CLINICAL AND PROGNOSTIC VALUE OF PROTEOLYSIS FACTORS IN CHILDREN WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

Abstract

BACKGROUND. One of the perspectives of modern Nephrology is the study of the mechanisms of nephrosclerosis in ADPKD. Matrix metalloproteinase system (MMP/TIMP)— enzymes that play a key role in the processes of proteolysis in the kidney. THE AIM: to determine the expression of the urine MMP-2, MMP-3 and MMP-9 and their inhibitors TIMP-1 and 2, PAI-I, to establish their relationship with the volume of the kidney corrected to the surface of the body and the functional state of the kidneys, an additional criterion of progression. PATIENTS AND METHODS. The study included 34 children with ADPKD. The level of MMP-2, MMP-3 and MMP-9 and their inhibitors TIMP-1 and 2, PAI-I were determined in urine by ELISA. RESULTS. eGFR in children with total kidney volume greater than 97‰ was significantly lower than in children with normal total kidney volume. In the group of children with a total volume of the kidneys more than 97 percentile,a statistically significant increase in the level of TIMP-1 and TIMP-2 and PAI-I in the urine, and a statistically significant low level of urinary excretion of MMP-3 and MMP-9, compared with the group of children with ADPKD with normal total volume of the kidneys. In the group of children with ADPKD and total kidney volume of more than 97 percentiles of an inverse correlation relationship between the level of eGFR and TIMP-2 and PAI-I, as well as a direct correlation relationship between the total volume of kidney and the urinary excretion of TIMP-1. CONCLUSION. MMP and its inhibitors play an important role in renal damage in children with ADPKD. These proteolysis factors are promising to use as an indicator of the severity of the accumulation of extracellular matrix, that is, monitoring the process of fibrosis, and used as a predictor of progression.