Background. Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease with an incidence of 1:400 to 1:1000, accounting for 7–10% of all patients with end-stage chronic renal disease. Predicting the rate of disease progression has become especially important today with the advent of tolvaptan, the first drug modifying ADPKD. Patients with a high likelihood of rapid disease progression should be selected for this treatment, as these patients are expected to have an optimal benefit/risk ratio. The system of matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of MMP – TIMP, type 1 plasminogen activator inhibitor - PAI-I) plays a key role in the processes of proteolysis in the kidney.
Objective. Determination of the blood serum levels of MMP-2, -3 and -9 and their inhibitors TIMP-1 and -2, PAI-I and their urinary excretion, estimating of the relationship of their changes with the ADPKD progression type, and assessment of the significance of disturbances in the MMP/TIMP system as an additional criterion for the progression of ADPKD.
Material and methods. The study included 36 children with ADPKD who were admitted to the Department of Hereditary and Acquired Kidney Diseases named after Prof. M.S. Ignatova of the Veltischev Research and Clinical Institute for Pediatrics of the Pirogov Russian National Research Medical University. The levels of MMP-2, MMP-3 and MMP-9 and their inhibitors TIMP-1 and -2, and PAI-I in blood serum and urine were determined by enzyme-linked immunosorbent assay.
Results. As a result of the analysis of the frequency of changes in proteolysis factors in blood and urine in children with ADPKD, depending on the disease progression type (slow progression/progression), the following data were obtained: in children with ADPKD progression, the frequency of increase in the level of TIMP-I in the blood (P=0.010; Cramer's V=0.479; OR=12; 95% CI, 1.79–80.3)) and urine (P=0.015; Cramer's V=0.482; OR=9.8; 95% CI, 1.84-51.9)) was statistically significantly higher. Also, the level of PAI-I in the blood (P=0.039; Cramer's V=0.396) and urine (P=0.022; Cramer's V=0.444) was statistically significantly higher in children with ADPKD progression. The chances of a progressive course increased by 6.3 times (95% CI, 1.27–31.2) with an increase in blood PAI-I level and by 9.0 times (95% CI, 1.55–52.2) with an increase in urine PAI-I level in children with progressive ADPKD compared to slow progression.
Conclusion. The ADPKD progression in childhood is manifested by an increase in the number of cysts and in the size of the kidneys with the preserved filtration function of the kidneys for a long time due to hyperfiltration. This study identifies children at risk for rapid kidney enlargement, i.e. a progressive course that may benefit from therapeutic interventions in the future. The data obtained from this study indicate that TIMP-1 and PAI-I can be considered as risk factors for the progression of ADPKD in children.

Keywords: PAI-I, tissue inhibitor of type 1 matrix metalloproteinases, autosomal dominant polycystic kidney disease, matrix metalloproteinase, children, progression