Factors of proteolysis in blood and urine as prognostic markers of progression of Alport syndrome in children

Abstract

BACKGROUND. Alport syndrome is a rare hereditary kidney disease that causes progressive renal failure. There are significant differences in the progression of the disease between patients with Alport syndrome. Identifying patients with a high risk of rapid progression in order to optimally balance benefits and risks for prescribing therapy has become particularly important at this time. In this study, we wanted to assess whether the factors of proteolysis in blood and urine are associated with the nature of the course and to assess their prognostic value for children with Alport syndrome. THE AIM: To determine the level in blood serum and urinary excretion of MMP-2, MMP-3 and MMP-9 and their inhibitors TIMP-1 and 2, PAI-I, to show the relationship of their changes with the character of the course of Alport syndrome in children as an additional criterion for progression. PATIENTS AND METHODS. The study included 32 children with Alport syndrome. The level of MMP-2, MMP-3 and MMP-9 and their inhibitors TIMP-1 and 2, PAI-I, in blood serum and urine was determined by ELISA. A decrease in eGFR of ≥ 30 % at 2 years from baseline was chosen to indicate a progressive course of Alport syndrome. RESULTS. 28.1 % of children with Alport syndrome had a progressive course of the dis ease, 71.9 % had a slowly progressive course. The frequency of a decrease in MMP-9 and an increase in TIMP-1 both in blood (88.9 versus 43.5 % and 77.8 versus 21.7 %; p = 0.044 and 0.006, respectively) and in urine (100 versus 47, 8 % and 88.9 versus 30.4 %; 0.012 and 0.005, respectively) were statistically significantly more often detected in children with Alport syndrome with a progressive course of the disease than in a slowly progressive course. CONCLUSION. Type 9 matrix metalloproteinase and type 1 tissue matrix metalloproteinase inhibitor can be considered as risk factors for the progression of Alport syndrome in children.