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Updated: Mar 9, 2026

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Assessment of urinary microparticles in normotensive patients with type 1 diabetes
Yuliya Lytvyn1, Fengxia Xiao2, Christopher R J Kennedy2
1Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
Aims/Hypothesis:
Assessment of urinary extracellular vesicles including exosomes and microparticles (MPs) is an emerging approach for non-invasive detection of renal injury. We have previously reported that podocyte-derived MPs are increased in diabetic mice in advance of albuminuria. Here, we hypothesised that type 1 diabetes and acute hyperglycaemia would increase urinary podocyte MP levels in uncomplicated diabetes.
Methods:
In this post hoc exploratory analysis, we examined archived urine samples from normoalbuminuric patients with uncomplicated type 1 diabetes studied under clamped euglycaemia and hyperglycaemia and compared with healthy controls. Urinary vesicles were assessed by electron microscopy and nanoparticle tracking while podocyte MPs were assessed by flow cytometry.
Results:
Neither vesicle size nor total number were significantly altered in type 1 diabetes or acute hyperglycaemia. By contrast, urinary podocyte MP levels were higher in type 1 diabetes (0.47 [0.00-3.42] MPs/μmol creatinine [Cr]) compared with healthy controls (0.00 [0.00-0.00] MPs/μmol Cr, p < 0.05) and increased under hyperglycaemic clamp (0.36 [0.00-4.15] MPs/μmol Cr during euglycaemia vs 2.70 [0.00-15.91] MPs/μmol Cr during hyperglycaemia, p < 0.05). Levels of urinary albumin to creatinine ratio and nephrin (surrogates of podocyte injury) were unchanged by type 1 diabetes or acute hyperglycaemia.
Conclusion/Interpretation:
Taken together, our data show that urinary podocyte MP levels are higher in patients with type 1 diabetes in advance of changes in other biomarkers (albuminuria, nephrin). Examination of podocyte MPs may serve as an early biomarker of glomerular injury in uncomplicated type 1 diabetes.
Insights
Urinary podocyte microparticles (MPs) are elevated in type 1 diabetes even before other signs of kidney damage appear. Acute high blood sugar also increases these podocyte MPs, suggesting they are an early biomarker for glomerular injury.
Area of Science:
- Nephrology
- Diabetology
- Biomarker Discovery
Background:
- Urinary extracellular vesicles, including exosomes and microparticles (MPs), are promising for non-invasive renal injury detection.
- Previous research indicated increased podocyte-derived MPs in diabetic mice before albuminuria onset.
Purpose of the Study:
- To investigate if type 1 diabetes and acute hyperglycemia increase urinary podocyte MP levels in uncomplicated diabetes.
- To assess podocyte MPs as an early biomarker of glomerular injury.
Main Methods:
- Post hoc analysis of archived urine samples from normoalbuminuric patients with type 1 diabetes under clamped euglycemia and hyperglycemia, compared to healthy controls.
- Assessment of urinary vesicles using electron microscopy and nanoparticle tracking.
- Quantification of podocyte MPs via flow cytometry.
Main Results:
- Urinary podocyte MP levels were significantly higher in type 1 diabetes patients compared to healthy controls.
- Podocyte MP levels increased further during acute hyperglycemia compared to euglycemia.
- No significant changes were observed in vesicle size, total vesicle number, urinary albumin-to-creatinine ratio, or nephrin levels.
Conclusions:
- Urinary podocyte MPs are elevated in type 1 diabetes preceding other established biomarkers of podocyte injury.
- Podocyte MPs may serve as an early, non-invasive biomarker for glomerular injury in uncomplicated type 1 diabetes.
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