Urinary Extracellular Vesicles as a Source of NGAL for Diabetic Kidney Disease Evaluation in Children and Adolescents With Type 1 Diabetes Mellitus
Journal
Frontiers in Endocrinology
ISSN
1664-2392
Date Issued
2022
Author(s)
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
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<jats:sec><jats:title>Background</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In the T1DM, 12% had MAU >20 mg/L, 6% ACR >30 mg/g, and 88% had eGFR >140 ml/min/1.72 m<jats:sup>2</jats:sup>. 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.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Urinary exosome-like extracellular vesicles could be a new source of early detection of tubular injury biomarkers of DKD in T1DM patients.</jats:p></jats:sec>
Cite this document
Ugarte, F., Santapau, D., Gallardo, V., Garfias, C., Yizmeyián, A., Villanueva, S., Sepúlveda, C., Rocco, J., Pasten, C., Urquidi, C., Cavada, G., San Martin, P., Cano, F., & Irarrázabal, C. E. (2022). Urinary extracellular vesicles as a source of ngal for diabetic kidney disease evaluation in children and adolescents with type 1 diabetes mellitus. Frontiers in Endocrinology, 12, 654269. https://doi.org/10.3389/fendo.2021.654269
Subjects
diabetic kidney disease
;
type 1 diabetes mellitus
;
children
;
ngal
;
urinary extracellular vesicles
;
biological marker
;
flotillin 1
;
gelatinase
;
hemoglobin
;
hemoglobin a1c
;
hypoxia inducible factor 1alpha
;
neutrophil gelatinase associated lipocalin
;
proteinase inhibitor
;
transcription factor nfat
;
adolescent
;
albumin to creatinine ratio
;
article
;
body mass
;
child
;
clinical article
;
creatinine blood level
;
cross-sectional study
;
diabetic nephropathy
;
diastolic blood pressure
;
estimated glomerular filtration rate
;
exosome
;
female
;
human
;
hypertension
;
insulin dependent diabetes mellitus
;
kidney function
;
kidney injury
;
male
;
mean arterial pressure
;
metabolic regulation
;
microalbuminuria
;
national health organization
;
protein expression
;
school child
;
systolic blood pressure
;
transmission electron microscopy
;
ultracentrifugation
;
urine sampling
;
western blotting
;
world health organization