title: Matrix metalloproteinases (MMP-2,9) and their tissue inhibitors (TIMP-1,2) as novel markers of stress response and atherogenesis in children with chronic kidney disease (CKD) on conservative treatment.
abstract: 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.
authors.affiliation: Department of Pediatric Nephrology, Wrocław Medical University, M. Skłodowskiej-Curie 50/52, 50-369, Wrocław, Poland.
authors.forename: Kinga
authors.initials: K
authors.lastname: Musiał
authors.forename: Danuta
authors.initials: D
authors.lastname: Zwolińska
mesh_terms: D000293:Adolescent; D050197:Atherosclerosis / Q000209:etiology*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D019040:E-Selectin / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D018841:HSP90 Heat-Shock Proteins / Q000097:blood; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications* / Q000628:therapy; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood*
chemical_list: D015415:Biomarkers; D019040:E-Selectin; D018841:HSP90 Heat-Shock Proteins; C533585:HSP90AA2P protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D002097:C-Reactive Protein; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
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