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Serum Matrix Metalloprotease‐1 and Vascular Endothelial Growth Factor–A Predict Cardiac Allograft Rejection
Author(s) -
Aharinejad S.,
Krenn K.,
Zuckermann A.,
Schäfer R.,
Gmeiner M.,
Thomas A.,
Aliabadi A.,
Schneider B.,
Grimm M.
Publication year - 2009
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2008.02470.x
Subject(s) - medicine , immunosuppression , vascular endothelial growth factor , matrix metalloproteinase , quartile , gastroenterology , transplantation , heart transplantation , urology , cardiology , vegf receptors , confidence interval
Cardiac allograft rejection is currently diagnosed from endomyocardial biopsies (EMB) that are invasive and impractical to repeat. A serological marker could facilitate rejection monitoring and minimize EMB‐associated risks. We investigated the relation of serum matrix metalloprotease (MMP)‐1 and vascular endothelial growth factor (VEGF)‐A concentrations to cardiac allograft rejection, using 1176 EMBs and serum samples obtained from 208 recipients. Acute cellular rejection was diagnosed in 186 EMBs. Mean week 1 and week 2 serum MMP‐1 concentrations predicted rejection (p = 0.001, AUC = 0.80). At the optimal cut‐off level of ≥7.5 ng/mL, MMP‐1 predicted rejection with 82% sensitivity and 72% specificity. Initial serum MMP‐1 <5.3 ng/mL (lowest quartile) was associated with rejection‐free outcome in 80% of patients. Both MMP‐1 (p < 0.001, AUC = 0.67–0.75) and VEGF‐A (p < 0.01, AUC = 0.62–0.67) predicted rejection on the next EMB, while rejection at EMB was identified only by VEGF‐A (p < 0.02, AUC = 0.70–0.77). Patients receiving combined cyclosporine‐A and everolimus had the lowest serum MMP‐1 concentrations. While serum MMP‐1 predicts rejection‐free outcome and VEGF‐A identifies rejection on EMB, both markers predict rejection in follow‐up of cardiac transplant recipients. Combination of serum MMP‐1 and VEGF‐A concentration may be a noninvasive prognostic marker of cardiac allograft rejection, and could have important implications for choice of surveillance and immunosuppression protocols.