Association between renal dysfunction and metalloproteinase (MMP)-9 activity in hypertensive patients

Abstract

Background and objective: Matrix metalloproteinases (MMPs) are involved in deleterious tissue remodeling associated with target organ damage in renal disease. The aim of this study was to study the association between renal dysfunction and activity of the inflammatory metalloproteinase MMP-9 in hypertensive patients with mild-moderate chronic kidney disease (CKD).

Material and methods: Plasmatic active MMP-9, total MMP-9, tissue inhibitor of MMP-9 (TIMP-1), MMP-9/TIMP-1 ratio and MMP-9-TIMP-1 interaction were analyzed in 37 hypertensive patients distributed by estimated glomerular filtration rate (eGFR) in 3 groups:>90, 90-60 y 60-30mL/min/1.73 m².

Results: Total MMP-9 was not different as eGFR declines. TIMP-1 was significantly increased in hypertensive patients with eGFR 60-30mL/min/1.73 m² (P<.01 versus>90mL/min/1.73 m²). This relates to the significant decrease in the interaction between MMP-9-TIMP-1 observed in patients with eGFR 60-30mL/min/1.73 m² (P<.01 versus>90mL/min/1.73 m²). Despite the systemic elevation of TIMP-1, active MMP-9 was significantly increased in hypertensive patients with eGFR 60-30mL/min/1.73 m² (P<.05 and P<0.01 versus>90 and 90-60mL/min/1.73 m², respectively). TIMP-1, active MMP-9 and MMP-9-TIMP-1 interaction significantly correlate with the decline in renal function, which was not observed with total MMP-9.

Conclusions: The progression of CKD, even in stages where the decline of renal function is still moderate, is associated with an increase in MMP-9 activity, which could be considered as a potential therapeutic target.

Keywords: Chronic kidney disease; Enfermedad renal crónica; Hipertensión; Hypertension; Inhibidor tisular de metaloproteinasas de matriz-1; Matrix metalloproteinase-9; Metalloproteinases; Metaloproteinasa de matriz-9; Metaloproteinasas; Tissue inhibitor of metalloproteinase-1.