Metabolomic Insight into Donation After Circulatory-Death Kidney Grafts in Porcine Autotransplant Model: Normothermic Ex Vivo Kidney Perfusion Compared with Hypothermic Machine Perfusion and Static Cold Storage
Abstract
1. Introduction
2. Results and Discussion
2.1. Influence of Warm Ischemia on Kidney Metabolomic Profiles
2.2. Comparison of Different Types of Kidney Preservation Methods
2.3. Changes Across Time
2.4. Influence of Transplantation Procedure on Kidney Grafts
3. Materials and Methods
3.1. Chemicals
3.2. Animal
3.3. Study Design
3.4. Liquid Chromatography–High Resolution Mass Spectrometry Analysis (LC–HRMS)
3.5. Data Processing and Statistical Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
RRT | Renal replacement therapy |
ECD | Expanded criteria donors |
SCDs | Standard criteria donors |
SPME | Solid-phase microextraction method |
SCS | Static cold storage |
HMP | Hypothermic machine perfusion |
DCD | Donation after circulatory death |
POD | Postoperative day |
LC–HRMS | Liquid Chromatography–High Resolution Mass Spectrometry |
PCA | Principal component analysis |
PLS-DA | Partial least squares discriminant analysis |
VIP | Variable importance in projection |
RM-ANOVA | One-way repeated measures analysis of variance |
WIT | Warm ischemia time |
IQR | Interquartile range |
IRI | Ischemia-reperfusion injury |
AKI | Acute kidney injury |
dIMP | Deoxyinosine monophosphate |
dAMP | Deoxyadenosine monophosphate |
dGMP | Deoxyguanosine monophosphate |
ITPA | Inosine triphosphatase |
PCr | Phosphocreatine |
CK | Creatine kinase |
AMI | Acute myocardial infarction |
CySSG | Cysteine-glutathione disulfide |
γ-GG | Gamma-glutamylglycine |
GGT | Gamma-glutamyl transferase |
ROC | Reactive oxygen species |
GSNO | S-nitrosoglutathione |
NO | Nitric oxide |
iNOS | Inducible nitric oxide synthase |
IAA | Indoleacrylic acid |
DHEAS | Dehydroepiandrosterone sulfate |
7-HOCA | 7alpha-hydroxy-3-oxo-4-cholestenoate |
DHT | Dihydrotestosterone |
UGT | UDP-glucuronosyltransferase |
CKD | Chronic kidney disease |
7-HOCA | 7alpha-Hydroxy-3-oxo-4-cholestenoate |
27-OHC | 27-hydroxycholesterol |
IDO | Indoleamine 2,3-dioxygenase |
GSH | Reduced glutathione |
CoA | Co-enzyme A |
ATP | Adenosine triphosphate |
LPA | Lysophosphatidic acids |
NR | Nicotinamide riboside |
References
- Czyżewski, Ł.; Sańko-Resmer, J.; Wyzgał, J.; Kurowski, A. Assessment of health-related quality of life of patients after kidney transplantation in comparison with hemodialysis and peritoneal dialysis. Ann. Transpl. 2014, 19, 576–585. [Google Scholar] [CrossRef]
- Schold, J.D.; Buccini, L.D.; Goldfarb, D.A.; Flechner, S.M.; Poggio, E.D.; Sehgal, A.R. Association between kidney transplant center performance and the survival benefit of transplantation versus dialysis. Clin. J. Am. Soc. Nephrol. 2014, 9, 1773–1780. [Google Scholar] [CrossRef]
- Axelrod, D.A.; Schnitzler, M.A.; Xiao, H.; Irish, W.; Tuttle-Newhall, E.; Chang, S.H.; Kasiske, B.L.; Alhamad, T.; Lentine, K.L. An economic assessment of contemporary kidney transplant practice. Am. J. Transplant. 2018, 18, 1168–1176. [Google Scholar] [CrossRef]
- Aubert, O.; Kamar, N.; Vernerey, D.; Viglietti, D.; Martinez, F.; Duong Van Huyen, J.-P.; Eladari, D.; Empana, J.-P.; Rabant, M.; Verine, J. Long term outcomes of transplantation using kidneys from expanded criteria donors: Prospective, population based cohort study. BMJ 2015, 351, h3557. [Google Scholar] [CrossRef]
- Molnar, M.Z.; Streja, E.; Kovesdy, C.P.; Shah, A.; Huang, E.; Bunnapradist, S.; Krishnan, M.; Kopple, J.D.; Kalantar-Zadeh, K. Age and the Associations of Living Donor and Expanded Criteria Donor Kidney with Kidney Transplant Outcomes. Am. J. Kidney Dis. 2012, 59, 841–848. [Google Scholar] [CrossRef]
- Rege, A.; Irish, B.; Castleberry, A.; Vikraman, D.; Sanoff, S.; Ravindra, K.; Collins, B.; Sudan, D. Trends in Usage and Outcomes for Expanded Criteria Donor Kidney Transplantation in the United States Characterized by Kidney Donor Profile Index. Cureus 2016, 8, e887. [Google Scholar] [CrossRef]
- Singh, S.K.; Kim, S.J. Does expanded criteria donor status modify the outcomes of kidney transplantation from donors after cardiac death? Am. J. Transplant. 2013, 13, 329–336. [Google Scholar] [CrossRef]
- Hart, A.; Lentine, K.L.; Smith, J.M.; Miller, J.M.; Skeans, M.A.; Prentice, M.; Robinson, A.; Foutz, J.; Booker, S.E.; Israni, A.K.; et al. OPTN/SRTR 2019 Annual Data Report: Kidney. Am. J. Transplant. 2021, 21 (Suppl. 2), 21–137. [Google Scholar] [CrossRef]
- Kaths, J.M.; Echeverri, J.; Chun, Y.M.; Cen, J.Y.; Goldaracena, N.; Linares, I.; Dingwell, L.S.; Yip, P.M.; John, R.; Bagli, D.; et al. Continuous Normothermic Ex Vivo Kidney Perfusion Improves Graft Function in Donation After Circulatory Death Pig Kidney Transplantation. Transplantation 2017, 101, 754–763. [Google Scholar] [CrossRef]
- Kaths, J.M.; Cen, J.Y.; Chun, Y.M.; Echeverri, J.; Linares, I.; Ganesh, S.; Yip, P.M.; John, R.; Bagli, D.; Mucsi, I.; et al. Continuous Normothermic Ex Vivo Kidney Perfusion Is Superior to Brief Normothermic Perfusion Following Static Cold Storage in Donation After Circulatory Death Pig Kidney Transplantation. Am. J. Transplant. 2017, 17, 957–969. [Google Scholar] [CrossRef]
- Kaths, J.M.; Echeverri, J.; Goldaracena, N.; Louis, K.S.; Chun, Y.M.; Linares, I.; Wiebe, A.; Foltys, D.B.; Yip, P.M.; John, R.; et al. Eight-hour continuous normothermic ex vivo kidney perfusion is a safe preservation technique for kidney transplantation: A new opportunity for the storage, assessment, and repair of kidney grafts. Transplantation 2016, 100, 1862–1870. [Google Scholar] [CrossRef]
- Hosgood, S.A.; Callaghan, C.J.; Wilson, C.H.; Smith, L.; Mullings, J.; Mehew, J.; Oniscu, G.C.; Phillips, B.L.; Bates, L.; Nicholson, M.L. Normothermic machine perfusion versus static cold storage in donation after circulatory death kidney transplantation: A randomized controlled trial. Nat. Med. 2023, 29, 1511–1519. [Google Scholar] [CrossRef]
- Moeckli, B.; Sun, P.; Lazeyras, F.; Morel, P.; Moll, S.; Pascual, M.; Bühler, L.H. Evaluation of donor kidneys prior to transplantation: An update of current and emerging methods. Transpl. Int. 2019, 32, 459–469. [Google Scholar] [CrossRef]
- Dare, A.J.; Pettigrew, G.J.; Saeb-Parsy, K. Preoperative assessment of the deceased-donor kidney: From macroscopic appearance to molecular biomarkers. Transplantation 2014, 97, 797–807. [Google Scholar] [CrossRef]
- Warmuzińska, N.; Łuczykowski, K.; Bojko, B. A Review of Current and Emerging Trends in Donor Graft-Quality Assessment Techniques. J. Clin. Med. 2022, 11, 487. [Google Scholar] [CrossRef]
- Wishart, D.S. Metabolomics: The principles and potential applications to transplantation. Am. J. Transplant. 2005, 5, 2814–2820. [Google Scholar] [CrossRef]
- Kvietkauskas, M.; Zitkute, V.; Leber, B.; Strupas, K.; Stiegler, P.; Schemmer, P. The role of metabolomics in current concepts of organ preservation. Int. J. Mol. Sci. 2020, 21, 6607. [Google Scholar] [CrossRef]
- Benincasa, G.; Viglietti, M.; Coscioni, E.; Napoli, C. “Transplantomics” for predicting allograft rejection: Real-life applications and new strategies from Network Medicine. Hum. Immunol. 2023, 84, 89–97. [Google Scholar] [CrossRef]
- Shen, G.; Moua, K.T.Y.; Perkins, K.; Johnson, D.; Li, A.; Curtin, P.; Gao, W.; McCune, J.S. Precision sirolimus dosing in children: The potential for model-informed dosing and novel drug monitoring. Front. Pharmacol. 2023, 14, 1126981. [Google Scholar] [CrossRef]
- Reyes-Garcés, N.; Gionfriddo, E.; Gómez-Ríos, G.A.; Alam, M.N.; Boyacı, E.; Pawliszyn, J. Advances in Solid Phase Microextraction and Perspective on Future Directions. Anal. Chem. 2018, 90, 302–360. [Google Scholar] [CrossRef]
- Hu, B.; Ouyang, G. In situ solid phase microextraction sampling of analytes from living human objects for mass spectrometry analysis. TrAC-Trends Anal. Chem. 2021, 143, 116368. [Google Scholar] [CrossRef]
- Sevgen, S.; Kara, G.; Kir, A.S.; Şahin, A.; Boyaci, E. A critical review of bioanalytical and clinical applications of solid phase microextraction. J. Pharm. Biomed. Anal. 2025, 252, 116487. [Google Scholar] [CrossRef]
- Warmuzińska, N.; Łuczykowski, K.; Stryjak, I.; Rosales-Solano, H.; Urbanellis, P.; Pawliszyn, J.; Selzner, M.; Bojko, B. The impact of normothermic and hypothermic preservation methods on kidney lipidome—Comparative study using chemical biopsy with microextraction probes. Front. Mol. Biosci. 2024, 11, 1341108. [Google Scholar] [CrossRef]
- Stryjak, I.; Warmuzińska, N.; Łuczykowski, K.; Jaroch, K.; Urbanellis, P.; Selzner, M.; Bojko, B. Metabolomic and lipidomic landscape of porcine kidney associated with kidney perfusion in heart beating donors and donors after cardiac death. Transl. Res. 2024, 267, 79–90. [Google Scholar] [CrossRef]
- Olkowicz, M.; Ribeiro, R.V.P.; Yu, F.; Alvarez, M.; Xin, Y.; Yu, J.; Rosales, M.; Adamson, P.; Bissoondath, C.; Smolenski, R.T.; et al. Dynamic Metabolic Changes During Prolonged Ex Situ Heart Perfusion Are Associated with Myocardial Functional Decline. Front. Immunol. 2022, 13, 859506. [Google Scholar] [CrossRef]
- Yang, X.; Kang, A.; Lu, Y.; Li, Y.; Guo, L.; Li, R.; Zhou, X. Exploratory metabolomic analysis based on UHPLC-Q-TOF-MS/MS to study hypoxia-reoxygenation energy metabolic alterations in HK-2 cells. Ren. Fail. 2023, 45, 2186715. [Google Scholar] [CrossRef]
- Nepomuceno, G.; Junho, C.V.C.; Carneiro-Ramos, M.S.; da Silva Martinho, H. Tyrosine and Tryptophan vibrational bands as markers of kidney injury: A renocardiac syndrome induced by renal ischemia and reperfusion study. Sci. Rep. 2021, 11, 15036. [Google Scholar] [CrossRef]
- Okada, A.; Nangaku, M.; Jao, T.-M.; Maekawa, H.; Ishimono, Y.; Kawakami, T.; Inagi, R. D-serine, a novel uremic toxin, induces senescence in human renal tubular cells via GCN2 activation. Sci. Rep. 2017, 7, 11168. [Google Scholar] [CrossRef]
- Patschan, D.; Patschan, S.; Matyukhin, I.; Hoffmeister, M.; Lauxmann, M.; Ritter, O.; Dammermann, W. Metabolomics in Acute Kidney Injury: The Experimental Perspective. J. Clin. Med. Res. 2023, 15, 283–291. [Google Scholar] [CrossRef]
- Sajid, M.I.; Nunez, F.J.; Amirrad, F.; Roosan, M.R.; Vojtko, T.; McCulloch, S.; Alachkar, A.; Nauli, S.M. Untargeted metabolomics analysis on kidney tissues from mice reveals potential hypoxia biomarkers. Sci. Rep. 2023, 13, 17516. [Google Scholar] [CrossRef]
- Nakajima, H. The Relation of Urinary 8-OHdG, A Marker of Oxidative Stress to DNA, and Clinical Outcomes for Ischemic Stroke. Open Neurol. J. 2012, 6, 51–57. [Google Scholar] [CrossRef]
- Xiang, X.; Zhu, J.; Dong, G.; Dong, Z. Epigenetic Regulation in Kidney Transplantation. Front. Immunol. 2022, 13, 861498. [Google Scholar] [CrossRef]
- You, L.; Han, Z.; Chen, H.; Chen, L.; Lin, Y.; Wang, B.; Fan, Y.; Zhang, M.; Luo, J.; Peng, F.; et al. The role of N6-methyladenosine (m6A) in kidney diseases. Front. Med. 2023, 10, 1247690. [Google Scholar] [CrossRef]
- Parker, M.D.; Chambers, P.A.; Lodge, J.P.A.; Pratt, J.R. Ischemia- reperfusion injury and its influence on the epigenetic modification of the donor kidney genome. Transplantation 2008, 86, 1818–1823. [Google Scholar] [CrossRef]
- Pang, Q.; Chen, H.; Wu, H.; Wang, Y.; An, C.; Lai, S.; Xu, J.; Wang, R.; Zhou, J.; Xiao, H. N6-methyladenosine regulators-related immune genes enable predict graft loss and discriminate T-cell mediate rejection in kidney transplantation biopsies for cause. Front. Immunol. 2022, 13, 1039013. [Google Scholar] [CrossRef]
- Behmanesh, M.; Sakumi, K.; Abolhassani, N.; Toyokuni, S.; Oka, S.; Ohnishi, Y.N.; Tsuchimoto, D.; Nakabeppu, Y. ITPase-deficient mice show growth retardation and die before weaning. Cell Death Differ. 2009, 16, 1315–1322. [Google Scholar] [CrossRef]
- Veres, G.; Radovits, T.; Seres, L.; Horkay, F.; Karck, M.; Szabó, G. Effects of inosine on reperfusion injury after cardiopulmonary bypass. J. Cardiothorac. Surg. 2010, 5, 106. [Google Scholar] [CrossRef]
- Módis, K.; Gerő, D.; Stangl, R.; Rosero, O.; Szijártó, A.; Lotz, G.; Mohácsik, P.; Szoleczky, P.; Coletta, C.; Szabó, C. Adenosine and inosine exert cytoprotective effects in an in vitro model of liver ischemia-reperfusion injury. Int. J. Mol. Med. 2013, 31, 437–446. [Google Scholar] [CrossRef]
- Vannucci, R.C.; Towfighi, J.; Vannucci, S.J. Secondary energy failure after cerebral hypoxia-ischemia in the immature rat. J. Cereb. Blood Flow Metab. 2004, 24, 1090–1097. [Google Scholar] [CrossRef]
- Maqdasy, S.; Lecoutre, S.; Renzi, G.; Frendo-Cumbo, S.; Rizo-Roca, D.; Moritz, T.; Juvany, M.; Hodek, O.; Gao, H.; Couchet, M.; et al. Impaired phosphocreatine metabolism in white adipocytes promotes inflammation. Nat. Metab. 2022, 4, 190–202. [Google Scholar] [CrossRef]
- Gabr, R.E.; El-Sharkawy, A.M.M.; Schär, M.; Weiss, R.G.; Bottomley, P.A. High-energy phosphate transfer in human muscle: Diffusion of phosphocreatine. Am. J. Physiol.-Cell Physiol. 2011, 301, 234–241. [Google Scholar] [CrossRef] [PubMed]
- Jiang, P.; Dai, W.; Yan, S.; Chen, Z.; Xu, R.; Ding, J.; Xiang, L.; Wang, S.; Liu, R.; Zhang, W. Biomarkers in the early period of acute myocardial infarction in rat serum and protective effects of Shexiang Baoxin Pill using a metabolomic method. J. Ethnopharmacol. 2011, 138, 530–536. [Google Scholar] [CrossRef] [PubMed]
- Sushentsev, N.; Hamm, G.; Flint, L.; Birtles, D.; Zakirov, A.; Richings, J.; Ling, S.; Tan, J.Y.; McLean, M.A.; Ayyappan, V.; et al. Metabolic imaging across scales reveals distinct prostate cancer phenotypes. Nat. Commun. 2024, 15, 5980. [Google Scholar] [CrossRef] [PubMed]
- Hendriks, K.D.W.; Brüggenwirth, I.M.A.; Maassen, H.; Gerding, A.; Bakker, B.; Porte, R.J.; Henning, R.H.; Leuvenink, H.G.D. Renal temperature reduction progressively favors mitochondrial ROS production over respiration in hypothermic kidney preservation. J. Transl. Med. 2019, 17, 265. [Google Scholar] [CrossRef]
- Jones, D.P. Redifining oxidative stress. Antioxid. Redox Signal. 2006, 8, 1865–1879. [Google Scholar] [CrossRef]
- Mujammami, M.; Nimer, R.M.; Al Mogren, M.; Almalki, R.; Alabdaljabar, M.S.; Benabdelkamel, H.; Abdel Rahman, A.M. Metabolomics Panel Associated with Cystic Fibrosis-Related Diabetes toward Biomarker Discovery. ACS Omega 2024, 9, 32873–32880. [Google Scholar] [CrossRef]
- Kumar, S.; Krishnan, S. Gamma glutamyl transferase as an atherogenic predictive marker in acute coronary syndrome. Int. J. Res. Med. Sci. 2017, 5, 1095. [Google Scholar] [CrossRef]
- Liu, Y.; Xia, C.; Wang, R.; Zhang, J.; Yin, T.; Ma, Y.; Tao, L. The opposite effects of nitric oxide donor, S-nitrosoglutathione, on myocardial ischemia/reperfusion injury in diabetic and non-diabetic mice. Clin. Exp. Pharmacol. Physiol. 2017, 44, 854–861. [Google Scholar] [CrossRef]
- Fan, H.; Le, J.W.; Sun, M.; Zhu, J.H. Pretreatment with S-Nitrosoglutathione Attenuates Septic Acute Kidney Injury in Rats by Inhibiting Inflammation, Oxidation, and Apoptosis. BioMed Res. Int. 2021, 2021, 6678165. [Google Scholar] [CrossRef]
- Aboobucker, S.; Suza, W.; Lorence, A. Characterization of Two Arabidopsis L-Gulono-1,4-lactone Oxidases, AtGulLO3 and AtGulLO5, Involved in Ascorbate Biosynthesis. React. Oxyg. Species 2017, 4, 389–417. [Google Scholar] [CrossRef]
- Semak, I.; Naumova, M.; Korik, E.; Terekhovich, V.; Wortsman, J.; Slominski, A. A novel metabolic pathway of melatonin: Oxidation by cytochromec. Biochemistry 2005, 44, 9300–9307. [Google Scholar] [CrossRef] [PubMed]
- Parlakpinar, H.; Ozer, M.K.; Sahna, E.; Vardi, N.; Cigremis, Y.; Acet, A. Amikacin-induced acute renal injury in rats: Protective role of melatonin. J. Pineal Res. 2003, 35, 85–90. [Google Scholar] [CrossRef] [PubMed]
- Tan, D.X.; Manchester, L.C.; Terron, M.P.; Flores, L.J.; Reiter, R.J. One molecule, many derivatives: A never-ending interaction of melatonin with reactive oxygen and nitrogen species? J. Pineal Res. 2007, 42, 28–42. [Google Scholar] [CrossRef] [PubMed]
- López-Burillo, S.; Tan, D.X.; Rodriguez-Gallego, V.; Manchester, L.C.; Mayo, J.C.; Sainz, R.M.; Reiter, R.J. Melatonin and its derivatives cyclic 3-hydroxymelatonin, N1-acetyl-N2-formyl-5-methoxykynuramine and 6-methoxymelatonin reduce oxidative DNA damage induced by Fenton reagents. J. Pineal Res. 2003, 34, 178–184. [Google Scholar] [CrossRef]
- Zhu, Z.-J.; Qi, Z.; Zhang, J.; Xue, W.-H.; Li, L.-F.; Shen, Z.-B.; Li, Z.-Y.; Yuan, Y.-L.; Wang, W.-B.; Zhao, J. Untargeted metabolomics analysis of esophageal squamous cell carcinoma discovers dysregulated metabolic pathways and potential diagnostic biomarkers. J. Cancer 2020, 11, 3944–3954. [Google Scholar] [CrossRef]
- Huang, Z.; Zhang, W.; An, Q.; Lang, Y.; Liu, Y.; Fan, H.; Chen, H. Exploration of the anti-hyperuricemia effect of TongFengTangSan (TFTS) by UPLC-Q-TOF/MS-based non-targeted metabonomics. Chin. Med. 2023, 18, 17. [Google Scholar] [CrossRef]
- Charalampopoulos, I.; Tsatsanis, C.; Dermitzaki, E.; Alexaki, V.-I.; Castanas, E.; Margioris, A.N.; Gravanis, A. Dehydroepiandrosterone and allopregnanolone protect sympathoadrenal medulla cells against apoptosis via antiapoptotic Bcl-2 proteins. Proc. Natl. Acad. Sci. USA 2004, 101, 8209–8214. [Google Scholar] [CrossRef]
- Jiménez, M.C.; Sun, Q.; Schürks, M.; Chiuve, S.; Hu, F.B.; Manson, J.E.; Rexrode, K.M. Low dehydroepiandrosterone sulfate is associated with increased risk of ischemic stroke among women. Stroke 2013, 44, 1784–1789. [Google Scholar] [CrossRef]
- Aragno, M.; Cutrin, J.C.; Mastrocola, R.; Perrelli, M.G.; Restivo, F.; Poli, G.; Danni, O.; Boccuzzi, G. Oxidative stress and kidney dysfunction due to ischemia/reperfusion in rat: Attenuation by dehydroepiandrosterone. Kidney Int. 2003, 64, 836–843. [Google Scholar] [CrossRef]
- Uchida, M.; Palmateer, J.M.; Herson, P.S.; Devries, A.C.; Cheng, J.; Hurn, P.D. Dose-dependent effects of androgens on outcome after focal cerebral ischemia in adult male mice. J. Cereb. Blood Flow Metab. 2009, 29, 1454–1462. [Google Scholar] [CrossRef]
- Rong, Y.; Kiang, T.K.L. Characterizations of human udp-glucuronosyltransferase enzymes in the conjugation of p-cresol. Toxicol. Sci. 2020, 176, 285–296. [Google Scholar] [CrossRef] [PubMed]
- Poesen, R.; Evenepoel, P.; de Loor, H.; Kuypers, D.; Augustijns, P.; Meijers, B. Metabolism, protein binding, and renal clearance of microbiota-derived p-cresol in patients with CKD. Clin. J. Am. Soc. Nephrol. 2016, 11, 1136–1144. [Google Scholar] [CrossRef] [PubMed]
- De Pascali, S.A.; Gambacorta, L.; Oswald, I.P.; Del Coco, L.; Solfrizzo, M.; Fanizzi, F.P. 1H NMR and MVA metabolomic profiles of urines from piglets fed with boluses contaminated with a mixture of five mycotoxins. Biochem. Biophys. Rep. 2017, 11, 9–18. [Google Scholar] [CrossRef] [PubMed]
- Chang, M.-C.; Chang, H.-H.; Chan, C.-P.; Yeung, S.-Y.; Hsien, H.-C.; Lin, B.-R.; Yeh, C.-Y.; Tseng, W.-Y.; Tseng, S.-K.; Jeng, J.-H. p-Cresol affects reactive oxygen species generation, cell cycle arrest, cytotoxicity and inflammation/atherosclerosis-related modulators production in endothelial cells and mononuclear cells. PLoS ONE 2014, 9, e114446. [Google Scholar] [CrossRef]
- Meijers, B.K.I.; Bammens, B.; De Moor, B.; Verbeke, K.; Vanrenterghem, Y.; Evenepoel, P. Free p-cresol is associated with cardiovascular disease in hemodialysis patients. Kidney Int. 2008, 73, 1174–1180. [Google Scholar] [CrossRef]
- Fang, J.G.; Bo, Z. Structure-activity relationship and mechanism of the tocopherol- regenerating activity of resveratrol and its analogues. J. Agric. Food Chem. 2008, 56, 11458–11463. [Google Scholar] [CrossRef]
- Wang, T.; Feng, W.; Ju, M.; Yu, H.; Guo, Z.; Sun, X.; Yang, K.; Liu, M.; Xiao, R. 27-hydroxycholesterol causes cognitive deficits by disturbing Th17/Treg balance and the related immune responses in mild cognitive impairment patients and C57BL/6J mice. J. Neuroinflammation 2023, 20, 305. [Google Scholar] [CrossRef]
- Heverin, M.; Meaney, S.; Lütjohann, D.; Diczfalusy, U.; Wahren, J.; Björkhem, I. Crossing the barrier: Net flux of 27-hydroxycholesterol into the human brain. J. Lipid Res. 2005, 46, 1047–1052. [Google Scholar] [CrossRef]
- Zhang, H.; Zhao, F.; Zhou, X.; Lou, G.; Li, K. Identification of Potential Biomarkers for Ovarian Cancer by Urinary Metabolomic Profiling. J. Proteome Res. 2013, 12, 505–512. [Google Scholar] [CrossRef]
- Olenchock, B.A.; Moslehi, J.; Baik, A.H.; Davidson, S.M.; Williams, J.; Gibson, W.J.; Chakraborty, A.A.; Pierce, K.A.; Miller, C.M.; Hanse, E.A.; et al. EGLN1 Inhibition and Rerouting of α-Ketoglutarate Suffice for Remote Ischemic Protection. Cell 2016, 164, 884–895. [Google Scholar] [CrossRef]
- Zakrocka, I.; Urbańska, E.M.; Załuska, W.; Kronbichler, A. Kynurenine Pathway after Kidney Transplantation: Friend or Foe? Int. J. Mol. Sci. 2024, 25, 9940. [Google Scholar] [CrossRef] [PubMed]
- Kaden, J.; Abendroth, D.; Völp, A.; Marzinzig, M. Dynamics and diagnostic relevance of kynurenine serum level after kidney transplantation. Ann. Transpl. 2015, 20, 327–337. [Google Scholar] [CrossRef]
- Altintas, R.; Parlakpinar, H.; Beytur, A.; Vardi, N.; Polat, A.; Sagir, M.; Odabas, G.P. Protective effect of dexpanthenol on ischemia-reperfusion-induced renal injury in rats. Kidney Blood Press. Res. 2012, 36, 220–230. [Google Scholar] [CrossRef] [PubMed]
- Yozgat, I.; Şahin, B.; Yıldırım Saral, N.; Ulusoy, Z.B.; Kılercik, M.; Çelik, H.; Danışoğlu, M.E.; Duman, S.; Oktay, B.; Serteser, M.; et al. Untargeted urinary metabolomic profiling in post-kidney transplant with different levels of kidney function. J. Res. Pharm. 2023, 27, 1673–1686. [Google Scholar] [CrossRef]
- Itoh, Y.; Yano, T.; Sendo, T.; Oishi, R. Clinical and experimental evidence for prevention of acute renal failure induced by radiographic contrast media. J. Pharmacol. Sci. 2005, 97, 473–488. [Google Scholar] [CrossRef]
- Wijermars, L.G.M.; Bakker, J.A.; de Vries, D.K.; van Noorden, C.J.F.; Bierau, J.; Kostidis, S.; Mayboroda, O.A.; Tsikas, D.; Schaapherder, A.F.; Lindeman, J.H.N. The hypoxanthine-xanthine oxidase axis is not involved in the initial phase of clinical transplantation-related ischemia-reperfusion injury. Am. J. Physiol.-Ren. Physiol. 2017, 312, F457–F464. [Google Scholar] [CrossRef]
- Cortinovis, M.; Aiello, S.; Mister, M.; Conde-Knape, K.; Noris, M.; Novelli, R.; Solini, S.; Rodriguez Ordonez, P.Y.; Benigni, A.; Remuzzi, G. Autotaxin Inhibitor Protects from Chronic Allograft Injury in Rat Kidney Allotransplantation. Nephron 2020, 144, 38–48. [Google Scholar] [CrossRef]
- Park, Y.C.; Oh, S.I.; Park, Y.H.; Park, S.C. Modulation by aspartate of ischemia/reperfusion-induced oxidative stress in rat liver. Exp. Mol. Med. 1997, 29, 19–23. [Google Scholar] [CrossRef]
- Zhao, K.; Tang, J.; Xie, H.; Liu, L.; Qin, Q.; Sun, B.; Qin, Z.; Sheng, R.; Zhu, J. Nicotinamide riboside attenuates myocardial ischemia-reperfusion injury via regulating SIRT3/SOD2 signaling pathway. Biomed. Pharmacother. 2024, 175, 116689. [Google Scholar] [CrossRef]
- Toropova, Y.G.; Pechnikova, N.A.; Zelinskaya, I.A.; Zhuravsky, S.G.; Kornyushin, O.V.; Gonchar, A.I.; Ivkin, D.Y.; Leonova, Y.V.; Karev, V.E.; Karabak, I.A. Nicotinamide riboside has protective effects in a rat model of mesenteric ischaemia-reperfusion. Int. J. Exp. Pathol. 2018, 99, 304–311. [Google Scholar] [CrossRef]
- Zhong, C.; Pu, L.Y.; Fang, M.M.; Gu, Z.; Rao, J.H.; Wang, X.H. Retinoic acid receptor α promotes autophagy to alleviate liver ischemia and reperfusion injury. World J. Gastroenterol. 2015, 21, 12381–12391. [Google Scholar] [CrossRef] [PubMed]
- Zhu, Z.; Zhu, J.; Zhao, X.; Yang, K.; Lu, L.; Zhang, F.; Shen, W.; Zhang, R. All-trans retinoic acid ameliorates myocardial ischemia/reperfusion injury by reducing cardiomyocyte apoptosis. PLoS ONE 2015, 10, e0133414. [Google Scholar] [CrossRef] [PubMed]
- Serhan, C.N.; Chiang, N.; Dalli, J.; Levy, B.D. Lipid mediators in the resolution of inflammation. Cold Spring Harb. Perspect. Biol. 2015, 7, a016311. [Google Scholar] [CrossRef] [PubMed]
- Kasuga, K.; Yang, R.; Porter, T.F.; Agrawal, N.; Petasis, N.A.; Irimia, D.; Toner, M.; Serhan, C.N. Rapid Appearance of Resolvin Precursors in Inflammatory Exudates: Novel Mechanisms in Resolution. J. Immunol. 2008, 181, 8677–8687. [Google Scholar] [CrossRef]
- Urbanellis, P.; Hamar, M.; Kaths, J.M.; Kollmann, D.; Linares, I.; Mazilescu, L.; Ganesh, S.; Wiebe, A.; Yip, P.M.; John, R.; et al. Normothermic Ex Vivo Kidney Perfusion Improves Early DCD Graft Function Compared with Hypothermic Machine Perfusion and Static Cold Storage. Transplantation 2020, 104, 947–955. [Google Scholar] [CrossRef]
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Stryjak, I.; Warmuzińska, N.; Łuczykowski, K.; Wnuk, K.; Rosales-Solano, H.; Janiszek, P.; Urbanellis, P.; Buszko, K.; Pawliszyn, J.; Selzner, M.; et al. Metabolomic Insight into Donation After Circulatory-Death Kidney Grafts in Porcine Autotransplant Model: Normothermic Ex Vivo Kidney Perfusion Compared with Hypothermic Machine Perfusion and Static Cold Storage. Int. J. Mol. Sci. 2025, 26, 6295. https://doi.org/10.3390/ijms26136295
Stryjak I, Warmuzińska N, Łuczykowski K, Wnuk K, Rosales-Solano H, Janiszek P, Urbanellis P, Buszko K, Pawliszyn J, Selzner M, et al. Metabolomic Insight into Donation After Circulatory-Death Kidney Grafts in Porcine Autotransplant Model: Normothermic Ex Vivo Kidney Perfusion Compared with Hypothermic Machine Perfusion and Static Cold Storage. International Journal of Molecular Sciences. 2025; 26(13):6295. https://doi.org/10.3390/ijms26136295
Chicago/Turabian StyleStryjak, Iga, Natalia Warmuzińska, Kamil Łuczykowski, Kacper Wnuk, Hernando Rosales-Solano, Patrycja Janiszek, Peter Urbanellis, Katarzyna Buszko, Janusz Pawliszyn, Markus Selzner, and et al. 2025. "Metabolomic Insight into Donation After Circulatory-Death Kidney Grafts in Porcine Autotransplant Model: Normothermic Ex Vivo Kidney Perfusion Compared with Hypothermic Machine Perfusion and Static Cold Storage" International Journal of Molecular Sciences 26, no. 13: 6295. https://doi.org/10.3390/ijms26136295
APA StyleStryjak, I., Warmuzińska, N., Łuczykowski, K., Wnuk, K., Rosales-Solano, H., Janiszek, P., Urbanellis, P., Buszko, K., Pawliszyn, J., Selzner, M., & Bojko, B. (2025). Metabolomic Insight into Donation After Circulatory-Death Kidney Grafts in Porcine Autotransplant Model: Normothermic Ex Vivo Kidney Perfusion Compared with Hypothermic Machine Perfusion and Static Cold Storage. International Journal of Molecular Sciences, 26(13), 6295. https://doi.org/10.3390/ijms26136295