Plasma and urinary matrix metalloproteinase-9 as a marker for detection of nephropathy in type 2 diabetic patients

Abstract

hyperfiltration and hyperperfusion, before the onset of any measurable clinical changes. [1] Subsequently, development of diabetic nephropathy mesangial expansion and changes in the matrix of glomerular and tubular basement membranes take place. [2,3] Hyperglycemia is associated with an increase in mesangial cell proliferation and hypertrophy, as well as increased matrix production and basement membrane thickening. [4,5] Mesangial cells are crucial for maintenance of glomerular capillary structure and for the modulation of glomerular filtration via smooth-muscle activity. In vitro studies have demonstrated that hyperglycemia is associated with increased mesangial cell matrix production and mesangial cell apoptosis. [6,7] The extracellular matrix (ECM) in the basement membrane of the kidney glomeruli is of particular importance for the filtration properties. Structural changes in mesangial and basement matrix are related to proteinuria and thus Background: Diabetic nephropathy (DN) is a serious complication in diabetes and now it has become the most common cause of end-stage renal disease (ESRD). Development of diabetic nephropathy is characterized by a thickening of the glomerular basement membrane and expansion of extracellular matrix proteins in the mesangial and tubulointerstitial areas, followed ultimately by progression to glomerular sclerosis and tubulointerstitial atrophy and fibrosis associated with renal dysfunction. Several growth factors, signaling pathways, along with hyperglycemia affect ECM synthesis and turnover in DN. Objective: The aim of this study was to evaluate the significance of plasma and urinary matrix metalloproteinase-9 (MMP-9) in type 2 diabetic patients with microalbuminuria. Materials and Methods: Fifty type 2 diabetic patients with more than 5 year diabetic duration in the age group of 35-60 years were selected for this study and 25 age-matched healthy individuals were selected as a control group. Plasma and urinary levels of MMP-9 were assessed by ELISA method and microalbumin by turbilatex method. Results: The plasma and urinary MMP-9 levels are significantly elevated in type 2 DM with microalbuminuria compared to normoalbuminuric type 2DM and also there is significant elevation observed in normoalbuminuric type 2 DM compared to controls. Conclusion: Plasma and urinary MMP-9 might be useful to detect early stages of nephropathy in T2DM patients. Hence, measurement of plasma and urinary MMP-9 could be useful diagnostic markers for the assessment of renal changes in type 2 diabetic patients even before the appearance of microalbuminuria.

Association of Serum Magnesium Levels with Matrix metalloproteinase-9 (MMP-9) Urine in Patients with Diabetic Kidney Disease Stage 1 and 2

“…When the kidneys get injured by the hyperglycemia process, a series of processes that occur will cause an increase in transforming growth factor-β (TGF-β) and produce a large number of ECM. 8,19,20 The limitations of this study including cross-sectional design so that various types of tests such as magnesium levels and MMP-9 urine were carried out at one time. This causes researchers to be unable to evaluate changes in various parameters that fluctuate.…”

“…Increased MMP-9 plays a role in the progression of renal fibrosis and is mainly secreted in the glomerulus, and is also found in the tubulointerstisium. 7,8 Matrix metalloproteinase-9 (MMP-9) is a proteolytic enzyme that degrades extracellular matrix (ECM) components consisting of gelatin, type IV collagen, and laminin. When the kidneys get injured, for example by *Correspondence: sonywibisono@yahoo.com © 2019 Biomolecular and Health Science Journal.…”

“…The next process MMP-9 will increase remodeling which causes tissue imbalance resulting in an accumulation of ECM deposition. 8 Research that studies the relationship between serum magnesium levels and MMP-9 has not been widely known. Considering the role of magnesium in the progressivity of DKD, we aim to examine the relationship between magnesium serum and MMP-9 urine in patients with DKD stage 1 and 2.…”

Diabetes and Renal Complications: An Overview on Pathophysiology, Biomarkers and Therapeutic Interventions

“…It has been demonstrated that high glucose increases the production of collagen type IV via activation of the endogenous TGF-β pathway [127]. Elevated urinary excretion of collagen type IV has been found in patients with diabetes and correlates with extracellular matrix expansion [128,129]. Genome-wide association studies performed in individuals with type 1 diabetes have identified that the most prominent protective variant against DKD is a missense mutation in the gene COL4A3, however, further studies are required to elucidate its role in this disease [130].…”

The experimental investigation of fibrinolytic system under the influence of flocalin in conditions of acute hypoxic kidney injury

“…In particular, in the case of kidney failure of metabolic origin the disturbance of homeostasis which leads to hemocoagulation and thrombosis takes place [6]. Additionally, the progression of kidney damage correlates with elevation in kidney mesangium cells and urine of type IV collagen which is a marker of decreased activity of proteolysis in the system of proteolysis/fibrinolysis [7]. It should also be noted that the inhibition of fibrinolysis is a sign of kidney failure, whereas chronic kidney disease is associated with simultaneous increase of thrombosis risk [8].…”