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,  < 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,  < 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.