Urine Levels of Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases in Children with Type 1 Diabetes Mellitus

Abstract

Objective: Histopathological changes in the kidney in type 1 diabetes mellitus (T1DM) begin before detection of microalbuminuria. Therefore, there is interest in finding a better biomarker for the early detection of diabetic kidney injury. The aim of this present study was to determine whether urinary indicators of fibrosis are detectable early in the development of T1DM in children and if they may predict progressive renal injury. Methods: Urinary matrix metalloproteinase 2 and 9 (MMP2 and MMP9), tissue inhibitor of metalloproteinase 1 and 2 (TIMP1 and TIMP2) and transforming growth factor-β1 (TGF-β1) were assessed in 33 patients with T1DM with normal renal functions and in 24 healthy controls. Microalbuminuria was not present in the patient group with the exception of three patients. The results were adjusted to urine creatinine (Cr) and the differences between patients and controls were evaluated. These measurements were repeated after one year and the results were compared with the first year results. Results: Urine MMP2/Cr, MMP9/Cr, TIMP1/Cr, TIMP2/Cr, TGF-β1/Cr were not different between the patient and control groups (p>0.05). There were also no significant differences between the first and second year results for these biomarkers (p>0.05). None of these parameters were correlated with hemoglobin A1c, body mass index and duration of T1DM. Interestingly, all parameters were negatively correlated to age of onset of T1DM (p<0.05). Conclusion: Our findings suggest that urinary biomarkers of fibrosis do not show an increase in diabetic children without microalbuminuria. The results also indicate that the risk of early fibrosis may increase as age of onset of T1DM decreases.

Matrix metalloproteinase −2, −9 and arterial stiffness in children and adolescents: The role of chronic kidney disease, diabetes, and hypertension

“…MMP-9 activity has been associated with resistant albuminuria, both in a diabetic rat model and in diabetes patients [ 30 ]. Similar to our findings one previous study showed low levels of urinary MMP-9 in type 1 diabetes pediatric patients without microalbuminuria [ 31 ].…”

Metalloproteinases and Their Inhibitors: Potential for the Development of New Therapeutics

“…Considering children with nephrotic syndrome displayed a higher level of MMP-1, -2, and -9, these MMPs have the potential to act as biomarkers for this disease [176]. However, one recent study has presented that the diabetic children urinary fibrosis biomarkers (levels of MMP-2, MMP-9, and TGF-β) versus the control group showed no significant difference [175]. Therefore, the role of MMPs in DKD is not yet fully understood.…”

“…This eventually leads to sclerosis and tubulointerstitial fibrosis, the hallmark of DKD pathogenesis [174]. Besides the major players, MMP-2 and MMP-9, TGF-β1 is recognized as a key factor that takes parts in the nephrotic fibrosis [175]. Considering children with nephrotic syndrome displayed a higher level of MMP-1, -2, and -9, these MMPs have the potential to act as biomarkers for this disease [176].…”