Key result
Children with chronic kidney disease exhibited significantly elevated serum concentrations of MMP-2, MMP-9, TIMP-1, and TIMP-2 compared to healthy controls, which worsened with renal failure progression.
Why the study?
Data on correlations between MMPs, TIMPs, and markers of stress response, inflammation, and endothelial dysfunction are scarce in adult CKD patients and absent in children.
Observational (n=61)
No
In children with CKD, the MMP/TIMP system is dysfunctional and correlates with markers of stress and endothelial damage, suggesting a role in early atherogenesis.
Answers are grounded in this paper and cite their sources.
Elevated MMP/TIMP levels in pediatric CKD may mark early vascular injury; leaves open causal role in atherogenesis and need for longitudinal confirmation.
The system of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) may play a key role in atherogenesis of chronic kidney disease (CKD) patients by its impact on matrix accumulation. Connections with inflammation, stress, or endothelial dysfunction are also probable. However, the data on correlations between these parameters in CKD patients are scarce in adults and absent in children. The aim of our study was to evaluate serum concentrations of MMP-2, MMP-9, TIMP-1, and TIMP-2, as well as their correlations with markers of stress response (Hsp90-α, anti-Hsp60), endothelial dysfunction (sE-selectin), and inflammation (high-sensitivity C-reactive protein) in CKD children treated conservatively. Thirty-seven patients were divided into two groups according to the CKD stage (gr.CKDI, 19 children with CKD stages 2-3; gr.CKDII, 18 subjects with CKD stages 4-5). Twenty-four age-matched healthy subjects served as controls. Serum concentrations of MMP-2, MMP-9, TIMP-1, TIMP-2, Hsp90-α, anti-Hsp60, and sE-selectin were assessed by ELISA. Median values of MMP-2, MMP-9, TIMP-1, and TIMP-2 were significantly higher in all CKD children vs. controls and were increased in patients with CKD stages 4-5 vs. CKD stages 2-3. Hsp90-α, anti-Hsp60, sE-selectin, and glomerular filtration rate predicted the values of MMPs and TIMPs. Chronic kidney disease in children is characterized by MMP/TIMP system dysfunction, aggravated by the progression of renal failure. Correlations between examined parameters, heat shock proteins, and markers of endothelial damage suggest the possibility of MMP/TIMP application as indicators of stress response and atherogenesis in children with CKD on conservative treatment.
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Musiał et al. (2010) conducted an observational in Chronic kidney disease (CKD) (n=61). Chronic kidney disease vs. Healthy controls was evaluated on Serum concentrations of MMP-2, MMP-9, TIMP-1, and TIMP-2 (p=<0.000001). Children with chronic kidney disease exhibited significantly elevated serum concentrations of MMP-2, MMP-9, TIMP-1, and TIMP-2 compared to healthy controls, which worsened with renal failure progression.
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