Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Apr;49(4):717-725.
doi: 10.1007/s11255-016-1495-5. Epub 2017 Jan 2.

Relationship between plasma levels of zonulin, bacterial lipopolysaccharides, D-lactate and markers of inflammation in haemodialysis patients

Affiliations

Relationship between plasma levels of zonulin, bacterial lipopolysaccharides, D-lactate and markers of inflammation in haemodialysis patients

Joanna Ficek et al. Int Urol Nephrol. 2017 Apr.

Abstract

Background: Increased permeability of the intestinal wall and intestinal dysbiosis may contribute to chronic systemic inflammation, one of the causes of accelerated atherosclerosis and cardiovascular morbidity and mortality burden in patients with chronic kidney disease. The aim of this study was to evaluate the association between markers of intestinal permeability and inflammation in haemodialysis (HD) patients.

Methods: Plasma concentration of zonulin, haptoglobin, TNFα, IL6, D-lactates and bacterial lipopolysaccharides (LPS) was assessed in blood samples obtained after overnight fast before midweek morning HD session in 150 stable, prevalent HD patients. Daily intake of energy and macronutrients was assessed on the basis of a food frequency questionnaire.

Results: Serum hsCRP level was increased in over 70% of patients. Plasma levels of zonulin [11.6 (10.9-12.3) vs 6.8 (5.8-7.8) ng/mL], IL6 [6.2 (1.0-10.3) vs 1.3 (1.0-2.0) pg/mL] and TNFα [5.9 (2.9-11.8) vs 1.6 (1.3-1.8) pg/mL], but not LPS and D-lactates were significantly higher in HD than in healthy controls. D-lactates and LPS levels were weakly associated with IL6 (R = 0.175; p = 0.03, and R = 0.241; p = 0.003). There was a borderline correlation between plasma zonulin and serum hsCRP (R = 0.159; p = 0.07), but not with IL6, LPS and D-lactates. In multiple regression, both serum CRP and plasma IL6 variability were explained by LPS (β = 0.143; p = 0.08 and β = 0.171; p = 0.04, respectively), only.

Conclusion: The weak association between plasma D-lactate, LPS and IL6 levels indicates that intestinal flora overgrowth or increased intestinal permeability contributes very slightly to the chronic inflammation development in HD patients.

Keywords: Chronic renal failure; D-Lactate; Haemodialysis; Inflammation; Intestinal permeability; Zonulin.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest

None of the authors has any conflict of interest, financial or otherwise.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Figures

Fig. 1
Fig. 1
Study flow chart
Fig. 2
Fig. 2
Plasma zonulin concentration in 150 haemodialysis patients and 30 control subjects
Fig. 3
Fig. 3
Plasma interleukin 6 concentration in subsequent d-lactates concentration tertiles
Fig. 4
Fig. 4
Correlations between plasma concentration of LPS and inflammatory markers: a IL6 (R = 0.241; p = 0.003) and b serum hsCRP level (R = 0.153; p = 0.06)

References

    1. Lindner A, Charra B, Sherrard DJ, Scribner BH. Accelerated atherosclerosis in prolonged maintenance hemodialysis. N Engl J Med. 1974;290:697–701. doi: 10.1056/NEJM197403282901301. - DOI - PubMed
    1. Wanner C, Zimmermann J, Schwedler S, Metzger T. Inflammation and cardiovascular risk in dialysis patients. Kidney Int Suppl. 2002;80:99–102. doi: 10.1046/j.1523-1755.61.s80.18.x. - DOI - PubMed
    1. Johnson RJ, Feehally J, Floege J. Comprehensive clinical nephrology. 5. Amsterdam: Elsevier Health Sciences, Saunders; 2014. pp. 916–1029.
    1. Pecoits-Filho R, Bárány P, Lindholm B, Heimbürger O, Stenvinkel P. Interleukin-6 is an independent predictor of mortality in patients starting dialysis treatment. Nephrol Dial Transplant. 2002;17:1684–1688. doi: 10.1093/ndt/17.9.1684. - DOI - PubMed
    1. Gupta J, Mitra N, Kanetsky PA, Devaney J, Wing MR, Reilly M, Shah VO, Balakrishnan VS, Guzman NJ, Girndt M, Periera BG, Feldman HI, Kusek JW, Joffe MM, Raj DS; CRIC Study Investigators Association between albuminuria, kidney function, and inflammatory biomarker profile in CKD in CRIC. Clin J Am Soc Nephrol. 2012;7:1938–1946. doi: 10.2215/CJN.03500412. - DOI - PMC - PubMed

MeSH terms