Kidney Week

Abstract: TH-OR074

Glomerular Sieving Index: Novel Marker of Glomerular Permeability and Disease Progression in Diabetes

Session Information

• Precision Medicine in Diabetic Kidney Disease: Biomarkers, Combination Therapies, and Treatment Response Prediction
  November 06, 2025 | Location: Room 372A, Convention Center
  Abstract Time: 04:40 PM - 04:50 PM

Category: Diabetic Kidney Disease

• 702 Diabetic Kidney Disease: Clinical

Authors

• Wipattanakitcharoen, Aschariya, King Chulalongkorn Memorial Hospital Department of Internal Medicine, Bangkok, Thailand

Aschariya Wipattanakitcharoen, MD

• Jintanapramote, Kavita, Bhumibhol Aduldej Hospital, Directorate of Medical Services, The Royal Thai Air Force, Bangkok, Thailand

Kavita Jintanapramote, MD

• Udomkarnjananun, Suwasin, King Chulalongkorn Memorial Hospital Department of Internal Medicine, Bangkok, Thailand

Suwasin Udomkarnjananun, MD

• Eiam-Ong, Somchai, King Chulalongkorn Memorial Hospital Department of Internal Medicine, Bangkok, Thailand

Somchai Eiam-Ong, MD

• Katavetin, Pisut, King Chulalongkorn Memorial Hospital Department of Internal Medicine, Bangkok, Thailand

Pisut Katavetin, MD

Background

Loss of glycosaminoglycans (GAGs) from the endothelial glycocalyx is a key pathophysiological change in diabetic kidney disease (DKD), leading to increased glomerular solute permeability and hydraulic permeability. We hypothesize that modeling changes in glomerular filtration rate (GFR) and urinary albumin excretion (UAE) due to endothelial GAGs loss will help clarify the relationship between glomerular sieving (S), GFR, and UAE.

Methods

We used an ultrastructural hydrodynamic model of glomerular filtration and a saturable endocytosis model of albumin reabsorption to simulate S, GFR, and UAE across varying endothelial GAG volume fractions.

Results

Our simulations revealed an approximately linear log-log relationship between the S and the UAE/GFR ratio, described by S = 0.0026 (UAE/GFR)^0.1290. Therefore, the expression (UAE/GFR)^0.1290 may serve as a proxy for glomerular sieving and could be referred to as a glomerular sieving index (GSI).

To validate this novel index, we compared the correlation of GSI with key pathological changes in DKD against that of UAE, the current marker of glomerular permeability. Its predictive value for adverse outcomes (sustained eGFR reduction ≥ 50% for ≥ 28 days, eGFR <15 mL/min/1.73 m² for ≥ 28 days, or death) was further assessed in a retrospective cohort of 1,386 individuals with diabetes, followed for a median of 11 years.

GSI demonstrated a higher correlation with glomerular basement membrane width (Pearson r =0.59 vs. 0.43) and mesangial volume (0.60 vs. 0.41) than that of UAE. The GSI outperformed UAE in predicting the primary composite endpoint—sustained eGFR reduction ≥50% for ≥28 days, eGFR <15 mL/min/1.73 m² for ≥28 days, or death—demonstrating a lower Akaike Information Criterion (4120 vs. 4181), lower 10-year Brier score (0.15 vs. 0.16), and a significantly higher C-index (0.662 vs. 0.647, p = 0.016)

Conclusion

GSI more closely reflects structural kidney changes and better predicts adverse outcomes in DKD than UAE, supporting its potential as an alternative marker of glomerular permeability and disease progression.

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.20251xe2gmx2