Abstract: TH-PO792
Serum Metalloproteinase-8 (MMP-8) and Tissue Inhibition of Metalloproteinase-1 (TIMP-1) Pretransplant Levels Predict Early Graft Function after Kidney Transplantation
Session Information
- Transplantation: Clinical - 2
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2102 Transplantation: Clinical
Authors
- Hendrikson, Kadri, Helsingin Seudun Yliopistollinen Keskussairaala, Helsinki, Finland
- Helanterä, Ilkka, Helsingin Seudun Yliopistollinen Keskussairaala, Helsinki, Finland
- Meri, Seppo, Helsingin Yliopisto, Helsinki, Finland
- Sorsa, Timo, Helsingin Yliopisto, Helsinki, Finland
- Ortiz, Fernanda, Helsingin Seudun Yliopistollinen Keskussairaala, Helsinki, Finland
Background
Matrix metalloproteinases (MMPs) have a major role in the degradation of components of the extracellular matrix, which results in tissue remodeling. Particularly MMP-8, released by polymorphonuclear neutrophils, has a role in mediating inflammation and kidney fibrosis. Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a natural inhibitor of MMP-8. MMPs have been suggested as a possible common pathway for chronic allograft nephropathy. MMP-8 role in renal transplantation has not been described.
Methods
We prospectively recruited 60 patients waitlisted for kidney transplantation. Patients were divided into 3 groups based on the graft function after surgery: delayed graft function (DGF: need of dialysis), immediate (IGF), and slow graft function (SGF: creatinine concentration over 2,2 mg/dl after 7 d pop). Follow-up data was obtained from the Finnish Transplant Registry. MMP-8 and TIMP-1 were measured in the serum from 59 patients obtained before transplant surgery. MMP-8 levels were determined by time-resolved immunofluorometric assay (IFMA), and TIMP-1 levels by ELISA. Mann-Whitney-U test was used to investigate differences across groups.
Results
MMP-8 concentration was highest and TIMP-1 the lowest in DGF, although not statistically different across DGF, SGF, and IFG (p=0.072 and p=0.060 respectively), but the MMP-8/TIMP-1 ratio was the highest in DGF group (p=0.029). We identified four outlier values, particularly in patients over 70 years old, without any other distinct characteristics explaining the high values. After removing outliers, MMP8 was statistically significantly higher in DGF than IGF (p=0.029). TIPM-1 concentration was lower in DGF (p=0.075) and MMP-8/TIPM-1 ratio was the highest in DGF vs IGF (p=0.014).
Conclusion
High pre-transplant concentrations of pro-inflammatory marker MMP-8 and lower TIMP-1 are related to delayed graft function.
Funding
- Private Foundation Support