Urinary Tissue Inhibitor of Metalloproteinase and Insulin-like Growth Factor-7 as Early Biomarkers of Delayed Graft Function After Kidney Transplantation

Abstract

Background. Recently, urinary tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-7 (IGFBP-7), markers for G1 cell cycle arrest, have been identified and validated in predicting the development of acute kidney injury in critically ill patients. It is unknown, however, whether these two biomarkers could predict the development of delayed graft function (DGF) after kidney transplantation (KT). Methods. This is a single-center, prospective, observational study. We enrolled 74 patients who underwent KT between August 2013 and December 2016. Urine sample were collected immediately after the operation. The primary outcome was development of DGF as defined by need for dialysis of more than 1 session within 7 days of KT. Results. Twenty-three patients (31%) were diagnosed with DGF. In univariate analysis, kidneys from expanded criteria donors, higher donor serum creatinine, lower donor estimated glomerular filtration rate, antithymoglobulin exposure, neutrophil gelatinase associated lipocalin, and urinary [TIMP-2] center dot [IGFBP7] were significantly different between early graft function and DGF. However, in multivariate analysis adjusting other factors, deceased donor and urinary [TIMP-2] center dot [IGFBP7] at 0 hours post-transplantation could predict the development of DGF. The receiver operating characteristic curve for prediction of DGF showed an area under the curve of 0.867 (sensitivity 0.86, specificity 0.71) for a cutoff value of 1.39. Conclusions. Our results indicate that urine [TIMP-2] center dot [IGFBP7] immediately after transplantation could be an early, predictive biomarker of DGF in kidney transplantation.