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

J Clin Pathol. 2020 Nov;73(11):713-721. doi: 10.1136/jclinpath-2020-206494. Epub 2020 Mar 17.

Abstract

Introduction: Diabetic 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.

Aims: To 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.

Methods: Ninety 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.

Results: Gene 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.

Conclusion: Our data suggest the potential use of NGAL and SMAD1 gene expression in peripheral blood and urine samples as early biomarkers of DN.

Keywords: diabetes; molecular biology; nephrology.

MeSH terms

  • Adult
  • Aged
  • Biomarkers / metabolism
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / diagnosis*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetic Nephropathies / diagnosis*
  • Diabetic Nephropathies / metabolism
  • Diabetic Nephropathies / pathology
  • Early Diagnosis
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Lipocalin-2 / genetics
  • Lipocalin-2 / metabolism*
  • Liquid Biopsy
  • Male
  • Middle Aged
  • ROC Curve
  • Smad1 Protein / genetics
  • Smad1 Protein / metabolism*

Substances

  • Biomarkers
  • LCN2 protein, human
  • Lipocalin-2
  • SMAD1 protein, human
  • Smad1 Protein