Urinary levels of matrix metalloproteinases and their tissue inhibitors in nephrotic children.
The aim of this study was to determine the effects of cyclosporine A (CyA) on urinary levels of matrix metalloproteinase 2 and 9 (MMP2, MMP9) and their tissue inhibitors 1 and 2 (TIMP1, TIMP2) in steroid-dependent nephrotic syndrome (SDNS). The study group (1) consisted of 18 children SDNS aged 3.5-17.0 years treated with CyA. All NS children were examined three times: (A) at proteinuria relapse, before CyA treatment, (B) after 6 months, and (C) after 12 months of CyA administration. The control group (2) consisted of 18 healthy children. Serum CyA level was assessed by immunofluorescence. Enzyme-linked immunosorbent assay kits for total human MMP2 and 9 and TIMP1 and 2 were obtained from R&D Systems. Compared with healthy controls, urinary MMP9/Cr in NS children before CyA was on the same level and increased during CyA treatment, and urinary TIMP1/Cr was twice as high and increased significantly during CyA treatment. MMP9/TIMP1 in NS children treated with CyA increased, but the difference was not statistically significant. Urinary MMP2/Cr was similar, and urinary TIMP2/Cr was significantly higher in children treated with CyA (p < 0.01). The MMP2/TIMP2 ratio in NS children treated with CyA was significantly lower in comparison with healthy controls (p < 0.01). A negative correlation was noted between urinary MMP2/TIMP2 ratio and serum CyA in NS children (r = -0.541, p < 0.01). An imbalance within the MMP2 and TIMP2 and MMP9 and TIMP1 system may play a role in the pathogenesis CyA nephropathy.
Wasilewska
Anna M
AM
Department of Pediatrics and Nephrology, Medical University of Białystok, Białystok, Poland. annwasil@interia.pl
Zoch-Zwierz
Walentyna M
WM
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000633:toxicity; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000502:physiology / Q000652:urine*; D020780:Matrix Metalloproteinase 9 / Q000502:physiology / Q000652:urine*; D009404:Nephrotic Syndrome / Q000652:urine*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000502:physiology / Q000652:urine*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000502:physiology / Q000652:urine*
D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D016572:Cyclosporine; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9