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Updated: Mar 28, 2026
Mouse Kidney Transplantation: Models of Allograft Rejection
Published on: October 11, 2014
Matrix Metalloproteinase-9 and Graft Preservation Injury in Clinical Renal Transplantation
A J Turunen1, L Lindgren2, K T Salmela3
1Department of Surgery, Kanta-Häme Central Hospital, Hämeenlinna, Finland.
Background:
Deleterious effects of matrix metalloproteinase-9 (MMP-9) have been established in experimental renal ischemia-reperfusion models but not in clinical renal transplantation thus far.
Methods:
We studied MMP-9 and its physiological inhibitor tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in 45 consecutive patients of a larger trial in renal transplantation: perioperative anti-thymocyte globulin (group A, n = 15), perioperative basiliximab (group B, n = 16), and conventional triple therapy (group C, n = 14). In addition to systemic blood samples, local blood samples were obtained simultaneously at 1 and 5 minutes after reperfusion from iliac artery and graft vein for calculation of transrenal changes. Because anti-thymocyte globulin activates inflammation, group A was analyzed separately. Groups B and C were pooled (group BC).
Results:
Anti-thymocyte globulin infusion caused a robust rise of MMP-9 in the systemic circulation in group A. No significant transrenal difference of MMP-9 or TIMP-1 occurred in either group during graft reperfusion. In group BC, strong transrenal release of MMP-9 at 1 minute after reperfusion correlated with cold ischemia time (R = 0.66, P = .0001) and was associated with delayed graft function (P = .052).
Conclusions:
Renal production of MMP-9 on graft reperfusion is associated with cold ischemia time and emergence of delayed graft function. MMP inhibition may offer a means to reduce reperfusion injury in renal transplantation.
Insights
Matrix metalloproteinase-9 (MMP-9) renal production during reperfusion correlates with cold ischemia time and delayed graft function. MMP inhibition may reduce reperfusion injury in kidney transplantation.
Area of Science:
- Nephrology
- Transplantation Immunology
- Biochemistry
Background:
- Matrix metalloproteinase-9 (MMP-9) has known detrimental effects in experimental renal ischemia-reperfusion.
- Its role in clinical renal transplantation has not been previously established.
Purpose of the Study:
- To investigate the role of MMP-9 and its inhibitor TIMP-1 in renal transplantation.
- To determine the association between MMP-9 levels, cold ischemia time, and delayed graft function.
Main Methods:
- Studied MMP-9 and TIMP-1 in 45 renal transplant patients receiving different immunosuppressive therapies.
- Collected systemic and local blood samples from iliac artery and graft vein post-reperfusion.
- Analyzed transrenal changes and correlated MMP-9 levels with clinical outcomes.
Main Results:
- Anti-thymocyte globulin infusion significantly increased systemic MMP-9.
- No significant transrenal MMP-9 or TIMP-1 differences were observed during reperfusion.
- Increased MMP-9 release at 1 minute post-reperfusion correlated with cold ischemia time and was associated with delayed graft function.
Conclusions:
- Renal MMP-9 production during reperfusion is linked to cold ischemia duration and delayed graft function.
- MMP inhibition presents a potential therapeutic strategy to mitigate reperfusion injury in kidney transplants.
