NGAL and SMAD1 gene expression in the early detection of diabetic nephropathy by liquid biopsy

Abstract

IntroductionDiabetic nephropathy (DN) is a disease that progresses with the slow and progressive decline of the glomerular filtration rate (GFR); the installation of this pathology is silent and one of the major causes of death in patients with diabetes.AimsTo identify new molecular biomarkers for early identification of the onset of DN in patients with type II diabetes mellitus (DM2). We studied the expression profile of the genes; suppressor of mothers against decapentaplegic type 1 (SMAD1), neutrophil gelatinase-associated lipocalin (NGAL) and type IV collagen (COLIV1A) in peripheral blood and urine sediment samples.MethodsNinety volunteers, 51 with DM2 and 39 healthy, were recruited from the Faculdade de Medicina do ABC outpatient clinic. We conducted an interview and collected anthropometric data, as well as blood and urine samples for biochemical evaluation and real-time PCR amplification of the genes of interest.ResultsGene expression data: peripheral blood NGAL (DM2 0.09758±0.1914 vs CTL 0.02293±0.04578), SMAD1 (blood: DM2 0.01102±0.04059* vs CTL 0.0001317±0.0003609; urine: DM2 0.7195±2.344* vs CTL 0.09812±0.4755), there was no significant expression of COLIV1A. These genes demonstrated good sensitivity and specificity in the receiving operating characteristic curve evaluation.ConclusionOur data suggest the potential use of NGAL and SMAD1 gene expression in peripheral blood and urine samples as early biomarkers of DN.

Early detection of diabetic nephropathy in patient with type 2 diabetes mellitus: A review of the literature

“…Peripheral blood NGAL gene expression was increased in patients with type 2 DM compared with healthy individuals (type 2 DM 0.09758 ± 0.1914* 2 −ΔCq vs CTL 0.02293 ± 0.04578). 25 The results showed a positive correlation between serum NGAL and HbA1c in T2DM patients with normoalbuminuria, 23 which is in agreement with DyabAllawi et al 2017 who showed significant correlation between serum NGAL and HbA1c % (r = 0.394, p = 0.03) 24…”

“…They suggest the potential use of SMAD1 gene expression in peripheral blood and urine samples as early biomarkers of DN. 25 …”

“…In these patients, they found no correlation between the expression of this gene and biochemical or any of the other studied parameters . 25 …”

New insights into diabetes mellitus and its complications: a narrative review

“…At present, the clinical diagnosis of DN mainly depends on the elevated urinary albumin excretion and reduced eGFR in the absence of other primary causes of kidney damage, lacking high sensitivity and specificity indicators to reflect the renal blood oxygen levels. A growing number of studies have focused on the biomarkers for early diagnosis of DN, which include (I) certain urinary microRNAs such as microRNA-210 and microRNA-34a (7), urinary kidney injury molecule 1 (KIM-1) and Chitinase-3-like protein 1 (YKL-40) (8), urinary E-cadherin ( 9); (II) serum galectin-3 and growth differentiation factor-15 (GDF-15) (10), serum pregnenolone sulfate, ganglioside GA1, phosphatidyl glycerol and all-trans-Carophyll yellow tested by direct flow through mass spectrometry (11); (III) suppressor of mothers against decapentaplegic type 1 (SMAD1) and neutrophil gelatinase-associated lipocalin (NGAL) gene expression in peripheral blood and urine samples (12). However, renal biopsy is still the gold standard to diagnose diabetic nephropathy.…”

Clinical value of INSL3 in the diagnosis and development of diabetic nephropathy

“…A number of studies have studied the relationship between abnormal expression of different genes and DN progression. For instance, Veiga et al 14 presented the eccentric expressions of NGAL and SMAD1 genes in blood and urine samples in DN patients by liquid biopsy, suggesting the potentials of NGAL and SMAD1 in DN early diagnosis. Gong et al 15 claimed that KLF4 serves as a protective regulator in DN by activating podocyte autophagy.…”