Abstract
Remodeling of extracellular matrix (ECM) is an important physiologic feature of normal growth and kidney development. Matrix metalloproteinase-2 and -9 (MMP-2 & -9), extracellular matrix degrading enzymes, are believed to involve in renal diseases. However, the contribution of circulating MMP-2 and -9 in the kidney transplant recipients have not yet been elucidated. In this study, together with the determination of serum creatinine, serum levels of proMMP-2 and proMMP-9 were measured by gelatin zymography in 353 kidney transplant recipients and 50 healthy controls to reveal that serum creatinine of kidney transplant recipients was significantly higher than that of healthy controls, but glomerular filtration rate (GFR) was significantly lower than healthy controls. In addition, along with the increase of serum levels of proMMP-2, the serum level of creatinine was increased and GFR was decreased. In contrary, along with the decrease of serum levels of proMMP-2, the serum level of creatinine was increased and GFR was decreased. Among various immunosupression regimens, a combination of rapamycin with cyclosporine (CsA) or tacrolimus (FK506) for kidney transplant recipients could lead to a significantly higher serum creatinine and proMMP-2 concentration, as compared with alone treatmented CsA or FK506. In addition, recipients with diabetes mellitus (DM) and post-transplant diabetes mellitus (PTDM) had significantly higher serum proMMP-2 concentrations compared to patients with DM. Furthermore, serum creatinine, proMMP-2 and proMMP-9 concentrations were not affected by dialysis types of recipients before transplantation. By linear regression, our results indicated a positive correlation of serum proMMP-2 concentration with post-transplantation time in kidney transplant recipients. From these results, it was suggested that the proliferation of kidney mesangial cells could enhance the proMMP-2 production, further increase serum proMMP-2, and in turn leading to glomerulosclerosis end in failure of kidney function.
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