Association Between Matrix Metalloproteinase-3 Activity and Glomerular Filtration Rate and Albuminuria Status in Patients With Type 2 Diabetes Mellitus

Iran J Kidney Dis. 2018 Jan;12(1):40-47.

Abstract

Introduction: Diabetic nephropathy is pictured as matrix accumulation and thickening of glomerular basal membrane. Matrix metalloproteinases (MMPs) are major proteases involved in extracellular matrix degradation. Moreover, plasminogen activator inhibitor-1 (PAI-1) primarily regulates plasmin dependent proteolysis. It plays a role in renal fibrosis causing extracellular matrix accumulation through inhibition of plasmin-dependent extracellular matrix degradation. This study investigated PAI-1 serum level and MMP-3 activity and their correlation with glomerular filtration rate in patients with diabetes mellitus.

Materials and methods: In a case-control design, serum PAI-1 concentrations and MMP-3 activity were measured in 80 patients with normoalbuminuria, microalbuminuria, and macroalbuminuria. Receiver operating characteristics curve analysis was used to assess the diagnostic accuracy of MMP-3 activity in discriminating albuminuria.

Results: In the patients with microalbuminuria, serum PAI-1 levels were higher compared with macroalbuminuric patients (P < .001). The patients with macroalbuminuria exhibited a significantly lower MMP-3 activity than the patients with microalbuminuria and normoalbuminuria (P < .001). No significant correlation was found between serum MMP-3 activity and serum PAI-1 levels in those with normoalbuminuria, microalbuminuria, and macroalbuminuria. The MMP-3 activity had a strong positive correlation with estimated glomerular filtration (r = 0.853, P < .001).

Conclusions: We found that there was a positive correlation between glomerular filtration rate and MMP-3 activity in diabetic patients. This concludes that MMP-3 may have a role in the pathogenesis of diabetic nephropathy progressions towards macroalbuminuria, and therefore, MMP-3 activity may be used in evaluating albuminuria status.

MeSH terms

  • Aged
  • Albuminuria / blood
  • Albuminuria / diagnosis
  • Albuminuria / etiology*
  • Albuminuria / physiopathology
  • Area Under Curve
  • Biomarkers / blood
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / diagnosis
  • Diabetic Nephropathies / etiology*
  • Diabetic Nephropathies / physiopathology
  • Female
  • Glomerular Filtration Rate*
  • Humans
  • Kidney / physiopathology*
  • Male
  • Matrix Metalloproteinase 3 / blood*
  • Middle Aged
  • Plasminogen Activator Inhibitor 1 / blood
  • Predictive Value of Tests
  • ROC Curve
  • Reproducibility of Results

Substances

  • Biomarkers
  • Plasminogen Activator Inhibitor 1
  • SERPINE1 protein, human
  • MMP3 protein, human
  • Matrix Metalloproteinase 3