Clinical value of determination of matrix metalloproteinases and their inhibitors in children with alport syndrome


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Abstract

Purpose. To determine the role of matrix metalloproteinases and their inhibitors in the progression of Alport syndrome in children for the development of an algorithm for predicting prognosis and the course of the disease. Materials and methods. In 32 children with Alport syndrome, determination of blood and urine levels of the major components of proteolysis - matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-9, and MMP-10), tissue inhibitors of matrix metalloproteinases (TIMP-1 and TIMP-2), and plasminogen activator inhibitor-I (РAI-I) - was performed. The control group consisted of 10 children without kidney disease. Results and discussion. In children with Alport syndrome, the levels of MMP-2 and MMP-3 inhibitors: TIMP-2, and РАI-1 (antigen) levels in blood, and urine MMP-3/Cr, MMP-9/Cr and TIMP-1/Cr levels were significantly higher compared with the control group. The urine TIMP-1/Cr levels in children with greater daily proteinuria (more than 30 mg/kg/day) were significantly higher and directly correlated with the daily loss of protein regardless of progression. In children with progressive Alport syndrome, direct correlations between the daily proteinuria and MMP-2/Cr in urine, the TIMP-1/Cr in urine, and between creatinine levels and MMP-1 in the blood, and MMP-10 in the blood were revealed; in the group without progression - inverse correlations between MMP-2/Cr in the urine and daily proteinuria and glomerular filtration rate were revealed. Conclusion. Thus, the identified relationships between matrix metalloproteinases and their inhibitors and clinical signs of Alport syndrome in children suggest an important role of matrix metalloproteinases and their inhibitors in the mechanisms of progression of disease, and justify the potentials for their use as criteria for progression of this disease.

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