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Published in: International Urology and Nephrology 1/2018

Open Access 01-01-2018 | Nephrology - Original Paper

Zonulin, inflammation and iron status in patients with early stages of chronic kidney disease

Authors: Ewelina Lukaszyk, Mateusz Lukaszyk, Ewa Koc-Zorawska, Anna Bodzenta-Lukaszyk, Jolanta Malyszko

Published in: International Urology and Nephrology | Issue 1/2018

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Abstract

Background/aims

Zonulin is the only known regulator of intestinal permeability. It is also considered as a potential inflammatory marker in several conditions such as diabetes and inflammatory bowel syndrome. The aim of the study was to investigate zonulin levels in patients with early stages of CKD and its possible correlation with inflammation, anemia and iron status parameters.

Methods

Eighty-eight patients with early stages of CKD and 23 healthy volunteers were enrolled in the study. Zonulin, hepcidin-25, soluble transferrin receptor, interleukin-6 and high-sensitivity C-reactive protein were measured using commercially available assays.

Results

Zonulin was significantly lower among patients with CKD in comparison with healthy volunteers. There were no statistically significant differences in zonulin concentration between patients with and without inflammation. Zonulin was significantly correlated with hepcidin only in patients with inflammation. Zonulin was neither related to iron nor related to ferritin.

Conclusions

Zonulin cannot be considered as an inflammatory marker in CKD. It does not play a role in the disturbances of iron metabolism in CKD. Its physiological role remains to be elucidated.
Literature
1.
go back to reference Fasano A (2009) Regulation of intercellular tight junctions by zonula occludens toxin and its eukaryotic analogue zonulin. Ann N Y Acad Sci 915:214e22 Fasano A (2009) Regulation of intercellular tight junctions by zonula occludens toxin and its eukaryotic analogue zonulin. Ann N Y Acad Sci 915:214e22
2.
go back to reference Tripathi A, Lammers KM, Goldblum S, Shea-Donohue T, Netzel-Arnett S, Buzza MS, Antalis TM, Vogel SN, Zhao A, Yang C, Arrietta MC, Meddings JB, Fasano A (2009) Identification of human zonulin, a physiological modulator of tight junction, as prehaproglobin-2. Proc Natl Acad Sci USA 106:16799CrossRefPubMedPubMedCentral Tripathi A, Lammers KM, Goldblum S, Shea-Donohue T, Netzel-Arnett S, Buzza MS, Antalis TM, Vogel SN, Zhao A, Yang C, Arrietta MC, Meddings JB, Fasano A (2009) Identification of human zonulin, a physiological modulator of tight junction, as prehaproglobin-2. Proc Natl Acad Sci USA 106:16799CrossRefPubMedPubMedCentral
3.
go back to reference Sapone A, de Magistris L, Pietzak M, Clemente MG, Tripathi A, Cucca F, Lampis R, Kryszak D, Cartenì M, Generoso M, Iafusco D, Prisco F, Laghi F, Riegler G, Carratu R, Counts D, Fasano A (2006) Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes 55:1443–1449CrossRefPubMed Sapone A, de Magistris L, Pietzak M, Clemente MG, Tripathi A, Cucca F, Lampis R, Kryszak D, Cartenì M, Generoso M, Iafusco D, Prisco F, Laghi F, Riegler G, Carratu R, Counts D, Fasano A (2006) Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes 55:1443–1449CrossRefPubMed
4.
go back to reference Jayashree B, Bibin YS, Prabhu D, Shanthirani CS, Gokulakrishnan K, Lakshmi BS, Mohan V, Balasubramanyam M (2014) Increased circulatory levels of lipopolysaccharide (LPS) and zonulin signify novel biomarkers of proinflammation in patients with type 2 diabetes. Mol Cell Biochem 388:203–210CrossRefPubMed Jayashree B, Bibin YS, Prabhu D, Shanthirani CS, Gokulakrishnan K, Lakshmi BS, Mohan V, Balasubramanyam M (2014) Increased circulatory levels of lipopolysaccharide (LPS) and zonulin signify novel biomarkers of proinflammation in patients with type 2 diabetes. Mol Cell Biochem 388:203–210CrossRefPubMed
5.
go back to reference Zhang D, Zhang L, Zheng Y, Yue F, Russell RD, Zeng Y (2014) Circulating zonulin levels in newly diagnosed Chinese type 2 diabetes patients. Diabetes Res Clin Pract 106:312–318CrossRefPubMed Zhang D, Zhang L, Zheng Y, Yue F, Russell RD, Zeng Y (2014) Circulating zonulin levels in newly diagnosed Chinese type 2 diabetes patients. Diabetes Res Clin Pract 106:312–318CrossRefPubMed
6.
go back to reference Vanuytsel T, Vermeire S, Cleynen I (2013) The role of Haptoglobin and its related protein, Zonulin, in inflammatory bowel disease. Tissue Barriers 1:e27321CrossRefPubMedPubMedCentral Vanuytsel T, Vermeire S, Cleynen I (2013) The role of Haptoglobin and its related protein, Zonulin, in inflammatory bowel disease. Tissue Barriers 1:e27321CrossRefPubMedPubMedCentral
7.
go back to reference Moreno-Navarrete JM, Sabater M, Ortega F, Ricart W, Fernández-Real JM (2012) Circulating zonulin, a marker of intestinal permeability, is increased in association with obesity-associated insulin resistance. PLoS ONE 7:e37160CrossRefPubMedPubMedCentral Moreno-Navarrete JM, Sabater M, Ortega F, Ricart W, Fernández-Real JM (2012) Circulating zonulin, a marker of intestinal permeability, is increased in association with obesity-associated insulin resistance. PLoS ONE 7:e37160CrossRefPubMedPubMedCentral
8.
go back to reference Łukaszyk E, Łukaszyk M, Koc-Żórawska E, Tobolczyk J, Bodzenta-Łukaszyk A, Małyszko J (2015) Iron status and inflammation in early stages of chronic kidney disease. Kidney Blood Press Res 40:366–373CrossRefPubMed Łukaszyk E, Łukaszyk M, Koc-Żórawska E, Tobolczyk J, Bodzenta-Łukaszyk A, Małyszko J (2015) Iron status and inflammation in early stages of chronic kidney disease. Kidney Blood Press Res 40:366–373CrossRefPubMed
9.
go back to reference Fasano A (2011) Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev 91:151–175CrossRefPubMed Fasano A (2011) Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev 91:151–175CrossRefPubMed
11.
go back to reference Fasano A, Catassi C (2001) Current approaches to diagnosis and treatment of celiac disease: an evolving spectrum. Gastroenterology 120:636–651CrossRefPubMed Fasano A, Catassi C (2001) Current approaches to diagnosis and treatment of celiac disease: an evolving spectrum. Gastroenterology 120:636–651CrossRefPubMed
12.
go back to reference Baumann H, Morella KK, Wong GH (1993) TNF-alpha, IL-1 beta, and hepatocyte growth factor cooperate in stimulating specific acute phase plasma protein genes in rat hepatoma cells. J Immunol 151:4248–4257PubMed Baumann H, Morella KK, Wong GH (1993) TNF-alpha, IL-1 beta, and hepatocyte growth factor cooperate in stimulating specific acute phase plasma protein genes in rat hepatoma cells. J Immunol 151:4248–4257PubMed
13.
go back to reference Smecuol E, Sugai E, Niveloni S, Vázquez H, Pedreira S, Mazure R, Moreno ML, Label M, Mauriño E, Fasano A, Meddings J, Bai JC (2005) Permeability, zonulin production, and enteropathy in dermatitis herpetiformis. Clin Gastroenterol Hepatol 3:335–341CrossRefPubMed Smecuol E, Sugai E, Niveloni S, Vázquez H, Pedreira S, Mazure R, Moreno ML, Label M, Mauriño E, Fasano A, Meddings J, Bai JC (2005) Permeability, zonulin production, and enteropathy in dermatitis herpetiformis. Clin Gastroenterol Hepatol 3:335–341CrossRefPubMed
14.
go back to reference Malyszko J, Koc-Zorawska E, Levin-Iaina N, Malyszko J (2014) Zonulin, iron status, and anemia in kidney transplant recipients: are they related? Transplant Proc 46:2644–2646CrossRefPubMed Malyszko J, Koc-Zorawska E, Levin-Iaina N, Malyszko J (2014) Zonulin, iron status, and anemia in kidney transplant recipients: are they related? Transplant Proc 46:2644–2646CrossRefPubMed
15.
go back to reference Przybyłowski P, Nowak E, Janik L, Wasilewski G, Kozlowska S, Małyszko J (2014) Zonulin and iron metabolism in heart transplant recipients. Transplant Proc 46:2856–2859CrossRefPubMed Przybyłowski P, Nowak E, Janik L, Wasilewski G, Kozlowska S, Małyszko J (2014) Zonulin and iron metabolism in heart transplant recipients. Transplant Proc 46:2856–2859CrossRefPubMed
16.
go back to reference Kotanko P, Carter M, Levin NW (2006) Intestinal bacterial microflora–a potential source of chronic inflammation in patients with chronic kidney disease. Nephrol Dial Transplant 21:2057–2060CrossRefPubMed Kotanko P, Carter M, Levin NW (2006) Intestinal bacterial microflora–a potential source of chronic inflammation in patients with chronic kidney disease. Nephrol Dial Transplant 21:2057–2060CrossRefPubMed
17.
go back to reference Klaus DA, Motal MC, Burger-Klepp U, Marschalek C, Schmidt EM, Lebherz-Eichinger D, Krenn CG, Roth GA (2013) Increased plasma zonulin in patients with sepsis. Biochem Med (Zagreb) 23:107–111CrossRef Klaus DA, Motal MC, Burger-Klepp U, Marschalek C, Schmidt EM, Lebherz-Eichinger D, Krenn CG, Roth GA (2013) Increased plasma zonulin in patients with sepsis. Biochem Med (Zagreb) 23:107–111CrossRef
18.
go back to reference Zhang D, Zhang L, Yue F, Zheng Y, Russell R (2015) Serum zonulin is elevated in women with polycystic ovary syndrome and correlates with insulin resistance and severity of anovulation. Eur J Endocrinol 72:29–36 Zhang D, Zhang L, Yue F, Zheng Y, Russell R (2015) Serum zonulin is elevated in women with polycystic ovary syndrome and correlates with insulin resistance and severity of anovulation. Eur J Endocrinol 72:29–36
19.
go back to reference Rittirsch D, Flierl MA, Nadeau BA, Day DE, Huber-Lang MS, Grailer JJ, Zetoune FS, Andjelkovic AV, Fasano A, Ward PA (2013) Zonulin as prehaptoglobin2 regulates lung permeability and activates the complement system. Am J Physiol Lung Cell Mol Physiol 304:L863–872CrossRefPubMedPubMedCentral Rittirsch D, Flierl MA, Nadeau BA, Day DE, Huber-Lang MS, Grailer JJ, Zetoune FS, Andjelkovic AV, Fasano A, Ward PA (2013) Zonulin as prehaptoglobin2 regulates lung permeability and activates the complement system. Am J Physiol Lung Cell Mol Physiol 304:L863–872CrossRefPubMedPubMedCentral
20.
go back to reference Ficek J, Wyskida K, Ficek R, Wajda J, Klein D, Witkowicz J, Rotkegel S, Spiechowicz-Zatoń U, Kocemba-Dyczek J, Ciepał J, Więcek A, Olszanecka-Glinianowicz M, Chudek J (2017) Relationship between plasma levels of zonulin, bacterial lipopolysaccharides, D-lactate and markers of inflammation in haemodialysis patients. Int Urol Nephrol 49:717–725CrossRefPubMedPubMedCentral Ficek J, Wyskida K, Ficek R, Wajda J, Klein D, Witkowicz J, Rotkegel S, Spiechowicz-Zatoń U, Kocemba-Dyczek J, Ciepał J, Więcek A, Olszanecka-Glinianowicz M, Chudek J (2017) Relationship between plasma levels of zonulin, bacterial lipopolysaccharides, D-lactate and markers of inflammation in haemodialysis patients. Int Urol Nephrol 49:717–725CrossRefPubMedPubMedCentral
21.
go back to reference Dschietzig TB, Boschann F, Ruppert J, Armbruster FP, Meinitzer A, Bankovic D, Mitrovic V, Melzer C (2016) Plasma zonulin and its association with kidney function, severity of heart failure, and metabolic inflammation. Clin Lab 62:2443–2447CrossRefPubMed Dschietzig TB, Boschann F, Ruppert J, Armbruster FP, Meinitzer A, Bankovic D, Mitrovic V, Melzer C (2016) Plasma zonulin and its association with kidney function, severity of heart failure, and metabolic inflammation. Clin Lab 62:2443–2447CrossRefPubMed
22.
23.
go back to reference Fasano A, Not T, Wang W, Uzzau S, Berti I, Tommasini A, Goldblum SE (2000) Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. Lancet 355:1518–1519CrossRefPubMed Fasano A, Not T, Wang W, Uzzau S, Berti I, Tommasini A, Goldblum SE (2000) Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. Lancet 355:1518–1519CrossRefPubMed
Metadata
Title
Zonulin, inflammation and iron status in patients with early stages of chronic kidney disease
Authors
Ewelina Lukaszyk
Mateusz Lukaszyk
Ewa Koc-Zorawska
Anna Bodzenta-Lukaszyk
Jolanta Malyszko
Publication date
01-01-2018
Publisher
Springer Netherlands
Published in
International Urology and Nephrology / Issue 1/2018
Print ISSN: 0301-1623
Electronic ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-017-1741-5

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