Urinary TIMP-2 Predicts the Presence and Duration of Delayed Graft Function in Donation After Circulatory Death Kidney Transplant Recipients

• Published in: Transplantation Vol. 103; no. 5; pp. 1014 - 1023
• Main Authors: Bank, Jonna R, Ruhaak, Renée, Soonawala, Darius, Mayboroda, Oleg, Romijn, Fred P, van Kooten, Cees, Cobbaert, Christa M, de Fijter, Johan W
• Format: Journal Article
• Language: English
• Published: United States Copyright Wolters Kluwer Health, Inc. All rights reserved 01-05-2019
• Subjects: Adult; Allografts - physiopathology; Biomarkers - urine; Cohort Studies; Delayed Graft Function - diagnosis; Delayed Graft Function - physiopathology; Delayed Graft Function - urine; Female; Glomerular Filtration Rate; Humans; Insulin-Like Growth Factor Binding Proteins - urine; Kidney - physiopathology; Kidney Transplantation - adverse effects; Male; Middle Aged; Reference Values; ROC Curve; Time Factors; Tissue Inhibitor of Metalloproteinase-2 - urine
• ISSN: 0041-1337; 1534-6080
• DOI: 10.1097/TP.0000000000002472

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 days 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, mycophenolate mofetil, and calcineurin inhibitor). Statistical analysis included receiver operating characteristic curves and multivariate logistic regression.
RESULTS.Fifty-one (69%) renal transplant recipients had fDGF, of which 14 experienced prolonged fDGF (≥21 days). TIMP-2/mOsm on day-1 and day-10 adequately identified patients with fDGF (area under the curve [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% confidence interval, 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% confidence interval, 0.72-0.95). Consecutive TIMP-2/mOsm values showed a decrease in TIMP-2/mOsm before an increase in estimated glomerular filtration rate, enabling us to monitor fDGF and predict resolution of fDGF.
CONCLUSIONS.Urinary TIMP-2, but not IGFBP7, is a promising biomarker to predict the occurrence and duration of fDGF in DCD kidney transplant recipients.