Matrix metalloproteinase −2, −9 and arterial stiffness in children and adolescents: The role of chronic kidney disease, diabetes, and hypertension

Background and aims

Matrix metalloproteinases (MMPs) may contribute to the pathogenesis of arterial stiffness inducing extracellular matrix remodeling. We aimed to compare MMP-2 and -9 levels in children with chronic kidney disease (CKD), type 1 diabetes (without chronic kidney disease) and healthy control and to investigate associations of MMPs levels with cardiovascular risk factors and markers of arterial stiffness.

Methods

The study population included 33 CKD, 18 type 1 diabetes patients, and 24 healthy controls. MMP-2, MMP-9, office blood pressure, pulse wave analysis, and carotid-femoral pulse wave velocity (cfPWV) measurements were performed.

Results

MMP-2 levels were higher in the CKD compared to the diabetes and control groups (p < 0.05). MMP-9 levels did not differ among groups. In hypertensive individuals logMMP-2 independently associated with PWV z score (β = 0.744, 95%CI 0.105 to 2.921, p < 0.05) after adjustment for age, sex, GRF, and phosphate levels. Creatinine levels correlated positively with MMP-2 in the CKD (r = 0.39, p < 0.05) and negatively in the diabetes group (r = −0.72, p < 0.05). Cholesterol levels correlated with MMP-2 in the diabetes group (r = 0.70, p < 0.05). Phosphate levels correlated with MMP-2 level in the control group (r = 0.67, p < 0.05). In multivariate regression model adjusted for age and sex, including phosphate and GRF as covariates, only phosphate predicted logMMP-2 levels (β = 0.333, 95%CI 0.060 to 0.671, p < 0.05).

Conclusions

MMP-2 associated with arterial stiffness in the presence of hypertension, while the role of MMP-9 is less clear in children with CKD or type 1 diabetes. Whether up-regulation of MMPs could predict poor outcomes in young high-risk patient groups need to be confirmed by future studies.