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Serum metalloproteinases MMP-2, MMP-9 and metalloproteinase tissue inhibitors TIMP-1 and TIMP-2 in patients on hemodialysis

  • Nephrology - Original Paper
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Abstract

Background

We assessed the effect of hemodialysis (HD) and chronic kidney disease (CKD) on the serum levels of metalloproteinase-2 (MMP-2), MMP-9 and metalloproteinase tissue inhibitors (TIMP-1) and TIMP-2.

Methods

18 patients on regular HD treatment with low-flux, cuprophane membrane, 15 non-dialyzed patients with CKD and 15 healthy controls were sampled. The serum MMP and TIMP concentrations were determined by ELISA assays.

Results

MMP-9, TIMP-1, and TIMP-2 serum levels were significantly decreased in HD patients to 32.7 ± 20.1 ng/ml, 178.8 ± 73.0 ng/ml, and 103.4 ± 55.3 ng/ml compared with 482.3 ± 139.5, 367.6 ± 75.5 ng/ml, and 299.7 ± 63.2 ng/ml in patients with CKD and 594.6 ± 154.7 ng/ml, 354.5 ± 81.2 ng/ml, and 272.4 ± 91.8 ng/ml in healthy controls, respectively, (P < 0.001 vs. HD patients). MMP-2 was lower in patients with CKD: 405.6 ± 106.1 ng/ml compared with 516.9 ± 81.7 ng/ml in controls (P = 0.02). The MMP-2/TIMP-2 ratio was increased in HD patients compared with both patients with CKD and controls. In the course of an HD session, MMP-2 and TIMP-1 serum levels were significantly decreased from pre-HD 570.0 ± 256.5 and 178.8 ± 66.9 ng/ml to post-HD 492.6 ± 212.5 and 144.6 ± 44.2 ng/ml (P = 0.004 and 0.013, respectively). However, the MMP-9/TIMP-1 ratio increased from pre-HD 0.15 (2.19) (median, range) to 0.23 (0.33) after a HD session (P = 0.03). CRP was positively correlated with MMP-9 and MMP-9/TIMP-1 ratio in HD patients and patients with CKD (r = 0.67; P = 0.03).

Conclusions

The MMP-9/TIMP-1 ratio increased during HD sessions, although their absolute levels were lowered. This change may represent a chronic state of enhanced fibrosis in patients undergoing HD.

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References

  1. Lelongt B, Legallicier B, Piedagnel R, Ronco PM (2001) Do matrix metalloproteinases MMP-2 and MMP-9 (gelatinases) play a role in renal development, physiology and glomerular diseases? Curr Opin Nephrol Hypertens 10:7–12

    Article  PubMed  CAS  Google Scholar 

  2. Zeisberg M, Maeshima Y, Mosterman B, Kalluri R (2002) Renal fibrosis. Extracellular matrix microenvironment regulates migratory behavior of activated tubular epithelial cells. Am J Pathol 6:2001–2008

    Google Scholar 

  3. Cheng S, Lovett DH (2003) Gelatinase A (MMP-2) is necessary and sufficient for renal tubular cell epithelial-mesenchymal transformation. Am J Pathol 6:1937–1949

    Google Scholar 

  4. Akahane T, Akahane M, Shah A, Thorgeirsson UP (2004) TIMP-1 stimulates proliferation of human aortic smooth muscle cells and Ras effector pathways. Biochem Biophys Res Commun 1:440–445

    Article  Google Scholar 

  5. Han X, Sun Y, Scott S, Bleich D (2001) Tissue inhibitor of metalloproteinase-1 prevents cytokine-mediated dysfunction and cytotoxicity in pancreatic islets and beta-cells. Diabetes 50:1047–1055

    Article  PubMed  CAS  Google Scholar 

  6. Foley RN, Parfrey PS, Sarnak MJ (1998) Clinical epidemiology of cardiovascular disease in chronic renal failure. Am J Kidney Dis 32:S112–S119

    Article  PubMed  CAS  Google Scholar 

  7. Hansson GK (2005) Inflammation, atherosclerosis and coronary artery disease. N Engl J Med 352:1685–1695

    Article  PubMed  CAS  Google Scholar 

  8. Preston GA, Barrett CV, Alcorta DA et al (2002) Serum matrix metalloproteinases MMP-2 and MMP-3 levels in dialysis patients vary independently of CRP and IL-6 levels. Nephron 92:817–823

    Article  PubMed  CAS  Google Scholar 

  9. Arenas MD, Alvarez-Ude F, Gil MT et al (2006) Application of NKF-K/DOQI clinical practice guidelines for bone metabolism and disease: changes of clinical practices and their effects on outcomes and quality standards in three haemodialysis units. Nephrol Dial Transplant 21:1663–1668

    Article  PubMed  Google Scholar 

  10. Chou FP, Chu SC, Cheng MC et al (2002) Effect of hemodialysis on the plasma level of type IV collagenases and their inhibitors. Clin Biochem 35:383–388

    Article  PubMed  CAS  Google Scholar 

  11. Chang HR, Yang SF, Li ML, Lin CC, Hsieh YS, Lian JD (2006) Relationships between circulating matrix metalloproteinase-2 and -9 and renal function in patients with chronic kidney disease. Clin Chim Acta 366:243–248

    Article  PubMed  CAS  Google Scholar 

  12. Deschamps AM, Yarbrough WM, Squires CE et al (2005) Trafficking of the membrane type-1 matrix metalloproteinase in ischemia and reperfusion: relation to interstitial membrane type-1 matrix metalloproteinase activity. Circulation 111:1166–1174

    Article  PubMed  CAS  Google Scholar 

  13. Pawlak K, Pawlak D, Mysliwiec M (2007) Long-term erythropoietin therapy does not affect metalloproteinases and their inhibitor levels, oxidative stress and inflammation in hemodialyzed patients. Am J Nephrol 27:221–225

    Article  PubMed  CAS  Google Scholar 

  14. Rysz J, Stolarek R, Banach M et al (2006) TNF-alfa priming effect on polymorphonuclear leukocytes reactive oxygen species generation and adhesion molecule expression in hemodialyzed patients. Arch Immunol Ther Exp 54:209–215

    Article  CAS  Google Scholar 

  15. Pourfarziani V, Einollahi B, Assari S et al (2007) A link between the outcome of living unrelated kidney transplantation and HLA compatibility: a preliminary rsrt. Arch Med Sci 3:108–111

    CAS  Google Scholar 

  16. Rysz J, Majewska E, Stolarek RA, Banach M, Cialkowska-Rysz A, Baj Z (2006) The increased levels of soluble TNFa receptors and cellular adhesion molecules in patients undergoing bioincompatible hemodialysis. Am J Nephrol 26:437–444

    Article  PubMed  CAS  Google Scholar 

  17. Barylski M, Banach M, Mikhailidis DP, Pawlicki L, Kowalski J (2008) Decreased kidney function as a risk factor for cardiovascular events in subjects with metabolic syndrome—a pilot study. Arch Med Sci 4:417–423

    Google Scholar 

  18. Rysz J, Banach M, Stolarek RA et al (2007) Serum matrix metalloproteinases MMP-2 and MMP-9 and metalloproteinase tissue inhibitors TIMP-1 and TIMP-2 in diabetic nephropathy. J Nephrol 20:444–452

    PubMed  CAS  Google Scholar 

  19. Pawlak K, Pawlak D, Mysliwiec M (2007) Serum matrix metalloproteinase-2 and increased oxidative stress are associated with carotid atherosclerosis in hemodialyzed patients. Atherosclerosis 190:199–204

    Article  PubMed  CAS  Google Scholar 

  20. Rysz J, Banach M, Ciałkowska-Rysz A, Stolarek R, Drozdz J, Okoński P (2006) Blood serum levels of IL-2, IL-6, IL-8, TNF-a and IL-1b in patients on maintenance hemodialysis. Cell Mol Immunol 3:151–154

    PubMed  CAS  Google Scholar 

  21. Rysz J, Aronow WS, Stolarek RS, Hannam S, Mikhailidis DP, Banach M (2009) Nephroprotective and clinical potential of statins in dialyzed patients. Expert Opin Ther Targets. 13:541–550

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, Lodz, Poland

    Jacek Rysz

  2. Department of Hypertension, Medical University of Lodz, Zeromskiego 113, 90-549, Lodz, Poland

    Maciej Banach

  3. Department of Cardiovascular Physiology, Medical University in Lodz, Lodz, Poland

    Robert A. Stolarek

  4. Department of Clinical Biochemistry, Royal Free Hospital Campus, University College London, London, UK

    Dimitri P. Mikhailidis

  5. Department of Palliative Medicine, Chair of Oncology, Medical University of Lodz, Lodz, Poland

    Aleksandra Cialkowska-Rysz

  6. Department of Pathophysiology and Clinical Immunology, Medical University of Lodz, Lodz, Poland

    Lech Pokoca & Zbigniew Baj

  7. Department of Anesthesiology and Intensive Care Unit, Medical University of Lodz, Lodz, Poland

    Mariusz Piechota

Authors
  1. Jacek Rysz
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  2. Maciej Banach
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  3. Robert A. Stolarek
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  4. Dimitri P. Mikhailidis
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  5. Aleksandra Cialkowska-Rysz
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  6. Lech Pokoca
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  7. Mariusz Piechota
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  8. Zbigniew Baj
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Corresponding author

Correspondence to Maciej Banach.

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Rysz, J., Banach, M., Stolarek, R.A. et al. Serum metalloproteinases MMP-2, MMP-9 and metalloproteinase tissue inhibitors TIMP-1 and TIMP-2 in patients on hemodialysis. Int Urol Nephrol 43, 491–498 (2011). https://doi.org/10.1007/s11255-009-9683-1

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  • DOI: https://doi.org/10.1007/s11255-009-9683-1

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