Cell cycle arrest biomarkers for the early detection of acute allograft dysfunction and acute rejection in living donor kidney transplantation: a cross-sectional study from Egypt

Background: Urinary tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) are G1 cell arrest biomarkers that have demonstrated accuracy and validity in predicting and diagnosing acute kidney injury (AKI). This study aimed to evaluate the validity of [TIMP-2]×[IGFBP7] in diagnosing acute allograft dysfunction and its utility in distinguishing acute rejection (AR) from nonrejection causes in kidney transplantation.

Methods: This study included 48 adult living donor kidney transplant recipients (KTRs; 18 with AR, 15 with nonrejection causes of AKI, and 15 with stable grafts). Urinary TIMP-2 and IGFBP7 were measured, and [TIMP-2]×[IGFBP7] was calculated in all subjects.

Results: IGFBP7, TIMP-2, and [TIMP-2]×[IGFBP7] were statistically significantly higher in KTRs with acute allograft dysfunction than in those with stable grafts. [TIMP-2]×[IGFBP7] was statistically significantly higher in KTRs with AR than in those with nonrejection AKI. [TIMP-2]×[IGFBP7] at a cutoff level of 0.278 (ng/mL)²/1,000 had an area under the curve (AUC) of 0.99 with a sensitivity of 100% and a specificity of 93.3% in diagnosing acute allograft dysfunction, while at a cutoff level of 0.803 (ng/mL)²/1,000 had an AUC of 0.939 with a sensitivity of 94.4% and a specificity of 83.3% in diagnosing AR.

Conclusions: Besides its role in the early detection of acute allograft dysfunction, [TIMP-2]×[IGFBP7] may help to differentiate between AR and nonrejection causes in KTRs. However, whether and how urinary [TIMP-2]×[IGFBP7] can be used in clinical diagnosis still requires further research.