Association of matrix metalloproteinase-2 and matrix metalloproteinase-9 with endothelial dysfunction, cardiovascular disease risk factors and thrombotic events in children with end-stage renal disease

Introduction. Cardiovascular disease (CVD) is the main cause of death in children with end-stage renal disease (ESRD). Matrix metalloproteinases (MMP-2 and MMP-9) are members of endopeptidases which contribute to CVD. The aim of this study was to evaluate the association of MMP-2 and MMP-9 with markers of endothelial dysfunction, soluble E-selectin and brachial flow-mediated dilatation; several biochemical risk factors of CVD; and thrombotic incidents in children with ESRD. Materials and Methods. Thirty-one children with ESRD and 18 healthy age-and sex-adjusted controls underwent measurement of serum levels of MMP-2, MMP-9, soluble E-selectin, phosphorus, calcium, parathyroid hormone, lipid profile, thrombotic factors, and albumin. Flow-mediated dilatation was measured in both groups by Doppler ultrasonography. Thrombotic events were assessed in patients with ESRD. Results. Matrix metalloproteinase-2 positively correlated with systolic and diastolic blood pressure, soluble E-selectin, creatinine, cholesterol, triglyceride, low-density lipoprotein cholesterol, phosphorus, and parathyroid hormone and negatively correlated with body mass index, hemoglobin, high-density lipoprotein cholesterol, and flow-mediated dilatation, while MMP-9 correlated with soluble E-selectin, phosphorus, parathyroid hormone, and albumin and negatively correlated with body mass index and hemoglobin. Six patients (19.3%) had thrombotic incidents. There was no significant difference between the levels of MMP-2 and MMP-9 in the children with and without thrombotic events. Conclusions. This study determined the associations of MMP-2 and MMP-9 with markers of endothelial dysfunction and several traditional and uremia related CVD risk factors in children with ESRD. No associations were found between these two MMPs and thrombotic events

Renal consequences of preterm birth

BACKGROUND: The developmental origin of health and disease concept identifies the brain, cardiovascular, liver, and kidney systems as targets of fetal adverse programming with adult consequences. As the limits of viability in premature infants have been pushed to lower gestational ages, the long-term impact of prematurity on kidneys still remains a significant burden during hospital stay and beyond. OBJECTIVES: The purpose of this study is to summarize available evidence, mechanisms, and short- and long-term renal consequences of prematurity and identify nephroprotective strategies and areas of uncertainty. RESULTS: Kidney size and nephron number are known to be reduced in surviving premature infants due to disruption of organogenesis at a crucial developmental time point. Inflammation, hyperoxia, and antiangiogenic factors play a role in epigenetic conditioning with potential life-long consequences. Additional kidney injury from hypoperfusion and nephrotoxicity results in structural and functional changes over time which are often unnoticed. Nephropathy of prematurity and acute kidney injury confound glomerular and tubular maturation of preterm kidneys. Kidney protective strategies may ameliorate growth failure and suboptimal neurodevelopmental outcomes in the short term. In later life, subclinical chronic renal disease may progress, even in asymptomatic survivors. CONCLUSION: Awareness of renal implications of therapeutic interventions and renal conservation efforts may lead to a variety of short and long-term benefits. Adequate monitoring and supplementation of microelement losses, gathering improved data on renal handling, and exploration of new avenues such as reliable markers of injury and new therapeutic strategies in contemporary populations, as well as long-term follow-up of renal function, is warranted