The Role of Endothelins, IL-18, and NGAL in Kidney Hypothermic Machine Perfusion

Tejchman, Karol; Nowacki, Adam; Kotfis, Katarzyna; Skwirczyńska, Edyta; Kotowski, Maciej; Zair, Labib; Ostrowski, Marek; Sieńko, Jerzy

doi:10.3390/biomedicines9040417

Cited by 5 publications

(3 citation statements)

References 63 publications

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“…On the other hand, L-FABP and IL-18 provided little value in predicting DGF. This is similar to the conclusion drawn by Ntrinias [24,27], but some researchers believe that IL-18/L-FABP can predict DGF [7,14]. These contradictory conclusions may require…”

Section: Approved Galley Proofsupporting

confidence: 82%

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Perfusate Neutrophil Gelatinase-Associated Lipocalin, Kidney Injury Molecular-1, Liver-Type Fatty Acid Binding Protein, and Interleukin-18 as Potential Biomarkers to Predict Delayed Graft Function and Long-Term Prognosis in Kidney Transplant Recipients: A Single-Center Retrospective Study

Sun

Gao

et al. 2023

Med Sci Monit

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This study was supported by grants from the Natural Science Foundation of Beijing (7212040) and the National Natural Science Foundation of China (82070764) Conflict of interest:None declared Background:Delayed graft function (DGF) caused by ischemia-reperfusion injury is a common pathophysiological process that should be monitored by specific biomarkers in addition to serum creatinine. Thus, this single-center retrospective study aimed to investigate the association between levels of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecular-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), and interleukin-18 (IL-18) in DGF associated with acute kidney injury in kidney transplant recipients (KTRs) and estimated glomerular filtration rate (eGFR) at 3 years post-transplant. Material/Methods:A total of 102 KTRs [14(13.7%) of DGF and 88(86.3%) of NON-DGF] were enrolled. DGF was defined as "dialysis is needed within 1 week after kidney transplantation". NGAL, KIM-1, L-FABP, and IL-18 were obtained from perfusate samples of donation-after-cardiac-death (DCD) kidneys, and measured by ELISA. Results:Compared to the NON-DGF group, KTRs in the DGF group had a statistically significant increase in levels of NGAL (P<0.001) and KIM-1 (P<0.001). Multiple logistic regression analyses showed that NGAL (OR=1.204, 95% CI 1.057-1.372, P=0.005) and KIM-1 (OR=1.248, CI=1.065-1.463, P=0.006) could be regarded as independent risk factors. The accuracy of NGAL and KIM-1 was 83.3% and 82.1%, respectively, calculated using the area under the receiver operating characteristic curve. Furthermore, the eGFR at 3 years post-transplant had a moderate negative correlation with NGAL (r=-0.208, P=0.036) and KIM-1 (r=-0.260, P=0.008). Conclusions:Our results support those from previous studies showing that perfusate levels of NGAL and KIM-1 are associated with DGF in KTRs and also with reduced eGFR at 3 years post-transplant.

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Section: Approved Galley Proofsupporting

confidence: 82%

“…The perfect definition of DGF is still controversial. In general, most transplantation centers define DGF as follows: renal function has not recovered within 1 week and requires dialysis, or the average creatinine reduction rate within 3 days postoperative is less than 10% [6,7]. However, this definition has some limitations.…”

Section: Introductionmentioning

confidence: 99%

Perfusate Neutrophil Gelatinase-Associated Lipocalin, Kidney Injury Molecular-1, Liver-Type Fatty Acid Binding Protein, and Interleukin-18 as Potential Biomarkers to Predict Delayed Graft Function and Long-Term Prognosis in Kidney Transplant Recipients: A Single-Center Retrospective Study

Sun

Gao

et al. 2023

Med Sci Monit

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“…Под воздействием провоспалительных цитокинов и адгезивного каскада активируется никотинамид аденин динуклеотидфосфат (НАДФН)-оксидаза, что вызывает продукцию большого количества АФК нейтрофилами [14]. Нейтрофилы блокируют капиллярное русло, предотвращая реперфузию, что приводит к некрозу тканей и усилению иммунного ответа [15]. Нейтрофилы секретируют провоспалительные цитокины и хемокины, создавая положительную обратную связь [16].…”

Section: Introductionunclassified

Use of polyclonal antibodies in brain-dead donors in kidney transplantation

Kuzmin

Manukovsky²,

Bagnenko

et al. 2022

RJTAO

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Objective. The objective of this study is to develop a therapeutic strategy for protecting grafts in order to improve the efficiency of kidney transplantation (KT) using polyclonal antibodies (pAbs) through elimination of activated forms of neutrophils, chemo- and cytokines from the donor’s bloodstream, and a decrease in the level of expression of adhesion molecules on the renal vascular endothelium at the pre-transplant stage.Materials and methods. In 2017, we developed and for the first time applied a therapeutic strategy for ischemia-reperfusion injury (IRI) in a brain-dead donor (BDD). Given the limited time interval after brain death has been diagnosed, Timoglobulin (Sanofi Genzyme, France) was administered to the donor at a dose of 8 mg/kg intravenously for 6 hours. Before drug administration and immediately before the start of cold perfusion, a complete blood count and renal transplant biopsy were performed. The study group included 10 BDDs (mean age 39.3 ± 4.4 years) who received anti-thymocyte globulin (ATG). The comparison group included 10 BDDs (mean age 38.5 ± 4.3 years) who did not undergo the new strategy. Donor kidneys were transplanted to 40 recipients (average age 47.5 ± 4.3 years), who were also divided into 2 groups, depending on the graft received (with and without ATG). At the organ donation center, a biobank of specimens from donors of various categories, including those using the IRI therapeutic strategy and recipients for retrospective assessment of the effectiveness of pAbs, was formed.Results. Clinical blood test results show that in the ATG group, there was stable leukopenia (neutropenia and lymphopenia) of 1.46 ± 0.18x109/l. Fifteen (75%) recipients of kidneys obtained from donors with ATG had immediate graft function; in the control group – 10 (50%) recipients.Conclusion. Data obtained testify to the prospects of implementing the proposed strategy in clinical practice, which will improve the quality of the resulting grafts and their suitability for subsequent transplantation, prolong graft functioning due to elimination of leukocytes as a factor of IRI, prevention of early allograft nephropathy, increase in the donor pool by using expanded criteria donors (ECDs).

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p66Shc signaling does not contribute to tubular damage induced by renal ischemia-reperfusion injury in rat

Miller

Regner

Sorokin

2022

Biochemical and Biophysical Research Communications

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The Role of Endothelins, IL-18, and NGAL in Kidney Hypothermic Machine Perfusion

Cited by 5 publications

References 63 publications

Perfusate Neutrophil Gelatinase-Associated Lipocalin, Kidney Injury Molecular-1, Liver-Type Fatty Acid Binding Protein, and Interleukin-18 as Potential Biomarkers to Predict Delayed Graft Function and Long-Term Prognosis in Kidney Transplant Recipients: A Single-Center Retrospective Study

Perfusate Neutrophil Gelatinase-Associated Lipocalin, Kidney Injury Molecular-1, Liver-Type Fatty Acid Binding Protein, and Interleukin-18 as Potential Biomarkers to Predict Delayed Graft Function and Long-Term Prognosis in Kidney Transplant Recipients: A Single-Center Retrospective Study

Use of polyclonal antibodies in brain-dead donors in kidney transplantation

p66Shc signaling does not contribute to tubular damage induced by renal ischemia-reperfusion injury in rat

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