Urinary excretion of matrix metalloproteinases and their inhibitors in type 1 diabetic patients with nephropathy


Bondar I.А.,Klimontov V.V., Romanov V.V.

1Department of endocrinology at State Education Institution of High Professional Education “ Novosibirsk State Medical University” Ministry of Health and Social Development of Russian Federation, Novosibirsk
Aim. Determination of urinary excretion of matrix metalloproteinases and their inhibitors in type 1 diabetic patients at different stages of diabetic nephropathy.
Methods. 64 patients were included into the study: 25 with normal albumin excretion rate (AER), 30 – with microalbuminuria, 9 – with macroalbuminua. The urinary excretion of albumin, α1-microglobulin, type IV collagen, transforming growth factor β1 (TGF-β1), matrix metalloproteinase 2 (MMP-2), matrix metalloproteinases 9 (MMP-9), tissue metalloproteinase inhibitor-1 (TIMP-1), tissue metalloproteinase inhibitor-2 (TIMP-2), plasminogen activator ingibitor-1 (PAI-1) was determined by ELISA. 10 healthy subjects served as controls. Kidney biopsy was performed in 22 patients.
Results. In normoalbuminuric patients urinary excretion of all determined mediators did not differed significantly from control. In patients with microalbuminuria urinary excretion of type IV collagen, TGF-β1, MMP-2, MMP-9 and PAI-1 excretion was increased significantly. Patients with macroalbuminuria had increased urinary excretion of α1-microglobulin, type IV collagen, TGF-β1, MMP-2, TIMP-1, TIMP-2 and PAI-1 as compared to control and normoalbuminuric patients. Urinary excretion of MMP-2, MMP-9 and their inhibitors correlated directly with albuminuria. ММP-2, TIMP-1, TIMP-2 and PAI-1 demonstrated the positive correlations with α1-microglobulin and type IV collagen. ММP-2 and PAI-1 correlated positively with TGF-β1. The positive correlation was found between TIMP-1 and glomerular volume as well as between TIMP-2, PAI-1 and fractional volume of interstitium in the renal cortex.
Conclusion: The urinary excretion of matrix metalloproteinases (MMP-2, MMP-9) and their inhibitors (TIMP-1, TIMP-2, PAI-1) is increased in type 1 diabetic patients with nephropathy

About the Autors


Bondar I.А. – professor, head of Department of endocrinology at State Education Institution of High Professional Education “ Novosibirsk State Medical University” Ministry of Health and Social Development of Russian Federation, Ph.D.
Klimontov V.V.- associate professor at Department of endocrinology at State Education Institution of High Professional Education “ Novosibirsk State Medical University” Ministry of Health and Social Development of Russian Federation, Ph.D.
Е-mail: klimontov@mail.ru;
Romanov V.V. – head of laboratory at LLC “Laboratory Diagnostics INVITRO” Ph.D.


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