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

Mahmoud M. Elnokeety; Wessam Mustafa Hussein; Samar Ahmed Abdelrazek; Mohamed Momtaz

doi:10.4285/kjt.23.0048

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Korean J Transplant 2023; 37(4): 250-259

Published online December 31, 2023

https://doi.org/10.4285/kjt.23.0048

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

Mahmoud M. Elnokeety¹, Wessam Mustafa Hussein¹, Samar Ahmed Abdelrazek², Mohamed Momtaz¹

¹Nephrology Unit, Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt
²Nasser Institute for Research and Treatment, Ministry of Health, Cairo, Egypt

Correspondence to: Mahmoud M. Elnokeety
Nephrology Unit, Department of Internal Medicine, Faculty of Medicine, Cairo University, Kasr Al-Ainy St, Cairo 11562, Egypt
E-mail: mnokeety77@cu.edu.eg

Received: August 18, 2023; Revised: November 5, 2023; Accepted: November 7, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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Abstract

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.

Keywords: Kidney transplantation, Urinary TIMP-2, Urinary IGFBP7, Acute allograft dysfunction, Acute rejection

HIGHLIGHTS

The role of urinary "tissue inhibitor of metalloproteinase-2"×"insulin-like growth factor-binding protein 7" ([TIMP-2]×[IGFBP7]) has been validated in the risk assessment of acute kidney injury (AKI) in intensive care unit patients.
Its role in assessing AKI in kidney transplantation still has not been thoroughly investigated.
Urinary [TIMP-2]×[IGFBP7] may detect AKI in kidney transplant recipients, identify those at higher risk for acute rejection (AR), and differentiate AR from other causes of AKI.