Urinary TIMP-2 predicts the presence and duration of delayed graft function in donation after circulatory death kidney transplant recipients

Background Urinary tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP7) have been validated as biomarkers for acute kidney injury. We investigated the performance of both markers in predicting the occurrence and duration of functionally defined delayed graft function (fDGF) in donation after circulatory death (DCD) kidney transplant recipients. Methods Urine samples of 74 DCD recipients were analyzed. TIMP-2 and IGFBP7 were measured with ELISA on postoperative day 1 to 7, day 10, week 6 and month 6 and values were corrected for osmolality (mOsm). Immunosuppression consisted of anti-CD25 antibody induction and triple maintenance therapy (steroids, MMF and CNI). Statistical analysis included receiver operating characteristic curves and multivariate logistic regression. Results Fifty-one renal transplant recipients had fDGF (69%), of which 14 experienced prolonged fDGF (≥21 days). TIMP-2/mOsm on day-1 and day-10 adequately identified patients with fDGF (AUC 0.91) and prolonged fDGF (AUC 0.80), respectively, whereas IGFBP7/mOsm did not (AUC 0.63 and 0.60). Multivariate analysis on day-1 identified 24-hour urinary creatinine excretion and TIMP-2/mOsm as significant predictors of fDGF (AUC 0.90, 95% CI 0.80-0.98). The best predictors of prolonged fDGF on day-10 were 24-hour urinary creatinine excretion, TIMP-2/mOsm and total warm ischemia time with an AUC of 0.85 (95% CI: 0.72-0.95). Consecutive TIMP-2/mOsm values showed a decrease in TIMP-2/mOsm prior to an increase in eGFR, enabling us to monitor fDGF and predict resolution of fDGF. Conclusion Urinary TIMP-2, but not IGFBP7, is a promising biomarker to predict the occurrence and duration of fDGF in DCD kidney transplant recipients. Corresponding author: Prof.dr. J.W. de Fijter, Leiden University Medical Center, Department of Nephrology, PO Box 9600, 2300 RC Leiden, the Netherlands. E-mail: jwdefijter@lumc.nl, Phone: +31-71-5262218, Fax: +31-71-5266868 AUTHORS CONTRIBUTION JRB participated in the study design, data collection and interpretation, analysis, and writing of the paper. RH participated in study design, data collection and interpretation (ELISAs). DS participated in study design and writing of the paper. OM participated in data analysis (clinical data). FPR participated in data interpretation and conducting ELISAs. CvK participated in study design, data interpretation and writing of the paper. CMC participated in the study design and data interpretation. JWdF participated in study design, data interpretation and writing of the paper. DISCLOSURES The authors of this manuscript declare no funding or conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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