Abstract
BackgroundTubular 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.MethodsThirty-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.ResultsIn 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.ConclusionUrinary exosome-like extracellular vesicles could be a new source of early detection of tubular injury biomarkers of DKD in T1DM patients.
Highlights
Diabetes Mellitus (DM) is one of the most prevalent nontransmissible chronic diseases [1]
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
Urinary exosome-like extracellular vesicles could be a new source of early detection of tubular injury biomarkers of diabetic kidney disease (DKD) in Type 1 DM (T1DM) patients
Summary
Diabetes Mellitus (DM) is one of the most prevalent nontransmissible chronic diseases [1]. DKD is a chronic microvascular complication affecting 30% of patients with type 1 diabetes mellitus (T1DM), 20% of patients with type 2 diabetes mellitus (T2DM), and is the most frequent cause of end-stage renal disease (ESRD), morbidity, and mortality [7, 8]. Microalbuminuria is currently considered the best predictor of the early stages of DKD [11,12,13,14]. Recently the literature has described that tubulointerstitial damage appears in the early stages of DKD, contributing to the progression of renal disease [15,16,17]. 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
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