Urinary Extracellular Vesicles as a Source of NGAL for Diabetic Kidney Disease Evaluation in Children and Adolescents With Type 1 Diabetes Mellitus

Francisca Ugarte, Daniela Santapau, Vivian Gallardo, Carolina Garfias, Anahí Yizmeyián, Soledad Villanueva, Carolina Sepúlveda, Jocelyn Rocco, Consuelo Pasten, Cinthya Urquidi, Gabriel Cavada, Pamela San Martin, Francisco Cano, Carlos E. Irarrázabal*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Background: Tubular damage has a role in Diabetic Kidney Disease (DKD). We evaluated the early tubulointerstitial damage biomarkers in type-1 Diabetes Mellitus (T1DM) pediatric participants and studied the correlation with classical DKD parameters. Methods: Thirty-four T1DM and fifteen healthy participants were enrolled. Clinical and biochemical parameters [Glomerular filtration Rate (GFR), microalbuminuria (MAU), albumin/creatinine ratio (ACR), and glycated hemoglobin A1c (HbA1c)] were evaluated. Neutrophil gelatinase-associated lipocalin (NGAL), Hypoxia-inducible Factor-1α (HIF-1α), and Nuclear Factor of Activated T-cells-5 (NFAT5) levels were studied in the supernatant (S) and the exosome-like extracellular vesicles (E) fraction from urine samples. Results: In the T1DM, 12% had MAU >20 mg/L, 6% ACR >30 mg/g, and 88% had eGFR >140 ml/min/1.72 m2. NGAL in the S (NGAL-S) or E (NGAL-E) fraction was not detectable in the control. The NGAL-E was more frequent (p = 0.040) and higher (p = 0.002) than NGAL-S in T1DM. The T1DM participants with positive NGAL had higher age (p = 0.03), T1DM evolution (p = 0.03), and serum creatinine (p = 0.003) than negative NGAL. The NGAL-E correlated positively with tanner stage (p = 0.0036), the median levels of HbA1c before enrollment (p = 0.045) and was independent of ACR, MAU, and HbA1c at the enrollment. NFAT5 and HIF-1α levels were not detectable in T1DM or control. Conclusion: Urinary exosome-like extracellular vesicles could be a new source of early detection of tubular injury biomarkers of DKD in T1DM patients.

Original languageEnglish
Article number654269
JournalFrontiers in Endocrinology
StatePublished - 3 Jan 2022

Bibliographical note

Funding Information:
We would like to thank our participants for their contribution and interest. We also thank Josefina Munita, a nurse from the Diabetes Mellitus Program, for her collaboration in logistic issues.

Publisher Copyright:
Copyright © 2022 Ugarte, Santapau, Gallardo, Garfias, Yizmeyián, Villanueva, Sepúlveda, Rocco, Pasten, Urquidi, Cavada, San Martin, Cano and Irarrázabal.


  • NGAL
  • children
  • diabetic kidney disease
  • type 1 diabetes mellitus
  • urinary extracellular vesicles


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