An analysis of the relationship between donor and recipient biomarkers and kidney graft function, dysfunction, and rejection

Abstract

BackgroundThe study aimed to find predictive biomarkers to evaluate donor kidney function to predict graft dysfunction as well as to assess an early signs of acute graft rejection. MethodTwenty-seven deceased donors and 54 recipients who underwent a successful kidney transplantation were enrolled in the study. An assessment was made in serum and urine from donors and recipients to measure the following biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase 2 (TIMP-2) and urinary N-acetyl-b-D-glucosaminidase (uNAG). These biomarkers were used to establish a model for predicting a reduced graft function (RGF) classified as either a delayed or slow graft function. ResultOur analysis suggest that out of four tested biomarkers, the serum TIMP-2 and uNAG levels of the donors had a predictive value for RGF; the area under the receiver operating characteristic curves (AUROC) of serum TIMP-2 and uNAG were 0.714 and 0.779, respectively. The combined best fitting prediction model of serum TIMP-2, uNAG, and creatinine levels was better in predicting RGF than the serum creatinine level alone. In addition, the recipient serum TIMP-2 level on the third day post-transplantation (D3) was associated with the estimated glomerular filtration rate (eGFR) on the seventh day post-transplantation (D7; OR 1.119, 95% CI 1.016–1.233, p = 0.022). Furthermore, the ROC curve value revealed that the AUROC of TIMP-2 on D3 was 0.99 (95% CI 0.97–1, p < 0.001), and this was the best predictive value of the renal function on D7. ConclusionsDonor serum TIMP-2 and uNAG levels are useful predictive biomarkers because they can provide the donor-based prediction for RGF.