Urinary Extracellular Vesicles as a Source of NGAL for Diabetic Kidney Disease Evaluation in Children and Adolescents With Type 1 Diabetes Mellitus
Date
2021
Type:
Article
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Abstract
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-1a (HIF-1a),
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-1a 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.
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Citation
Ugarte F, Santapau D, Gallardo V, Garfias C, Yizmeyia´ n A, Villanueva S, Sepu´lveda C, Rocco J, Pasten C, Urquidi C, Cavada G, San Martin P, Cano F and Irarra´ zabal CE (2022) Urinary Extracellular Vesicles as a Source of NGAL for Diabetic Kidney Disease Evaluation in Children and Adolescents With Type 1 Diabetes Mellitus. Front. Endocrinol. 12:654269. doi: 10.3389/fendo.2021.654269
Keywords
Diabetic kidney disease, Type 1 diabetes mellitus, Children, NGAL, Urinary extracellular vesicles