The clinical value of the determination of matrix metalloproteinases and their inhibitors in children with autosomal dominant polycystic kidney disease


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Abstract

Aim. Determination of the features of changes of matrix metalloproteinases and their inhibitors as criteria of disease progression in children with autosomal dominant kidney disease. Methods. The study included 26 children (15 boys and 11 girls ) aged 4 to 16 years (mean age - 11.7 ± 4.81) with autosomal dominant polycystic kidney disease. Main components of proteolysis - matrix metalloproteinases (MMP -1, MMP -2, MMP -3, MMP -9), tissue inhibitors of matrix metalloproteinases (TIMP-1 and TIMP-2) and plasminogen activator inhibitor type 1 (РАI-1) were evaluated in blood and urine by Elisa. Results. Arterial hypertension was revealed in 35 % of cases. Significant correlations between indices of time of arterial hypertension, glomerular filtration rate and ММР, TIMP and РАI -1 were identified. The relationship between the MMP-3, MMP-9, РАI-1 blood levels, TIMP-1 urine levels, and total kidney volume on CT was found. Excretion of MMP-9 and TIMP-1 in the urine increase with increasing volume of nephrosclerosis on SPECT - CT. Increasing the volume of cysts on SPECT - CT accompanies with increase of blood and urine MMP-2 levels, and urine TIMP-1 levels. Reduction of integral reuptake index leads to the increase levels of matrix metalloproteinase inhibitors: TIMP -1 in urine and the activity of РАI -1 in the blood. Conclusion. The relationships between matrix metalloproteinases and their inhibitors and clinical signs of autosomal dominant polycystic kidney disease in children suggest an important role of matrix metalloproteinases and their inhibitors in the mechanisms of disease progression through their participation in the development of fibrotic changes, and justifies the search for new approaches to inhibit fibrosis in renal tissue aimed tothe correction of imbalances in the system of ММР/ММР inhibitors.

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