Prediction models combining zonulin, LPS, and LBP predict acute kidney injury and hepatorenal syndrome-acute kidney injury in cirrhotic patients.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
11 08 2023
11 08 2023
Historique:
received:
14
04
2023
accepted:
04
08
2023
medline:
16
8
2023
pubmed:
12
8
2023
entrez:
11
8
2023
Statut:
epublish
Résumé
The development of acute kidney injury (AKI) and hepatorenal syndrome-acute kidney injury (HRS-AKI) in cirrhosis has been associated with intestinal barrier dysfunction and gut-kidney crosstalk. We use the related markers such as zonulin, lipopolysaccharides (LPS), and lipopolysaccharide-binding protein (LBP) to predict AKI and HRS-AKI in cirrhotic patients and evaluate their in vitro effects on intestinal (Caco-2) cells and renal tubular (HK-2) cells. From 2013 to 2020, we enrolled 70 cirrhotic patients and developed prediction models for AKI and HRS-AKI over a six-month period. There were 13 (18.6%) and 8 (11.4%) cirrhotic patients developed AKI and HRS-AKI. The prediction models incorporated zonulin, LPS, LBP, C-reactive protein, age, and history of hepatitis B for AKI, and zonulin, LPS, LBP, total bilirubin, and Child-Pugh score for HRS-AKI. The area under curve (AUC) for the prediction of AKI and HRS-AKI was 0.94 and 0.95, respectively. Furthermore, the conditioned medium of LPS+hrLBP pre-treated Caco-2 cells induced apoptosis, necrosis, and zonulin release in HK-2 cells, demonstrating the communication between them. This study found that zonulin, LPS, and LBP are potential practical markers for predicting AKI and HRS-AKI in cirrhotic patients, which may serve as potential targets for renal outcomes in cirrhotic patients.
Identifiants
pubmed: 37567912
doi: 10.1038/s41598-023-40088-7
pii: 10.1038/s41598-023-40088-7
pmc: PMC10421946
doi:
Substances chimiques
Lipopolysaccharides
0
lipopolysaccharide-binding protein
0
zonulin
0
Biomarkers
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
13048Informations de copyright
© 2023. Springer Nature Limited.
Références
du Cheyron, D., Bouchet, B., Parienti, J. J., Ramakers, M. & Charbonneau, P. The attributable mortality of acute renal failure in critically ill patients with liver cirrhosis. Intensive Care Med. 31, 1693–1699 (2005).
pubmed: 16244877
Tariq, R. et al. Incidence, mortality and predictors of acute kidney injury in patients with cirrhosis: A systematic review and meta-analysis. J. Clin. Transl. Hepatol. 8, 135–142 (2020).
pubmed: 32832393
pmcid: 7438348
Cardenas, A. & Arroyo, V. Hepatorenal syndrome. Ann. Hepatol. 2, 23–29 (2003).
pubmed: 15094702
Flamm, S. L. et al. The current management of hepatorenal syndrome-acute kidney injury in the United States and the potential of terlipressin. Liver Transpl. 27, 1191–1202 (2021).
pubmed: 33848394
pmcid: 8457138
Abarca Rozas, B., Mestas Rodríguez, M., Widerström Isea, J., Lobos Pareja, B. & Vargas Urra, J. A current view on the early diagnosis and treatment of acute kidney failure. Medwave 20, e7928 (2020).
pubmed: 32544152
Ning, Y. et al. Impact of acute kidney injury on the risk of mortality in patients with cirrhosis: A systematic review and meta-analysis. Ren. Fail. 44, 1–14 (2022).
pubmed: 36380739
pmcid: 9673785
Muciño-Bermejo, J., Carrillo-Esper, R., Uribe, M. & Méndez-Sánchez, N. Acute kidney injury in critically ill cirrhotic patients: A review. Ann. Hepatol. 11, 301–310 (2012).
pubmed: 22481447
Angeli, P., Garcia-Tsao, G., Nadim, M. K. & Parikh, C. R. News in pathophysiology, definition and classification of hepatorenal syndrome: A step beyond the International Club of Ascites (ICA) consensus document. J. Hepatol. 71, 811–822 (2019).
pubmed: 31302175
Russ, K. B., Stevens, T. M. & Singal, A. K. Acute kidney injury in patients with cirrhosis. J. Clin. Transl. Hepatol. 3, 195–204 (2015).
pubmed: 26623266
pmcid: 4663201
Arroyo, V. et al. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. Int. Ascites Club. Hepatol. 23, 164–176 (1996).
Bernardi, M., Moreau, R., Angeli, P., Schnabl, B. & Arroyo, V. Mechanisms of decompensation and organ failure in cirrhosis: From peripheral arterial vasodilation to systemic inflammation hypothesis. J. Hepatol. 63, 1272–1284 (2015).
pubmed: 26192220
Li, J., Moturi, K. R., Wang, L., Zhang, K. & Yu, C. Gut derived-endotoxin contributes to inflammation in severe ischemic acute kidney injury. BMC Nephrol. 20, 16 (2019).
pubmed: 30634931
pmcid: 6329050
Ding, C. et al. Probiotics ameliorate renal ischemia-reperfusion injury by modulating the phenotype of macrophages through the IL-10/GSK-3β/PTEN signaling pathway. Pflug. Arch. 471, 573–581 (2019).
Li, X., Yuan, F. & Zhou, L. Organ crosstalk in acute kidney injury: Evidence and mechanisms. J. Clin. Med. 11, 6637 (2022).
pubmed: 36431113
pmcid: 9693488
Ghosh, S. S., Wang, J., Yannie, P. J. & Ghosh, S. Intestinal barrier dysfunction, LPS translocation, and disease development. J. Endocr. Soc. 4, bvz039 (2020).
pubmed: 32099951
pmcid: 7033038
Fasano, A. Zonulin and its regulation of intestinal barrier function: The biological door to inflammation, autoimmunity, and cancer. Physiol. Rev. 91, 151–175 (2011).
pubmed: 21248165
Wang, W., Uzzau, S., Goldblum, S. E. & Fasano, A. Human zonulin, a potential modulator of intestinal tight junctions. J. Cell Sci. 113(Pt 24), 4435–4440 (2000).
pubmed: 11082037
Albillos, A. et al. Increased lipopolysaccharide binding protein in cirrhotic patients with marked immune and hemodynamic derangement. Hepatology 37, 208–217 (2003).
pubmed: 12500206
Akira, S. & Takeda, K. Toll-like receptor signalling. Nat. Rev. Immunol. 4, 499–511 (2004).
pubmed: 15229469
Lewis, C. V. & Taylor, W. R. Intestinal barrier dysfunction as a therapeutic target for cardiovascular disease. Am. J. Physiol. Heart Circ. Physiol. 319, H1227–H1233 (2020).
pubmed: 32986965
pmcid: 7792706
Cani, P. D. et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56, 1761–1772 (2007).
pubmed: 17456850
Pijls, K. E., Jonkers, D. M. A. E., Elamin, E. E., Masclee, A. A. M. & Koek, G. H. Intestinal epithelial barrier function in liver cirrhosis: An extensive review of the literature. Liver Int. 33, 1457–1469 (2013).
pubmed: 23879434
Voulgaris, T. A. et al. Serum zonulin levels in patients with liver cirrhosis: Prognostic implications. World J. Hepatol. 13, 1394–1404 (2021).
pubmed: 34786174
pmcid: 8568570
Männistö, V. et al. Serum lipopolysaccharides predict advanced liver disease in the general population. JHEP Rep. 1, 345–352 (2019).
pubmed: 32039385
pmcid: 7005654
Eguchi, A. et al. Branched-chain amino acids protect the liver from cirrhotic injury via suppression of activation of lipopolysaccharide-binding protein, toll-like receptor 4, and signal transducer and activator of transcription 3, as well as Enterococcus faecalis translocation. Nutrition 86, 111194 (2021).
pubmed: 33743328
Al-Obaide, M. A. I. et al. Gut microbiota-dependent trimethylamine-N-oxide and serum biomarkers in patients with T2DM and advanced CKD. J. Clin. Med. 6, 86 (2017).
pubmed: 28925931
pmcid: 5615279
Ficek, J. et al. Relationship between plasma levels of zonulin, bacterial lipopolysaccharides, D-lactate and markers of inflammation in haemodialysis patients. Int. Urol. Nephrol. 49, 717–725 (2017).
pubmed: 28044237
pmcid: 5357507
Kuo, N. R. et al. Low lymphocyte-to-monocyte ratio, calcitriol level, and CD206 level predict the development of acute-on-chronic liver failure in patients cirrhosis with acute decompensation. J. Chin. Med. Assoc. 86, 265–273 (2023).
pubmed: 36727703
Khwaja, A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin. Pract. 120, c179-184 (2012).
pubmed: 22890468
Singer, M. et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 315, 801–810 (2016).
pubmed: 26903338
pmcid: 4968574
Sarin, S. K. et al. Acute-on-chronic liver failure: Consensus recommendations of the Asian Pacific association for the study of the liver (APASL): An update. Hepatol. Int. 13, 353–390 (2019).
pubmed: 31172417
Gopalakrishnan, S., Tripathi, A., Tamiz, A. P., Alkan, S. S. & Pandey, N. B. Larazotide acetate promotes tight junction assembly in epithelial cells. Peptides 35(1), 95–101 (2012).
pubmed: 22401910
Slifer, Z. M. et al. Larazotide acetate induces recovery of ischemia-injured porcine jejunum via repair of tight junctions. PLoS ONE 16(4), e0250165 (2021).
pubmed: 33886649
pmcid: 8061941
Murashima, M. et al. Inflammation as a predictor of acute kidney injury and mediator of higher mortality after acute kidney injury in non-cardiac surgery. Sci. Rep. 9(1), 20260 (2019).
pubmed: 31889082
pmcid: 6937243
Gameiro, J. et al. Prediction of acute kidney injury in cirrhotic patients: A new score combining renal, liver and inflammatory markers. Int. J. Nephrol. Renovasc. Dis. 11, 149–154 (2018).
pubmed: 29731657
pmcid: 5923222
Sherman, D. S., Fish, D. N. & Teitelbaum, I. Assessing renal function in cirrhotic patients: Problems and pitfalls. Am. J. Kidney Dis. 41, 269–278 (2003).
pubmed: 12552488
Jo, S. K., Yang, J., Hwang, S. M., Lee, M. S. & Park, S. H. Role of biomarkers as predictors of acute kidney injury and mortality in decompensated cirrhosis. Sci. Rep. 9, 14508 (2019).
pubmed: 31601879
pmcid: 6787185
Negroni, A. et al. Apoptosis, necrosis, and necroptosis in the gut and intestinal homeostasis. Mediat. Inflamm. 2015, 250762 (2015).
Drago, S. et al. Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scand. J. Gastroenterol. 41, 408–419 (2006).
pubmed: 16635908
Yoshioka, N. et al. Intestinal macrophages involved in the homeostasis of the intestine have the potential for responding to LPS. Anticancer Res. 29, 4861–4865 (2009).
pubmed: 20032448
El Asmar, R. et al. Host-dependent zonulin secretion causes the impairment of the small intestine barrier function after bacterial exposure. Gastroenterology 123, 1607–1615 (2002).
pubmed: 12404235
Ling, X., Linglong, P., Weixia, D. & Hong, W. Protective effects of bifidobacterium on intestinal barrier function in LPS-induced enterocyte barrier injury of Caco-2 monolayers and in a rat NEC model. PLoS ONE 11, e0161635 (2016).
pubmed: 27551722
pmcid: 4995054
Ranoa, D. R. E., Kelley, S. L. & Tapping, R. I. Human lipopolysaccharide-binding protein (LBP) and CD14 independently deliver triacylated lipoproteins to toll-like receptor 1 (TLR1) and TLR2 and enhance formation of the ternary signaling complex. J. Biol. Chem. 288, 9729–9741 (2013).
pubmed: 23430250
pmcid: 3617275
Fasano, A. Physiological, pathological, and therapeutic implications of zonulin-mediated intestinal barrier modulation: Living life on the edge of the wall. Am. J. Pathol. 173, 1243–1252 (2008).
pubmed: 18832585
pmcid: 2570116
Kriz, W., Kaissling, B. & Le Hir, M. Epithelial-mesenchymal transition (EMT) in kidney fibrosis: Fact or fantasy?. J. Clin. Invest. 121, 468–474 (2011).
pubmed: 21370523
pmcid: 3026733
Zhao, L. et al. LPS-induced epithelial-mesenchymal transition of intrahepatic biliary epithelial cells. J. Surg. Res. 171, 819–825 (2011).
pubmed: 20691985
Qin, Y. et al. Lipopolysaccharide induces epithelial-mesenchymal transition of alveolar epithelial cells cocultured with macrophages possibly via the JAK2/STAT3 signaling pathway. Hum. Exp. Toxicol. 39, 224–234 (2020).
pubmed: 31610697
Úbeda, M. et al. Obeticholic acid reduces bacterial translocation and inhibits intestinal inflammation in cirrhotic rats. J. Hepatol. 64, 1049–1057 (2016).
pubmed: 26723896
Liu, S. Y. et al. Pioglitazone ameliorates acute endotoxemia-induced acute on chronic renal dysfunction in cirrhotic ascitic rats. Cells 10, 3044 (2021).
pubmed: 34831270
pmcid: 8616474
Dong, T., Aronsohn, A., Gautham Reddy, K. & Te, H. S. Rifaximin decreases the incidence and severity of acute kidney injury and hepatorenal syndrome in cirrhosis. Dig. Dis. Sci. 61, 3621–3626 (2016).
pubmed: 27655104
Troisi, J. et al. The therapeutic use of the zonulin inhibitor AT-1001 (Larazotide) for a variety of acute and chronic inflammatory diseases. Curr. Med. Chem. 28, 5788–5807 (2021).
pubmed: 33397225