript summarizes a nephrology session focused on early detection, mechanisms, and treatment response stratification in diabetic kidney disease (DKD), especially in youth-onset type 2 diabetes.<br /><br />A longitudinal Renal AIR/Renal HERITAGE analysis followed obese and youth-onset type 2 diabetes participants into young adulthood. Despite modest improvements in HbA1c and BMI, albuminuria increased (41% elevated at follow-up). Gold-standard measurements showed a rapid transition from hyperfiltration to declining measured GFR and reduced renal plasma flow over ~3 years, alongside MRI evidence of increasing kidney volume (suggesting hypertrophy) and rising kidney R2* (indicating reduced oxygen availability/hypoxia). Broader cohort analyses linked higher R2* with CKD status.<br /><br />A second talk introduced the Glomerular Sieving Index (GSI), derived from physiologic modeling to better reflect glomerular permeability than albuminuria alone, particularly when nephron loss lowers albumin excretion despite persistent permeability. In a 1,386-person cohort, GSI predicted major renal outcomes better than urine albumin excretion and correlated more strongly with histologic changes.<br /><br />Other presentations addressed precision therapy: a proteomic classifier using four proteins identified likely non-responders to canagliflozin in CREDENCE; SGLT2 inhibitors appeared to reverse a curated HIF1A/hypoxia gene regulatory network in human DKD and hypoxic organoids; modeling suggested sodagliflozin could reduce estimated 10-year cardiovascular risk in type 1 diabetes, especially in higher kidney-risk groups.<br /><br />Additional studies examined renal functional reserve as a predictor of SGLT2 “eGFR dip,” reproducibility of dapagliflozin albuminuria response using Bayesian N-of-1 trials, real-world finerenone use showing meaningful UACR reductions with manageable hyperkalemia, and retrospective evidence that triple therapy (RASi+SGLT2i+GLP-1RA) may slow eGFR decline and reduce albuminuria versus mono/dual therapy.

Asset Subtitle

Moderator(s): Christos Argyropoulos, Laura Pyle

Presentation(s):

Trajectory from Glomerular Hyperfiltration to Rapid GFR Decline in Youth with Obesity and Type 2 Diabetes as They Transition to Young Adulthood - Phoom Narongkiatikhun
Glomerular Sieving Index: Novel Marker of Glomerular Permeability and Disease Progression in Diabetes - Aschariya Wipattanakitcharoen
Identifying Nonresponders to SGLT2 Inhibitors in the CREDENCE Trial: Biomarker-Guided Approach for Targeting Alternative Therapies - Sok Cin Tye
SGLT2 Inhibitors Reverse Hypoxia-Inducible Factor (HIF)-1A Regulatory Network Activation in Diabetic Kidney Disease - Jennifer A. Schaub
Cardiovascular Risk Prediction Modelling with Sotagliflozin in Type 1 Diabetes: Analysis of inTandem 1-3 Trials - Vikas Sridhar
Renal Functional Reserve Predicts GFR Response to Empagliflozin but Not Linagliptin or Sulfonylureas in Patients with Type 2 Diabetes - Marcel Muskiet
Reproducibility of Placebo-Corrected Albuminuria Responses to Dapagliflozin in Type 2 Diabetes and CKD: Bayesian N-of-1 Trial Approach - Jelle Beernink
Dosing, Treatment Patterns, Urine Albumin-to-Creatinine Ratio (UACR) Changes, and Safety with Finerenone Treatment in Routine Care: FINE-REAL Interim Analysis - Ricardo Correa-Rotter
Potential of Triple Therapy in Diabetic Kidney Disease - Lean Alkhatib

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

Meta Tag

Date 11/6/2025

Pathway 1 Diabetic Kidney Disease

Session ID 519833

Keywords

diabetic kidney disease (DKD)

youth-onset type 2 diabetes

early detection biomarkers

hyperfiltration to GFR decline

measured GFR (gold-standard)

renal plasma flow reduction

kidney MRI R2*

renal hypoxia and HIF1A signaling

glomerular sieving index (GSI)

albuminuria and UACR

SGLT2 inhibitors (canagliflozin/dapagliflozin/sotagliflozin)

finerenone and hyperkalemia

triple therapy (RASi + SGLT2i + GLP-1RA)