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Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
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Diagnostic roles of urinary kidney microvesicles in diabetic nephropathy

Fang-Hao Cai1,2, Wen-Yan Wu1,2, Xu-Jie Zhou1,2

  • 1Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China.

Annals of Translational Medicine
|December 14, 2020
PubMed
Abstract

Insights

Urinary microvesicles (MVs) from kidney cells can help diagnose diabetic nephropathy (DN) and reflect its pathology. Elevated MVs indicate kidney damage, aiding in understanding DN's diverse features.

Area of Science:

  • Nephrology
  • Diabetology
  • Biomarker Discovery

Background:

  • Diabetic nephropathy (DN) pathology involves glomeruli, tubulointerstitium, and endothelium.
  • Stressed or damaged kidney cells release microvesicles (MVs) into urine.
  • The diagnostic and reflective capacity of urinary MVs in DN is currently unclear.

Purpose of the Study:

  • To investigate urinary MVs from podocytes, proximal tubules, and endothelial cells as diagnostic biomarkers for DN.
  • To determine if urinary MVs correlate with specific pathological features of DN.
  • To explore the potential of MVs in understanding DN heterogeneity.

Main Methods:

  • Quantified urinary podocyte, proximal tubular, and endothelial cell-derived MVs using flow cytometry in 49 DN patients and 29 proteinuric controls.
  • Semi-quantitatively scored renal glomerular, tubulointerstitial, and vascular lesions.
  • Analyzed the relevance of urinary MV levels to renal pathology.

Main Results:

  • Diabetic nephropathy patients exhibited higher urinary MVs from podocytes, proximal tubules, and endothelial cells compared to controls.
  • A combination of podocyte nephrin+ MVs and diabetic retinopathy achieved 89.7% specificity and 88.9% sensitivity for DN diagnosis.
  • Urinary proximal tubular MVs correlated with tubular injury severity, and endothelial MVs correlated with vascular injury degree.

Conclusions:

  • Urinary kidney-specific cell-derived MVs show potential as noninvasive biomarkers for diagnosing DN in diabetic proteinuric patients.
  • Elevated MV levels may reflect corresponding renal pathological lesions.
  • Urinary MVs can assist physicians in assessing the heterogeneity of DN.
Keywords:
Diabetic nephropathy (DN)diagnosismicrovesiclerenal pathology

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