Urinary transglutaminase 2 as a potent biomarker to predict interstitial fibrosis and tubular atrophy of kidney allograft during early posttransplant period in deceased donor kidney transplantation

Kim, Jee Yeon; Wee, Yu‐Mee; Choi, Monica Young; Jung, Hyo Won; Choi, Ji Yoon; Kwon, Hyun Wook; Jung, Joohee; Cho, Yong Mee; Go, Heounjeong; Han, Minkyu; Kim, Young Hoon; Han, Duck Jong; Shin, Sung

doi:10.4174/astr.2019.97.1.27

Cited by 7 publications

(5 citation statements)

References 31 publications

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“…Besides the urine markers in this study, urine N-acetyl-beta-glucosamynidase, tissue transglutaminase (tTG), transforming growth factor-β (TGF-β), Matrix metalloproteinases (MMPs), and so on are also the research hotspots. 17 , 18 , 19 , 20 This suggests that a single marker is not enough to monitor the occurrence and outcome of AKI accurately, and combined markers may be more effective. For example, urine IL-18 combined with KIM-1 is considered to have the best diagnostic value for AKI that already exists, and urine NGAL combined with IL-18 is the best marker for the diagnosis of early AKI, while urine Nacetyl-beta-glucosamynidase combined with KIM-1 and IL-18 is an ideal marker for the prognosis of AKI.…”

Section: Discussionmentioning

confidence: 99%

Value of urine IL-8, NGAL and KIM-1 for the early diagnosis of acute kidney injury in patients with ureteroscopic lithotripsy related urosepsis

Tan¹,

Zhao²,

Peng³

et al. 2022

Chinese Journal of Traumatology

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Purpose To investigate the clinical value of urine interleukin-18 (IL-8), neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) for the early diagnosis of acute kidney injury (AKI) in patients with ureteroscopic lithotripsy (URL) related urosepsis. Methods A retrospective study was carried out in 157 patients with urosepsis after URL. The patients were divided into AKI group and non-AKI group according to the Kidigo guideline and urine IL-8, NGAL and KIM-1 levels were detected by enzyme-linked immunosorbent assay at 0, 4, 12, 24 and 48 h after the surgery. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of these three biomarkers for postoperative AKI. Results The level of urine IL-8, NGAL and KIM-1 in AKI group was significantly higher than that in non-AKI group at 4, 12, 24 and 48 h ( p < 0.01). The ROC analysis showed the combined detection of urine IL-8, NGAL and KIM-1 at 12 h had a larger area under curve (AUC) than a single marker (0.997, 95% CI : 0.991–0.998), and the sensitivity and specificity were 98.2% and 96.7%, respectively. Pearson correlation analysis showed that the levels of urine NGAL at 4, 12, 24 and 48 h in AKI patients were positively correlated with the levels of urine KIM-1 and IL-18 ( p < 0.01). Conclusion AKI could be quickly recognized by the elevated level of urine IL-8, NGAL and KIM-1 in patients with URL-related urosepsis. Combined detection of the three urine biomarkers at 12 h after surgery had a better diagnostic performance, which may be an important reference for the early diagnosis of AKI.

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Section: Discussionmentioning

confidence: 99%

Value of urine IL-8, NGAL and KIM-1 for the early diagnosis of acute kidney injury in patients with ureteroscopic lithotripsy related urosepsis

Tan¹,

Zhao²,

Peng³

et al. 2022

Chinese Journal of Traumatology

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“…TG2 is excreted at increased levels into the urine of patients with renal fibrosis (20). To investigate whether this increase is specific to patients with fibrotic remodeling of the kidneys, or also observed upon systemic fibrotic remodeling, we analyzed TG2 levels in urine samples from 30 SSc patients and 20 healthy volunteers.…”

Section: Resultsmentioning

confidence: 99%

Amelioration of Fibrotic Remodeling of Human 3‐Dimensional Full‐Thickness Skin by Transglutamase 2 Inhibition

Zhang

Trinh-Minh

Matei

et al. 2023

Arthritis & Rheumatology

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ObjectiveFibrotic tissues are characterized by excessive crosslinking between extracellular matrix (ECM) proteins, rendering them more resistant to degradation. Although increased crosslinking of ECM is thought to play an important role for progression of tissue fibrosis, enhanced ECM crosslinking has not yet been targeted therapeutically in systemic sclerosis (SSc). Here, we investigated the role of transglutaminase 2 (TG2), a central crosslinking enzyme, in the activation of SSc fibroblasts.MethodsWe assessed TG2 expression and activity using TG2 staining, Western blotting, and TG2 activity assays. We inhibited TG2 in fibroblasts cultured under standard 2‐dimensional conditions and in a 3‐dimensional full‐thickness equivalent skin model using monoclonal inhibitory anti‐TG2 antibodies.ResultsTG2 expression was increased in the skin of patients with SSc compared with healthy controls, with levels particularly high in patients with SSc‐associated interstitial lung disease. TG2 expression and TG2 activity were also increased in SSc dermal fibroblasts. Moreover, the levels of circulating TG2 in the plasma samples from SSc patients were increased versus samples from healthy controls. Anti‐TG2 antibodies did not show consistent antifibrotic effects across different fibroblast cell lines under 2‐dimensional culture conditions; however, anti‐TG2 antibodies effectively reduced transforming growth factor β–induced dermal thickening, myofibroblast differentiation, and collagen accumulation in the 3‐dimensional full‐thickness model of human skin.ConclusionWe provide the first evidence, to our knowledge, that inhibition of TG2 might be a potential antifibrotic approach in SSc. Our findings have translational potential as anti‐TG2 antibodies are currently evaluated in a phase II clinical trial in chronic allograft injury and would thus be available for clinical studies in SSc (ClinicalTrials.gov identifier: NCT04335578).image

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“…Increased urinary TG2 levels depict allograft inflammation or fibrosis in kidney transplant patients [ 56 ], and in CKD patients, urinary TG2 levels could be considered a potential biomarker for CKD progression [ 21 ]. Previous studies have demonstrated the mechanisms underlying TG2 associated-ECM accumulation.…”

Section: Discussionmentioning

confidence: 99%

Inhibiting Transglutaminase 2 Mediates Kidney Fibrosis via Anti-Apoptosis

et al. 2022

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Transglutaminase 2 (TG2) is a calcium-dependent transamidating acyltransferase enzyme of the protein-glutamine γ-glutamyltransferase family implicated in kidney injury. In this study, we identified associations between TG2 and chronic kidney disease (CKD) identified by visualizing TG2 in kidney biopsy samples derived from CKD patients using immunohistochemistry and measuring the plasma TG2 concentrations. Our study revealed a connection between TG2 and the pathological markers of kidney disease. We showed high plasma TG2 levels in samples from patients with advanced CKD. In addition, we observed an increase in TG2 expression in tissues concomitant with advanced CKD in human samples. Moreover, we investigated the effect of TG2 inhibition on kidney injury using cystamine, a well-known competitive inhibitor of TG2. TG2 inhibition reduced apoptosis and accumulation of extracellular molecules (ECM) such as fibronectin and pro-inflammatory cytokine IL-8. Collectively, the increased expression of TG2 that was observed in advanced CKD, hence inhibiting TG2 activity, could protect kidney cells from ECM molecule accumulation, apoptosis, and inflammatory responses, thereby preventing kidney fibrosis.

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Urinary transglutaminase 2 as a potent biomarker to predict interstitial fibrosis and tubular atrophy of kidney allograft during early posttransplant period in deceased donor kidney transplantation

Cited by 7 publications

References 31 publications

Value of urine IL-8, NGAL and KIM-1 for the early diagnosis of acute kidney injury in patients with ureteroscopic lithotripsy related urosepsis

Value of urine IL-8, NGAL and KIM-1 for the early diagnosis of acute kidney injury in patients with ureteroscopic lithotripsy related urosepsis

Amelioration of Fibrotic Remodeling of Human 3‐Dimensional Full‐Thickness Skin by Transglutamase 2 Inhibition

Inhibiting Transglutaminase 2 Mediates Kidney Fibrosis via Anti-Apoptosis

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